Impact of COVID-19 on the Microbiome and Inflammatory Status of Type 2 Diabetes Patients.

The severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic has advanced our understanding of the host-microbiome-virus interplay. Several studies in various geographical regions report that SARS-CoV-2 infection disrupts the intestinal microbiota, allowing pathogenic bacteria such as Enterobacteriaceae to thrive, and triggering more severe disease outcomes. Here, we profile the microbiota of 30 individuals, 15 healthy controls and 15 type 2 diabetes (T2D) patients, before and after coronavirus disease 2019 (COVID-19). Despite similar viral loads in both patients and controls, SARS-CoV-2 infection led to exacerbated microbiome changes in T2D patients, characterized by higher levels of Enterobacteriaceae, loss of butyrate producers and an enrichment in fungi such as Candida spp. and Aspergillus spp. Several members of the microbiota were associated with more severe clinical and inflammatory (IL-8 and IL-17) parameters. Future studies to delineate the connection between cytokine release and microbiota disturbances will enhance our understanding of whether these microbial shifts directly impact the cytokine storm in COVID-19 patients or whether they are consecutive to the critical disease.

In Silico and Experimental Investigation of the Biological Potential of Some Recently Developed Carprofen Derivatives

The efficient regioselective bromination and iodination of the nonsteroidal anti-inflammatory drug (NSAID) carprofen were achieved by using bromine and iodine monochloride in glacial acetic acid. The novel halogenated carprofen derivatives were functionalized at the carboxylic group by esterification. The regioselectivity of the halogenation reaction was evidenced by NMR spectroscopy and confirmed by X-ray analysis. The compounds were screened for their in vitro antibacterial activity against planktonic cells and also for their anti-biofilm effect, using Gram-positive bacteria (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212) and Gram-negative bacteria (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). The cytotoxic activity of the novel compounds was tested against HeLa cells. The pharmacokinetic and pharmacodynamic profiles of carprofen derivatives, as well as their toxicity, were established by in silico analyses.

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.

Antiviral Immunity in SARS-CoV-2 Infection: From Protective to Deleterious Responses.

After two previous episodes, in 2002 and 2012, when two highly pathogenic coronaviruses (SARS, MERS) with a zoonotic origin emerged in humans and caused fatal respiratory illness, we are today experiencing the COVID-19 pandemic produced by SARS-CoV-2. The main question of the year 2021 is if naturally- or artificially-acquired active immunity will be effective against the evolving SARS-CoV-2 variants. This review starts with the presentation of the two compartments of antiviral immunity-humoral and cellular, innate and adaptive-underlining how the involved cellular and molecular actors are intrinsically connected in the development of the immune response in SARS-CoV-2 infection. Then, the SARS-CoV-2 immunopathology, as well as the derived diagnosis and therapeutic approaches, will be discussed.

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands.

Novel complexes of type [Cu(N-N)(dmtp)2(OH2)](ClO4)2·dmtp ((1) N-N: 2,2'-bipyridine; (2) L: 1,10-phenantroline and dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine) were designed in order to obtain biologically active compounds. Complexes were characterized as mononuclear species that crystallized in the space group P-1 of the triclinic system with a square pyramidal geometry around the copper (II). In addition to the antiproliferative effect on murine melanoma B16 cells, complex (1) exhibited low toxicity on normal BJ cells and did not affect membrane integrity. Complex (2) proved to be a more potent antimicrobial in comparison with (1), but both compounds were more active in comparison with dmtp-both against planktonic cells and biofilms. A stronger antimicrobial and antibiofilm effect was noticed against the Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). Both electron paramagnetic resonance (EPR) and Saccharomyces cerevisiae studies indicated that the complexes were scavengers rather than reactive oxygen species promoters. Their DNA intercalating capacity was evidenced by modifications in both absorption and fluorescence spectra. Furthermore, both complexes exhibited nuclease-like activity, which increased in the presence of hydrogen peroxide.

Sintered and 3D-Printed Bulks of MgB2-Based Materials with Antimicrobial Properties.

Pristine high-density bulk disks of MgB2 with added hexagonal BN (10 wt.%) were prepared using spark plasma sintering. The BN-added samples are machinable by chipping them into desired geometries. Complex shapes of different sizes can also be obtained by the 3D printing of polylactic acid filaments embedded with MgB2 powder particles (10 wt.%). Our present work aims to assess antimicrobial activity quantified as viable cells (CFU/mL) vs. time of sintered and 3D-printed materials. In vitro antimicrobial tests were performed against the bacterial strains Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Enterococcus faecium DSM 13590, and Enterococcus faecalis ATCC 29212; and the yeast strain Candida parapsilosis ATCC 22019. The antimicrobial effects were found to depend on the tested samples and microbes, with E. faecium being the most resistant and E. coli the most susceptible.

