The Effect of Mesenchymal Stem Cells Derived-Conditioned Media in Combination with Oral Anti-Androgenic Drugs on Male Pattern Baldness: An Animal Study.

OBJECTIVE: Androgenetic alopecia (AGA) is a prevalent form of hair loss, mainly caused by follicular sensitivity to androgens. Despite developing different anti-androgen treatment options, the success rate of these treatments has been limited. Using animal models, this study evaluated the therapeutic effects of umbilical cord (UC) stem cell conditioned media (CM) combined with oral anti-androgens for hair regeneration. MATERIALS AND METHODS: In this experimental study, Poloxamer 407 (P407) was used as a drug carrier for subcutaneous testosterone injection. AGA models were treated with oral finasteride, oral flutamide, and CM injections. Samples were thoroughly evaluated and compared using histological, stereological, and molecular analyses. RESULTS: Injecting CM-loaded hydrogel alone or combined with oral intake of anti-androgens improved hair regeneration. These treatments could promote hair growth by inducing hair follicles in the anagen stage and shortening the telogen and catagen phases. Furthermore, the combination treatment led to an upregulation of hair induction gene expression with a downregulation of inflammation genes. CONCLUSION: Through a reduction in inflammation, injection of CM-loaded hydrogel alone or combined with oral intake of anti-androgens induces the hair cell cycle with regeneration in damaged follicles. Hence, this could be a promising therapeutic method for AGA patients.

Exosomes at the crossroad between therapeutic targets and therapy resistance in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinomas (HNSCCs) are aggressive and clinically challenging tumours that require a multidisciplinary management approach. Despite significant therapy improvements, HNSCC patients have a poor prognosis with a 5-year survival rate of about 65%. As recently recognised key players in cancer, exosomes are extracellular vesicles (EVs) with a diameter of nearly 50-120 nm which transport information from one cell to another. Exosomes are actively involved in various aspects of tumour initiation, development, metastasis, immune regulation, therapy resistance, and therapeutic applications. However, current knowledge of the role of exosomes in the pathophysiological processes of HNSCC is still in its infancy, and additional studies are needed. In this review, we summarise and discuss the relevance of exosomes in mediating local immunosuppression and therapy resistance of HNSCC. We also review the most recent studies that have explored the therapeutic potential of exosomes as cancer vaccines, drug carriers or tools to reverse the drug resistance of HNSCC.

Inhibitory effects of selected antibiotics on the activities of α-amylase and α-glucosidase: In-vitro, in-vivo and theoretical studies.

Antibiotics are effective drugs that are used to treat infectious diseases either by killing bacteria or slowing down their growth. The well-adapted structural features of antibiotics for the inhibition/activation of enzymes include several available hydrogen bond (H-bond) acceptors and donors, flexible backbone and hydrophobic nature. The substrates of α-amylase and α-glucosidase, known as key absorbing enzymes, have functional groups (OH groups) rembling antibiotics. Given the possibility of developing in diabetics and the significant association between diabetes and infection, the present study was conducted to investigate the influences of tetracycline (TET), kanamycin (KANA), lincomycin (LIN), erythromycin (ERM) and azithromycin (AZM) on α-glucosidase and α-amylase activities with calculating IC50 and Ki values. Also, the efficacy of antibiotics after oral administration was evaluated by analysis of blood glucose concentrations in rats, as well as a molecular docking analysis was explored. α-glucosidase and α-amylase activities were inhibited in a dose dependent fashion by TET with an IC50 of 38.7 ±â€¯1.4 and 47.8 ±â€¯3.2 µM respectively, by KANA with an IC50 of 46.2 ±â€¯1.6 and 65.1 ±â€¯1.6, by LIN with an IC50 of 59.1 ±â€¯2.1 and 51.3 ±â€¯4.1, by ERM with an IC50 of 94.9 ±â€¯4.7 and 65.7 ±â€¯3.8 and by AZM with an IC50 of 69.4 ±â€¯4.4 and 103.6 ±â€¯6.2. Moreover, the Ki values of TET were calculated as 4.4 ±â€¯0.6 and 8.4 ±â€¯0.8 µM for α-glucosidase and α-amylase in a competitive-mode and mixed-mode inhibition. In addition, to communicate with the active site of α-glucosidase and α-amylase respectively, TET presented a binding energy of -9.8 and -8.8 kcal/mol, KANA -7.9 and -7.1, LIN -7.8 and -6.7, ERM -6.8 and -6.4, and AZM -6.4 and -7.5 kcal/mol. In-vivo studies also suggested a decrease in the blood glucose concentration after administering TET compared to the positive controls (P < 0.01). The results obtained from the present research can therefore help the scientific community explore the possible interconnection between the clinical side-effects of antibiotics and their α-glucosidase and α-amylase inhibitory properties, as the target enzymes in hypoglycemia conditions.

