Risks and Benefits of SGLT-2 Inhibitors for Type 1 Diabetes Patients Using Automated Insulin Delivery Systems-A Literature Review.

The primary treatment for autoimmune Diabetes Mellitus (Type 1 Diabetes Mellitus-T1DM) is insulin therapy. Unfortunately, a multitude of clinical cases has demonstrated that the use of insulin as a sole therapeutic intervention fails to address all issues comprehensively. Therefore, non-insulin adjunct treatment has been investigated and shown successful results in clinical trials. Various hypoglycemia-inducing drugs such as Metformin, glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, amylin analogs, and Sodium-Glucose Cotransporters 2 (SGLT-2) inhibitors, developed good outcomes in patients with T1DM. Currently, SGLT-2 inhibitors have remarkably improved the treatment of patients with diabetes by preventing cardiovascular events, heart failure hospitalization, and progression of renal disease. However, their pharmacological potential has not been explored enough. Thus, the substantial interest in SGLT-2 inhibitors (SGLT-2is) underlines the present review. It begins with an overview of carrier-mediated cellular glucose uptake, evidencing the insulin-independent transport system contribution to glucose homeostasis and the essential roles of Sodium-Glucose Cotransporters 1 and 2. Then, the pharmacological properties of SGLT-2is are detailed, leading to potential applications in treating T1DM patients with automated insulin delivery (AID) systems. Results from several studies demonstrated improvements in glycemic control, an increase in Time in Range (TIR), a decrease in glycemic variability, reduced daily insulin requirements without increasing hyperglycemic events, and benefits in weight management. However, these advantages are counterbalanced by increased risks, particularly concerning Diabetic Ketoacidosis (DKA). Several clinical trials reported a higher incidence of DKA when patients with T1DM received SGLT-2 inhibitors such as Sotagliflozin and Empagliflozin. On the other hand, patients with T1DM and a body mass index (BMI) of ≥27 kg/m2 treated with Dapagliflozin showed similar reduction in hyperglycemia and body weight and insignificantly increased DKA incidence compared to the overall trial population. Additional multicenter and randomized studies are required to establish safer and more effective long-term strategies based on patient selection, education, and continuous ketone body monitoring for optimal integration of SGLT-2 inhibitors into T1DM therapeutic protocol.

Valorization of Gleditsia triacanthos Invasive Plant Cellulose Microfibers and Phenolic Compounds for Obtaining Multi-Functional Wound Dressings with Antimicrobial and Antioxidant Properties.

Gleditsia triacanthos is an aggressive invasive species in Eastern Europe, producing a significant number of pods that could represent an inexhaustible resource of raw material for various applications. The aim of this study was to extract cellulose from the Gleditsia triacanthos pods, characterize it by spectrophotometric and UHPLC-DAD-ESI/MS analysis, and use it to fabricate a wound dressing that is multi-functionalized with phenolic compounds extracted from the leaves of the same species. The obtained cellulose microfibers (CM) were functionalized, lyophilized, and characterized by ATR-FTIR and SEM. The water absorption and retention capacity as well as the controlled release of phenolic compounds with antioxidant properties evaluated in temporal dynamics were also determined. The antimicrobial activity against reference and clinical multi-drug-resistant Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, Candida albicans, and Candida parapsilosis strains occurred immediately after the contact with the tested materials and was maintained for 24 h for all tested microbial strains. In conclusion, the multi-functionalized cellulose microfibers (MFCM) obtained from the reproductive organs of an invasive species can represent a promising alternative for the development of functional wound dressings with antioxidant and antimicrobial activity, as well as being a scalable example for designing cost-effective, circular bio-economy approaches to combat the accelerated spread of invasive species.

Development and Sequential Analysis of a New Multi-Agent, Anti-Acne Formulation Based on Plant-Derived Antimicrobial and Anti-Inflammatory Compounds.

