The Potential of Targeting Autophagy-Related Non-coding RNAs in the Treatment of Alzheimer's and Parkinson's Diseases.

Clearance of accumulated protein aggregates is one of the functions of autophagy. Recently, a clearer understanding of non-coding RNAs (ncRNAs) functions documented that ncRNAs have important roles in several biological processes associated with the development and progression of neurodegenerative disorders. Subtypes of ncRNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA), are commonly dysregulated in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Dysregulation of these non-coding RNAs has been associated with inhibition or stimulation of autophagy. Decreased miR-124 led to decreased/increased autophagy in experimental model of Alzheimer and Parkinson diseases. Increased BACE1-AS showed enhanced autophagy in Alzheimer disease by targeting miR-214-3p, Beclin-1, LC3-I/LC3-II, p62, and ATG5. A significant increase in NEAT1led to stimulated autophagy in experimental model of PD by targeting PINK1, LC3-I, LC3-II, p62 and miR-374c-5p. In addition, increased BDNF-AS and SNHG1 decreased autophagy in MPTP-induced PD by targeting miR-125b-5p and miR-221/222, respectively. The upregulation of circNF1-419 and circSAMD4A resulted in an increased autophagy by regulating Dynamin-1 and miR-29c 3p, respectively. A detailed discussion of miRNAs, circRNAs, and lncRNAs in relation to their autophagy-related signaling pathways is presented in this study.

Non-coding RNAs and Aquaporin 4: Their Role in the Pathogenesis of Neurological Disorders.

Neurological disorders are a major group of non-communicable diseases affecting quality of life. Non-Coding RNAs (ncRNAs) have an important role in the etiology of neurological disorders. In studies on the genesis of neurological diseases, aquaporin 4 (AQP4) expression and activity have both been linked to ncRNAs. The upregulation or downregulation of several ncRNAs leads to neurological disorder progression by targeting AQP4. The role of ncRNAs and AQP4 in neurological disorders is discussed in this review.

Non-Coding RNAs and Neurodegenerative Diseases: Information of their Roles in Apoptosis.

Apoptosis can be known as a key factor in the pathogenesis of neurodegenerative disorders. In disease conditions, the rate of apoptosis expands and tissue damage may become apparent. Recently, the scientific studies of the non-coding RNAs (ncRNAs) has provided new information of the molecular mechanisms that contribute to neurodegenerative disorders. Numerous reports have documented that ncRNAs have important contributions to several biological processes associated with the increase of neurodegenerative disorders. In addition, microRNAs (miRNAs), circular RNAs (circRNAs), as well as, long ncRNAs (lncRNAs) represent ncRNAs subtypes with the usual dysregulation in neurodegenerative disorders. Dysregulating ncRNAs has been associated with inhibiting or stimulating apoptosis in neurodegenerative disorders. Therefore, this review highlighted several ncRNAs linked to apoptosis in neurodegenerative disorders. CircRNAs, lncRNAs, and miRNAs were also illustrated completely regarding the respective signaling pathways of apoptosis.

Outsmarting trogocytosis to boost CAR NK/T cell therapy.

Chimeric antigen receptor (CAR) NK and T cell therapy are promising immunotherapeutic approaches for the treatment of cancer. However, the efficacy of CAR NK/T cell therapy is often hindered by various factors, including the phenomenon of trogocytosis, which involves the bidirectional exchange of membrane fragments between cells. In this review, we explore the role of trogocytosis in CAR NK/T cell therapy and highlight potential strategies for its modulation to improve therapeutic efficacy. We provide an in-depth analysis of trogocytosis as it relates to the fate and function of NK and T cells, focusing on its effects on cell activation, cytotoxicity, and antigen presentation. We discuss how trogocytosis can mediate transient antigen loss on cancer cells, thereby negatively affecting the effector function of CAR NK/T cells. Additionally, we address the phenomenon of fratricide and trogocytosis-associated exhaustion, which can limit the persistence and effectiveness of CAR-expressing cells. Furthermore, we explore how trogocytosis can impact CAR NK/T cell functionality, including the acquisition of target molecules and the modulation of signaling pathways. To overcome the negative effects of trogocytosis on cellular immunotherapy, we propose innovative approaches to modulate trogocytosis and augment CAR NK/T cell therapy. These strategies encompass targeting trogocytosis-related molecules, engineering CAR NK/T cells to resist trogocytosis-induced exhaustion and leveraging trogocytosis to enhance the function of CAR-expressing cells. By overcoming the limitations imposed by trogocytosis, it may be possible to unleash the full potential of CAR NK/T therapy against cancer. The knowledge and strategies presented in this review will guide future research and development, leading to improved therapeutic outcomes in the field of immunotherapy.

