Publications by authors named "Farhana Ferdousi"

23 Publications

  • Page 1 of 1

Luteolin Modulates Neural Stem Cells Fate Determination: Study on Human Neural Stem Cells, and Study on LPS-Induced Depression Mice Model.

Front Cell Dev Biol 2021 1;9:753279. Epub 2021 Nov 1.

Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan.

Luteolin is a natural flavone with neurotrophic effects observed on different neuronal cell lines. In the present study, we aimed to assess the effect of luteolin on hNSCs fate determination and the LPS-induced neuroinflammation in a mouse model of depression with astrocytogenesis defect. hNSCs were cultured in basal cell culture medium (control) or medium supplemented with luteolin or AICAR, a known inducer of astrogenesis. A whole-genome transcriptomic analysis showed that luteolin upregulated the expressions of genes related to neurotrophin, dopaminergic, hippo, and Wnt signaling pathways, and downregulated the genes involved in p53, TNF, FOXO, and Notch signaling pathways. We also found that astrocyte-specific gene GFAP, as well as other genes of the key signaling pathways involved in astrogenesis such as Wnt, BMP, and JAK-STAT pathways were upregulated in luteolin-treated hNSCs. On the other hand, neurogenesis and oligodendrogenesis-related genes, , , and , were downregulated in luteolin-treated hNSCs. Furthermore, immunostaining showed that percentages of GFAP+ cells were significantly higher in luteolin- and AICAR-treated hNSCs compared to control hNSCs. Additionally, RT-qPCR results showed that luteolin upregulated the expressions of , , and , whereas the expression of remained unchanged. Next, we evaluated the effects of luteolin in LPS-induced mice model of depression that represents defects in astrocytogenesis. We found that oral administration of luteolin (10 mg/Kg) for eight consecutive days could decrease the immobility time on tail suspension test, a mouse behavioral test measuring depression-like behavior, and attenuate LPS-induced inflammatory responses by significantly decreasing IL-6 production in mice brain-derived astrocytes and serum, and TNFα and corticosterone levels in serum. Luteolin treatment also significantly increased mature BDNF, dopamine, and noradrenaline levels in the hypothalamus of LPS-induced depression mice. Though the behavioral effects of luteolin did not reach statistical significance, global gene expression analyses of mice hippocampus and brain-derived NSCs highlighted the modulatory effects of luteolin on different signaling pathways involved in the pathophysiology of depression. Altogether, our findings suggest an astrocytogenic potential of luteolin and its possible therapeutic benefits in neuroinflammatory and neurodegenerative diseases. However, further studies are required to identify the specific mechanism of action of luteolin.
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http://dx.doi.org/10.3389/fcell.2021.753279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591246PMC
November 2021

Antidepressant- and anxiolytic-like activities of Rosmarinus officinalis extract in rodent models: Involvement of oxytocinergic system.

Biomed Pharmacother 2021 Dec 12;144:112291. Epub 2021 Oct 12.

Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan; Open Innovation Laboratory for Food and Medicinal Resource Engineering, National Institute of Advanced Industrial Science and Technology (AIST) and University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan; Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan; Tsukuba Life Science Innovation Program (T-LSI), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8577 Ibaraki, Japan. Electronic address:

Background: Oxytocin (OXT), a neuropeptide involved in mammal reproductive and prosocial behaviors, has been reported to interact with various stressor-provoked neurobiological changes, including neuroendocrine, neurotransmitter, and inflammatory processes. In view of disturbances in psychosocial relationships due to social isolation and physical distancing measures amid the COVID-19 pandemic, being one of the triggering factors for the recent rise in depression and anxiety, OXT is a potential candidate for a new antidepressant.

Methods: In this present study, we have aimed to investigate the effects of oral administration of Rosmarinus officinalis extract (RE), extracted from distillation residue of rosemary essential oil, on central OXT level in the context of other stress biomarkers and neurotransmitter levels in mice models. Tail suspension test (TST) and elevated plus maze test (EPMT) following LPS injection were employed to assess depressive- and anxiety-like behavior in mice, respectively.

Findings: Pretreatment with RE for seven days significantly improved behavior in TST and EPMT. Whole-genome microarray analysis reveals that RE significantly reversed TST stress-induced alterations in gene expressions related to oxytocinergic and neurotransmitter pathways and inflammatory processes. In both models, RE significantly increased central Oxt and Oxtr expressions, as well as OXT protein levels. RE also significantly attenuated stress-induced changes in serum corticosterone, brain and serum BDNF levels, and brain neurotransmitters levels in both models.

Interpretation: Altogether, our study is the first to report antidepressant- and anxiolytic-like activities of RE through modulating oxytocinergic system in mice brain and thus highlights the prospects of RE in the treatment of depressive disorders of psychosocial nature.
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http://dx.doi.org/10.1016/j.biopha.2021.112291DOI Listing
December 2021

Maslinic Acid Attenuates Denervation-Induced Loss of Skeletal Muscle Mass and Strength.

Nutrients 2021 Aug 25;13(9). Epub 2021 Aug 25.

Tsukuba Life Science Innovation Program (T-LSI), University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.

