Neuroprotective effects of ginsenosides Rh1 and Rg2 on neuronal cells

<p>Abstract</p> <p>Background</p> <p>The present study investigates the effects of ginsenosides Rh₁and Rg₂against 6-hydroxydopamine (6-OHDA), a neurotoxin on SH-SY5Y cells and PC-12 cells. The effects of these two ginsenosides on neuronal differentiation are also examined.</p> <p>Methods</p> <p>LDH assay was used to measure cell viability after exposure to 6-OHDA and ginsenosides. Neuronal differentiation was evaluated by changes in cell morphology and density of neurite outgrowths. Western blotting was used to determine the ginsenosides' effects on activation of extracellular signal-regulated protein kinases (ERKs).</p> <p>Results</p> <p>Rh₁and Rg₂attenuated 6-OHDA toxicity in SH-SY5Y cells and induced neurite outgrowths in PC-12 cells. 6-OHDA-induced ERK phosphorylation was decreased by Rh₁and Rg₂. 20(R)-form and 20(S)-form of the ginsenosides exerted similar effects in inducing neurite outgrowths in PC-12 cells.</p> <p>Conclusion</p> <p>The present study demonstrates neuroprotective effects of ginsenosides Rh₁and Rg₂on neuronal cell lines. These results suggest potential Chinese medicine treatment for neurodegenerative disorders (<it>eg </it>Parkinson's disease).</p

Auricular acupuncture treatment for insomnia: A systematic review

Objectives: To review trials on the efficacy and safety of auricular acupuncture (AA) treatment for insomnia and to identify the most commonly used auricular acupoints for treating insomnia in the studies via a frequency analysis. Data sources: The international electronic databases searched included: (1) AMED; (2) the Cochrane library; (3) CINAHL; (4) EMBASE; and (5) MEDLINE.® Chinese electronic databases searched included: (1) VIP Information; (2) CBMdisc; and (3) CNKI. Study selection: Any randomized controlled trials using AA as an intervention without using any co-interventions for insomnia were included. Studies using AA versus no treatment, placebo, sham AA, or Western medicine were included. Data extraction: Two (2) independent reviewers were responsible for data extraction and assessment. The efficacy of AA was estimated by the relative risk (RR) using a meta-analysis. Results: Eight hundred and seventy eight (878) papers were searched. Six (6) trials (402 treated with AA among 673 participants) that met the inclusion criteria were retrieved. A meta-analysis showed that AA was chosen with a higher priority among the treatment subjects than among the controls (p < 0.05). The recovery and improvement rates produced by AA was significantly higher than those of diazepam (p < 0.05). The rate of success was higher when AA was used for enhancement of sleeping hours up to 6 hours in treatment subjects (p < 0.05). The efficacy of using Semen vaccariae ear seeds was better than that of the controls (p < 0.01); while magnetic pearls did not show statistical significance (p = 0.28). Six (6) commonly used auricular acupoints were Shenmen (100%), Heart (83.33%), Occiput (66.67%), Subcortex (50%), Brain and Kidney (each 33.33%, respectively). Conclusions: AA appears to be effective for treating insomnia. Because the trials were low quality, further clinical trials with higher design quality, longer duration of treatment, and longer follow-up should be conducted. © Mary Ann Liebert, Inc.published_or_final_versio

Aberrant Transferrin and Ferritin Upregulation Elicits Iron Accumulation and Oxidative Inflammaging Causing Ferroptosis and Undermines Estradiol Biosynthesis in Aging Rat Ovaries by Upregulating NF-Κb-Activated Inducible Nitric Oxide Synthase: First Demonstration of an Intricate Mechanism

We report herein a novel mechanism, unraveled by proteomics and validated by in vitro and in vivo studies, of the aberrant aging-associated upregulation of ovarian transferrin and ferritin in rat ovaries. The ovarian mass and serum estradiol titer plummeted while the ovarian labile ferrous iron and total iron levels escalated with age in rats. Oxidative stress markers, such as nitrite/nitrate, 3-nitrotyrosine, and 4-hydroxy-2-nonenal, accumulated in the aging ovaries due to an aberrant upregulation of the ovarian transferrin, ferritin light/heavy chains, and iron regulatory protein 2(IRP2)-mediated transferrin receptor 1 (TfR1). Ferritin inhibited estradiol biosynthesis in ovarian granulosa cells in vitro via the upregulation of a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p65/p50-induced oxidative and inflammatory factor inducible nitric oxide synthase (iNOS). An in vivo study demonstrated how the age-associated activation of NF-κB induced the upregulation of iNOS and the tumor necrosis factor α (TNFα). The downregulation of the keap1-mediated nuclear factor erythroid 2-related factor 2 (Nrf2), that induced a decrease in glutathione peroxidase 4 (GPX4), was observed. The aberrant transferrin and ferritin upregulation triggered an iron accumulation via the upregulation of an IRP2-induced TfR1. This culminates in NF-κB-iNOS-mediated ovarian oxi-inflamm-aging and serum estradiol decrement in naturally aging rats. The iron accumulation and the effect on ferroptosis-related proteins including the GPX4, TfR1, Nrf2, Keap1, and ferritin heavy chain, as in testicular ferroptosis, indicated the triggering of ferroptosis. In young rats, an intraovarian injection of an adenovirus, which expressed iron regulatory proteins, upregulated the ovarian NF-κB/iNOS and downregulated the GPX4. These novel findings have contributed to a prompt translational research on the ovarian aging-associated iron metabolism and aging-associated ovarian diseases