The effects of spirulina intake on clinical and metabolic parameters in Alzheimer's disease: A randomized, double-blind, controlled trial.

The current study aimed to determine the effects of spirulina intake on cognitive function and metabolic status among patients with Alzheimer's disease (AD). This randomized, double-blind, controlled clinical trial was done among 60 subjects with AD. Patients were randomly assigned to receive either 500 mg/day spirulina or a placebo (each n = 30) twice a day for 12 weeks. Mini-mental state examination score (MMSE) was recorded in all patients before and after intervention. Blood samples were obtained at baseline and after 12 weeks' intervention to determine metabolic markers. Compared with placebo, spirulina intake resulted in a significant improvement in MMSE score (spirulina group: +0.30 ± 0.99 vs. Placebo group: -0.38 ± 1.06, respectively, p = 0.01). In addition, spirulina intake decreased high-sensitivity C-reactive protein (hs-CRP) (spirulina group: -0.17 ± 0.29 vs. Placebo group: +0.05 ± 0.27 mg/L, p = 0.006), fasting glucose (spirulina group: -4.56 ± 7.93 vs. Placebo group: +0.80 ± 2.95 mg/dL, p = 0.002), insulin (spirulina group: -0.37 ± 0.62 vs. Placebo group: +0.12 ± 0.40 µIU/mL, p = 0.001) and insulin resistance (spirulina group: -0.08 ± 0.13 vs. Placebo group: 0.03 ± 0.08, p = 0.001), and increased insulin sensitivity (spirulina group: +0.003 ± 0.005 vs. Placebo group: -0.001 ± 0.003, p = 0.003) compared with the placebo. Overall, our study showed that spirulina intake for 12 weeks in patients with AD improved cognitive function, glucose homeostasis parameters, and hs-CRP levels.

Non-coding RNAs and glioma: Focus on cancer stem cells.

Glioblastoma and gliomas can have a wide range of histopathologic subtypes. These heterogeneous histologic phenotypes originate from tumor cells with the distinct functions of tumorigenesis and self-renewal, called glioma stem cells (GSCs). GSCs are characterized based on multi-layered epigenetic mechanisms, which control the expression of many genes. This epigenetic regulatory mechanism is often based on functional non-coding RNAs (ncRNAs). ncRNAs have become increasingly important in the pathogenesis of human cancer and work as oncogenes or tumor suppressors to regulate carcinogenesis and progression. These RNAs by being involved in chromatin remodeling and modification, transcriptional regulation, and alternative splicing of pre-mRNA, as well as mRNA stability and protein translation, play a key role in tumor development and progression. Numerous studies have been performed to try to understand the dysregulation pattern of these ncRNAs in tumors and cancer stem cells (CSCs), which show robust differentiation and self-regeneration capacity. This review provides recent findings on the role of ncRNAs in glioma development and progression, particularly their effects on CSCs, thus accelerating the clinical implementation of ncRNAs as promising tumor biomarkers and therapeutic targets.

Can Berberine Serve as a New Therapy for Parkinson's Disease?

Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurodegeneration and deposition of alpha-synuclein. Mechanisms associated with PD etiology include oxidative stress, apoptosis, autophagy, and abnormalities in neurotransmission, to name a few. Drugs used to treat PD have shown significant limitations in their efficacy. Therefore, recent focus has been placed on the potential of active plant ingredients as alternative, complementary, and efficient treatments. Berberine is an isoquinoline alkaloid that has shown promise as a pharmacological treatment in PD, given its ability to modulate several molecular pathway associated with the disease. Here, we review contemporary knowledge supporting the need to further characterize berberine as a potential treatment for PD.

The role of aquaporin 4 in brain tumors: implications for pathophysiology, diagnosis and therapy.

Primary brain tumors are a heterogeneous group of tumors that arise from cells intrinsic to the central nervous system (CNS). Aquaporin-4 (AQP4) has been implicated in the pathogenesis of brain tumors. Previous reports have documented a relationship between AQP4 and several molecular pathways associated with the etiology of brain tumors, such as apoptosis, invasion and cell migration. AQP4 affects apoptosis via cytochrome C, Bad and Bcl-2, as well as invasion and migration via IDO1/TDO-Kyn-AhR axis, lncRNA LINC00461, miR-216a, miRNA-320a and MMPs. In addition, inhibition of AQP4 mitigates the progression of brain tumors. This review summarizes current knowledge and evidence regarding the relationship between AQP4 and brain tumors, and the mechanisms involved.

