Nutritional ingredients and prevention of chronic diseases by fermented koumiss: a comprehensive review.

Koumiss, a traditional fermented dairy product made from fresh mare milk, is a sour beverage that contains an abundance of microbial communities, including lactic acid bacteria, yeast and others. Firstly, probiotics such as Lacticaseibacillus in koumiss can induce the secretion of immunoglobulin G in serum and interleukin-2 in the spleen while beneficial Saccharomyces can secrete antibacterial compounds such as citric acid and ascorbic acid for specific immunopotentiation. Additionally, more isoflavone in koumiss can regulate estrogen levels by binding to its receptors to prevent breast cancer directly. Bile salts can be converted into bile acids such as taurine or glycine by lactic acid bacteria to lower cholesterol levels in vivo. Butyric acid secretion would be increased to improve chronic gastrotis by regulating intestinal flora with lactic acid bacteria. Finally, SCFA and lCFA produced by Lacticaseibacillus inhibit the reproduction of pathogenic microorganisms for diarrhea prevention. Therefore, exploring the mechanisms underlying multiple physiological functions through utilizing microbial resources in koumiss represents promising avenues for ameliorating chronic diseases.

Multisensory Integration in Caenorhabditis elegans in Comparison to Mammals.

Multisensory integration refers to sensory inputs from different sensory modalities being processed simultaneously to produce a unitary output. Surrounded by stimuli from multiple modalities, animals utilize multisensory integration to form a coherent and robust representation of the complex environment. Even though multisensory integration is fundamentally essential for animal life, our understanding of the underlying mechanisms, especially at the molecular, synaptic and circuit levels, remains poorly understood. The study of sensory perception in Caenorhabditis elegans has begun to fill this gap. We have gained a considerable amount of insight into the general principles of sensory neurobiology owing to C. elegans' highly sensitive perceptions, relatively simple nervous system, ample genetic tools and completely mapped neural connectome. Many interesting paradigms of multisensory integration have been characterized in C. elegans, for which input convergence occurs at the sensory neuron or the interneuron level. In this narrative review, we describe some representative cases of multisensory integration in C. elegans, summarize the underlying mechanisms and compare them with those in mammalian systems. Despite the differences, we believe C. elegans is able to provide unique insights into how processing and integrating multisensory inputs can generate flexible and adaptive behaviors. With the emergence of whole brain imaging, the ability of C. elegans to monitor nearly the entire nervous system may be crucial for understanding the function of the brain as a whole.

Expression and function of chondroitin 4-sulfate and chondroitin 6-sulfate in human glioma.

Key molecules promoting migration and invasion exist in the extracellular matrix, and include chondroitin 4-sulfate (C4S) and chondroitin 6-sulfate (C6S), functionally important carbohydrate chains of chondroitin sulfate proteoglycans that participate in regulating cancer development. Here, we show that C4S and C6S expression is upregulated in human glioma tissues, when compared to normal brain tissue, and that the extent of upregulation positively correlated with glioma malignancy. Treatment of cultured glioma cells with C4S and C6S enhanced cell viability, migration, and invasion, increased MMP-2 and MMP-9 levels, enhanced N-cadherin, but reduced E-cadherin expression. Inhibition of expression of the two CS synthetic enzymes chondroitin 4-O-sulfotransferase-1 (C4ST-1/CHST11) and chondroitin 6-O-sulfotransferase-1 (C6ST-1/CHST3) suppressed cell viability, migration and invasion, reduced MMP-2 and MMP-9 expression, and reduced N-cadherin expression, but increased E-cadherin levels. The C4S- and C6S-enhanced epithelial-to-mesenchymal transition and expression of MMP-2 occurred via activation of the PI3K/AKT signaling pathway, known to be involved in promoting cell migration and invasion. In immune-deficient larval zebrafish, C4S and C6S increased the numbers of viable tumor cells, thereby promoting glioma cell proliferation. The present observations point to a novel role of C4S and C6S in human glioma cell functions, thus possibly representing targets in glioma therapy.

An Overview of Experimental and Clinical Spinal Cord Findings in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that occurs mainly in the elderly and presenile life stages. It is estimated that by the year 2050, 135 million people will be affected by AD worldwide, representing a huge burden to society. The pathological hallmarks of AD mainly include intracellular neurofibrillary tangles (NFTs) caused by hyperphosphorylation of tau protein, formation of extracellular amyloid plaques, and massive neural cell death in the affected nervous system. The pathogenesis of AD is very complicated, and recent scientific research on AD is mainly concentrated on the cortex and hippocampus. Although the spinal cord is a pivotal part of the central nervous system, there are a limited number of studies focusing on the spinal cord. As an extension of the brain, the spinal cord functions as the bridge between the brain and various parts of the body. However, pathological changes in the spinal cord in AD have not been comprehensively and systematically studied at present. We here review the existing progress on the pathological features of AD in the spinal cord.

Identification and characterization of synthetic chondroitin-4-sulfate binding peptides in neuronal functions.

