scholarly journals Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Patricia Soriano Roque ◽  
Mehdi Hooshmandi ◽  
Laura Neagu-Lund ◽  
Shelly Yin ◽  
Noosha Yousefpour ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
General Anesthesia ◽  
Preventive Treatment ◽  
Intranasal Insulin ◽  
Translational Repressor ◽  
Beneficial Effects ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Preclinical And Clinical Studies

AbstractLong-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.

scholarly journals Grape Seed Procyanidin B2 Protects Porcine Ovarian Granulosa Cells against Oxidative Stress-Induced Apoptosis by Upregulating let-7a Expression

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Jia-Qing Zhang ◽  
Xian-Wei Wang ◽  
Jun-Feng Chen ◽  
Qiao-Ling Ren ◽  
Jing Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Critical Role ◽  
Grape Seed ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Oxidative stress is a causal factor and key promoter of all kinds of reproductive disorders related to granulosa cell (GC) apoptosis that acts by dysregulating the expression of related genes. Various studies have suggested that grape seed procyanidin B2 (GSPB2) may protect GCs from oxidative injury, though the underlying mechanisms are not fully understood. Therefore, whether the beneficial effects of GSPB2 are associated with microRNAs, which have been suggested to play a critical role in GC apoptosis by regulating the expression of protein-coding genes, was investigated in this study. The results showed that GSPB2 treatment protected GCs from a H2O2-induced apoptosis, as detected by an MTT assay and TUNEL staining, and increased let-7a expression in GCs. Furthermore, let-7a overexpression markedly increased cell viability and inhibited H2O2-induced GC apoptosis. Furthermore, the overexpression of let-7a reduced the upregulation of Fas expression in H2O2-treated GCs at the mRNA and protein levels. Dual-luciferase reporter assay results indicated that let-7a directly targets the Fas 3′-UTR. Furthermore, the overexpression of let-7a enhanced the protective effects of GSPB2 against GC apoptosis induced by H2O2. These results indicate that GSPB2 inhibits H2O2-induced apoptosis of GCs, possibly through the upregulation of let-7a.

scholarly journals Combinations of Calcitriol with Anticancer Treatments for Breast Cancer: An Update

2021 ◽  
Vol 22 (23) ◽  
pp. 12741
Author(s):  
Mariana Segovia-Mendoza ◽  
Janice García-Quiroz ◽  
Lorenza Díaz ◽  
Rocío García-Becerra
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Risk Factor ◽  
Cell Differentiation ◽  
Epidemiological Studies ◽  
Antineoplastic Drugs ◽  
Beneficial Effects ◽  
Therapeutic Benefits ◽  
Underlying Mechanisms ◽  
Preclinical And Clinical Studies

Preclinical, clinical, and epidemiological studies indicate that vitamin D3 (VD) deficiency is a risk factor for the development of breast cancer. Underlying mechanisms include the ability of calcitriol to induce cell differentiation, inhibit oncogenes expression, and modify different signaling pathways involved in the control of cell proliferation. In addition, calcitriol combined with different kinds of antineoplastic drugs has been demonstrated to enhance their beneficial effects in an additive or synergistic fashion. However, a recognized adjuvant regimen based on calcitriol for treating patients with breast cancer has not yet been fully established. Accordingly, in the present work, we review and discuss the preclinical and clinical studies about the combination of calcitriol with different oncological drugs, aiming to emphasize its main therapeutic benefits and opportunities for the treatment of this pathology.

scholarly journals Beneficial Effects of Sagacious Confucius’ Pillow Elixir on Cognitive Function in Senescence-Accelerated P8 Mice (SAMP8) via the NLRP3/Caspase-1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zhitao Hou ◽  
Fengjin Li ◽  
Jing Chen ◽  
Yitian Liu ◽  
Changyuan He ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Neuronal Degeneration ◽  
Blue Staining ◽  
Beneficial Effects ◽  
Caspase 1 ◽  
Pathogenic Factors ◽  
Hippocampal Ca1 ◽  
Underlying Mechanisms ◽  
Samp8 Mice

