Icariin: A Potential Neuroprotective Agent in Alzheimer’s Disease and Parkinson’s Disease

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases worldwide. They are characterized by the loss of neurons and synapses in special parts of the central nervous system (CNS). There is no definitive treatment for AD and PD, but extensive studies are underway to identify the effective drugs which can slow the progression of these diseases by affecting the factors involved in their pathophysiology (i.e., aggregated proteins, neuroinflammation, and oxidative stress). Icariin, a natural compound isolated from Epimedii herba, is known because of its anti-inflammatory and anti-oxidant properties. In this regard, there are numerous studies indicating its potential as a natural compound against the progression of CNS disorders, such as neurodegenerative diseases. Therefore, this review aims to re-examine findings on the pharmacologic effects of icariin on factors involved in the pathophysiology of AD and PD.

     

Probiotics importance and their immunomodulatory properties

Mammalian intestine contains a large diversity of commensal microbiota, which is far more than the number of host cells. Probiotics play an insecure and protective role against the colonization of intestinal pathogenic microbes and increase mucosal integrity by stimulating epithelial cells. Probiotics have innate capabilities in many ways, including receptor antagonism, receptor expression, binding and expression of adapter proteins, expression of negative regulatory signal molecules, induction of microRNAs, endotoxin tolerance, and ultimately secretion of immunomodulatory proteins, lipids, and metabolites to modulate the immune system. Probiotic bacteria can affect homeostasis, inflammation, and immunopathology through direct or indirect effects on signaling pathways as immunosuppressant or activators. Probiotics suppress inflammation by inhibiting various signaling pathways such as the nuclear factor-κB (NF-κβ) pathway, possibly related to alterations in mitogen-activated protein kinases and pattern recognition receptors pathways. Probiotics can also inhibit the binding of lipopolysaccharides to the CD14 receptor, thereby reducing the overall activation of NF-κβ and producing proinflammatory cytokines. Some effects of modulation by probiotics include cytokine production by epithelial cells, increased mucin secretion, increased activity of phagocytosis, and activation of T and natural killer T cells, stimulation of immunoglobulin A production and decreased T cell proliferation. Intestinal microbiota has a major impact on the systemic immune system. Specific microbiota controls the differentiation of cells in lamina propria, in which Th17 cells secrete interleukin 17. The presence of Th17 and Treg cells in the small intestine is associated with intestinal microbiota, with the preferential Treg differentiation and the absence of Th17 cells, possibly reflecting alterations in the lamina propria cytokines and the intestinal gut microbiota.     

Stem cell-based cell therapy for neuroprotection in stroke: A review

Neurological disorders, such as stroke, are triggered by a loss of neurons and glial cells. Ischemic stroke remains a substantial problem for industrialized countries. Over the previous few decades our understanding about the pathophysiology of stroke has enhanced, nevertheless, more awareness is required to advance the field of stroke recovery. Existing therapies are incapable to adequately relief the disease outcome and are not appropriate to all patients. Meanwhile, the majority of patients continue to show neurological deficits even subsequent effective thrombolysis, recuperative therapies are immediately required that stimulate brain remodeling and repair once stroke damage has happened. Cell therapy is emergent as a hopeful new modality for increasing neurological recovery in ischemic stroke. Numerous types of stem cells from various sources have been identified and their possibility and efficiency for the treatment of stroke have been investigated. Stem cell therapy in patients with stroke using adult stem cells have been first practiced in clinical trials since 15 years ago. Even though stem cells have revealed a hopeful role in ischemic stroke in investigational studies besides early clinical pilot studies, cellular therapy in human is still at a primary stage. In this review, we summarize the types of stem cells, various delivery routes, and clinical application of stem cell-based therapy for stroke treatment.     

Retracted: Terbium-sensitized fluorescence method for the determination of dopamine in biological fluids and tablet formulation

The following article from Luminescence, Terbium‐sensitized fluorescence method for the determination of dopamine in biological fluids and tablet formulation by Vahid Shahinfard, Ali Ehsani, Vahid Panahi‐Azar, Negar Kabir Yousefi and Morteza Salek Jalali, published online on 12th January 2012 in Wiley Online Library ( www.onlinelibrary.wiley.com ), has been retracted by agreement between the authors, the journal Editor in Chief, Professor L. J. Kricka and Wiley‐Blackwell. The retraction has been agreed due to data in the article is not being reproducible. Copyright © 2012 John Wiley & Sons, Ltd.     