Chondroitin sulfate proteoglycans (CSPGs), up-regulated in and around the glial scar after mammalian spinal cord injury, have been suggested to be key inhibitory molecules for functional recovery by impeding axonal regrowth/sprouting and synaptic rearrangements. CSPG-mediated inhibition is mainly associated with the glycosaminoglycan chains of CSPGs, and chondroitin-4-sulfate (C4S) is the predominant sulfated structure that regulates axonal guidance and growth in the adult nervous system. With the aim to find molecules that neutralize the inhibitory functions of C4S, we screened a phage display library for peptides binding to C4S. From the phage clones binding to C4S we selected three peptides for further analysis. We observed that these peptides bind to C4S, but not chondroitin-6-sulfate, heparin sulfate or dermatan sulfate, in a concentration-dependent and saturable manner, whereas the scrambled peptides showed highly reduced or no binding to C4S. The C4S-binding peptides, but not their scrambled counterparts, when added to cultures of mouse cerebellar neurons and human neuroblastoma cells, neutralized the inhibitory functions of the C4S- and CSPG-coated substrate on cell adhesion, neuronal migration and neurite outgrowth. These results indicate that the C4S-binding peptides neutralize several inhibitory functions of CSPGs, suggesting that they may be beneficial in repairing mammalian nervous system injuries.

Spinal cord injury induced Neuregulin 1 signaling changes in mouse prefrontal cortex and hippocampus.

Accumulated evidence has recently demonstrated that spinal cord injury (SCI) can lead to chronic damage in a wide range of brain regions. Neuregulin 1 (Nrg1) signaling has been broadly recognized as an important mechanism contributing to neural differentiation and regeneration. We here studied the effect of SCI on Nrg1 signaling in prefrontal cortex (PFC) and hippocampus (HIP) in a mouse model. As was indicated by the increased levels of GFAP and Iba-1, our results demonstrated that SCI significantly induced activation of astrocytes and microglial cells in both PFC and HIP. In addition, both western blot and morphological assay demonstrated that Nrg1 was altered in both regions at 8 weeks post SCI, which was accompanied with decreased phosphorylation levels of its cognitive receptors Neu and ErbB4. Our combined results indicated that SCI can influence Nrg1 signaling, which may contribute to the worsening of pathophysiological changes in major brain regions during SCI. These results also suggested that exogenous Nrg1 treatment may have a therapeutic role in counteracting SCI-induced brain damage.

Honokiol Eliminates Glioma/Glioblastoma Stem Cell-Like Cells Via JAK-STAT3 Signaling and Inhibits Tumor Progression by Targeting Epidermal Growth Factor Receptor.

Malignant gliomas are the most aggressive forms of brain tumors; whose metastasis and recurrence contribute to high rates of morbidity and mortality. Glioma stem cell-like cells are a subpopulation of tumor-initiating cells responsible for glioma tumorigenesis, metastasis, recurrence and resistance to therapy. Epidermal growth factor receptor (EGFR) has been reported to be dysregulated in most cancers, including gliomas and its functions are closely linked to initiating tumor metastasis and a very poor prognosis. In search for compounds that may reduce the tumorigenic potential of gliomas/glioblastomas honokiol attracted our attention. Honokiol, purified from the bark of traditional Chinese herbal medicine Magnolia species, is beneficial in vitro and in animal models via a variety of pharmacological effects, including anti-inflammatory, anti-angiogenetic, anti-arrhythmic and antioxidant activities, as well as anti-proliferative and proapoptotic effects in a wide range of human cancer cells. However, its effects on glioma cells are unknown. Here, we used different concentrations of honokiol in treating U251 and U-87 MG human glioma/glioblastoma cells in cell culture. Results showed that honokiol inhibited glioma cell viability and colony formation and promoted apoptosis. It also inhibited glioma cell migration/proliferation and invasion. In addition, honokiol promoted apoptosis and reduced Bcl-2 expression, accompanied by increase in Bax expression. Honokiol reduced expression of EGFR, CD133 and Nestin. Moreover, honokiol inhibited the activation of both AKT and ERK signaling pathways, increased active caspase-3 level and reduced phosphorylation of STAT3. U-87 MG xenografts in nude mice and in immunotolerant zebrafish yolk sac showed that honokiol inhibits tumor growth and metastasis. Altogether, results indicate that honokiol reduces tumorigenic potentials, suggesting hopes for honokiol to be useful in the clinical management of glioma/glioblastoma.

Trimebutine Promotes Glioma Cell Apoptosis as a Potential Anti-tumor Agent.

Gliomas are the most common primary brain tumors with a usually fatal malignancy. They are associated with a poor prognosis although multiple therapeutic options have been available. Trimebutine is one of the prokinetic agents and it has been mainly used for treatment of disorders of the gastrointestinal (GI) tract such as irritable bowel syndrome. However, its effects on glioma cells remain unknown. Here, we used various concentrations of trimebutine to treat SHG44, U251, and U-87 MG human glioma/glioblastoma cells. And combined experiments of MTT, colony formation assay, and wound healing assay, as well as western blot and immunofluorescence staining were used to evaluate the effects of trimebutine on glioma cells. The results demonstrated that trimebutine significantly inhibited cell viability and colony formation. A significant inhibition of glioma cell migration was also indicated by wound healing assay. In addition, trimebutine promoted cell apoptosis and induced Bcl-2 downregulation, accompanied with Bax upregulation. Both immunofluorescence staining and western blot results showed that trimebutine increased the level of active Caspase-3. Moreover, trimebutine reduced the activation of both AKT and ERK signaling pathways. In subcutaneous U-87 MG cell xenograft tumors in nude mice, trimebutine significantly inhibited tumor growth. More TUNEL-positive apoptotic cells in tumor sections were observed in trimebutine-treated mice when compared to the vehicle control. Reduced Bcl-2 and upregulated Bax, as well as perturbed p-AKT and p-ERK signaling pathways were also observed in trimebutine-treated xenograft tissues. Our combined data indicated that trimebutine may be potentially applied for the clinical management of glioma/glioblastoma.