Evaluation of ThT augmentation and RLS inner filter effect caused by highly fluorescent coumarin derivative and establishing it as true inhibitor of amyloid fibrillation.

Screening of inhibitors that slow down or suppress amyloid fibrils formation relies on some simple but sensitive spectroscopy techniques. Thioflavin T (ThT) fluorescence assay is one of the most common, amyloid specific and sensitive method. However, if an inhibitor is itself fluorescent in the ThT fluorescence range, its screening becomes complicated and require complementary assays. One of such molecules, 6, 7-dihydroxycoumarin (6, 7-DHC, also known as aesculetin, esculetin, and cichorigenin) is fluorescent in the ThT emission range and absorbs in the ThT excitation range. Therefore, it can produce a subtractive effect attributed to primary inner filter effect and/or additive effect due to its self-fluorescence in ThT assay. Our study shows that 6, 7-DHC produces an additive effect in ThT fluorescence, which is minimized at high concentration of ThT and decrease in ThT fluorescence is solely due to its inhibitory effect against HSA fibrillation. These ThT fluorescence-based results are verified through other complementary assays, such as Rayleigh and dynamic light scattering and amyloid-specific Congo red binding assay. Furthermore, hydrophobicity reduction is studied through Nile red (NR) and kinetics through far-UV circular dichroism (far-UV CD) in place of the most commonly employed ThT assay owing to extremely high fluorescence of 6, 7-DHC during initial incubation period.

Mesenchymal Stromal Cell-Derived Tailored Exosomes Treat Bacteria-Associated Diabetes Foot Ulcers: A Customized Approach From Bench to Bed.

Exosomes are nano-vesicles of endosomal origin inherited with characteristics of drug delivery and cargo loading. Exosomes offer a diverse range of opportunities that can be exploited in the treatment of various diseases post-functionalization. This membrane engineering is recently being used in the management of bacteria-associated diabetic foot ulcers (DFUs). Diabetes mellitus (DM) is among the most crippling disease of society with a large share of its imposing economic burden. DM in a chronic state is associated with the development of micro- and macrovascular complications. DFU is among the diabetic microvascular complications with the consequent occurrence of diabetic peripheral neuropathy. Mesenchymal stromal cell (MSC)-derived exosomes post-tailoring hold promise to accelerate the diabetic wound repair in DFU associated with bacterial inhabitant. These exosomes promote the antibacterial properties with regenerative activity by loading bioactive molecules like growth factors, nucleic acids, and proteins, and non-bioactive substances like antibiotics. Functionalization of MSC-derived exosomes is mediated by various physical, chemical, and biological processes that effectively load the desired cargo into the exosomes for targeted delivery at specific bacterial DFUs and wound. The present study focused on the application of the cargo-loaded exosomes in the treatment of DFU and also emphasizes the different approaches for loading the desired cargo/drug inside exosomes. However, more studies and clinical trials are needed in the domain to explore this membrane engineering.

Newer Horizon of Mesenchymal Stem Cell-Based Therapy in the Management of SARS-CoV-2-Associated Mucormycosis: A Safe Hope for Future Medicine.

SARS-CoV-2-infected patients are reported to show immunocompromised behavior that gives rise to a wide variety of complications due to impaired innate immune response, cytokine storm, and thrombo-inflammation. Prolonged use of steroids, diabetes mellitus, and diabetic ketoacidosis (DKA) are some of the factors responsible for the growth of Mucorales in such immunocompromised patients and, thus, can lead to a life-threatening condition referred to as mucormycosis. Therefore, an early diagnosis and cell-based management cosis is the need of the hour to help affected patients overcome this severe condition. In addition, extended exposure to antifungal drugs/therapeutics is found to initiate hormonal and neurological complications. More recently, mesenchymal stem cells (MSCs) have been used to exhibit immunomodulatory function and proven to be beneficial in a clinical cell-based regenerative approach. The immunomodulation ability of MSCs in mucormycosis patient boosts the immunity by the release of chemotactic proteins. MSC-based therapy in mucormycosis along with the combination of short-term antifungal drugs can be utilized as a prospective approach for mucormycosis treatment with promising outcomes. However, preclinical and in mucormyIn mucormycosis, the hyphae of clinical trials are needed to establish the precise mechanism of MSCs in mucormycosis treatment.