Maslinic acid (MA) is a pentacyclic triterpene abundant in olive peels. MA reportedly increases skeletal muscle mass and strength in older adults; however, the underlying mechanism is unknown. This study aimed to investigate the effects of MA on denervated muscle atrophy and strength and to explore the underlying molecular mechanism. Mice were fed either a control diet or a 0.27% MA diet. One week after intervention, the sciatic nerves of both legs were cut to induce muscle atrophy. Mice were examined 14 days after denervation. MA prevented the denervation-induced reduction in gastrocnemius muscle mass and skeletal muscle strength. Microarray gene expression profiling in gastrocnemius muscle demonstrated several potential mechanisms for muscle maintenance. Gene set enrichment analysis (GSEA) revealed different enriched biological processes, such as myogenesis, PI3/AKT/mTOR signaling, TNFα signaling via NF-κB, and TGF-β signaling in MA-treated mice. In addition, qPCR data showed that MA induced expression and suppressed the expressions of   and . Altogether, our results suggest the potential of MA as a new therapeutic and preventive dietary ingredient for muscular atrophy and strength.
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http://dx.doi.org/10.3390/nu13092950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468537PMC
August 2021

Comprehensive transcriptome analysis of erythroid differentiation potential of olive leaf in haematopoietic stem cells.

J Cell Mol Med 2021 08 27;25(15):7229-7243. Epub 2021 Jun 27.

R&D Center for Tailor-Made QOL, University of Tsukuba, Tsukuba, Japan.

Anaemia is one of the leading causes of disability in young adults and is associated with increased morbidity and mortality in elderly. With a global target to reduce the disease burden of anaemia, recent researches focus on novel compounds with the ability to induce erythropoiesis and regulate iron homeostasis. We aimed to explore the biological events and potential polypharmacological effects of water-extracted olive leaf (WOL) on human bone marrow-derived haematopoietic stem cells (hHSCs) using a comprehensive gene expression analysis. HPLC analysis identifies six bioactive polyphenols in the WOL. Treatment with WOL for 12 days regulated gene expressions related to erythroid differentiation, oxygen homeostasis, iron homeostasis, haem metabolism and Hb biosynthesis in hHSCs. Functional clustering analysis reveals several major functions of WOL such as ribosomal biogenesis and mitochondrial translation machinery, glycolytic process, ATP biosynthesis and immune response. Additionally, the colonies of both primitive and mature erythroid progenitors, CFU-E and BFU-E, were significantly increased in WOL-treated hHSCs. The expressions of erythroid markers, CD47, glycophorin A (GYPA), and transferrin receptor (TFRC) and adult Hb subunits-HBA and HBB were also confirmed in immunofluorescent staining and flow cytometer analysis in WOL-treated hHSCs. It is well known that induction of lineage-specific differentiation, as well as the maturation of early haematopoietic precursors into fully mature erythrocytes, involves multiple simultaneous biological events and complex signalling networks. In this regard, our genome-wide transcriptome profiling with microarray study on WOL-treated hHSCs provides general insights into the multitarget prophylactic and/or therapeutic potential of WOL in anaemia and other haematological disorders.
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http://dx.doi.org/10.1111/jcmm.16752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335692PMC
August 2021

Human Amniotic Epithelial Cells as a Tool to Investigate the Effects of Cyanidin 3--Glucoside on Cell Differentiation.

Int J Mol Sci 2021 Apr 5;22(7). Epub 2021 Apr 5.

Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan.

Cyanidin, a kind of anthocyanin, has been reported to have chemotherapeutic activities in humans. Human amniotic epithelial cells (hAECs) are considered a potential source of pluripotent stem cells. hAECs have been used as a novel tool in regenerative cellular therapy and cell differentiation studies. In this study, to explore the effects of cyanidin-3--glucoside (Cy3G) on hAECs and their mechanisms, we investigated the transcriptomic changes in the Cy3G-treated cells using microarray analysis. Among the differentially expressed genes (Fold change > 1.1; -value < 0.05), 109 genes were upregulated and 232 were downregulated. Ratios of upregulated and downregulated genes were 0.22% and 0.47% of the total expressed genes, respectively. Next, we explored the enriched gene ontology, i.e., the biological process, molecular function, and cellular component of the 37 upregulated (>1.3-fold change) and 124 downregulated (<1.3-fold change) genes. Significantly enriched biological processes by the upregulated genes included "response to muscle activity," and the genes involved in this gene ontology (GO) were and , which function in the adipocyte. On the other hand, the cell cycle biological process was significantly enriched by the downregulated genes, including some from the gene family. An adipogenesis-associated gene was also included in the cell cycle biological process. Thus, our findings suggest the prospects of Cy3G in modulating adipocyte differentiation in hAECs.
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http://dx.doi.org/10.3390/ijms22073768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038597PMC
April 2021

Regulating cell fate of human amnion epithelial cells using natural compounds: an example of enhanced neural and pigment differentiation by 3,4,5-tri-O-caffeoylquinic acid.

Cell Commun Signal 2021 02 24;19(1):26. Epub 2021 Feb 24.

Alliance for Research On the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan.

