Pathophysiological Concepts in Multiple Sclerosis and the Therapeutic Effects of Hydrogen Sulfide.

Introduction: Multiple sclerosis (MS) is generally known as a manageable but not yet curable autoimmune disease affecting central nervous system. A potential therapeutic approach should possess several properties: Prevent immune system from damaging the brain and spinal cord, promote differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes to produce myelin, prevent the formation of fibronectin aggregates by astrocytes to inhibit scar formation, and enhance function of healthy endothelial cells (ECs).

Methods: To determine if an increase in sulfur contents through H2S, a potent antioxidant known to induce protective autophagy in cells, could provide the above desired outcomes, peripheral blood mononuclear cells (PBMNCs), OCPs, astrocytes, and ECs were treated with NaHS (50 μM) in vitro.

Dopamine treatment attenuates acute kidney injury in a rat model of deep hypothermia and rewarming - The role of renal H2S-producing enzymes.

Hypothermia and rewarming produces organ injury through the production of reactive oxygen species. We previously found that dopamine prevents hypothermia and rewarming-induced apoptosis in cultured cells through increased expression of the H2S-producing enzyme cystathionine β-Synthase (CBS). Here, we investigate whether dopamine protects the kidney in deep body cooling and explore the role of H2S-producing enzymes in an in vivo rat model of deep hypothermia and rewarming.

Functionalized nanoscale β-1,3-glucan to improve Her2+ breast cancer therapy: In vitro and in vivo study.

We fabricated a targeted delivery system for doxorubicin (Dox) using β-1,3-glucan (Glu) as a carrier and decorated by trastuzumab antibody having the status of targeting agent against Her2+ breast tumors. Glu-Dox conjugates were also functionalized with polyethylenimine (PEI) intended for increasing specific cellular uptake of prepared nanoparticles. The self-assembled nanoparticles were prepared through conjugation of Dox- [Glu-Dox-] using succinic anhydride (Sa) in place of a linker.

Increased protein aggregation in Zucker diabetic fatty rat brain: identification of key mechanistic targets and the therapeutic application of hydrogen sulfide.

Background: Diabetes and particularly high blood glucose levels are implicated in neurodegeneration. One of the hallmarks of neurodegeneration is protein aggregation. We investigated the presence of protein aggregation in the frontal brain of Zucker diabetic fatty (ZDF) rats, an animal model for diabetes.

Reduction of body temperature governs neutrophil retention in hibernating and nonhibernating animals by margination.

Hibernation consists of periods of low metabolism, called torpor, interspersed by euthermic arousal periods. During deep and daily (shallow) torpor, the number of circulating leukocytes decreases, although circulating cells, is restored to normal numbers upon arousal. Here, we show that neutropenia, during torpor, is solely a result of lowering of body temperature, as a reduction of circulating also occurred following forced hypothermia in summer euthermic hamsters and rats that do not hibernate.

The role of endogenous H2S formation in reversible remodeling of lung tissue during hibernation in the Syrian hamster.

During hibernation, small mammals alternate between periods of metabolic suppression and low body temperature ('torpor') and periods of full metabolic recovery with euthermic temperatures ('arousal'). Previously, we demonstrated marked structural remodeling of the lung during torpor, which is rapidly reversed during arousal. We also found that cooling of hamster cells increased endogenous production of H(2)S through the enzyme cystathionine-β-synthase (CBS).

Induction of VMAT-1 and TPH-1 expression induces vesicular accumulation of serotonin and protects cells and tissue from cooling/rewarming injury.

DDT₁ MF-2 hamster ductus deferens cells are resistant to hypothermia due to serotonin secretion from secretory vesicles and subsequent cystathionine beta synthase (CBS) mediated formation of H₂S. We investigated whether the mechanism promoting resistance to hypothermia may be translationally induced in cells vulnerable to cold storage. Thus, VMAT-1 (vesicular monoamino transferase) and TPH-1 (tryptophan hydroxylase) were co-transfected in rat aortic smooth muscle cells (SMAC) and kidney tissue to create a serotonin-vesicular phenotype (named VTSMAC and VTkidney, respectively).

Thiolated chitosan nanoparticles as a delivery system for antisense therapy: evaluation against EGFR in T47D breast cancer cells.

Thiolated chitosan has high transfection and mucoadhesive properties. We investigated the potential of two recently synthesized polymers: NAC-C (N-acetyl cysteine-chitosan) and NAP-C (N-acetyl penicillamine-chitosan) in anticancer drug delivery targeting epidermal growth factor receptor (EGFR). Doxorubicin (DOX) and antisense oligonucleotide (ASOND)-loaded polymer nanoparticles were prepared in water by a gelation process.

Serotonin and dopamine protect from hypothermia/rewarming damage through the CBS/H2S pathway.

Biogenic amines have been demonstrated to protect cells from apoptotic cell death. Herein we show for the first time that serotonin and dopamine increase H(2)S production by the endogenous enzyme cystathionine-β-synthase (CBS) and protect cells against hypothermia/rewarming induced reactive oxygen species (ROS) formation and apoptosis. Treatment with both compounds doubled CBS expression through mammalian target of rapamycin (mTOR) and increased H(2)S production in cultured rat smooth muscle cells.

Reversible remodeling of lung tissue during hibernation in the Syrian hamster.

During hibernation, small rodents such as hamsters cycle through phases of strongly suppressed metabolism with low body temperature (torpor) and full restoration of metabolism and body temperature (arousal). Remarkably, the repetitive stress of cooling-rewarming and hypoxia does not cause irreversible organ damage. To identify adaptive mechanisms protecting the lungs, we assessed histological changes as well as the expression and localization of proteins involved in tissue remodeling in lungs from Syrian hamsters at different phases of hibernation using immunohistochemical staining and western blot analysis.