Quercetin and Glioma: Which Signaling Pathways are Involved?

Gliomas are the most common brain tumors. These tumors commonly exhibit continuous growth without invading surrounding brain tissues. Dominant remedial approaches suffer limited therapy and survival rates. Although some progress has been made in conventional glioma treatments, these breakthroughs have not yet proven sufficient for treating this malignancy. The remedial options are limited given gliomas' aggressive metastasis and drug resistance. Quercetin, a flavonoid, is an anti-oxidative, anti-allergic, antiviral, anti-inflammatory, and anticancer compound. Multiple lines of evidence have shown that Quercetin has anti-tumor effects, documenting this natural compound exerts its pharmacological effects by targeting a variety of cellular and molecular processes, i.e., apoptosis, metastasis, and autophagy. Herein, we summarize various cellular and molecular pathways that are affected by Quercetin in gliomas.

Aquaporin 4 in Traumatic Brain Injury: From Molecular Pathways to Therapeutic Target.

Traumatic brain injury (TBI) is known as an acute degenerative pathology of the central nervous system, and has been shown to increase brain aquaporin 4 (AQP4) expression. Various molecular mechanisms affect AQP4 expression, including neuronal high mobility group box 1, forkhead box O3a, vascular endothelial growth factor, hypoxia-inducible factor-1 α (HIF-1 α) sirtuin 2, NF-κB, Malat1, nerve growth factor and Angiotensin II receptor type 1. In addition, inhibition of AQP4 with FK-506, MK-801 (indirectly by targeting N-methyl-D-aspartate receptor), inactivation of adenosine A2A receptor, levetiracetam, adjudin, progesterone, estrogen, V1aR inhibitor, hypertonic saline, erythropoietin, poloxamer 188, brilliant blue G, HIF-1alpha inhibitor, normobaric oxygen therapy, astaxanthin, epigallocatechin-3-gallate, sesamin, thaliporphine, magnesium, prebiotic fiber, resveratrol and omega-3, as well as AQP4 gene silencing lead to reduced edema upon TBI. This review summarizes current knowledge and evidence on the relationship between AQP4 and TBI, and the potential mechanisms involved.

Probiotics and the Treatment of Parkinson's Disease: An Update.

Parkinson's disease (PD) is a progressive neurological disorder characterized by motor and non-motor features. Although some progress has been made in conventional PD treatments, these breakthroughs have yet to show high efficacy in treating this neurodegenerative disease. Probiotics are live microorganisms that confer health benefits on the host when administered in adequate amounts. Probiotics have putative anticancer, antioxidative, anti-inflammatory, and neuroprotective effects. Multiple lines of evidence show that probiotics control and improve several motor and non-motor symptoms in patients and experimental animal models of PD. Probiotic supplementation mediates these pharmacological effects by targeting a variety of cellular and molecular processes, i.e., oxidative stress, inflammatory and anti-inflammatory pathways, as well as apoptosis. Herein, we summarize the effects of probiotics on motor and non-motor symptoms as well as various cellular and molecular pathways in PD.

Aquaporin 4 and brain-related disorders: Insights into its apoptosis roles.

Brain-related disorders are leading global health problems. Various internal and external factors are involved in the progression of brain-related disorders. Inflammatory pathways, oxidative stresses, apoptosis, and deregulations of various channels are critical players in brain-related disorder pathogenesis. Among these players, aquaporins (AQP) have critical roles in various physiological and pathological conditions. AQPs are water channel molecules that permit water to cross the hydrophobic lipid bilayers of cellular membranes. AQP4 is one of the important members of AQP family. AQPs are involved in controlling apoptosis pathways in brain-related disorders. In this regard, several reports have evaluated the pathological effects of AQP4 by targeting the apoptosis-related processes in brain-related disorders. Here, for the first time, we highlight the impact of AQP4 on apoptosis-related processes in brain-related disorders.

Therapeutic Potential of Resveratrol in the Treatment of Glioma: Insights into its Regulatory Mechanisms.