Isoflavonoid-Antibiotic Thin Films Fabricated by MAPLE with Improved Resistance to Microbial Colonization.

Staphylococcus aureus (Gram-positive) and Pseudomonas aeruginosa (Gram-negative) bacteria represent major infectious threats in the hospital environment due to their wide distribution, opportunistic behavior, and increasing antibiotic resistance. This study reports on the deposition of polyvinylpyrrolidone/antibiotic/isoflavonoid thin films by the matrix-assisted pulsed laser evaporation (MAPLE) method as anti-adhesion barrier coatings, on biomedical surfaces for improved resistance to microbial colonization. The thin films were characterized by Fourier transform infrared spectroscopy, infrared microscopy, and scanning electron microscopy. In vitro biological assay tests were performed to evaluate the influence of the thin films on the development of biofilms formed by Gram-positive and Gram-negative bacterial strains. In vitro biocompatibility tests were assessed on human endothelial cells examined for up to five days of incubation, via qualitative and quantitative methods. The results of this study revealed that the laser-fabricated coatings are biocompatible and resistant to microbial colonization and biofilm formation, making them successful candidates for biomedical devices and contact surfaces that would otherwise be amenable to contact transmission.

Present and Future Perspectives on Therapeutic Options for Carbapenemase-Producing Enterobacterales Infections.

Carbapenem-resistant Enterobacterales (CRE) are included in the list of the most threatening antibiotic resistance microorganisms, being responsible for often insurmountable therapeutic issues, especially in hospitalized patients and immunocompromised individuals and patients in intensive care units. The enzymatic resistance to carbapenems is encoded by different ß-lactamases belonging to A, B or D Ambler class. Besides compromising the activity of last-resort antibiotics, CRE have spread from the clinical to the environmental sectors, in all geographic regions. The purpose of this review is to present present and future perspectives on CRE-associated infections treatment.

SARS-CoV-2: From Structure to Pathology, Host Immune Response and Therapeutic Management.

Coronaviruses are large, enveloped viruses with a single-stranded RNA genome, infecting both humans and a wide range of wild and domestic animals. SARS-CoV-2, the agent of the COVID-19 pandemic, has 80% sequence homology with SARS-CoV-1 and 96-98% homology with coronaviruses isolated from bats. The spread of infection is favored by prolonged exposure to high densities of aerosols indoors. Current studies have shown that SARS-CoV-2 is much more stable than other coronaviruses and viral respiratory pathogens. The severe forms of infection are associated with several risk factors, including advanced age, metabolic syndrome, diabetes, obesity, chronic inflammatory or autoimmune disease, and other preexisting infectious diseases, all having in common the pre-existence of a pro-inflammatory condition. Consequently, it is essential to understand the relationship between the inflammatory process and the specific immune response in SARS-CoV-2 infection. In this review, we present a general characterization of the SARS-CoV-2 virus (origin, sensitivity to chemical and physical factors, multiplication cycle, genetic variability), the molecular mechanisms of COVID-19 pathology, the host immune response and discuss how the inflammatory conditions associated with different diseases could increase the risk of COVID-19. Last, but not least, we briefly review the SARS-CoV-2 diagnostics, pharmacology, and future approaches toward vaccine development.

SARS-CoV-2: From Structure to Pathology, Host Immune Response and Therapeutic Management

Coronaviruses are large, enveloped viruses with a single-stranded RNA genome, infecting both humans and a wide range of wild and domestic animals. SARS-CoV-2, the agent of the COVID-19 pandemic, has 80% sequence homology with SARS-CoV-1 and 96-98% homology with coronaviruses isolated from bats. The spread of infection is favored by prolonged exposure to high densities of aerosols indoors. Current studies have shown that SARS-CoV-2 is much more stable than other coronaviruses and viral respiratory pathogens. The severe forms of infection are associated with several risk factors, including advanced age, metabolic syndrome, diabetes, obesity, chronic inflammatory or autoimmune disease, and other preexisting infectious diseases, all having in common the pre-existence of a pro-inflammatory condition. Consequently, it is essential to understand the relationship between the inflammatory process and the specific immune response in SARS-CoV-2 infection. In this review, we present a general characterization of the SARS-CoV-2 virus (origin, sensitivity to chemical and physical factors, multiplication cycle, genetic variability), the molecular mechanisms of COVID-19 pathology, the host immune response and discuss how the inflammatory conditions associated with different diseases could increase the risk of COVID-19. Last, but not least, we briefly review the SARS-CoV-2 diagnostics, pharmacology, and future approaches toward vaccine development.