Hesperetin Increases Lifespan and Antioxidant Ability Correlating with IIS, HSP, mtUPR, and JNK Pathways of Chronic Oxidative Stress in .

Hesperetin (Hst) is a common citrus fruit flavonoid with antioxidant, anti-inflammatory, and anti-neurodegenerative effects. To explore the antioxidant and anti-aging effects and mechanisms of Hst, we induced chronic oxidative stress in using low-concentration HO and examined its effects on lifespan, healthy life index, reactive oxygen species (ROS), antioxidant enzymes, and transcriptomic metrics. Hst significantly prolonged lifespan, increased body bending and pharyngeal pumping frequency, decreased ROS accumulation, and increased antioxidant enzyme activity in normal and stressed .

Role of TPEN in Amyloid-β-Induced Neuronal Damage Correlating with Recovery of Intracellular Zn and Intracellular Ca Overloading.

The overproduction of neurotoxic amyloid-β (Aβ) peptides in the brain is a hallmark of Alzheimer's disease (AD). To determine the role of intracellular zinc ion (Zn) dysregulation in mediating Aβ-related neurotoxicity, this study aimed to investigate whether N, N, N', N'‑tetrakis (2‑pyridylmethyl) ethylenediamine (TPEN), a Zn‑specific chelator, could attenuate Aβ‑induced neurotoxicity and the underlying mechanism. We used the 3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay to measure the viability of primary hippocampal neurons.

Genistein Promotes Anti-Heat Stress and Antioxidant Effects via the Coordinated Regulation of IIS, HSP, MAPK, DR, and Mitochondrial Pathways in .

To determine the anti-heat stress and antioxidant effects of genistein and the underlying mechanisms, lipofuscin, reactive oxygen species (ROS), and survival under stress were first detected in ); then the localization and quantification of the fluorescent protein was determined by detecting the fluorescently labeled protein mutant strain; in addition, the aging-related mRNAs were detected by applying real-time fluorescent quantitative PCR in . The results indicate that genistein substantially extended the lifespan of under oxidative stress and heat conditions; and remarkably reduced the accumulation of lipofuscin in under hydrogen peroxide (HO) and 35 °C stress conditions; in addition, it reduced the generation of ROS caused by HO and upregulated the expression of , , , , , , , and , whereas it downregulated the expression of and in similarly, it upregulated the expression of , , , , , , , , , and , whereas it downregulated the expression of , , , and in at 35 °C; moreover, it increased the accumulation of HSP-16.2 and SKN-1 proteins in nematodes under 35 °C and HO conditions; however, it failed to prolong the survival time in the deleted mutant MQ130 nematodes under 35 °C and HO conditions.

Losartan Potassium and Verapamil Hydrochloride Compound Transdermal Drug Delivery System: Formulation and Characterization.

In this study, we developed a sustained-release transdermal delivery system containing losartan potassium (LP) and verapamil hydrochloride (VPH). LP and VPH have low bioavailability and long half-life. Therefore, the development of an optimum administration mode is necessary to overcome these drawbacks and enhance the antihypertensive effect.

Excessive Zinc Ion Caused PC12 Cell Death Correlating with Inhibition of NOS and Increase of RAGE in Cells.

Zinc ion (Zn) is an important functional factor; however, excessive Zn can be toxic. To understand the neurotoxicity of excessive Zn and the underlying mechanism, PC12 cells were treated with excessive Zn and Zn plus N, N, N', N'-Tetrakisethylenediamine (TPEN), a zinc ion chelator agent. Trypan blue and 3-(4,5-dimethyl-2- thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, thiazolyl blue tetrazolium bromide (MTT) assays were used to test cell viability; the relative kits were used to detect the activity of NOS synthase and the content of the receptor for advanced glycation end product (RAGE) in cells.

TPEN attenuates amyloid-β-induced neuronal damage with changes in the electrophysiological properties of voltage-gated sodium and potassium channels.