Glioma is a prevalent primary tumor of the brain and spinal cord. Several biological pathways play an important role in the pathogenesis of glioma, including apoptosis, autophagy, cell cycle arrest, migration, and invasion. The low efficacy of chemotherapy and radiation therapy has forced researchers to evaluate alternative treatments for glioma. In this regard, flavonoids have been studied. Resveratrol is a flavonoid with distinct pharmacological activities that has been used in the treatment of various diseases. Several recent studies have also focused on its therapeutic efficacy against glioma. Resveratrol exerts its pharmacological attributes by regulating various molecular and cellular pathways. Here, we review contemporary knowledge in support of the use of resveratrol in the treatment of glioma and its effects on various molecular and cellular mechanisms.

Non-Coding RNAs and Brain Tumors: Insights Into Their Roles in Apoptosis.

A major terrifying ailment afflicting the humans throughout the world is brain tumor, which causes a lot of mortality among pediatric and adult solid tumors. Several major barriers to the treatment and diagnosis of the brain tumors are the specific micro-environmental and cell-intrinsic features of neural tissues. Absence of the nutrients and hypoxia trigger the cells' mortality in the core of the tumors of humans' brains: however, type of the cells' mortality, including apoptosis or necrosis, has been not found obviously. Current studies have emphasized the non-coding RNAs (ncRNAs) since their crucial impacts on carcinogenesis have been discovered. Several investigations suggest the essential contribution of such molecules in the development of brain tumors and the respective roles in apoptosis. Herein, we summarize the apoptosis-related non-coding RNAs in brain tumors.

An Update on the Effects of Probiotics on Gastrointestinal Cancers.

Because of their increasing prevalence, gastrointestinal (GI) cancers are regarded as an important global health challenge. Microorganisms residing in the human GI tract, termed gut microbiota, encompass a large number of living organisms. The role of the gut in the regulation of the gut-mediated immune responses, metabolism, absorption of micro- and macro-nutrients and essential vitamins, and short-chain fatty acid production, and resistance to pathogens has been extensively investigated. In the past few decades, it has been shown that microbiota imbalance is associated with the susceptibility to various chronic disorders, such as obesity, irritable bowel syndrome, inflammatory bowel disease, asthma, rheumatoid arthritis, psychiatric disorders, and various types of cancer. Emerging evidence has shown that oral administration of various strains of probiotics can protect against cancer development. Furthermore, clinical investigations suggest that probiotic administration in cancer patients decreases the incidence of postoperative inflammation. The present review addresses the efficacy and underlying mechanisms of action of probiotics against GI cancers. The safety of the most commercial probiotic strains has been confirmed, and therefore these strains can be used as adjuvant or neo-adjuvant treatments for cancer prevention and improving the efficacy of therapeutic strategies. Nevertheless, well-designed clinical studies are still needed for a better understanding of the properties and mechanisms of action of probiotic strains in mitigating GI cancer development.

Neuroprotective effects of probiotics bacteria on animal model of Parkinson's disease induced by 6-hydroxydopamine: A behavioral, biochemical, and histological study.

Parkinson's disease (PD) is an age-associated, progressive, and common neurodegenerative disorder. It is characterized by dopaminergic neuron degeneration in the substantia nigra pars compacta. The involvement of oxidative stress, inflammation, and dysbiosis in PD has been confirmed and probiotics also have the ability to regulate the mentioned mechanisms. Here, we assessed probiotics supplementation effects on experimental model of PD. Thirty Male Wistar rats were divided into three groups for a 14-day treatment. It was shown that a mixture of probiotics containing Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum could improve rotational behavior, cognitive function, lipid peroxidation, and neuronal damage in the group received probiotic supplementation compared to the other groups (P < 0001, P < .001, and P = .026, respectively). Taken together, these findings revealed that probiotics supplementation could be an appropriate complementary treatment for PD.

Therapeutic Potential of Berberine in the Treatment of Glioma: Insights into Its Regulatory Mechanisms.

Glioma is known as one of the most common primary intracranial tumors accounting for four-fifths of malignant brain tumors. There are several biological pathways that play a synergistic, pathophysiological role in glioma, including apoptosis, autophagy, oxidative stress, and cell cycle arrest. According to previous rese arches, the drugs used in the treatment of glioma have been associated with significant limitations. Therefore, improved and/or new therapeutic platforms are required. In this regard, multiple flavonoids and alkaloids have been extensively studied in the treatment of glioma. Berberine is a protoberberine alkaloid with wide range of pharmacological activities, applicable to various pathological conditions. Few studies have reported beneficial roles of berberine in glioma. Berberine exerts its pharmacological functions in glioma by controlling different molecular and cellular pathways. We reviewed the existing knowledge supporting the use of berberine in the treatment of glioma and its effects on molecular and cellular mechanisms.

