The dual face of microglia (M1/M2) as a potential target in the protective effect of nutraceuticals against neurodegenerative diseases

The pathophysiology of different neurodegenerative illnesses is significantly influenced by the polarization regulation of microglia and macrophages. Traditional classifications of macrophage phenotypes include the pro-inflammatory M1 and the anti-inflammatory M2 phenotypes. Numerous studies demonstrated dynamic non-coding RNA modifications, which are catalyzed by microglia-induced neuroinflammation. Different nutraceuticals focus on the polarization of M1/M2 phenotypes of microglia and macrophages, offering a potent defense against neurodegeneration. Caeminaxin A, curcumin, aromatic-turmerone, myricetin, aurantiamide, 3,6′-disinapoylsucrose, and resveratrol reduced M1 microglial inflammatory markers while increased M2 indicators in Alzheimer’s disease. Amyloid beta-induced microglial M1 activation was suppressed by andrographolide, sulforaphane, triptolide, xanthoceraside, piperlongumine, and novel plant extracts which also prevented microglia-mediated necroptosis and apoptosis. Asarone, galangin, baicalein, and a-mangostin reduced oxidative stress and pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha in M1-activated microglia in Parkinson’s disease. Additionally, myrcene, icariin, and tenuigenin prevented the nod-like receptor family pyrin domain-containing 3 inflammasome and microglial neurotoxicity, while a-cyperone, citronellol, nobiletin, and taurine prevented NADPH oxidase 2 and nuclear factor kappa B activation. Furthermore, other nutraceuticals like plantamajoside, swertiamarin, urolithin A, kurarinone, Daphne genkwa flower, and Boswellia serrata extracts showed promising neuroprotection in treating Parkinson’s disease. In Huntington’s disease, elderberry, curcumin, iresine celosia, Schisandra chinensis, gintonin, and pomiferin showed promising results against microglial activation and improved patient symptoms. Meanwhile, linolenic acid, resveratrol, Huperzia serrata, icariin, and baicalein protected against activated macrophages and microglia in experimental autoimmune encephalomyelitis and multiple sclerosis. Additionally, emodin, esters of gallic and rosmarinic acids, Agathisflavone, and sinomenine offered promising multiple sclerosis treatments. This review highlights the therapeutic potential of using nutraceuticals to treat neurodegenerative diseases involving microglial-related pathways

Toxic Effects of Trichloroethylene on Rat Neuroprogenitor Cells

Trichloroethylene (TCE) is a common volatile organic solvent which is considered as an ubiquitous environmental pollutant. It is claimed to be a developmental neurotoxicant. Our group evaluated previously its impact on three-dimensional neurospheres in vitro. The current work aims to investigate the neurotoxic effects of a lower concentration of TCE on the same system. To perform the experiment, neural progenitor cells were obtained from the brains of nine newborn rats. Afterward, these cells were cultured in both growth and differentiation media to get the neurospheres. Cell cultures were divided into two groups: group 1 (control), group 2 (exposed to 0.25 μM TCE). Neurospheres were photographed at different durations and assessment of the morphological changes such as proliferation and differentiation of neurospheres was done. In addition, cell viability, apoptosis, and necrosis were analyzed using flow cytometry to clarify the mechanism of involved cytotoxicity. The results revealed that TCE-treated neurospheres showed significantly decreased proliferation on days 7 and 14. These cells failed to show the neurogenic differentiation seen in the neurospheres of the control group. Furthermore, a highly significant decrease in viability and a significant increase in the number of apoptotic cells were observed in the treated cells in comparison to the control group. The present work confirmed that TCE, at very low doses relevant to daily life exposure in humans, caused neurotoxic effects in 3D neurosphere model through the affection of neural proliferation and differentiation as well as disturbance of cell viability and apoptosis

The cardioprotective effects of secoisolariciresinol diglucoside (flaxseed lignan) against cafeteria diet-induced cardiac fibrosis and vascular injury in rats: an insight into apelin/AMPK/FOXO3a signaling pathways

Introduction: Fast food is a major risk factor for atherosclerosis, a leading cause of morbidity and mortality in the Western world. Apelin, the endogenous adipokine, can protect against cardiovascular disease via activating its receptor, APJ. Concurrently, secoisolariciresinol diglucoside (SDG), a flaxseed lignan extract (FLE), showed a therapeutic impact on atherosclerosis. The current study aimed to examine the effect of SDG on cafeteria diet (CAFD)-induced vascular injury and cardiac fibrosis via tracking the involvement of the apelin/APJ pathway.Methods: Thirty male rats were allocated into control, FLE-, CAFD-, CAFD/FLE-, and CAFD/FLE/F13A-treated rats, where F13A is an APJ blocker. All treatments lasted for 12 weeks.Results and discussion: The CAFD-induced cardiovascular injury was evidenced by histological distortions, dyslipidemia, elevated atherogenic indices, cardiac troponin I, collagen percentage, glycogen content, and apoptotic markers. CAFD increased both the gene and protein expression levels of cardiac APJ, apelin, and FOXO3a, in addition to increasing endothelin-1, VCAM1, and plasminogen activator inhibitor-1 serum levels and upregulating cardiac MMP-9 gene expression. Moreover, CAFD reduced serum paraoxonase 1 and nitric oxide levels, cardiac AMPK, and nuclear Nrf2 expression. FLE attenuated CAFD-induced cardiovascular injury. Such effect was reduced in rats receiving the APJ blocker, implicating the involvement of apelin/APJ in FLE protective mechanisms.Conclusion: FLE supplementation abrogated CAFD-induced cardiac injury and endothelial dysfunction in an apelin/APJ-dependent manner