To understand the role of intracellular zinc ion (Zn) dysregulation in mediating age-related neurodegenerative changes, particularly neurotoxicity resulting from the generation of excessive neurotoxic amyloid-β (Aβ) peptides, this study aimed to investigate whether N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a Zn-specific chelator, could attenuate Aβ-induced neurotoxicity and the underlying electrophysiological mechanism. We used the 3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay to measure the viability of hippocampal neurons and performed single-cell confocal imaging to detect the concentration of Zn in these neurons. Furthermore, we used the whole-cell patch-clamp technique to detect the evoked repetitive action potential (APs), the voltage-gated sodium and potassium (K) channels of primary hippocampal neurons.

Two-Dimensional Conjugated Benzo[1,2-b:4,5-b']diselenophene-Based Copolymer Donor Enables Large Open-Circuit Voltage and High Efficiency in Selenophene-based Organic Solar Cells.

A two-dimensional electron-rich fused-ring moiety (ClBDSe) based on benzo[1,2-b:4,5-b']diselenophene is synthesized. Three copolymers (PBDT-Se, PBDSe-T, and PBDSe-Se) are obtained by manipulating the connection types and number of selenophene units on the conjugated main chains with two 2D fused-ring units and two different π-bridges, respectively. In comparison with PBDT-Se and PBDSe-Se, PBDSe-T with benzo[1,2-b:4,5-b']diselenophene unit and thiophene π-bridge exhibits the deepest HOMO energy level and the strongest crystallinity in neat films.

Development and evaluation of 1-deoxynojirimycin sustained-release delivery system: In vitro and in vivo characterization studies.

We aimed to establish a 1-Deoxynojirimycin (DNJ) sustained-release delivery system to improve the hypoglycemic effect of DNJ. We used a transdermal diffusion meter in an in vitro orthogonal experiment to determine the optimal composition of the DNJ sustained-release transdermal system. Based on the in vitro analysis results, a sustained-release patch was prepared, and its pharmacokinetics and other properties were determined in vivo.

Effects of early-life zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns.

Objective: To investigate the effect of maternal zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns.

Methods: Pregnant rats were divided into zinc adequate (ZA), zinc deficient (ZD), and paired fed (PF) groups. Serum zinc contents and AKP activity in mother rats and offspring at P21 (end of lactation) and P60 (weaned, adult) were detected.

Genistein inhibits amyloid peptide 25-35-induced neuronal death by modulating estrogen receptors, choline acetyltransferase and glutamate receptors.

Purpose: To explore genistein, the most active component of soy isoflavones, on viability, expression of estrogen receptor (ER) subtypes, choline acetyltransferase (ChAT), and glutamate receptor subunits in amyloid peptide 25-35-induced hippocampal neurons, providing valuable data and basic information for neuroprotective effect of genistein in Aβ-induced neuronal injury.

Methods: We established an in vitro model of Alzheimer's disease by exposing primary hippocampal neurons of newborn rats to amyloid peptide 25-35 (20 μM) for 24 h and observing the effects of genistein (10 μM, 3 h) on viability, expression of ER subtypes, ChAT, NMDA receptor subunit NR2B and AMPA receptor subunit GluR2 in Aβ-induced hippocampal neurons.

Results: We found that amyloid peptide 25-35 exposure reduced the viability of hippocampal neurons.

Flexible and Expandable Robot for Tissue Therapies - Modeling and Design.

Objective: Implantable technologies should be mechanically compliant with the tissue in order to maximize tissue quality and reduce inflammation during tissue reconstruction. We introduce the development of a flexible and expandable implantable robotic (FEIR) device for the regenerative elongation of tubular tissue by applying controlled and precise tension to the target tissue while minimizing the forces produced on the surrounding tissue.

Methods: We introduce a theoretical framework based on iterative beam theory static analysis for the design of an expandable robot with a flexible rack.

Curcumin inhibits alloxan-induced pancreatic islet cell damage via antioxidation and antiapoptosis.