The antibacterial and anti-inflammatory potential of natural, plant-derived compounds has been reported in many studies. Emerging evidence indicates that plant-derived essential oils and/or their major compounds may represent a plausible alternative treatment for acne, a prevalent skin disorder in both adolescent and adult populations. Therefore, the purpose of this study was to develop and subsequently analyze the antimicrobial activity of a new multi-agent, synergic formulation based on plant-derived antimicrobial compounds (i.e., eugenol, ß-pinene, eucalyptol, and limonene) and anti-inflammatory agents for potential use in the topical treatment of acne and other skin infections. The optimal antimicrobial combinations selected in this study were eugenol/ß-pinene/salicylic acid and eugenol/ß-pinene/2-phenoxyethanol/potassium sorbate. The possible mechanisms of action revealed by flow cytometry were cellular permeabilization and inhibition of efflux pumps activity induced by concentrations corresponding to sub-minimal inhibitory (sub-MIC) values. The most active antimicrobial combination represented by salycilic acid/eugenol/ß-pinene/2-phenoxyethanol/potassium sorbate was included in a cream base, which demonstrated thermodynamic stability and optimum microbiological characteristics.

Microbiota analysis in individuals with type two diabetes mellitus and end­stage renal disease: A pilot study.

Chronic kidney disease (CKD) is a widespread health concern, which affects ~9.1% of the global population and 12-15% of individuals in upper-middle income countries. Notably, ~2% of patients with CKD progress to end-stage renal disease (ESRD), which leads to a substantial decline in the quality of life, an increased risk of mortality and significant financial burden. Patients with ESRD often still suffer from uremia and uremic syndromes, due to the accumulation of toxins between dialysis sessions and the inadequate removal of protein-bound toxins during dialysis. A number of these toxins are produced by the gut microbiota through the fermentation of dietary proteins or cholines. Furthermore, the gut microbial community serves a key role in maintaining metabolic and immune equilibrium in individuals. The present study aimed to investigate the gut microbiota patterns in individuals with type 2 diabetes mellitus (T2DM) and ESRD via quantitative PCR analysis of the 16S and 18S ribosomal RNA of selected members of the gut microbiota. Individuals affected by both T2DM and ESRD displayed distinctive features within their intestinal microbiota. Specifically, there were increased levels of Gammaproteobacteria observed in these patients, and all subjects exhibited a notably increased presence of Enterobacteriaceae compared with healthy individuals. This particular microbial community has established connections with the presence of inflammatory processes in the colon. Moreover, the elevated levels of Enterobacteriaceae may serve as an indicator of an imbalance in the intestinal microbiota, a condition known as dysbiosis. In addition, the Betaproteobacteria phylum was significantly more prevalent in the stool samples of patients with both T2DM and ESRD when compared with the control group. In conclusion, the present pilot study focused on gut microbiome alterations in T2DM and ESRD. Understanding the relationship between dysbiosis and CKD may identify new areas of research and therapeutic interventions aimed at modulating the gut microbiota to improve the health and outcomes of individuals with CKD and ESRD.

Insights into the physico-chemical and biological characterization of sodium lignosulfonate - silver nanosystems designed for wound management.