The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium inaugural meeting report

The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium is a novel, interdisciplinary initiative comprised of experts across many fields, including genomics, data analysis, engineering, public health, and architecture. The ultimate goal of the MetaSUB Consortium is to improve city utilization and planning through the detection, measurement, and design of metagenomics within urban environments. Although continual measures occur for temperature, air pressure, weather, and human activity, including longitudinal, cross-kingdom ecosystem dynamics can alter and improve the design of cities. The MetaSUB Consortium is aiding these efforts by developing and testing metagenomic methods and standards, including optimized methods for sample collection, DNA/RNA isolation, taxa characterization, and data visualization. The data produced by the consortium can aid city planners, public health officials, and architectural designers. In addition, the study will continue to lead to the discovery of new species, global maps of antimicrobial resistance (AMR) markers, and novel biosynthetic gene clusters (BGCs). Finally, we note that engineered metagenomic ecosystems can help enable more responsive, safer, and quantified cities

L-carnitine alleviated acute lung injuries induced by potassium dichromate in rats: involvement of Nrf2/HO-1 signaling pathway

The activation of the Nrf2/HO-1 signaling pathway regulates cellular antioxidant stress and exerts anti-inflammatory and cytoprotective effects against acute lung injury (ALI). The present study aimed to evaluate the therapeutic role of L-carnitine (LC) against potassium dichromate (PD) - induced acute lung injury in adult male albino rats via modulation of Nrf2/HO-1 signaling pathway. For this purpose, forty rats were randomly allocated into 5 groups (8 rats each). The normal group received intranasal (i.n.) saline, while the ALI group received intranasal instillation of PD as a single dose of 2 mg/kg. The 3d – 5th groups received PD then after 24 h administered L-carnitine (25, 50 and 100 mg/kg; orally) for 3 consecutive days. The therapeutic effect of L-carnitine was evaluated by assessment of serum levels of glutathione (GSH) and malondialdehyde (MDA) along with measurement of lung contents of transforming growth factor β1 (TGFβ1), protein kinase B (AKT), Nuclear factor erythroid-2 related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 enzyme (NQO1) and glutathione cysteine ligase modifier subunit (GCLM) expression. Post-treatment with L-carnitine effectively increased the levels of GSH and AKT, elevated Nrf2 and its target genes and decreased the levels of MDA and TGFβ1 in comparison with PD control rats. Additionally, L-carnitine effectively reduced the number of goblet cell, inhibited the mucus formation in bronchioles and interstitial inflammatory infiltrate as well as alleviated the destruction of alveolar walls, and the congestion of blood vessels in lung tissue induced by PD. Our findings showed that L-carnitine may be a promising therapeutic agent against PD-induced acute lung injury

Sitagliptin Potentiates the Anti-Neoplastic Activity of Doxorubicin in Experimentally-Induced Mammary Adenocarcinoma in Mice: Implication of Oxidative Stress, Inflammation, Angiogenesis, and Apoptosis

Sitagliptin (STG) is a highly selective dipeptidyl peptidase-4 inhibitor recently used in the treatment of type 2 diabetes. The current study aimed to investigate the anti-neoplastic effect of STG alone and in combination with Doxorubicin (Dox), a known chemotherapeutic agent but with ominous side effects. After intramuscular inoculation of 2 × 106 Ehrlich tumor cells, Female Swiss mice were divided into tumor-bearing control, STG-treated, Dox-treated, and a combination of STG and Dox-treated groups. The results showed a significant reduction in the tumor growth of the treated animals in comparison with those of the positive control group with a more prominent effect in the co-treated group. Where, the anti-proliferative and apoptotic effect of STG, and its chemo-sensitizing ability, when used in combination with Dox, was mediated by modulation of oxidative stress (MDA and GSH), attenuation of tumor inflammation (IL-6 and IL-1β), and angiogenesis (VEGF), suppressing proliferation (β-catenin and cyclin-D1) and enhancement of apoptosis (survivin, p53, caspase 3). Thus, in conclusion, STG as adjunctive therapy for Dox could be a strategy for the treatment of breast cancer patients, by their ability in hindering cell proliferation and minimizing the associated oxidative and inflammatory adverse reactions

Sitagliptin Potentiates the Anti-Neoplastic Activity of Doxorubicin in Experimentally-Induced Mammary Adenocarcinoma in Mice: Implication of Oxidative Stress, Inflammation, Angiogenesis, and Apoptosis

