The role of statins in amyotrophic lateral sclerosis: protective or not?

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons characterized by muscle weakness, muscle twitching, and muscle wasting. ALS is regarded as the third-most frequent neurodegenerative disease, subsequent to Alzheimer's disease (AD) and Parkinson's disease (PD). The World Health Organization (WHO) in 2007 declared that prolonged use of statins may induce development of ALS-like syndrome and may increase ALS risk. Subsequently, different studies have implicated statins in the pathogenesis of ALS. In contrast, results from preclinical and clinical studies highlighted the protective role of statins against ALS neuropathology. Recently, meta-analyses and systematic reviews illustrated no association between long-term use of statins and ALS risk. These findings highlighted controversial points regarding the effects of statins on ALS pathogenesis and risk. The neuroprotective effects of statins against the development and progression of ALS may be mediated by regulating dyslipidemia and inflammatory changes. However, the mechanism for induction of ALS neuropathology by statins may be related to the dysregulation of liver X receptor signaling (LXR) signaling in the motor neurons and reduction of cholesterol, which has a neuroprotective effect against ALS neuropathology. Nevertheless, the exact role of statins on the pathogenesis of ALS was not fully elucidated. Therefore, this narrative review aims to discuss the role of statins in ALS neuropathology.

The anti-inflammatory properties of vinpocetine mediates its therapeutic potential in management of atherosclerosis.

Atherosclerosis (AS) formation is enhanced by different mechanisms including cytokine generation, vascular smooth muscle cell proliferation, and migration. One of the recent treatments towards endothelial dysfunction and AS is Vinpocetine (VPN). VPN is a potent inhibitor of phosphodiesterase enzyme 1 (PDE-1) and has anti-inflammatory and antioxidant effects through inhibition the expression of nuclear factor kappa B (NF-κB). VPN has been shown to be effective against the development and progression of AS. However, the underlying molecular mechanism was not fully clarified. Consequently, objective of the present review was to discuss the mechanistic role of VPN in the pathogenesis AS. Most of pro-inflammatory cytokines that released from macrophages are inhibited by action of VPN through NF-κB-dependent mechanism. VPN blocks monocyte adhesion and migration by constraining the expression and action of pro-inflammatory cytokines. As well, VPN is effective in reducing of oxidative stress a cornerstone in the pathogenesis of AS through inhibition of NF-κB and PDE1. VPN promotes plaque stability and prevents the erosion and rupture of atherosclerotic plaque. In conclusion, VPN through mitigation of inflammatory and oxidative stress, and improvement of plaque stability effects could be effective agent in the management of AS.

Role of ketogenic diet in neurodegenerative diseases focusing on Alzheimer diseases: The guardian angle.

The ketogenic diet (KD) is a low-carbohydrate, adequate protein and high-fat diet. KD is primarily used to treat refractory epilepsy. KD was shown to be effective in treating different neurodegenerative diseases. Alzheimer disease (AD) is the first common neurodegenerative disease in the world characterized by memory and cognitive impairment. However, the underlying mechanism of KD in controlling of AD and other neurodegenerative diseases are not discussed widely. Therefore, this review aims to revise the fundamental mechanism of KD in different neurodegenerative diseases focusing on the AD. KD induces a fasting-like which modulates the central and peripheral metabolism by regulating mitochondrial dysfunction, oxidative stress, inflammation, gut-flora, and autophagy in different neurodegenerative diseases. Different studies highlighted that KD improves AD neuropathology by regulating synaptic neurotransmission and inhibiting of neuroinflammation and oxidative stress. In conclusion, KD improves cognitive function and attenuates the progression of AD neuropathology by reducing oxidative stress, mitochondrial dysfunction, and enhancing neuronal autophagy and brain BDNF.

Combined oncolytic virotherapy gold nanoparticles as synergistic immunotherapy agent in breast cancer control.

Combining viruses and nanoparticles may be a way to successfully treat cancer and minimize adverse effects. The current work aimed to evaluate the efficacy of a specific combination of gold nanoparticles (GNPs) and Newcastle disease virus (NDV) to enhance the antitumor effect of breast cancer in both in vitro and in vivo models. Two human breast cancer cell lines (MCF-7 and AMJ-13) and a normal epithelial cell line (HBL-100) were used and treated with NDV and/or GNPs. The MTT assay was used to study the anticancer potentials of NDV and GNP. The colony formation assay and apoptosis markers were used to confirm the killing mechanisms of NDV and GNP against breast cancer cell lines. p53 and caspase-9 expression tested by the qRT-PCR technique. Our results showed that combination therapy had a significant killing effect against breast cancer cells. The findings demonstrated that NDV and GNPs induced apoptosis in cancer cells by activating caspase-9, the p53 protein, and other proteins related to apoptosis, which holds promise as a combination therapy for breast cancer.

Graphene oxide-induced, reactive oxygen species-mediated mitochondrial dysfunctions and apoptosis: high-dose toxicity in normal cells.

Aim: The cytotoxic effects of graphene oxide nanoparticles (GONPs) using MTT assays, observance of apoptotic markers, and oxidative stress were outlined. Materials & methods: Rat embryonic fibroblasts (REFs) and human epithelial breast cells (HBLs) were used at 250, 500 and 750 µg/ml concentrations. Results: Significant cytotoxic and apoptotic effects were observed. Analyses of CYP2E1 and malondialdehyde concentrations in REF and HBL-100 cell lines after exposing to GONPs confirmed the nanomaterials toxicity. However, the glutathione levels in REF and HBL-100 cell lines showed a substantial reduction compared with the control. The cytochrome CYP2E1, glutathione, malondialdehyde and caspase-3 alterations provided a plausible interlinked relationship. Conclusion: The study confirmed the GONPs cytotoxic effects on REF and HBL-100 cell lines. The outcome suggested caution in wide-spread applications of GONPs, which could have implications for occupational health also.

Bacterial extracellular vesicles induced oxidative stress and mitophagy through mTOR pathways in colon cancer cells, HT-29: Implications for bioactivity.

Bacterial-extracellular-vesicles (BEVs) derived from Escherichia coli, strain-A5922, were used as a therapeutic tool to treat colon cancer cells, HT-29. BEVs induced oxidative stress, and observed mitochondrial autophagy, known as mitophagy, were crucial in initiation of treatment. The mitophagy, induced by the BEVs in HT-29 cells, produced adenocarcinomic cytotoxicity, and stopped the cells growth. The trigger for mitophagy, and an increase in productions of reactive oxygen species led to cellular oxidative stress, that eventually led to cells death. A reduction in the mitochondrial membrane potential, and an increase in the PINK1 expressions confirmed the oxidative stress involvements. The BEVs triggered cytotoxicity, and mitophagy in the HT-29 carcinoid cells, channelized through the Akt/mTOR pathways connecting the cellular oxidative stress, effectively played its part to cause cells death. These findings substantiated the BEVs' potential as a plausible tool for treating, and possibly preventing the colorectal cancer.