Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-FOXO1 pathway

Sirtuin1 (SIRT1) and forkhead box transcription factor O subfamily 1 (FOXO1) play vital roles in the maintenance of hippocampal neuronal homeostasis during aging. Our previous study showed that melatonin, a hormone mainly secreted by the pineal gland, restored the impaired memory of aged mice. Age-related neuronal energy deficits contribute to the pathogenesis of several neurodegenerative disorders. An attempt has been made to determine whether the effect of melatonin is mediated through the SIRT1-FOXO1 pathways. The present results showed that aged mice (22 months old) exhibited significantly downregulated SIRT1, FOXO1, and melatonin receptors MT1 and MT2 protein expression but upregulated tumor suppressor protein 53 (p53), acetyl-p53 protein (Ac-p53), mouse double minute 2 homolog (MDM2), Dickkopf-1 (DKK1) protein expression in mouse hippocampus com- pared with the young group. Melatonin treatment (10 mg/kg, daily in drinking water for 6 months) in aged mice significantly attenuated the age-induced downregulation of SIRT1, FOXO1, MT1 and MT2 protein expression and attenuated the age-induced increase in p53, ac-p53, MDM2, and DKK1 protein and mRNA expression. Mel- atonin decreased p53 and MDM2 expression, which led to a decrease in FOXO1 degradation. These present results suggest that melatonin may help the hippocampal neuronal homeostasis by increasing SIRT1, FOXO1 and mela- tonin receptors expression while decreasing DKK1 expression in the aging hippocampus. DKK1 can be induced by the accumulation of amyloid β (Aβ) which is the major hallmark of Alzheimer’s disease

Melatonin Regulates Aging and Neurodegeneration through Energy Metabolism, Epigenetics, Autophagy and Circadian Rhythm Pathways

Brain aging is linked to certain types of neurodegenerative diseases and identifying new therapeutic targets has become critical. Melatonin, a pineal hormone, associates with molecules and signaling pathways that sense and influence energy metabolism, autophagy, and circadian rhythms, including insulin-like growth factor 1 (IGF-1), Forkhead box O (FoxOs), sirtuins and mammalian target of rapamycin (mTOR) signaling pathways. This review summarizes the current understanding of how melatonin, together with molecular, cellular and systemic energy metabolisms, regulates epigenetic processes in the neurons. This information will lead to a greater understanding of molecular epigenetic aging of the brain and anti-aging mechanisms to increase lifespan under healthy conditions

Draft genome sequence data of heavy metal-resistant Morganella morganii WA01/MUTU, a silver nanoparticle (AgNP) synthesising bacterium

Morganella morganii WA01/MUTU is a heavy metal tolerant strain capable of producing silver nanoparticles (AgNPs) from AgNO3. Here we present the draft genome sequence of M. morganii WA01/MUTU isolated from a water sample collected in Nakhon Pathom province, Thailand. The draft genome was sequenced on the Illumina NextSeq 550 sequencer. The genome consisted of 34 contigs with a total size of 3,991,804 bp, an N50 value of 364,423 bp and a GC content of 50.93%. The digital DNA-DNA hybridisation (dDDH) between WA01/MUTU and Morganella morganii (NBRC 3848) was 83.9%, identifying the strain as Morganella morganii. The data presented here can be used in comparative genomics to identify gene clusters involved in AgNP biosynthesis and secondary metabolite production. The draft genome sequence data was deposited at NCBI under Bioproject accession number PRJNA493966

Attenuation of oxidative stress-induced neuronal cell death by Hydnophytum formicarum Jack.