Chronic wounds represent one of the complications that might occur from the disruption of wound healing process. Recently, there has been a rise in interest in employing nanotechnology to develop novel strategies for accelerating wound healing. The aim of the present study was to use a green synthesis method to obtain AgNPs/NaLS systems useful for wounds management and perform an in-depth investigation of their behavior during and post-synthesis as well as of their biological properties. The colloids obtained from silver nanoparticles (AgNPs) and commercial sodium lignosulfonate (NaLS) in a single-pot aqueous procedure have been fully characterized by UV-Vis, FT-IR, DLS, TEM, XRD, and XPS to evaluate the synthesis efficiency and to provide new insights in the process of AgNPs formation and NaLS behavior in aqueous solutions. The effects of various concentrations of NaLS (0-16 mg/mL) and AgNO3 (0-20 mM) and of two different temperatures on AgNPs formation have been analyzed. Although the room temperature is feasible for AgNPs synthesis, the short mixing at 70 °C significantly increases the speed of nanoparticle formation and storage stability. In all experimental conditions AgNPs of 20-40 nm in size have been obtained. The antimicrobial activity assessed quantitatively on clinical and reference bacterial strains, both in suspension and biofilm growth state, revealed a broad antimicrobial spectrum, the most intensive inhibitory effect being noticed against Pseudomonas aeruginosa and Escherichia coli strains. The AgNP/NaLS enhanced the NO extracellular release, potentially contributing to the microbicidal and anti-adherence activity by protein oxidation. Both AgNP/NaLS and NaLS were non-hemolytic (hemolytic index<5%, 2.26 ± 0.13% hemolysis) and biocompatible (102.17 ± 3.43 % HaCaT cells viability). The presence of AgNPs increased the antioxidative activity and induced a significant cytotoxicity on non-melanoma skin cancer cells (62.86 ± 8.27% Cal-27 cells viability). Taken together, all these features suggest the multivalent potential of these colloids for the development of novel strategies for wound management, acting by preventing infection-associated complications and supporting the tissue regeneration.

Electrospun/3D-Printed Bicomponent Scaffold Co-Loaded with a Prodrug and a Drug with Antibacterial and Immunomodulatory Properties.

This work reports the construction of a bicomponent scaffold co-loaded with both a prodrug and a drug (BiFp@Ht) as an efficient platform for wound dressing, by combining the electrospinning and 3D-printing technologies. The outer component consisted of a chitosan/polyethylene oxide-electrospun membrane loaded with the indomethacin-polyethylene glycol-indomethacin prodrug (Fp) and served as a support for printing the inner component, a gelatin methacryloyl/sodium alginate hydrogel loaded with tetracycline hydrochloride (Ht). The different architectural characteristics of the electrospun and 3D-printed layers were very well highlighted in a morphological analysis performed by Scanning Electron Microscopy (SEM). In vitro release profile studies demonstrated that both Fp and Ht layers were capable to release the loaded therapeutics in a controlled and sustained manner. According to a quantitative in vitro biological assessment, the bicomponent BiFp@Ht scaffold showed a good biocompatibility and no cytotoxic effect on HeLa cell cultures, while the highest proliferation level was noted in the case of HeLa cells seeded onto an Fp nanofibrous membrane. Furthermore, the BiFp@Ht scaffold presented an excellent antimicrobial activity against the E. coli and S. aureus bacterial strains, along with promising anti-inflammatory and proangiogenic activities, proving its potential to be used for wound dressing.

Microbial Polysaccharide-Based Formulation with Silica Nanoparticles; A New Hydrogel Nanocomposite for 3D Printing.

Natural polysaccharides are highly attractive biopolymers recommended for medical applications due to their low cytotoxicity and hydrophilicity. Polysaccharides and their derivatives are also suitable for additive manufacturing, a process in which various customized geometries of 3D structures/scaffolds can be achieved. Polysaccharide-based hydrogel materials are widely used in 3D hydrogel printing of tissue substitutes. In this context, our goal was to obtain printable hydrogel nanocomposites by adding silica nanoparticles to a microbial polysaccharide's polymer network. Several amounts of silica nanoparticles were added to the biopolymer, and their effects on the morpho-structural characteristics of the resulting nanocomposite hydrogel inks and subsequent 3D printed constructs were studied. FTIR, TGA, and microscopy analysis were used to investigate the resulting crosslinked structures. Assessment of the swelling characteristics and mechanical stability of the nanocomposite materials in a wet state was also conducted. The salecan-based hydrogels displayed excellent biocompatibility and could be employed for biomedical purposes, according to the results of the MTT, LDH, and Live/Dead tests. The innovative, crosslinked, nanocomposite materials are recommended for use in regenerative medicine.