The present study elucidates the possible protective effects of curcumin on β-cells damaged by oxidative stress and its significance in controlling diabetes mellitus in in vitro experiments. Pancreatic islet (RIN-m5F) cells were treated with 25 mmol/L alloxan (AXN) to induce cell damage and the protective effects of curcumin were observed. The results showed that curcumin significantly promoted the cellular activity of AXN-treated RIN-m5F cells, decreased the ratio of apoptosis, downregulated the level of malondialdehyde, upregulated the levels of superoxide dismutase and reactive oxygen species, increased the expression of Bcl-2, cleaved caspase-3, and cleaved PARP1, and decreased the expression of Bax in AXN-treated cells.

The Underlying Mechanisms of Curcumin Inhibition of Hyperglycemia and Hyperlipidemia in Rats Fed a High-Fat Diet Combined With STZ Treatment.

Curcumin is the main secondary metabolite of and other spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect of curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170-190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF + STZ group), and a high-fat diet combined with curcumin and STZ group (HF + Cur + STZ group).

Postnatal Expression Patterns of Estrogen Receptor Subtypes and Choline Acetyltransferase in Different Regions of the Papez Circuit.

The Papez circuit is crucial for several brain functions, including long-term memory and emotion. Estradiol modulates cognitive functions based on the expression pattern of its receptor subtypes including estrogen receptor (ER) α, β, and G protein-coupled receptor 30 (GPR30). Similarly, the activity in the cholinergic system correlates with several brain functions, such as learning and memory.

Metformin inhibits Aβ -induced apoptotic cell death in SH-SY5Y cells.

Metformin, a first-line drug for type-2 diabetes, plays a potentially protective role in preventing Alzheimer's disease (AD), but its underlying mechanism is unclear. In this study, Aβ -treated SH-SY5Y cells were used as a cell model of AD to investigate the neuroprotective effect of metformin, as well as its underlying mechanisms. We found that metformin decreased the cell apoptosis rate and death, ratio of Bcl-2/Bax, and expression of NR2A and NR2B, and increased the expression of LC3 in Aβ -treated SH-SY5Y cells.

Genistein Inhibits Aβ-Induced Neuronal Death with Changes in the Electrophysiological Properties of Voltage-Gated Sodium and Potassium Channels.

We established a model of Alzheimer's disease in vitro by exposing primary hippocampal neurons of neonatal Wistar rats to the β-Amyloid peptide fragment 25-35, Aβ. We then observed the effects of genistein, a type of soybean isoflavone, on Aβ-incubated hippocampal neuron viability, and the electrophysiological properties of voltage-gated sodium channels (Na) and potassium channels (K) in the hippocampal neurons. Aβ exposure reduced the viability of hippocampal neurons, decreased the peak amplitude of voltage-activated sodium channel currents (I), and significantly reduced I at different membrane potentials.

Genistein inhibits Aβ -induced SH-SY5Y cell damage by modulating the expression of apoptosis-related proteins and Ca influx through ionotropic glutamate receptors.

In this study, we investigated the protective effects of genistein against SH-SY5Y cell damage induced by β-amyloid 25-35 peptide (Aβ ) and the underlying mechanisms. Aβ-induced neuronal death, apoptosis, glutamate receptor subunit expression, Ca ion concentration, amino acid transmitter concentration, and apoptosis-related factor expression were evaluated to determine the effects of genistein on Aβ-induced neuronal death and apoptosis. The results showed that genistein increased the survival of SH-SY5Y cells and decreased the level of apoptosis induced by Aβ .

Neuronal death/apoptosis induced by intracellular zinc deficiency associated with changes in amino-acid neurotransmitters and glutamate receptor subtypes.

In the present study, a model of zinc deficiency was developed by exposing primary neurons to an N,N,N',N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN)-containing medium. The cell survival rate, apoptosis rate, intracellular and extracellular concentrations of 4 amino acids, and the expression of 2 glutamate receptor subtypes α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (GluR2)and N-methyl-d-aspartate receptor subtype 2B (NR2B) were evaluated in zinc-deficient cells. The results revealed that zinc deficiency led to a decrease in cell viability and an increase in the apoptosis rate.