Sagacious Confucius’ Pillow Elixir (SCPE) is a traditional Chinese medicine that is mainly used for cognitive impairment in aging; however, the underlying mechanisms remain unclear. Aging is one of the most important pathogenic factors leading to inflammation and pyroptosis in the hippocampus, which may be a potential mechanism in elderly patients with cognitive impairment. Here, we examined whether SCPE could improve cognitive impairment in SAMP8 mice by reducing hippocampal inflammation and pyroptosis. Seven-month-old senescence-accelerated P8 mice (SAMP8) received SCPE (2.3 g/kg/day; 4.6 g/kg/day; 9.2 g/kg/day) for 28 days. Cognitive function and morphometric examinations were performed followed by water maze testing, hematoxylin-eosin staining, Congo red staining, toluidine blue staining, and TUNEL analysis of hippocampal CA1 and CA3 regions. Escape latency increased and times across platforms decreased in SAMP8 mice; however, both of them were normalized by SCPE after 28 days. Aging caused significant pyroptosis in hippocampal CA1 and CA3 regions, as evidenced by neuronal degeneration and necrosis, amyloid deposition, and decreased Nissl body amounts after cognitive impairment, which were greatly improved by SCPE. SCPE reduced serum IL-1β, IL-6, IL-18, and TNF-α levels and reduced hippocampal NLRP3, ASC, caspase-1, GSDM-D, IL-1β, IL-6, IL-18, and Aβ expression. Thus, SCPE exerts an antipyroptotic effect in aging, mainly by suppressing the NLRP3/caspase-1 signaling pathway.

Novel Findings of Anti-cancer Property of Propofol

2018 ◽  
Vol 18 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Jiaqiang Wang ◽  
Chien-shan Cheng ◽  
Yan Lu ◽  
Xiaowei Ding ◽  
Minmin Zhu ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Intravenous Anesthetic ◽  
The Past ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Recent Attention

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.

scholarly journals Dysregulation of Astrocyte–Neuronal Communication in Alzheimer’s Disease

2021 ◽  
Vol 22 (15) ◽  
pp. 7887
Author(s):  
Carmen Nanclares ◽  
Andres Mateo Baraibar ◽  
Alfonso Araque ◽  
Paulo Kofuji
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Neuronal Excitability ◽  
Active Role ◽  
Ionic Homeostasis ◽  
Neuronal Communication ◽  
Structural Support

Recent studies implicate astrocytes in Alzheimer’s disease (AD); however, their role in pathogenesis is poorly understood. Astrocytes have well-established functions in supportive functions such as extracellular ionic homeostasis, structural support, and neurovascular coupling. However, emerging research on astrocytic function in the healthy brain also indicates their role in regulating synaptic plasticity and neuronal excitability via the release of neuroactive substances named gliotransmitters. Here, we review how this “active” role of astrocytes at synapses could contribute to synaptic and neuronal network dysfunction and cognitive impairment in AD.

scholarly journals Dehulled Adlay Consumption Modulates Blood Pressure in Spontaneously Hypertensive Rats and Overweight and Obese Young Adults

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2305
Author(s):  
Wan-Ju Yeh ◽  
Jung Ko ◽  
Wei-Yi Cheng ◽  
Hsin-Yi Yang
Keyword(s):  
Blood Pressure ◽  
Daily Intake ◽  
Experimental Period ◽  
Overweight And Obesity ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Beneficial Effects ◽  
Underlying Mechanisms ◽  
Grain Foods

High blood pressure is a crucial risk factor for many cardiovascular diseases, and a diet rich in whole-grain foods may modulate blood pressure. This study investigated the effects of dehulled adlay consumption on blood pressure in vivo. We initially fed spontaneous hypertensive rats diets without (SHR group) or with 12 or 24% dehulled adlay (SHR + LA and SHR + HA groups), and discovered that it could limit blood pressure increases over a 12-week experimental period. Although we found no significant changes in plasma, heart, and kidney angiotensin-converting enzyme activities, both adlay-consuming groups had lower endothelin-1 and creatinine concentrations than the SHR group; the SHR + HA group also had lower aspartate aminotransferase and uric acid levels than the SHR group did. We later recruited 23 participants with overweight and obesity, and they consumed 60 g of dehulled adlay daily for a six-week experimental period. At the end of the study, we observed a significant decrease in the group’s systolic blood pressure (SBP), and the change in SBP was even more evident in participants with high baseline SBP. In conclusion, our results suggested that daily intake of dehulled adlay had beneficial effects in blood-pressure management. Future studies may further clarify the possible underlying mechanisms for the consuming of dehulled adlay as a beneficial dietary approach for people at risk of hypertension.

Beneficial effects of natural compounds on experimental liver ischemia-reperfusion injury

2021 ◽  
Author(s):  
Camila Dossi ◽  
Romina Vargas ◽  
Rodrigo Valenzuela ◽  
Luis Videla
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Natural Compounds ◽  
Liver Ischemia ◽  
Hepatic Surgery ◽  
Beneficial Effects ◽  
Underlying Mechanisms ◽  
Experimental Liver

Liver ischemia-reperfusion injury (IRI) is a phenomenon inherent to hepatic surgery that severely compromises the organ functionality, whose underlying mechanisms involve cellular and molecular interrelated processes leading to the development...

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