Rapid induction of dopaminergic neuron-like cells from human fibroblasts by autophagy activation with only 2-small molecules.

The dopaminergic neurons are responsible for the release of dopamine. Several diseases that affect motor function, including Parkinson's disease (PD), are rooted in inadequate dopamine (DA) neurotransmission. The study's goal was to create a quick way to make dopaminergic neuron-like cells from human fibroblasts (hNF) using only two small molecules: hedgehog pathway inhibitor 1 (HPI-1) and neurodazine (NZ). Two small compounds have been shown to induce the transdifferentiation of hNF cells into dopaminergic neuron-like cells. After 10 days of treatment, hNF cells had a big drop in fibroblastic markers (Col1A1, KRT18, and Elastin) and a rise in neuron marker genes (TUJ1, PAX6, and SOX1). Different proteins and factors related to dopaminergic neurons (TH, TUJ1, and dopamine) were significantly increased in cells that behave like dopaminergic neurons after treatment. A study of the autophagy signaling pathway showed that apoptotic genes were downregulated while autophagy genes (LC3, ATG5, and ATG12) were significantly upregulated. Our results showed that treating hNF cells with both HPI-1 and NZ together can quickly change them into mature neurons that have dopaminergic activity. However, the current understanding of the underlying mechanisms involved in nerve guidance remains unstable and complex. Ongoing research in this field must continue to advance for a more in-depth understanding. This is crucial for the safe and highly effective clinical application of the knowledge gained to promote neural regeneration in different neurological diseases.

Nanoencapsulated cordyceps extract enhances collagen synthesis and skin cell regeneration through antioxidation and autophagy.

Oxidative stress from reactive oxygen species is the main cause of skin ageing. Cordycepin, a bioactive compound of Cordyceps militaris, contains antioxidant activity. This study examined extracellular matrix, antioxidant effect, autophagy activity, and skin regeneration in human dermal fibroblasts (HDFs) under normal and oxidative stress conditions. Slow disintegration was used to create nano-encapsulated cordyceps extract. HDFs were cultured and treated with 1 M cordycepin, 1 M medium, 0.1 M cordyceps medium loaded nanoparticles (CMP), or 1 mM H2O2. HDFs' senescent phenotypes were assessed, including cell proliferation, ROS scavenging, collagen and elastin synthesis, antioxidant activity, and wound healing. CMP size averaged 184.5 ± 95.2 nm increased cell proliferation and reduced H2O2-induced ROS. Thus, HDFs treated for 48 h increased skin regeneration activity 2.76-fold by expressing extracellular matrix and rescuing H2O2-induced damaged cells. It was significant that this CMP inhibited H2O2-induced oxidative stress and induced autophagy to regenerate HDFs. The developed CMP could be used in cosmetics.

Enhancing Neurological Competence of Nanoencapsulated Cordyceps/Turmeric Extracts in Human Neuroblastoma SH-SY5Y Cells.

Introduction: Neurological diseases, including Alzheimer's, Parkinson's diseases, and brain cancers, are reportedly caused by genetic aberration and cellular malfunction. Herbs with bioactive compounds that have anti-oxidant effects such as cordyceps and turmeric, are of interest to clinical applications due to their minimal adverse effects. The aim of study is to develop the nanoencapsulated cordyceps and turmeric extracts and investigate their capability to enhance the biological activity and improve neuronal function. Methods: Human neuroblastoma SH-SY5Y cells were utilized as a neuronal model to investigate the properties of nanoencapsulated cordyceps or turmeric extracts, called CMP and TEP, respectively. SH-SY5Y cells were treated with either CMP or TEP and examined the biological consequences, including neuronal maturation and neuronal function. Results: The results showed that both CMP and TEP improved cellular uptake efficiency within 6 h by 2.3 and 2.8 times, respectively. Besides, they were able to inhibit cellular proliferation of SH-SY5Y cells up to 153- and 218-fold changes, and increase the expression of mature neuronal markers (TUJ1, PAX6, and NESTIN). Upon the treatment of CMP and TEP, the expression of dopaminergic-specific genes (LMX1B, FOXA2, EN1, and NURR1), and the secretion level of dopamine were significantly improved up to 3.3-fold and 3.0-fold, respectively, while the expression of Alzheimer genes (PSEN1, PSEN2, and APP), and the secretion of amyloid precursor protein were significantly reduced by 32-fold and 108-fold, respectively. Importantly, the autophagy activity was upregulated by CMP and TEP at 6.3- and 5.5-fold changes, respectively. Conclusions: This finding suggested that the nanoencapsulated cordyceps and turmeric extracts accelerated neuronal maturation and alleviated neuronal pathology in human neural cells. This paves the way for nanotechnology-driven drug delivery systems that could potentially be used as an alternative medicine in the future for neurological diseases.