Effects of flaxseed oil supplementation on biomarkers of inflammation and oxidative stress in patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to analyze the effects of flaxseed oil supplementation on biomarkers of inflammation and oxidative stress in patients with metabolic syndrome (MetS) and related disorders. METHODS: Databases including PubMed, Scopus, EMBASE, Web of Science, and Cochrane Central library were searched until January 31th, 2019. RESULTS: 14 effect sizes from 12 studies were identified eligible to be included in current meta-analysis. Flaxseed supplementation resulted in a significant reduction in interleukin 6 (IL-6) (WMD: -0.22; 95% CI: -0.43, -0.01) and malondialdehyde (MDA) (WMD: -0.17; 95% CI: -0.31, -0.03) and a significant increase in total antioxidant capacity (TAC) levels (WMD: 137.25; 95% CI: 68.04, 206.47). Flaxseed oil supplementation did not affect other biomarkers of inflammation and oxidative stress. CONCLUSIONS: Overall, this meta-analysis demonstrated flaxseed oil supplementation decreased IL-6 and MDA levels, and increased TAC, but did not affect other biomarkers of inflammation and oxidative stress among patients with MetS and related disorders. This suggests that flaxseed oil supplementation may have played an indirect role in improved clinical symptoms in diseases with metabolic disorders.

PIWI-interacting RNAs and PIWI proteins in glioma: molecular pathogenesis and role as biomarkers.

Glioma is the most common primary brain tumor, and is a major health problem throughout the world. Today, researchers have discovered many risk factors that are associated with the initiation and progression of gliomas. Studies have shown that PIWI-interacting RNAs (piRNAs) and PIWI proteins are involved in tumorigenesis by epigenetic mechanisms. Hence, it seems that piRNAs and PIWI proteins may be potential prognostic, diagnostic or therapeutic biomarkers in the treatment of glioma. Previous studies have demonstrated a relationship between piRNAs and PIWI proteins and some of the molecular and cellular pathways in glioma. Here, we summarize recent evidence and evaluate the molecular mechanisms by which piRNAs and PIWI proteins are involved in glioma. Video abstract.

Breast cancer risk factors in Iran: a systematic review & meta-analysis.

OBJECTIVES: Breast cancer is known as one of the deadliest forms of cancer, and it is increasing globally. There are a variety of proven and controversial risk factors for this malignancy. Herein, we aimed to undertake a systematic review and meta-analysis focus on the epidemiology of breast cancer risk factors in Iran. METHODS: We performed a systematic search via PubMed, Scopus, Web of Science, and Persian databases for identifying studies published on breast cancer risk factors up to March 2019. Meta-analyses were done for risk factors reported in more than one study. We calculated odds ratios (ORs) with corresponding 95% confidence intervals (CIs) using a fixed/random-effects models. RESULTS: Thirty-nine studies entered into the meta-analysis. Pooling of ORs showed a significant harmful effect for risk factors including family history (OR: 1.80, 95%CI 1.47-2.12), hormonal replacement therapy (HRT) (OR: 5.48, 95%CI 0.84-1.74), passive smokers (OR: 1.68, 95%CI 1.34-2.03), full-term pregnancy at age 30 (OR: 3.41, 95%CI 1.19-5.63), abortion (OR: 1.84, 95%CI 1.35-2.33), sweets consumption (OR: 1.71, 95%CI 1.32-2.11) and genotype Arg/Arg (crude OR: 1.59, 95%CI 1.07-2.10), whereas a significant protective effect for late menarche (OR: 0.58, 95%CI 0.32-0.83), nulliparity (OR: 0.68, 95%CI 0.39-0.96), 13-24 months of breastfeeding (OR: 0.68, 95%CI 0.46-0.90), daily exercise (OR: 0.59, 95%CI 0.44-0.73) and vegetable consumption (crude OR: 0.28, 95%CI 0.10-0.46). CONCLUSIONS: This study suggests that factors such as family history, HRT, passive smokers, late full-term pregnancy, abortion, sweets consumption and genotype Arg/Arg might increase risk of breast cancer development, whereas late menarche, nulliparity, 13-24 months breastfeeding, daily exercise and vegetable consumption had an inverse association with breast cancer development.