Over the past years, Human Amnion Epithelial Cells (hAECs), a placental stem cell, are gaining higher attention from the scientific community as they showed several advantages over other types of stem cells, including availability, easy accessibility, reduced rejection rate, non-tumorigenicity, and minimal legal constraint. Recently, natural compounds are used to stimulate stem cell differentiation and proliferation and to enhance their disease-treating potential. A polyphenolic compound 3,4,5-Tri-O-Caffeoylquinic Acid (TCQA) has been previously reported to induce human neural stem cell differentiation and may affect melanocyte stem cell differentiation as well. In this study, TCQA was tested on 3D cultured hAECs after seven days of treatment, and then, microarray gene expression profiling was conducted of TCQA-treated and untreated control cells on day 0 and day 7. Analyses revealed that TCQA treatment significantly enriched pigment and neural cells sets; besides, genes linked with neurogenesis, oxidation-reduction process, epidermal development, and metabolism were positively regulated. Interestingly, TCQA stimulated cell cycle arrest-related pathways and differentiation signaling. On the other hand, TCQA decreased interleukins and cytokines expression and this due to its anti-inflammatory properties as a polyphenolic compound. Results were validated to highlight the main activities of TCQA on hAECs, including differentiation, cell cycle arrest, and anti-inflammatory. This study highlights the important role of hAECs in regenerative medicine and the use of natural compounds to regulate their fate. Video abstract.
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http://dx.doi.org/10.1186/s12964-020-00697-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903623PMC
February 2021

Rosemary Tea Consumption Alters Peripheral Anxiety and Depression Biomarkers: A Pilot Study in Limited Healthy Volunteers.

J Am Coll Nutr 2021 Feb 10:1-10. Epub 2021 Feb 10.

Laboratory of Metabolic Biophysics and Applied Pharmacology (LR12ES02), Faculty of Medicine of Sousse, University of Sousse, Sousse, Tunisia.

.is traditionally used as an infusion in the treatment of several diseases and in particular against neuropsychiatric disorders, such as anxiety and depression. It was established that rosemary extracts show an antidepressant effect on animal models. However, to the best of our knowledge, there is no scientific data that highlights the therapeutic effects of rosemary intake on human mental health.This study investigated whether rosemary tea consumption affects the plasma levels of anxiety and depression biomarkers in healthy volunteers.Twenty-two healthy volunteers aged between 20 and 50 years old consumed rosemary tea prepared from 5 g of dried rosemary in 100 mL boiled water once a day for 10 days. Plasma concentrations of Brain-Derived Neurotrophic Factor (BDNF), Interleukine-6 (IL-6), Interleukine-4 (IL-4), Tumor Necrosis Factor- alpha (TNF-α), Interferon-gamma (IFNϒ), and cortisol were measured by enzyme-linked immunosorbent assay using commercial ELISA kits (R&D systems) before rosemary consumption and at the end of the experiment.Rosemary tea consumption significantly increased the concentration of BDNF([BDNF]D0 = 22363.86 ± 12987.66 pg/mL, [BDNF]D10 = 41803.64 ± 28109.19,  = 0.006) and TNF-α([TNF-α] D0 = 39.49 ± 14.44 pg/mL, [TNF-α] D10 = 56.24 ± 39.01,  = 0.016). However, a slight variation that was statistically non-significant in INFϒ, cortisol, IL-4, IL-6 levels and in the ratio IL-4/INFϒ was observed ( > 0.05).Our findings highlight the promising anxiolytic and/or antidepressant effects of rosemary tea consumption in healthy volunteers since it increases the level of the most reliable depression biomarker BDNF. However, more powerful studies with larger sample size, carefully-chosen target population and, an extended intervention period are required.
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http://dx.doi.org/10.1080/07315724.2021.1873871DOI Listing
February 2021

New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis.

Front Cell Dev Biol 2020 4;8:577259. Epub 2020 Nov 4.

National Institute of Advanced Industrial Science and Technology (AIST)-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), Tsukuba, Ibaraki, Japan.

Squalene (Sq) is a natural compound, found in various plant oils, algae, and larger quantity in deep-sea shark liver. It is also known as an intermediate of cholesterol synthesis in plants and animals including humans. Although evidences demonstrated its antioxidant, anticancer, hypolipidemic, and hepatoprotective and cardioprotective effects, its biological effects in cellular function might have been underestimated because of the water-insoluble property. To overcome this hydrophobicity, we synthesized new amphiphilic Sq derivative (HH-Sq). On the other hand, adipose-derived stem cells (ASCs) are a valuable source in regenerative medicine for its ease of accessibility and multilineage differentiation potential. Nevertheless, impaired cellular functions of ASCs derived from diabetic donor have still been debated controversially. In this study, we explored the effect of the HH-Sq in comparison to Sq on the adipocyte differentiation of ASCs obtained from subjects with type 2 diabetes. Gene expression profile by microarray analysis at 14 days of adipogenic differentiation revealed that HH-Sq induced more genes involved in intracellular signaling processes, whereas Sq activated more transmembrane receptor pathway-related genes. In addition, more important number of down-regulated and up-regulated genes by Sq and HH-Sq were not overlapped, suggesting the compounds might not only have difference in their chemical property but also potentially exert different biological effects. Both Sq and HH-Sq improved metabolism of adipocytes by enhancing genes associated with energy homeostasis and insulin sensitivity, , , and . Interestingly, Sq increased significantly early adipogenic markers and lipogenic gene expression such as , , and , but not HH-Sq. As a consequence, smaller and fewer lipid droplet formation was observed in HH-Sq-treated adipocytes. Based on our findings, we report that both Sq and HH-Sq improved adipocyte metabolism, but only HH-Sq prevented excessive lipogenesis without abrogating adipocyte differentiation. The beneficial effect of HH-Sq provides an importance of synthesized derivatives from a natural compound with therapeutic potentials in the application of cell therapies.
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http://dx.doi.org/10.3389/fcell.2020.577259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672044PMC
November 2020

Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells.

Front Cell Dev Biol 2020 5;8:578036. Epub 2020 Nov 5.

School of Integrative and Global Majors (SIGMA), University of Tsukuba, Tsukuba, Japan.

Human amnion epithelial cells (hAECs), derived from discarded term placenta, is anticipated as a new stem cell resource because of their advantages over embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), such as no risk of tumorigenicity and minimal ethical issue. hAECs have been reported to differentiate into hepatic-like cells (HLCs) with variable functionalities suitable for cell-based therapy of end-stage liver diseases, drug screening, and drug toxicity tests. On the other hand, a new research stream has been evolving to use natural compounds as stimulants of stem cell differentiation because of their high availability and minimum side effects. Isorhamnetin is a naturally occurring flavonoid commonly found in fruits and vegetables and has been reported to improve hepatic fibrosis and steatosis. In this present study, we have screened the differentiation potential of isorhamnetin in hAECs. The cells were grown on 3D cell culture and were treated with 20 μM of synthesized isorhamnetin for 10 days without adding any additional growth factors. DNA microarray global gene expression analysis was conducted for differentially expressed genes between isorhamnetin-treated and untreated control cells, gene expression validation was carried out using RT-qPCR method, and finally, several hepatic functions were assessed. Microarray analysis showed that isorhamnetin could activate essential biological processes, molecular functions, and signaling pathways for hepatic differentiation. Hepatic progenitor markers, and , were upregulated in the isorhamnetin-treated hAECs. was downregulated, while was upregulated on Day 10. Furthermore, isorhamnetin-treated cells could show increased CYP enzyme mRNA levels, ICG uptake and release, glycogen storage activity, and urea secretion. Additionally, isorhamnetin-treated cells did not show any trace of transdifferentiation evident by significant downregulation of several colon- and cholangiocyte-specific markers. However, longer treatment with isorhamnetin did not promote hepatic maturation. Altogether, our findings indicate that isorhamnetin has a promising effect on directing the hepatic-lineage specific differentiation in hAECs.
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http://dx.doi.org/10.3389/fcell.2020.578036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674172PMC
November 2020

Sugarcane ( L.) Top Extract Ameliorates Cognitive Decline in Senescence Model SAMP8 Mice: Modulation of Neural Development and Energy Metabolism.

Front Cell Dev Biol 2020 6;8:573487. Epub 2020 Oct 6.

School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Japan.

Age-related biological alterations in brain function increase the risk of mild cognitive impairment and dementia, a global problem exacerbated by aging populations in developed nations. Limited pharmacological therapies have resulted in attention turning to the promising role of medicinal plants and dietary supplements in the treatment and prevention of dementia. Sugarcane ( L.) top, largely considered as a by-product because of its low sugar content, in fact contains the most abundant amounts of antioxidant polyphenols relative to the rest of the plant. Given the numerous epidemiological studies on the effects of polyphenols on cognitive function, in this study, we analyzed polyphenolic constituents of sugarcane top and examined the effect of sugarcane top ethanolic extract (STEE) on a range of central nervous system functions and . Orally administrated STEE rescued spatial learning and memory deficit in the senescence-accelerated mouse prone 8 (SAMP8) mice, a non-transgenic strain that spontaneously develops a multisystemic aging phenotype including pathological features of Alzheimer's disease. This could be correlated with an increased number of hippocampal newborn neurons and restoration of cortical monoamine levels in STEE-fed SAMP8 mice. Global genomic analysis by microarray in cerebral cortices showed multiple potential mechanisms for the cognitive improvement. Gene set enrichment analysis (GSEA) revealed biological processes such as neurogenesis, neuron differentiation, and neuron development were significantly enriched in STEE-fed mice brain compared to non-treated SAMP8 mice. Furthermore, STEE treatment significantly regulated genes involved in neurotrophin signaling, glucose metabolism, and neural development in mice brain. Our results suggest that STEE treatment enhances the metabolic activity of neuronal cells promoting glucose metabolism with significant upregulation of genes, namely , , , and . STEE also stimulated proliferation of human neural stem cells (hNSCs), regulated bHLH factor expression and induced neuronal differentiation and astrocytic process lengthening. Altogether, our findings suggest the potential of STEE as a dietary intervention, with promising implications as a novel nutraceutical for cognitive health.
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http://dx.doi.org/10.3389/fcell.2020.573487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573230PMC
October 2020

Effects of Isorhamnetin in Human Amniotic Epithelial Stem Cells and Its Cardioprotective Effects .