Objective: To investigate protective effects of Hydnophytum formicarum Jack. (H. formicarum) extracts via regulation of SIRT1-FOXO3a-ADAM10 signaling and antioxidant activity against H2O2-induced neurotoxicity in neuroblastoma SH-SY5Y cells. Methods: Cell viability and apoptosis of neuronal cells pretreated with H. formicarum Jack. extracts under oxidative stress were determined by MTT assay and flow cytometry. The intracellular reactive oxygen species (ROS) was performed using Carboxy-DCFDA assay. Additionally, a profile of protein expressions related to neuroprotection was detected by western blot analysis. Results: The plant extracts (methanol and ethyl acetate) elicited protective effects on the neuronal cell death as performed by the MTT assay and by apoptosis analysis via the activation of BCL-2. Both ethyl acetate and methanol extracts exerted inhibitory effects against H2O2-induced ROS generation in the SH-SY5Y cells. Furthermore, the possible mechanism of neuroprotection of H. formicarum Jack. was observed through its antioxidant properties by maintaining the levels of catalase and SOD2 proteins as well as activating SIRT1-FOXO3a pathway. Importantly, pretreatment of neuronal cells with H. formicarum Jack. significantly recovered the levels of ADAM10 protein compared with the H2O2 treatment alone. Conclusions: The recent findings suggest the protective effects of H. formicarum Jack. plant extracts on attenuating H2O2-induced neurotoxicity in human SH-SY5Y cells

Development of an immunoFET biosensor for the detection of biotinylated PCR product

ImmunoFET (IMFET) biosensor is a simple platform for the detection of biotinylated products of polymerase chain reaction (PCR). Construction of the IMFET biosensor started with adsorption of 1.5 mg/mL of protein A (PA) onto the insulated gate surface of ISFET for 90 min. Next, the immobilized 1/500 dilution of anti-biotin antibody was adsorbed onto the PA layer for 60 min. The IMFET biosensor was subsequently ready for detection of the biotinylated amplicon. The IMFET biosensor showed highly specific binding to the biotinylated PCR product of the phaE gene of Haloquadratum walsbyi DSM 16854. The phaE gene is a biomarker of polyhydroxyalkanoate (PHA) producers that contain PHA synthase class III. The lowest amount of DNA template of H. walsbyi DSM 16854 that the IMFET biosensor could detect was 125 fg. The IMFET biosensor has a lower amount of detection compared with a DNA lateral flow biosensor from our previous study. The degree of linearity of the biosensor signal was influenced by the concentration of the biotinylated amplicon. The IMFET biosensor also has a short response time (approximately 30 times) to detect the phaE amplicon compared to an agarose gel electrophoresis. The IMFET biosensor is a promising tool for the detection of the biotinylated PCR product, and it can be integrated into a micro total analysis system (μTAS). Keywords: Engineering, Biochemistry, Bioengineering, Biotechnology, Microbiolog

High-fat diet-induced plasma protein and liver changes in obese rats can be attenuated by melatonin supplementation

Obesity triggers changes in protein expression in various organs that might participate in the pathogenesis of obesity. Melatonin has been reported to prevent or attenuate such pathological protein changes in several chronic diseases. However, such melatonin effects on plasma proteins have not yet been studied in an obesity model. Using a proteomic approach, we investigated the effect of melatonin on plasma protein profiles after rats were fed a high-fat diet (HFD) to induce obesity. We hypothesized that melatonin would attenuate abnormal protein expression in obese rats. After 10weeks of the HFD, animals displayed increased body weight and fat accumulation as well as increased glucose levels, indicating an obesity-induced prediabetes mellitus-like state. Two-dimensional gel electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry revealed 12 proteins whose expression was altered in response to the HFD and the melatonin treatment. The altered proteins are related to the development of liver pathology, such as cirrhosis (α1-antiproteinase), thrombosis (fibrinogen, plasminogen), and inflammation (mannose-binding protein A, complement C4, complement factor B), contributing to liver steatosis or hepatic cell death. Melatonin treatment most probably reduced the severity of the HFD-induced obesity by reducing the amplitude of HFD-induced plasma protein changes. In conclusion, we identified several potential biomarkers associated with the progression of obesity and its complications, such as liver damage. Furthermore, our findings reveal melatonin's beneficial effect of attenuating plasma protein changes and liver pathogenesis in obese rats.journal article2017 Jun2017 05 05importe