Snapshot of the pollution-driven metabolic and microbiota changes in Carassius gibelio from Bucharest leisure lakes.

In the last decades, increased intakes of contaminants and the habitats' destruction have produced drastic changes in the aquatic ecosystems. The environmental contaminants can accumulate in aquatic organisms, leading to the disturbance of the antioxidant/prooxidant balance in fish. In this context, we evaluated the level of organic, inorganic and microbiological pollutants in four leisure lakes (Chitila, Floreasca, Tei and Vacaresti) from Bucharest, the largest city of Romania, in order to compare their effects on hepatopancreas and gills metabolism and antioxidant defense mechanisms in Carassius gibelio, the most known and widespread freshwater fish in this country. The lowest level of oxidative stress was recorded in the case of fish collected from the Vacaresti lake, a protected wetland area where aquatic organisms live in wild environmental conditions. In contrast, significant oxidative changes were observed in the hepatopancreas and gills of fish from the Chitila, Floreasca and Tei lakes, such as reduced glutathione S-transferase activity and glutathione level, and increased degree of lipid peroxidation, being correlated with elevated levels of pesticides (such as 2,4'-methoxychlor) and Escherichia coli load in these organs. Although different patterns of pollutants' accumulation were observed, no important interindividual variations in cytosine methylation degree were determined. In conclusion, the presence and concentrations of metals, pesticides and antibiotics varied with the analyzed tissue and sampling site, and were correlated with changes in the cellular redox homeostasis, but without significantly affecting the epigenetic mechanisms.

Electrospun Nanofibrous Membranes Based on Citric Acid-Functionalized Chitosan Containing rGO-TEPA with Potential Application in Wound Dressings.

The present research work is focused on the design and investigation of electrospun composite membranes based on citric acid-functionalized chitosan (CsA) containing reduced graphene oxide-tetraethylene pentamine (CsA/rGO-TEPA) as materials with opportune bio-properties for applications in wound dressings. The covalent functionalization of chitosan (CS) with citric acid (CA) was achieved through the EDC/NHS coupling system and was checked by 1H-NMR spectroscopy and FTIR spectrometry. The mixtures to be electrospun were formulated by adding three concentrations of rGO-TEPA into the 1/1 (w/w) CsA/poly (ethylene oxide) (PEO) solution. The effect of rGO-TEPA concentration on the morphology, wettability, thermal stability, cytocompatibility, cytotoxicity, and anti-biofilm activity of the nanofibrous membranes was extensively investigated. FTIR and Raman results confirmed the covalent and non-covalent interactions that appeared between the system's compounds, and the exfoliation of rGO-TEPA sheets within the CsA in the presence of PEO (CsA/P) polymer matrix, respectively. SEM analysis emphasized the nanofibrous architecture of membranes and the presence of rGO-TEPA sheets entrapped into the CsA nanofiber structure. The MTT cellular viability assay showed a good cytocompatibility with the highest level of cell development and proliferation registered for the CsA/P composite nanofibrous membrane with 0.250 wt.% rGO-TEPA. The designed nanofibrous membranes could have potential applications in wound dressings, given that they showed a good anti-biofilm activity against Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus bacterial strains.

Macrophage-targeted mannose-decorated PLGA-vegetable oil hybrid nanoparticles loaded with anti-inflammatory agents.