Serum heat shock protein 70 and oxidized LDL in patients with type 2 diabetes: does sex matter?

Several studies suggest that the response to various stressors differs between the sexes. We aimed to study serum HSP70 and levels of oxidized-LDL (ox-LDL) as markers of oxidative stress in men and women with type 2 diabetes. We quantified serum HSP70 and levels of ox-LDL in three cohorts; patients with newly diagnosed diabetes, patients with long-standing diabetes and normal controls. The cohort of patients with newly diagnosed diabetes was followed up for 3 months under glucose-lowering therapy with metformin. Our findings showed that serum HSP70 level was increased in women with long-standing diabetes in comparison with men. HSP70 did not decrease after glucose lowering therapy in women with newly diagnosed diabetes, but it did decrease in men. There was no significant difference on ox-LDL between men and women in any of the studied cohorts. It decreased significantly in the cohort of patients with newly diagnosed diabetes after treatment, regardless of sex. There was no significant correlation between HSP70 and ox-LDL in any of the studied cohorts except among normal women. We suggest that diabetes induces an immune response and impairs cellular defense mechanisms against oxidative stress more commonly in women with type 2 diabetes than in men.     

Lithospermum officinale callus produces shikalkin

To study biosynthetic abilities of Lithospermum officinale, callus formation from young leaves and stems of the plant was induced on Linsmaier-Skoog medium supplemented with 2,4-D (10⁻⁶ M) and kinetin (10⁻⁵ M). Maintaining the calli on this medium resulted in polyphenolic compounds production. Their transfer onto White medium containing IAA (10⁻⁷ M) and kinetin (10⁻⁵ M) resulted in the production of a red naphthoquinonic pigment named shikalkin. Shikalkin production from callus cultures was suppressed on the White medium containing NAA instead of IAA. This observation indicates that both shikalkin and polyphenolic acids biosynthetic pathways exist in the L. officinale callus cells and a regulatory system counterbalances the ratio of shikalkin to polyphenolic acids.     

Macrophage polarity in cancer: A review

Macrophages are the most abundant cells within the tumor stroma displaying noticeable plasticity, which allows them to perform several functions within the tumor microenvironment. Tumor-associated macrophages commonly refer to an alternative M2 phenotype, exhibiting anti-inflammatory and pro-tumoral effects. M2 cells are highly versatile and multi-tasking cells that directly influence multiple steps in tumor development, including cancer cell survival, proliferation, stemness, and invasiveness along with angiogenesis and immunosuppression. M2 cells perform these functions through critical interactions with cells related to tumor progression, including Th2 cells, cancer-associated fibroblasts, cancer cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells. M2 cells also have negative cross-talks with tumor suppressor cells, including cytotoxic T cells and natural killer cells. Programed death-1 (PD-1) is one of the key receptors expressed in M2 cells that, upon interaction with its ligand PD-L1, plays cardinal roles for induction of immune evasion in cancer cells. In addition, M2 cells can neutralize the effects of the pro-inflammatory and anti-tumor M1 phenotype. Classically activated M1 cells express high levels of major histocompatibility complex molecules, and the cells are strong killers of cancer cells. Therefore, orchestrating M2 reprogramming toward an M1 phenotype would offer a promising approach for reversing the fate of tumor and promoting cancer regression. Macrophage switching toward an anti-inflammatory M1 phenotype could be used as an adjuvant with other approaches, including radiotherapy and immune checkpoint blockades, such as anti-PD-L1/PD-1 strategies.     

Is it true that gut microbiota is considered as panacea in cancer therapy?

Recent studies demonstrated that a combination of the gut microbiome has the vital effect on the efficacy of anticancer immune therapies. Regulatory effects of microbiota have been shown in different types of cancer therapies such as chemotherapy and immunotherapy. Immune-checkpoint-blocked therapies are the recent efficient cancer immunotherapy strategies. The target of immune-checkpoint blocking is cytotoxic T lymphocyte protein-4 (CTLA-4) or blockade of programmed death-1 (PD-1) protein and its ligand programmed death ligand 1 (PD-L1) that they have been considered as cancer immunotherapy in recent years. In the latest studies, it have been demonstrated that several gut bacteria such as Akkermansia muciniphila, Bifidobacterium spp., Faecalibacterium spp., and Bacteroides fragilis have the regulatory effects on PD-1, PD-L1, and CTLA-4 blocked anticancer therapy outcome.