Front Cell Dev Biol 2020 29;8:578197. Epub 2020 Sep 29.

School of Integrative and Global Majors (SIGMA), University of Tsukuba, Tsukuba, Japan.

Cardiac hypertrophy and fibrosis are major pathophysiologic disorders that lead to serious cardiovascular diseases (CVDs), such as heart failure and arrhythmia. It is well known that transforming growth factor β (TGFβ) signaling pathways play a major role in the proliferation of cardiac hypertrophy and fibrosis, which is mainly stimulated by angiotensin II (AgII). This study aimed to investigate the cardioprotective potential of isorhamnetin (ISO) in human amniotic epithelial stem cells (hAESCs) through global gene expression analysis and to confirm its beneficial effects on cardiac hypertrophy and fibrosis in the AgII-induced model. , biological processes including TGFβ, collagen-related functions, and inflammatory processes were significantly suppressed in ISO pretreated hAESCs. , continuous AgII infusion using an osmotic pump induced significant pathological fibrosis and myocardial hypertrophy, which were remarkably suppressed by ISO pretreatment. ISO was found to reverse the enhanced TGFβ and Collagen type I alpha 1 mRNA expression induced by AgII exposure, which causes cardiovascular remodeling in ventricular tissue. These findings indicate that ISO could be a potential agent against cardiac hypertrophy and fibrosis.
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http://dx.doi.org/10.3389/fcell.2020.578197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552739PMC
September 2020

Microarray analysis of verbenalin-treated human amniotic epithelial cells reveals therapeutic potential for Alzheimer's Disease.

Aging (Albany NY) 2020 03 29;12(6):5516-5538. Epub 2020 Mar 29.

Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba 305-8577, Ibaraki, Japan.

Alzheimer's disease (AD) has become a major world health problem as the population ages. There is still no available treatment that can stop or reverse the progression of AD. Human amnion epithelial cells (hAECs), an alternative source for stem cells, have shown neuroprotective and neurorestorative potentials when transplanted . Besides, studies have suggested that stem cell priming with plant-derived bioactive compounds can enhance stem cell proliferation and differentiation and improve the disease-treating capability of stem cells. Verbenalin is an iridoid glucoside found in medicinal herbs of Verbenaceae family. In the present study, we have conducted microarray gene expression profiling of verbenalin-treated hAECs to explore its therapeutic potential for AD. Gene set enrichment analysis revealed verbenalin treatment significantly enriched AD-associated gene sets. Genes associated with lysosomal dysfunction, pathologic angiogenesis, pathologic protein aggregation, circadian rhythm, age-related neurometabolism, and neurogenesis were differentially expressed in the verbenalin-treated hAECs compared to control cells. Additionally, the neuroprotective effect of verbenalin was confirmed against amyloid beta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. Our present study is the first to report the therapeutic potential of verbenalin for AD; however, further in-depth research in the and models are required to confirm our preliminary findings.
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http://dx.doi.org/10.18632/aging.102985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138585PMC
March 2020

Isorhamnetin Alleviates Steatosis and Fibrosis in Mice with Nonalcoholic Steatohepatitis.

Sci Rep 2019 11 7;9(1):16210. Epub 2019 Nov 7.

School of Integrative and Global Majors (SIGMA), University of Tsukuba, Tsukuba, Ibaraki, 305-8572, Japan.

Nonalcoholic steatohepatitis (NASH) is the most severe and progressive form of nonalcoholic fatty liver disease (NAFLD), which can lead to life-threatening conditions, however, there is still no approved drug for the treatment of NASH. In this study we used human-like NASH mouse model and treated orally with isorhamnetin at a dose of 50 mg/kg to analyze the effect of isorhamnetin on the progression of NASH. NASH-induced mice represented severe steatosis with inflammation, and fibrosis in liver accompanied with high level of liver injury markers in serum. Isorhamnetin treatment reduced intrahepatic lipid accumulation and TG content by inhibiting de novo lipogenic pathway in NASH-induced mice. Consistent with this, isorhamnetin-treated NASH mice showed improved liver injury markers, reduced collagen deposition as well as decreased gene expression of fibrogenic markers. Taken together, here we showed for the first time that synthesized isorhamnetin alleviates pathologic features of NASH and thus can potentially contribute to NASH drug development.
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http://dx.doi.org/10.1038/s41598-019-52736-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838085PMC
November 2019

Antifibrotic effect of methylated quercetin derivatives on TGFβ-induced hepatic stellate cells.

Biochem Biophys Rep 2019 Dec 16;20:100678. Epub 2019 Aug 16.

School of Integrative and Global Majors (SIGMA), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan.