Sitagliptin (STG) is a highly selective dipeptidyl peptidase-4 inhibitor recently used in the treatment of type 2 diabetes. The current study aimed to investigate the anti-neoplastic effect of STG alone and in combination with Doxorubicin (Dox), a known chemotherapeutic agent but with ominous side effects. After intramuscular inoculation of 2 × 106 Ehrlich tumor cells, Female Swiss mice were divided into tumor-bearing control, STG-treated, Dox-treated, and a combination of STG and Dox-treated groups. The results showed a significant reduction in the tumor growth of the treated animals in comparison with those of the positive control group with a more prominent effect in the co-treated group. Where, the anti-proliferative and apoptotic effect of STG, and its chemo-sensitizing ability, when used in combination with Dox, was mediated by modulation of oxidative stress (MDA and GSH), attenuation of tumor inflammation (IL-6 and IL-1β), and angiogenesis (VEGF), suppressing proliferation (β-catenin and cyclin-D1) and enhancement of apoptosis (survivin, p53, caspase 3). Thus, in conclusion, STG as adjunctive therapy for Dox could be a strategy for the treatment of breast cancer patients, by their ability in hindering cell proliferation and minimizing the associated oxidative and inflammatory adverse reactions

Potential Utility of Sodium Selenate as an Adjunct to Metformin in Treating Type II Diabetes Mellitus in Rats: A Perspective on Protein Tyrosine Phosphatase

Metformin is widely regarded as the standard first-line antidiabetic agent, in terms of efficacy and safety profiles. However, in most patients with type II diabetes mellitus (T2DM), it was found that metformin alone is not enough to adequately control hyperglycemia. Thus, we designed this study with the aim to investigate the effect of sodium selenate, a protein tyrosine phosphatase (PTP) inhibitor, individually and as an adjunct to metformin, on a rat model that simulates the metabolic characteristics of human T2DM. T2DM model was achieved by feeding the rats with high-fat, high-fructose diet (HFFD) for 8 weeks followed by a low dose of streptozotocin (STZ) (35 mg/kg/day, i.p.). Changes in serum glucose, insulin, adiponectin, homeostasis model assessment of insulin resistance (HOMA-IR) index, and the lipid profile were assessed. In addition, the level of reduced glutathione (GSH) and the activity of PTP were determined in the liver. Results showed that the addition of sodium selenate to metformin was able to restore hepatic GSH back to normal levels. Also, this combination therapy corrected the altered serum total cholesterol (TC), triglycerides (TG), and adiponectin levels. In conclusion, additive therapeutic effect was recorded when sodium selenate was used as an adjunct to metformin

Green HRM and green competitive advantage in hotel and tourism industry: a mediated moderation model using eco-innovation and green psychological climate

This study investigates the impact of green HRM (GHRM) on green competitive advantage (GCA), examining the mediating role of eco-innovation and the moderating role of green psychological climate (GPC). The study surveyed 472 fulltime employees in five-star hotels and travel agencies, developing and testing a five-hypothesis research model using PLS-SEM. Results revealed that GHRM positively impacts GCA and eco-innovation. Eco-innovation positively impacts GCA. In addition, GPC has a positive moderating influence on the relationship between GHRM and eco-innovation. Furthermore, Eco-innovation significantly mediates the relationship between GHRM and GCA

Novel Neuroprotective Potential of Bunchosia armeniaca (Cav.) DC against Lipopolysaccharide Induced Alzheimer’s Disease in Mice

Bunchosia armeniaca (Cav.) DC (Malpighiaceae) is one of the well-known traditionally used remedies worldwide. This study aims to explore the leaves’ metabolome via Quadrupole-Time-of-Flight-Liquid-Chromatography-Mass Spectrometry and to investigate the neuroprotective effect of leaves using lipopolysaccharide (LPS) induced Alzheimer’s disease model. Mice were administered LPS (0.25 mg/kg/day; intraperitoneal) as well as methanolic extract (BME), dichloromethane (BDMF), and butanol (BBF) fractions (each 200 mg/kg/day; oral) for one week. BME and BBF improved behavioral activity on the Y maze test, decreased brain content of inflammatory markers such as nuclear factor kappa B and interleukin 1 beta, and prevented the elevation of cytochrome P450 2E1, and glial fibrillary acidic protein compared to the LPS-administered group. Histopathological examination of several brain parts confirmed the neuroprotective effect of the tested extracts. In addition, BBF exhibited higher activity in all tested in vitro antioxidant and acetylcholinesterase inhibition assays. Metabolic profiling offered tentative identification of 88 metabolites, including mainly flavonoids, phenolic acids, and coumarins. Several detected metabolites, such as quercetin, apigenin, baicalin, vitexin, and resveratrol, had previously known neuroprotective effects. The current study highlighted the possible novel potential of B. armeniaca in preventing memory impairment, possibly through its antioxidant effect and inhibition of acetylcholinesterase, inflammatory and oxidative stress mediators