Extracellular nanomatrix-induced self-organization of neural stem cells into miniature substantia nigra-like structures with therapeutic effects on Parkinsonian rats

Substantia nigra (SN) is a complex and critical region of the brain wherein Parkinson's disease (PD) arises from the degeneration of dopaminergic neurons. Miniature SN‐like structures (mini‐SNLSs) constructed from novel combination of nanomaterials and cell technologies exhibit promise as potentially curative cell therapies for PD. In this work, a rapid self‐organization of mini‐SNLS, with an organizational structure and neuronal identities similar to those of the SN in vivo, is achieved by differentiating neural stem cells in vitro on biocompatible silica nanozigzags (NZs) sculptured by glancing angle deposition, without traditional chemical growth factors. The differentiated neurons exhibit electrophysiological activity in vitro. Diverse physical cues and signaling pathways that are determined by the nanomatrices and lead to the self‐organization of the mini‐SNLSs are clarified and elucidated. In vivo, transplantation of the neurons from a mini‐SNLS results in an early and progressive amelioration of PD in rats. The sculptured medical device reported here enables the rapid and specific self‐organization of region‐specific and functional brain‐like structures without an undesirable prognosis. This development provides promising and significant insights into the screening of potentially curative drugs and cell therapies for PD

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Quantification of neuropeptides in the central nervous system of the wobbler mouse during the progression of the motor neuron disease: a study by radioimmunoassay andimmunocytochemistry

published_or_final_versionAnatomyMasterMaster of Philosoph

Therapeutic Intervention in Cancer by Isoliquiritigenin from Licorice: A Natural Antioxidant and Redox Regulator

Oxidative stress could lead to a variety of body dysfunctions, including neurodegeneration and cancer, which are closely associated with intracellular signal transducers such as reactive oxygen species (ROS). It has been suggested that ROS is the upstream regulator of autophagy, and that it provides a negative feedback regulation to remove oxidative damage. Defects in the ROS-autophagic redox homeostasis could lead to the increased production of ROS and the accumulation of damaged organelles that in turn promote metabolic reprogramming and induce tumorigenesis. One significant characteristic of pancreatic cancer is the reprogramming of cellular energy metabolism, which facilitates the rapid growth, invasiveness, and the survival of cancer cells. Thus, the rectification of metabolic dysfunction is essential in therapeutic cancer targeting. Isoliquiritigenin (ISL) is a chalcone obtained from the plant Glycyrrhiza glabra, which is a powdered root licorice that has been consumed for centuries in different regions of the world. ISL is known to be a natural antioxidant that possesses diversified functions, including redox regulation in cells. This review contains discussions on the herbal source, biological properties, and anticancer potential of ISL. This is the first time that the anticancer activities of ISL in pancreatic cancer has been elucidated, with a coverage of the involvement of antioxidation, metabolic redox regulation, and autophagy in pancreatic cancer development. Furthermore, some remarks on related compounds of the isoflavonoid biosynthetic pathway of ISL will also be discussed

Figure 11

<p>(A) Unilateral administration of 6-hydroxydopamine in striatum induces a significant degeneration of ipsilateral substantia nigra through the nigrostriatal pathway. (B) The expression of nestin-immunoreactive reactive astrocytes is found to peak at post-lesion day 3. Low levels of expression of brain derived neurotrophic factor in reactive astrocytes are found in the ipsilateral striatum as well as the ipsilateral substantia nigra. Expression of glial cell-line derived neurotrophic factor is found in the ipsilateral striatum only. (C) The expression of nestin in reactive astrocytes drops to a low level in both ipsilateral striatum and ipsilateral substantia nigra at post-lesion day 7. However, the expressions of the brain-derived neurotrophic factor and glial cell-line neurotrophic factor in the reactive astrocytes are found to be peaked at the same period. The expression of brain-derived neurotrophic factor can be found in the neurones of the ipislateral striatum and substantia nigra, as well as the contralateral striatum, but in a small amount. (D) No expressions of nestin, brain derived neurotrophic factor and glial cell-line derived neurotrophic factor immunoreactivities are found in the striatum and substantia nigra at post-lesion day 14.</p