Thiazolidinedione derivatives (TZDs) have attracted attention because of their pharmacological effects. For example, certain TZDs have been reported to ameliorate type II diabetes by binding and activating PPARs (peroxisome proliferator-activated receptors). Nonetheless, no information is available on the interaction between the heterocyclic 2, 4-thiazolidinedione (2,4-TZD) moiety and serum albumin, which could affect the pharmacokinetics and pharmacodynamics of TZDs. In this study, we investigated the binding of 2,4-TZD to human serum albumin (HSA). Intrinsic fluorescence spectroscopy revealed a 1:1 binding stoichiometry between 2,4-TZD and HSA with a binding constant (K_b) of 1.69 ± 0.15 × 10³ M⁻¹ at 298 K. Isothermal titration calorimetry studies showed that 2,4-TZD/HSA binding was an exothermic and spontaneous reaction. Molecular docking analysis revealed that 2,4-TZD binds to HSA subdomain IB and that the complex formed is stabilized by van der Waal’s interactions and hydrogen bonds. Molecular dynamics simulation confirmed the stability of the HSA-TZD complex. Further, circular dichroism and 3D fluorescence studies showed that the global conformation of HSA was slightly altered by 2,4-TZD binding, enhancing its stability. The results obtained herein further help in understanding the pharmacokinetic properties of thiazolidinedione.

Natural polysaccharides exhibit beneficial immune modulatory effects, including immune stimulatory and anti-cancer activities. In this study, we examined the effect of Codium fragile polysaccharide (CFP) on natural killer (NK) cell activation, and its effect on tumor-bearing mice. Intravenous CFP treatment of C57BL/6 mice resulted in the upregulation of CD69, which is a marker associated with NK cell activation. In addition, intracellular levels of interferon (IFN)-γ and the cytotoxic mediators perforin and granzyme B were markedly increased in response to the CFP treatment of splenic NK cells. IFN-γ production by NK cells was directly induced by CFP, whereas the upregulation of CD69 and cytotoxic mediators required IL-12. Finally, intraperitoneal treatment with CFP prevented CT-26 (murine carcinoma) tumor cell infiltration in the lungs, without significantly reducing the body weight. In addition, treatment with CFP prevented B16 melanoma cell infiltration in the lung of C57BL/6 mice. Moreover, the anti-tumor effect was diminished by the depletion of NK cells. Therefore, these data suggest that CFP may be used as an NK cell stimulator to produce a phenomenon that contributes to anti-cancer immunity.

Introduction: Protein-derived biogenic syntheses of inorganic nanoparticles have gained immense attention because of their broad spectrum of applications. Proteins offer a reducing environment to enable the synthesis of nanoparticles and encapsulate synthesized nanoparticles and provide them temporal stability in addition to biocompatibility. Methods: In the present study, Benincasa hispida fruit proteins were used to synthesize silver nanoparticles (AgNPs) at 37 °C over five days of incubation. The synthesis of AgNPs was confirmed by UV-Vis spectroscopy, TEM, zeta potential, and DLS analyses. Further, these NPs depicted antibacterial and antibiofilm effects. Additionally, the anticancer activities of nanoparticles were also tested against the lung cancer cell line (A549) with respect to the normal cell line (NRK) using MTT assay. Further, the estimation of ROS generation through DCFH-DA staining along with a reduction in mitochondrial membrane potential by Mito Tracker Red CMX staining was carried out. Moreover, nuclear degradation in the AgNPs treated cells was cross-checked by DAPI staining. Results: The average size of AgNPs was detected to be 27 ± 1 nm by TEM analysis, whereas surface encapsulation by protein was determined by FTIR spectroscopy. These NPs were effective against bacterial pathogens such as Escherichia coli, Staphylococcus aureus, Salmonella enteric, and Staphylococcus epidermis with MICs of 148.12 μg/mL, 165.63 μg/mL, 162.77 μg/mL, and 124.88 μg/mL, respectively. Furthermore, these nanoparticles inhibit the formation of biofilms of E. coli, S. aureus, S. enteric, and S. epidermis by 71.14%, 73.89%, 66.66%, and 64.81%, respectively. Similarly, these nanoparticles were also found to inhibit (IC50 = 57.11 μM) the lung cancer cell line (A549). At the same time, they were non-toxic against NRK cells up to a concentration of 200 μM. Discussion: We successfully synthesized potentially potent antibacterial, antibiofilm and anticancer biogenic AgNPs.

The endoplasmic reticulum (ER) is an important subcellular organelle that is involved in numerous activities required to achieve and maintain functional proteins in addition to its role in the biosynthesis of lipids and as a repository of intracellular Ca²⁺. The inability of the ER to cope with protein folding beyond its capacity causes disturbances that evoke ER stress. Cells possess molecular mechanisms aimed at clearing unwanted cargo from the ER lumen as an adaptive response, but failing to do so navigates the system towards cell death. This systemic approach is called the unfolded protein response. Aging insults cells through various perturbations in homeostasis that involve curtailing ER function by mitigating the expression of its resident chaperones and enzymes. Here the unfolded protein response (UPR) cannot protect the cell due to the weakening of its protective arm, which exacerbates imbalanced homeostasis. Aging predisposed breast malignancy activates the UPR, but tumor cells maneuver the mechanistic details of the UPR, favoring tumorigenesis and thereby eliciting a treacherous condition. Tumor cells exploit UPR pathways via crosstalk involving various signaling cascades that usher tumor cells to immortality. This review aims to present a collection of data that can delineate the missing links of molecular signatures between aging and breast cancer.

IgLON5 is a cell adhesion protein belonging to the immunoglobulin superfamily and has important cellular functions. The objective of this study was to determine the role played by IgLON5 during myogenesis. We found IgLON5 expression progressively increased in C2C12 myoblasts during transition from the adhesion to differentiation stage. IgLON5 knockdown (IgLON5_kd) cells exhibited reduced cell adhesion, myotube formation, and maturation and reduced expressions of different types of genes, including those coding for extracellular matrix (ECM) components (COL1a1, FMOD, DPT, THBS1), cell membrane proteins (ITM2a, CDH15), and cytoskeletal protein (WASP). Furthermore, decreased IgLON5 expression in FMOD_kd, DPT_kd, COL1a1_kd, and ITM2a_kd cells suggested that IgLON5 and these genes mutually control gene expression during myogenesis. IgLON5 immunoneutralization resulted in significant reduction in the protein level of myogenic markers (MYOD, MYOG, MYL2). IgLON5 expression was higher in the CTX-treated gastrocnemius mice muscles (day 7), which confirmed increase expression of IgLON5 during muscle. Collectively, these results suggest IgLON5 plays an important role in myogenesis, muscle regeneration, and that proteins in ECM and myoblast membranes form an interactive network that establishes an essential microenvironment that ensures muscle stem cell survival.