Quercetin (QCT) and isorhamnetin (ISO), natural flavonoids, were both shown to possess antifibrotic activity in and models of hepatic fibrosis. Although ISO is a direct metabolite of QCT differing by a methyl group, it has been reported to be absorbed more adequately and eliminated slower than QCT after oral administration. Our aim of the study was to investigate biological effect of mono-methylated QCT derivatives against fibrosis using rat hepatic stellate cells (HSC-T6). All test derivatives were synthesized from QCT. HSC-T6 cells were induced by TGFβ and treated with derivatives followed by cell proliferation assay, immunofluorescence staining of αSMA, and gene expression analysis of fibrosis markers. All compounds showed a dose- and time-dependent antiproliferation effect. ISO, 3-O-methylquercetin (3MQ), and rhamnetin (RHA) reduced αSMA mRNA; 3MQ prevented the augmentation of collagen I mRNA; and compounds, except azaleatin and 3MQ, reduced Timp1 mRNA expression in TGFβ-induced HSCs. In conclusion, each compound had singular effect against different features of fibrosis depending on the position of methyl group although the further mechanism of action of compounds during fibrosis development remains to be investigated. These findings suggest that antifibrotic effect of quercetin can be enhanced by adding methyl group on functionally important position.
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http://dx.doi.org/10.1016/j.bbrep.2019.100678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711851PMC
December 2019

Exploring the Potential Role of Rosmarinic Acid in Neuronal Differentiation of Human Amnion Epithelial Cells by Microarray Gene Expression Profiling.

Front Neurosci 2019 24;13:779. Epub 2019 Jul 24.

Alliance for Research on the Mediterranean and North Africa, University of Tsukuba, Tsukuba, Japan.

In the present study, we conducted microarray gene expression profiling to explore the direction of differentiation of human amnion epithelial cells (hAECs) treated with rosmarinic acid (RA). hAECs have several clinical advantages over other types of stem cells, including availability, low immunogenicity, low rejection rate, non-tumorigenicity, and less ethical constraint. On the other hand, RA is a phenolic compound having several health benefits, including neuroprotective and antidepressant-like activities. In this study, hAECs were isolated from discarded term placenta and were treated with 20 μM RA for 7 days. Microarray gene expression profiling was conducted for three biological replicates of RA-treated and untreated control cells on day 0 and day 7. Gene set enrichment analysis, and gene annotation and pathway analysis were conducted using online data mining tools GSEA and DAVID. Gene expression profiling showed that RA treatment biased hAECs toward ectodermal lineage progression, regulated transcription factors involved in neuronal differentiation, regulated neural specific epigenetic modifiers and several extracellular signaling pathways of neural induction, and significantly inhibited Notch signaling pathway. Gene expression profiling of RA-treated hAECs reveals for the first time a potential role of RA in neural induction and neuronal differentiation of hAECs. Having a naturally occurring compound as differentiation inducer as well as a readily available source of stem cells would have great advantages for the cell-based therapies. Findings from our genome-wide analysis could provide a foundation for further in-depth investigation.
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http://dx.doi.org/10.3389/fnins.2019.00779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667736PMC
July 2019

Antidepressant-Like Effect of Ferulic Acid via Promotion of Energy Metabolism Activity.

Mol Nutr Food Res 2019 10 22;63(19):e1900327. Epub 2019 Aug 22.

Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan.

Scope: Ferulic acid (FA), a natural phenolic phytochemical abundantly present in whole grains, herbs, and dried fruits, exhibits anti-inflammatory, antioxidant, and neuroprotective effects. In the present study, the antidepressant-like effects of FA in male ICR mice using tail suspension test (TST) are investigated and its molecular mechanisms are explored.

Methods And Results: Oral administration of FA at a dose of 5 mg kg for 7 days significantly reduces immobility of mice compared to vehicle-administered control group. Microarray and real-time PCR analyses reveal that FA upregulates the expression of several genes associated with cell survival and proliferation, energy metabolism, and dopamine synthesis in mice limbic system of brain. Interestingly, it is found that FA, unlike antidepressant drug bupropion, strongly promotes energy metabolism. Additionally, FA increases catecholamine (dopamine and noradrenaline), brain-derived neurotrophic factor, and ATP levels, and decreases glycogen levels in the limbic system of the mice brain.

Conclusion: The research provides the first evidence that FA enhances energy production, which can be the underlying mechanism of the antidepressant-like effects of FA observed in this study.
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http://dx.doi.org/10.1002/mnfr.201900327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790570PMC
October 2019

Modulation of the neurotransmitter systems through the anti-inflammatory and antidepressant-like effects of squalene from Aurantiochytrium sp.

PLoS One 2019 28;14(6):e0218923. Epub 2019 Jun 28.

Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Ibaraki, Japan.