This work pledge to extend the therapeutic windows of hybrid nanoparticulate systems by engineering mannose-decorated hybrid nanoparticles based on poly lactic-co-glycolic acid (PLGA) and vegetable oil for efficient delivery of two lipophilic anti-inflammatory therapeutics (Celecoxib-CL and Indomethacin-IMC) to macrophages. The mannose surface modification of nanoparticles is achieved via O-palmitoyl-mannose spacer during the emulsification and nanoparticles assembly process. The impact of targeting motif on the hydrodynamic features (RH, PdI), stability (ζ-potential), drug encapsulation efficiency (DEE) is thoroughly investigated. Besides, the in vitro biocompatibility (MTT, LDH) and susceptibility of mannose-decorated formulations to macrophage as well their immunomodulatory activity (ELISA) are also evaluated. The monomodal distributed mannose-decorated nanoparticles are in the range of nanometric size (RH < 115 nm) with PdI < 0.20 and good encapsulation efficiency (DEE = 46.15% for CL and 76.20% for IMC). The quantitative investigation of macrophage uptake shows a 2-fold increase in fluorescence (RFU) of cells treated with mannose-decorated formulations as compared to non-decorated ones (p < 0.001) suggesting an enhanced cell uptake respectively improved macrophage targeting while the results of ELISA experiments suggest the potential immunomodulatory properties of the designed mannose-decorated hybrid formulations.

Common themes in antimicrobial and anticancer drug resistance.

Antimicrobial and anticancer drug resistance represent two of the main global challenges for the public health, requiring immediate practical solutions. In line with this, we need a better understanding of the origins of drug resistance in prokaryotic and eukaryotic cells and the evolutionary processes leading to the occurrence of adaptive phenotypes in response to the selective pressure of therapeutic agents. The purpose of this paper is to present some of the analogies between the antimicrobial and anticancer drug resistance. Antimicrobial and anticancer drugs share common targets and mechanisms of action as well as similar mechanisms of resistance (e.g., increased drug efflux, drug inactivation, target alteration, persister cells' selection, protection of bacterial communities/malignant tissue by an extracellular matrix, etc.). Both individual and collective stress responses triggered by the chemotherapeutic agent involving complex intercellular communication processes, as well as with the surrounding microenvironment, will be considered. The common themes in antimicrobial and anticancer drug resistance recommend the utility of bacterial experimental models for unraveling the mechanisms that facilitate the evolution and adaptation of malignant cells to antineoplastic drugs.

Crosslinked Collagenic Scaffold Behavior Evaluation by Physico-Chemical, Mechanical and Biological Assessments in an In Vitro Microenvironment.

Wound healing-associated difficulties continue to drive biotechnological creativeness into complex grounds. The sophisticated architecture of skin wound sites and the intricate processes involved in the response to the use of regenerative devices play a critical role in successful skin regeneration approaches and their possible outcomes. Due to a plethora of complications involved in wound healing processes as well as the coordination of various cellular mechanisms, biomimetic approaches seems to be the most promising starting ground. This study evaluates the behavior of a crosslinked, porous collagen scaffold obtained by lyophilization and dehydrothermal reticulation (DHT). We address the key physio-chemical and mechanical factors, such as swelling, density and porosity, mechano-dynamic properties, SEM and TG-DSC, as well as important biological outcomes regarding scaffold biocompatibility and cellular metabolic activity, cytokine expression in inflammation, apoptosis and necrosis, as well as hemocompatibility and biodegradation. The mechanical and visco-elastic behavior are correlated, with the samples found to present similar thermal behavior and increased rigidity after DHT treatment. High biocompatibility rates were obtained, with no inflammatory stimulation and a reduction in necrotic cells. Higher percentages of cellular early apoptosis were observed. The hemocompatibility rate was under 2%, coagulation effects expressed after 4 min, and the DHT scaffold was more resistant to the biodegradation of collagenase compared with the untreated sample.

Mitigation of Cellular and Bacterial Adhesion on Laser Modified Poly (2-Methacryloyloxyethyl Phosphorylcholine)/Polydimethylsiloxane Surface.

