Drug-resistant infectious diseases pose a substantial challenge and threat to medical regimens. While adaptive laboratory evolution provides foresight for encountering such situations, it has inherent limitations. Novel drug delivery systems (DDSs) have garnered attention for overcoming these hurdles. Multi-stimuli responsive DDSs are particularly effective due to their reduced background leakage and targeted drug delivery to specific host sites for pathogen elimination. Bacterial infections create an acidic state in the microenvironment (pH: 5.0–5.5), which differs from normal physiological conditions (pH: 7.4). Infected areas are characterized by the overexpression of hyaluronidase, gelatinase, phospholipase, and other virulence factors. Consequently, several effective stimuli-responsive DDSs have been developed to target bacterial pathogens. Additionally, biofilms, structured communities of bacteria encased in a self-produced polymeric matrix, pose a significant challenge by conferring resistance to conventional antimicrobial treatments. Recent advancements in nano-drug delivery systems (nDDSs) show promise in enhancing antimicrobial efficacy by improving drug absorption and targeting within the biofilm matrix. nDDSs can deliver antimicrobials directly to the biofilm, facilitating more effective eradication of these resilient bacterial communities. Herein, this review examines challenges in DDS development, focusing on enhancing antibacterial activity and eradicating biofilms without adverse effects. Furthermore, advances in immune system modulation and photothermal therapy are discussed as future directions for the treatment of bacterial diseases.

Several outbreaks of highly pathogenic avian influenza (HPAI) in poultry have already been documented across the world, causing major economic losses. Research on diverse perspectives for future HPAI outbreaks’ prevention is desperately needed. It is critical to determine high-risk areas for HPAI outbreaks in order to develop high-level biosecurity in all such areas. The aim of this study is to identify high-risk areas as hotspots for high rates of birds’ infection and mortality and culling. We used “hierarchical clustering on principal components” (HCPC) to classify infected poultry farms in South Korea based on the point prevalence rate, infections, and deaths in susceptible birds. The linear combination of the original predictors was determined using “principal component analysis (PCA)”. Based on PCA, we applied the hierarchical clustering algorithm, which divided the data into four clusters based on the dissimilarity matrix. These four groups of poultry farms were identified on the basis of five variables. According to the findings based on the HCPC method, poultry farms in “cluster 4” had significantly higher average bird infections with high mortality when compared to other clusters. Similarly, the poultry farms in “cluster 2” had robust average bird culling in place to limit bird infectivity and mortality due to a high number of susceptible birds. The poultry farms belonging to “cluster 3” had a significantly higher average point prevalence rate of HPAI H5N6 cases than the rest of the clusters. Based on this study, it is recommended that poultry farms with a high number of infections and mortality in susceptible birds should implement proper biosecurity management to control HPAI infections while avoiding the culling of a large number of birds.

Ahmad S, et al. J Vet Sci. 2022 Feb;23(3):e36. https://doi.org/10.4142/jvs.21278

Inflammation is a defense mechanism that protects the body from infections. However, chronic inflammation causes damage to body tissues. Thus, controlling inflammation and investigating anti-inflammatory mechanisms are keys to preventing and treating inflammatory diseases, such as sepsis and rheumatoid arthritis. In continuation with our work related to the discovery of bioactive natural products, a polyphenol, catechin-7,4′-O-digallate (CDG), was isolated from Woodfordia uniflora, which has been used as a sedative and remedy for skin infections in the Dhofar region of Oman. Thus far, no study has reported the anti-inflammatory compounds derived from W. uniflora and the mechanisms underlying their action. To investigate the effects of CDG on the regulation of inflammation, we measured the reduction in nitric oxide (NO) production following CDG treatment in immortalized mouse Kupffer cells (ImKCs). CDG treatment inhibited NO production through the downregulation of inducible nitric oxide synthase expression in lipopolysaccharide (LPS)-stimulated ImKCs. The anti-inflammatory effects of CDG were mediated via the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, an important inflammatory-response-associated signaling pathway. Moreover, CDG treatment has regulated the expression of pro-inflammatory cytokines, such as IL-6 and IL-1β. These results suggested the anti-inflammatory action of CDG in LPS-stimulated ImKCs.

Lignans are known to be an important class of phenylpropanoid secondary metabolites. In the course of our studies on the chemodiversity of lignans, the necessity arose to develop a method for the fast detection and identification of bioactive lignan subclasses. In this study, we detected 10 lignan derivatives of different extracts of F. viridissima by UHPLC-ESI-QTOF-MS. Lignan glycosides (1 and 2), lignans (3 and 4), and lignan dimers (5–10) were identified by analysis of their exact masses and MSe spectra along with the characteristic mass fragmentation patterns and molecular formulas. We further investigated NO inhibitory effects of F. viridissima fractions and their major lignan derivatives to evaluate those anti-inflammatory effects. The methylene chloride fraction of F. viridissima as well as compounds 8 and 10 showed potent dose-dependent NO inhibitory effects on RAW 264.7 cells. Corresponding to the NO inhibition by compounds 8 and 10, lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expression was notably reduced by both compounds. Our combined data with the bioactive results and the component analysis by UHPLC-ESI-QTOF-MS suggest that the methylene chloride fraction of F. viridissima roots could be potential anti-inflammatory agents and these are related to major lignans including dimeric dibenzylbutyrolactone lignans.