Although algae have been the focal point of biofuel research, studies on their biological activities have been limited. In recent years, however, the importance of algae as sources of functional ingredients has been recognized due to their health beneficial effects. In this study, we evaluated the antidepressant-like activities of ethanol extract of Aurantiochytrium sp. (EEA) in the forced swimming test (FST)-induced depression in ICR mice. Imipramine, a commercially available tricyclic antidepressant drug, was used as positive control. Animals were administered EEA orally for 14 consecutive days and were subjected to the locomotor activity testing. Additionally, changes in gene expression in mice brain were assessed by real-time PCR and microarray assays to understand the molecular mechanisms underlying the effect of EEA. We found that the immobility time in FST was significantly reduced in the EEA-treated mice compared to that of in the control mice. Microarray and real-time PCR results revealed that EEA treatment induced changes in several genes in mice brain associated with pro-inflammation and dopaminergic, cholinergic, glutamatergic, and serotonergic synapses. It has previously been reported that several cytokines, such as IL-6 and TNF-α, which mediate neuroinflammation, are also responsible for indirectly altering brain neurotransmitter levels in neuropsychiatric disorders. Therefore, the regulation of the expression of pro-inflammatory genes in EEA-administered mice brain is considered to contribute to the enhancement of neurotransmitter systems-related gene expression in our study. Moreover, our in vitro study suggested that squalene, a component produced by Aurantiochytrium, was one of the active substances in EEA. In conclusion, our study provides the first evidence that Aurantiochytrium sp. can reduce neuroinflammation that may contribute to the modulation of the neurotransmitter systems, which could underlie its antistress and antidepressant effects.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218923PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599144PMC
February 2020

3,4,5-Tricaffeoylquinic acid induces adult neurogenesis and improves deficit of learning and memory in aging model senescence-accelerated prone 8 mice.

Aging (Albany NY) 2019 01;11(2):401-422

Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, 1-1-1 Tennodai, Tsukuba City, Ibaraki 305-8572, Japan.

Caffeoylquinic acid (CQA) is a natural polyphenol with evidence of antioxidant and neuroprotective effects and prevention of deficits in spatial learning and memory. We studied the cognitive-enhancing effect of 3,4,5-tricaffeoylquinic acid (TCQA) and explored its cellular and molecular mechanism in the senescence-accelerated mouse prone 8 (SAMP8) model of aging and Alzheimer's disease as well as in human neural stem cells (hNSCs). Mice were fed with 5 mg/kg of TCQA for 30 days and were tested in the Morris water maze (MWM). Brain tissues were collected for immunohistochemical detection of bromodeoxyuridine (BrdU) to detect activated stem cells and newborn neurons. TCQA-treated SAMP8 exhibited significantly improved cognitive performance in MWM compared to water-treated SAMP8. TCQA-treated SAMP8 mice also had significantly higher numbers of BrdU+/glial fibrillary acidic protein (GFAP+) and BrdU+/Neuronal nuclei (NeuN+) cells in the dentate gyrus (DG) neurogenic niche compared with untreated SAMP8. In hNSCs, TCQA induced cell cycle arrest at G0/G1, actin cytoskeleton organization, chromatin remodeling, neuronal differentiation, and bone morphogenetic protein signaling. The neurogenesis promoting effect of TCQA in the DG of SAMP8 mice might explain the cognition-enhancing influence of TCQA observed in our study, and our hNSCs in aggregate suggest a therapeutic potential for TCQA in aging-associated diseases.
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http://dx.doi.org/10.18632/aging.101748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366991PMC
January 2019

Particulate matters and gaseous pollutants in indoor environment and Association of ultra-fine particulate matters (PM) with lung function.

Environ Sci Pollut Res Int 2019 Feb 4;26(6):5475-5484. Epub 2019 Jan 4.

Department of Chemistry, University of Dhaka, Dhaka, 1000, Bangladesh.

Real-time particulate matters (PM, PM, PM, PM, PM, and TSP) with AEROCET 531S (USA), gaseous pollutants (NO and TVOC) with Aeroquel 500 gas sampler (NZ) were measured from the indoor air of houses at four residential locations in Dhaka, Bangladesh. PM samples were collected on quartz filters with a dual channel dust sampler (IPM-FDS 2510, India) for selected trace metal determination from five houses of Dhaka. Respiratory function of the occupants was assessed by using a peak expiratory flow meter (Rossmax PF 120). Mean PM, PM, and PM concentrations were 46.1 ± 13.4, 76.0 ± 16.2, and 203.9 ± 44.8 μg m, respectively. Higher enrichment factors of Pb, Zn, and Ni were found for traffic, industrial, and constructional activities. The correlation between indoor and outdoor PM (R = 0.42) and ratios (I/O < 1) suggesting indoor air was effected by outdoor air. The concentration of NO (0.076 ± 0.007 ppm) and TVOC (90.0 ± 46.0 ppm) was found above than other studies. The average total hazard ratio (THR) in Dhaka was 9.06 and has the highest exposure to air pollutants (PM, PM, NO) in Khilkhet (THR 10.1) residents. A negative association between ultra-fine particles (PM) and peak flow rate measurements of the residents living in these houses indicates that inhalations of ultra-fine particles has great influence on the reduced lung efficiency.
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http://dx.doi.org/10.1007/s11356-018-4043-2DOI Listing
February 2019

Ethanol Extract of 18W-13a Strain Possesses Anti-inflammatory Effects on Murine Macrophage RAW264 Cells.

Front Physiol 2018 26;9:1205. Epub 2018 Sep 26.

Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.