Nowadays, using polymers with specific characteristics to coat the surface of a device to prevent undesired biological responses can represent an optimal strategy for developing new and more efficient implants for biomedical applications. Among them, zwitterionic phosphorylcholine-based polymers are of interest due to their properties to resist cell and bacterial adhesion. In this work, the Matrix-Assisted Laser Evaporation (MAPLE) technique was investigated as a new approach for functionalising Polydimethylsiloxane (PDMS) surfaces with zwitterionic poly(2-Methacryloyloxyethyl-Phosphorylcholine) (pMPC) polymer. Evaluation of the physical-chemical properties of the new coatings revealed that the technique proposed has the advantage of achieving uniform and homogeneous stable moderate hydrophilic pMPC thin layers onto hydrophobic PDMS without any pre-treatment, therefore avoiding the major disadvantage of hydrophobicity recovery. The capacity of modified PDMS surfaces to reduce bacterial adhesion and biofilm formation was tested for Gram-positive bacteria, Staphylococcus aureus (S. aureus), and Gram-negative bacteria, Escherichia coli (E. coli). Cell adhesion, proliferation and morphology of human THP-1 differentiated macrophages and human normal CCD-1070Sk fibroblasts on the different surfaces were also assessed. Biological in vitro investigation revealed a significantly reduced adherence on PDMS-pMPC of both E. coli (from 29 × 10 6 to 3 × 102 CFU/mL) and S. aureus (from 29 × 106 to 3 × 102 CFU/mL) bacterial strains. Additionally, coated surfaces induced a significant inhibition of biofilm formation, an effect observed mainly for E. coli. Moreover, the pMPC coatings improved the capacity of PDMS to reduce the adhesion and proliferation of human macrophages by 50% and of human fibroblast by 40% compared to unmodified scaffold, circumventing undesired cell responses such as inflammation and fibrosis. All these highlighted the potential for the new PDMS-pMPC interfaces obtained by MAPLE to be used in the biomedical field to design new PDMS-based implants exhibiting long-term hydrophilic profile stability and better mitigating foreign body response and microbial infection.

Melatonin-Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions.

Melatonin is a pineal indolamine, allegedly known as a circadian rhythm regulator, and an antioxidative and immunomodulatory molecule. In both experimental and clinical trials, melatonin has been shown to have positive effects in various pathologies, as a modulator of important biochemical pathways including inflammation, oxidative stress, cell injury, apoptosis, and energy metabolism. The gut represents one of melatonin's most abundant extra pineal sources, with a 400-times-higher concentration than the pineal gland. The importance of the gut microbial community-namely, the gut microbiota, in multiple critical functions of the organism- has been extensively studied throughout time, and its imbalance has been associated with a variety of human pathologies. Recent studies highlight a possible gut microbiota-modulating role of melatonin, with possible implications for the treatment of these pathologies. Consequently, melatonin might prove to be a valuable and versatile therapeutic agent, as it is well known to elicit positive functions on the microbiota in many dysbiosis-associated conditions, such as inflammatory bowel disease, chronodisruption-induced dysbiosis, obesity, and neuropsychiatric disorders. This review intends to lay the basis for a deeper comprehension of melatonin, gut microbiota, and host-health subtle interactions.

Effect of the Antimicrobial Agents Peppermint Essential Oil and Silver Nanoparticles on Bone Cement Properties.

The main problems directly linked with the use of PMMA bone cements in orthopedic surgery are the improper mechanical bond between cement and bone and the absence of antimicrobial properties. Recently, more research has been devoted to new bone cement with antimicrobial properties using mainly antibiotics or other innovative materials with antimicrobial properties. In this paper, we developed modified PMMA bone cement with antimicrobial properties proposing some experimental antimicrobial agents consisting of silver nanoparticles incorporated in ceramic glass and hydroxyapatite impregnated with peppermint oil. The impact of the addition of antimicrobial agents on the structure, mechanical properties, and biocompatibility of new PMMA bone cements was quantified. It has been shown that the addition of antimicrobial agents improves the flexural strength of the traditional PMMA bone cement, while the yield strength values show a decrease, most likely because this agent acts as a discontinuity inside the material rather than as a reinforcing agent. In the case of all samples, the addition of antimicrobial agents had no significant influence on the thermal stability. The new PMMA bone cement showed good biocompatibility and the possibility of osteoblast proliferation (MTT test) along with a low level of cytotoxicity (LDH test).