DNA methylation mechanism of intracellular zinc deficiency-induced injury in primary hippocampal neurons in the rat brain.

Objective: To explore Zn deficiency-induced neuronal injury in relation to DNA methylation, providing valuable data and basic information for clarifying the mechanism of Zn deficiency-induced neuronal injury.

Methods: Cultured hippocampal neurons were exposed to the cell membrane-permeant Zn chelator N,N,N',N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) (2 μM), and to TPEN (2 μM) plus ZnSO (5 μM) for 24 hours. We analyzed intracellular Zn levels, neuronal viability, and protein/mRNA levels for DNA (cytosine-5) methyltransferase 1 (DNMT1), DNA (cytosine-5-) methyltransferase 3 alpha (DNMT3a), methyl CpG binding protein 2 (MeCP2), Brain-derived neurotrophic factor (BDNF), and growth arrest and DNA-damage-inducible, beta (GADD45b) in the treated neurons.

Zn reduction induces neuronal death with changes in voltage-gated potassium and sodium channel currents.

In the present study, cultured rat primary neurons were exposed to a medium containing N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a specific cell membrane-permeant Zn chelator, to establish a model of free Zn deficiency in neurons. The effects of TPEN-mediated free Zn ion reduction on neuronal viability and on the performance of voltage-gated sodium channels (VGSCs) and potassium channels (Kvs) were assessed. Free Zn deficiency 1) markedly reduced the neuronal survival rate, 2) reduced the peak amplitude of I, 3) shifted the I activation curve towards depolarization, 4) modulated the sensitivity of sodium channel voltage-dependent inactivation to a depolarization voltage, and 5) increased the time course of recovery from sodium channel inactivation.

Genistein inhibits hypoxia, ischemic-induced death, and apoptosis in PC12 cells.

A hypoxia/ischemia neuronal model was established in PC12 cells using oxygen-glucose deprivation (OGD). OGD-induced neuronal death, apoptosis, glutamate receptor subunit GluR2 expression, and potassium channel currents were evaluated in the present study to determine the effects of genistein in mediating the neuronal death and apoptosis induced by hypoxia and ischemia, as well as its underlying mechanism. OGD exposure reduced the cell viability, increased apoptosis, decreased the GluR2 expression, and decreased the voltage-activated potassium currents.

The cognitive impairment induced by zinc deficiency in rats aged 0∼2 months related to BDNF DNA methylation changes in the hippocampus.

Objective: This study was carried out to understand the effects of zinc deficiency in rats aged 0∼2 months on learning and memory, and the brain-derived neurotrophic factor (BDNF) gene methylation status in the hippocampus.

Methods: The lactating mother rats were randomly divided into three groups (n = 12): zinc-adequate group (ZA: zinc 30 mg/kg diet), zinc-deprived group (ZD: zinc 1 mg/kg diet), and a pair-fed group (PF: zinc 30 mg/kg diet), in which the rats were pair-fed to those in the ZD group. After weaning (on day 23), offspring were fed the same diets as their mothers.

Genistein inhibition of OGD-induced brain neuron death correlates with its modulation of apoptosis, voltage-gated potassium and sodium currents and glutamate signal pathway.

In the present study, we established an in vitro model of hypoxic-ischemia via exposing primary neurons of newborn rats to oxygen-glucose deprivation (OGD) and observing the effects of genistein, a soybean isoflavone, on hypoxic-ischemic neuron viability, apoptosis, voltage-activated potassium (Kv) and sodium (Nav) currents, and glutamate receptor subunits. The results indicated that OGD exposure reduced the viability and increased the apoptosis of brain neurons. Meanwhile, OGD exposure caused changes in the current-voltage curves and current amplitude values of voltage-activated potassium and sodium currents; OGD exposure also decreased GluR2 expression and increased NR2 expression.