In this study, the effects of an ethanolic extract of 18W-13a strain (AM18W-13a) on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264 murine macrophages were studied. Pre-treatment with the AM18W-13a extract significantly suppressed the LPS-induced production of nitric oxide and pro-inflammatory cytokines. RAW264 cells treated with the AM18W-13a extract for 1 and 24 h were subjected to DNA microarray analyses for detecting the differentially expressed genes. The treatment of RAW264 cells with the AM18W-13a extract for 24 h significantly suppressed the expression of several genes associated with inflammation or chemotaxis. Furthermore, treatment with the AM18W-13a extract for 1 h suppressed the expression of , but induced the expression of and in RAW264 cells. Additionally, the AM18W-13a extract significantly enhanced the expression of certain anti-inflammatory mediators. This study is the first report of the anti-inflammatory effects of the AM18W-13a extract and its mechanism of action in LPS-stimulated murine macrophages.
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http://dx.doi.org/10.3389/fphys.2018.01205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168648PMC
September 2018

Identification of Essential Containers for Aedes Larval Breeding to Control Dengue in Dhaka, Bangladesh.

Trop Med Health 2015 Dec 11;43(4):253-64. Epub 2015 Sep 11.

Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine, University of Tsukuba , Tennodai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan.

Dengue fever (DF), one of the most important emerging arboviral diseases, is transmitted through the bite of container breeding mosquitoes Aedes aegypti and Aedes albopictus. A household entomological survey was conducted in Dhaka from August through October 2000 to inspect water-holding containers in indoor, outdoor, and rooftop locations for Aedes larvae. The objective of this study was to determine mosquito productivity of each container type and to identify some risk factors of households infested with Aedes larvae. Of 9,222 households inspected, 1,306 (14.2%) were positive for Aedes larvae. Of 38,777 wet containers examined, 2,272 (5.8%) were infested with Aedes larvae. Containers used to hold water, such as earthen jars, tanks, and drums were the most common containers for larval breeding. Tires in outdoor and rooftop locations of the households were also important for larval breeding. Although present in abundance, buckets were of less importance. Factors such as independent household, presence of a water storage system in the house, and fully/partly shaded outdoors were found to be significantly associated with household infestation of Aedes larvae. Identification and subsequent elimination of the most productive containers in a given area may potentially reduce mosquito density to below a level at which dengue transmission may be halted.
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http://dx.doi.org/10.2149/tmh.2015-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4689612PMC
December 2015

Reversed Phase SPE and GC-MS Study of Polycyclic Aromatic Hydrocarbons in Water Samples from the River Buriganga, Bangladesh.

Int Sch Res Notices 2014 29;2014:234092. Epub 2014 Oct 29.

Department of Chemistry, University of Dhaka, Dhaka 1000, Bangladesh.

Polycyclic aromatic hydrocarbons (PAHs) are semivolatile organic compounds (SVOCs) categorized as persistent organic pollutants (POPs). PAHs are ubiquitous in terrestrial, atmospheric, and particularly aquatic environments throughout the world and have been detected in lakes, ground waters, and rivers. This research work involved the analysis of five PAHs, anthracene, fluorene, naphthalene, phenanthrene, and pyrene, in water sample collected from the river Buriganga, Bangladesh. The extraction of water samples was carried out by reversed phase solid-phase extraction (RP-SPE) technique with C-18 SPE cartridges. A solvent mixture of dichloromethane and hexane (1 : 2) with a flow rate of 0.5 mL/min was used as eluent. Percentage recoveries of five PAHs for this technique were in the range of 81.47 ± 1.16 to 98.60 ± 0.61%. PAHs quantification was achieved by using an ion trap gas chromatography mass spectrometer (GC-MS) interfaced to gas chromatography (GC) equipped with a fused silica capillary column. Helium was used as carrier gas with a flow rate of 1.0 mL/min. The commonly detected PAH compounds in the river water were anthracene, naphthalene, and phenanthrene at the concentration ranges of 0.451 to 3.201, 0.033 to 3.1131, and 0.320 to 2.546 μg/mL, respectively. The results reflect that PAHs presented in this river water were mostly from petrogenic and pyrogenic sources.
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http://dx.doi.org/10.1155/2014/234092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908253PMC
June 2016

Visceral Leishmaniasis Eradication is a Reality: Data from a Community-based Active Surveillance in Bangladesh.

Trop Med Health 2012 Dec 22;40(4):133-9. Epub 2012 Dec 22.

Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan.

More than 20 million people in Bangladesh are considered at risk of developing visceral leishmaniasis (VL). A community-based active surveillance was conducted in eight randomly selected villages in a highly endemic area of Bangladesh from 2006 to 2008. A total of 6,761 individuals living in 1,550 mud-walled houses were included in the active surveillance. Rapid rK39 dipstick tests were conducted throughout the study period to facilitate the case diagnosis. Individuals with previous or current clinical leishmaniasis were identified on the basis of the case definition of the VL elimination program. Untreated cases of suspected VL were referred to the hospital for treatment. Socioeconomic and environmental information including bed net use was also collected. In 2006, the annual incidence of clinical leishmaniasis in the study area was 141.9 cases per 10,000 population, which was significantly increased by the following year owing to community-based active surveillance for case detection and reporting. However, early case detection and early referral for treatment led to a significant decrease in incidence in 2008. This study suggests that community-based active surveillance using a simple diagnostic tool might play a role in achieving the goal of the VL elimination program.
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http://dx.doi.org/10.2149/tmh.2012-25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598070PMC
December 2012
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