Synthesis and Characterization of Electrospun Composite Scaffolds Based on Chitosan-Carboxylated Graphene Oxide with Potential Biomedical Applications.

This research study reports the development of chitosan/carboxylated graphene oxide (CS/GO-COOH) composite scaffolds with nanofibrous architecture using the electrospinning method. The concept of designed composite fibrous material is based on bringing together the biological properties of CS, mechanical, electrical, and biological characteristics of GO-COOH with the versatility and efficiency of ultra-modern electrospinning techniques. Three different concentrations of GO-COOH were added into a chitosan (CS)-poly(ethylene oxide) (PEO) solution (the ratio between CS/PEO was 3/7 (w/w)) and were used in the synthesis process of composite scaffolds. The effect of GO-COOH concentration on the spinnability, morphological and mechanical features, wettability, and biological properties of engineered fibrous scaffolds was thoroughly investigated. FTIR results revealed the non-covalent and covalent interactions that could take place between the system's components. The SEM micrographs highlighted the nanofibrous architecture of scaffolds, and the presence of GO-COOH sheets along the composite CS/GO-COOH nanofibers. The size distribution graphs showed a decreasing trend in the mean diameter of composite nanofibers with the increase in GO-COOH content, from 141.40 nm for CS/PG 0.1% to 119.88 nm for CS/PG 0.5%. The dispersion of GO-COOH led to composite scaffolds with increased elasticity; the Young's modulus of CS/PG 0.5% (84 ± 4.71 MPa) was 7.5-fold lower as compared to CS/PEO (662 ± 15.18 MPa, p < 0.0001). Contact angle measurements showed that both GO-COOH content and crosslinking step influenced the surface wettability of scaffolds, leading to materials with ~1.25-fold higher hydrophobicity. The in vitro cytocompatibility assessment showed that the designed nanofibrous scaffolds showed a reasonable cellular proliferation level after 72 h of contact with the fibroblast cells.

Design of new bioinspired GO-COOH decorated alginate/gelatin hybrid scaffolds with nanofibrous architecture: structural, mechanical and biological investigations.

The current research study deals with the design and investigation of novel bioinspired and biocompatible GO-COOH decorated hybrid polymeric scaffolds with nanofibrous architecture as biomaterials with highly appropriate features for functional restoration of damaged tissue. Gelatin and alginate, two biobased-polymers with excellent biocompatibility, high microenvironment biomimicry and ability for proper guidance of cell development in combination with carboxylated graphene oxide (GO-COOH), embody the matrix of electrospun hybrid scaffolds. The underlying principle is based on various types of interactions that can take place between the functionalities of the system's entities (proved by DLS) and their synergy in improving the structural integrity, mechanical tailorability and biological performances of the new nanofibrous GO-COOH decorated hybrid scaffolds. The nanofibrous structure along with the presence of GO-COOH are established by SEM. The new covalent bonds formed between various functionalities of the protein-polysaccharide-GO-COOH system are proved by FTIR and XPS. The physico-chemical state of GO-COOH lattices within the hybrid structures is investigated by Raman spectrometry. The interpenetrated network of bicomponent structures determines a 10-fold increase of Young's modulus as compared to monocomponent counterparts while the dispersion of GO-COOH significantly increases the elasticity of materials. The biological results (MTT and LDH assays) indicate a good cytocompatibility of crosslinked bicomponent AGS scaffolds; the metabolic cellular activity is substantially improved following the GO-COOH addition, suggesting that GO-COOH can support the cell adhesion, growth and proliferation.

Gut Dysbiosis and Clostridioides difficile Infection in Neonates and Adults.