Can any "non-specific charge modification within microtubule binding domains of Tau" be a prerequisite of the protein amyloid aggregation? An in vitro study on the 1N4R isoform.

The aggregation of Tau into amyloid fibrils is a hallmark of neurodegenerative diseases such as Alzheimer's disease (AD). Compared to the Aß peptide, tau pathology more closely tracks changes in brain function that are responsible for the onset of early symptoms in AD. Tau belongs to the class of intrinsically disordered protein and folds into an ordered ß-structure during aggregation, a process that appears in many cases to be preceded by hyperphosphorylation of Tau monomers. Although Tau fibrils can be formed by heparin-induced aggregation of un-phosphorylated recombinant Tau, it is important to understanding the paradox of Tau's random-like conformations and aggregation propensity. In this study, to look into the effect of charge neutralization on Tau aggregation propensity, solvent accessible lysine residues were chemically acetylated/pseudo-phosphorylated. All Tau variants did not aggregate in the absence of the polyanionic factor; however, in contrast to the wild-type protein, acetylated and pseudo-phosphorylated variants were not able to aggregate even in the presence of the polyanionic cofactor. These aggregation incompetent Tau variants may be good analogs for the phosphorylated Tau, to explore more about the exact role of the phosphorylated Tau monomers in AD progress.

Appraisal of role of the polyanionic inducer length on amyloid formation by 412-residue 1N4R Tau protein: A comparative study.

In many neurodegenerative diseases, formation of protein fibrillar aggregates has been observed as a major pathological change. Neurofibrillary tangles, mainly composed of fibrils formed by the microtubule-associated protein; Tau, are a hallmark of a group of neurodegenerative diseases such as Alzheimer's disease. Tau belongs to the class of natively unfolded proteins and partially folds into an ordered ß-structure during aggregation. Polyanionic cofactors such as heparin are commonly used as inducer of Tau aggregation in vitro. The role of heparin in nucleation and elongation steps during Tau fibril formation is not fully understood. In the current study, aggregation kinetics as well as structure of Tau amyloid fibrils, by using the 1N4R isoform, have been reproducibly determined in the presence of heparin and the shorter molecule; enoxaparin. The kinetic studies demonstrated that heparin (not enoxaparin) efficiently accelerates Tau amyloid formation and revealed, mechanistically, that the molecular weight of the inducer is important in accelerating amyloidogenesis. The kinetic parameter values of Tau amyloid aggregation, especially, the amyloid aggregation extent, were relatively different in the presence of heparin and enoxaparin, at various stoichiometries of the inducers binding. Also, based on the results, obtained from CD, FTIR, AFM and XRD studies, it may be suggested that the inducer length plays a critical role mainly in the nucleation process, so that it determines that oligomers lie on or off the pathway of Tau fibrillization. The biochemical results herein suggest that the chemical environment of the extracellular matrix as well as localization of distinct glycosaminoglycans may influence deposition behavior of Tau amyloidosis.