In this review, we focus on gut microbiota profiles in infants and adults colonized (CDC) or infected (CDI) with Clostridioides difficile. After a short update on CDI epidemiology and pathology, we present the gut dysbiosis profiles associated with CDI in adults and infants, as well as the role of dysbiosis in C. difficile spores germination and multiplication. Both molecular and culturomic studies agree on a significant decrease of gut microbiota diversity and resilience in CDI, depletion of Firmicutes, Bacteroidetes, and Actinobacteria phyla and a high abundance of Proteobacteria, associated with low butyrogenic and high lactic acid-bacteria levels. In symptomatic cases, microbiota deviations are associated with high levels of inflammatory markers, such as calprotectin. In infants, colonization with Bifidobacteria that trigger a local anti-inflammatory response and abundance of Ruminococcus, together with lack of receptors for clostridial toxins and immunological factors (e.g., C. difficile toxins neutralizing antibodies) might explain the lack of clinical symptoms. Gut dysbiosis amelioration through administration of "biotics" or non-toxigenic C. difficile preparations and fecal microbiota transplantation proved to be very useful for the management of CDI.

Point-of-Care Testing-The Key in the Battle against SARS-CoV-2 Pandemic.

The deleterious effects of the coronavirus disease 2019 (COVID-19) pandemic urged the development of diagnostic tools to manage the spread of disease. Currently, the "gold standard" involves the use of quantitative real-time polymerase chain reaction (qRT-PCR) for SARS-CoV-2 detection. Even though it is sensitive, specific and applicable for large batches of samples, qRT-PCR is labour-intensive, time-consuming, requires trained personnel and is not available in remote settings. This review summarizes and compares the available strategies for COVID-19: serological testing, Point-of-Care Testing, nanotechnology-based approaches and biosensors. Last but not least, we address the advantages and limitations of these methods as well as perspectives in COVID-19 diagnostics. The effort is constantly focused on understanding the quickly changing landscape of available diagnostic testing of COVID-19 at the clinical levels and introducing reliable and rapid screening point of care testing. The last approach is key to aid the clinical decision-making process for infection control, enhancing an appropriate treatment strategy and prompt isolation of asymptomatic/mild cases. As a viable alternative, Point-of-Care Testing (POCT) is typically low-cost and user-friendly, hence harbouring tremendous potential for rapid COVID-19 diagnosis.

The in vitro and in vivo anti-virulent effect of organic acid mixtures against Eimeria tenella and Eimeria bovis.

Eimeria tenella and Eimeria bovis are complex parasites responsible for the condition of coccidiosis, that invade the animal gastrointestinal intestinal mucosa causing severe diarrhoea, loss of appetite or abortions, with devastating impacts on the farming industry. The negative impacts of these parasitic infections are enhanced by their role in promoting the colonisation of the gut by common foodborne pathogens. The aim of this study was to test the anti-Eimeria efficacy of maltodextrin, sodium chloride, citric acid, sodium citrate, silica, malic acid, citrus extract, and olive extract individually, in vitro and in combination, in vivo. Firstly, in vitro infection models demonstrated that antimicrobials reduced (p < 0.05), both singly and in combination (AG), the ability of E. tenella and E. bovis to infect MDBK and CLEC-213 epithelial cells, and the virulence reduction was similar to that of the anti-coccidial drug Robenidine. Secondly, using an in vivo broiler infection model, we demonstrated that AG reduced (p = 0.001) E. tenella levels in the caeca and excreted faeces, reduced inflammatory oxidative stress, improved the immune response through reduced ROS, increased Mn-SOD and SCFA levels. Levels of IgA and IgM were significantly increased in caecal tissues of broilers that received 0.5% AG and were associated with improved (p < 0.0001) tissue lesion scores. A prophylactic approach increased the anti-parasitic effect in vivo, and results indicated that administration from day 0, 5 and 10 post-hatch reduced tissue lesion scores (p < 0.0001) and parasite excretion levels (p = 0.002). Conclusively, our in vitro and in vivo results demonstrate that the natural antimicrobial mixture (AG) reduced parasitic infections through mechanisms that reduced pathogen virulence and attenuated host inflammatory events.