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| 2. |
- Chen, Lu, et al.
(författare)
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Fourteen complete mitochondrial genomes of butterflies from the genus Lethe (Lepidoptera, Nymphalidae, Satyrinae) with mitogenome-based phylogenetic analysis
- 2020
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543. ; 112:6, s. 4435-4441
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Tidskriftsartikel (refereegranskat)abstract
- The mitochondrial genome (mitogenome) can help us understand the phylogenetic relationships within the genus Lethe and the subfamily Satyrinae. In this study, we sequenced the complete mitogenomes of 14 Lethe species, which range in size from 15,225 to 15,271 bp, with both 37 genes (13 PCGs, 22 tRNAs, 2 rRNAs) and a noncoding A + T-rich region. The gene arrangement and orientation is similar to typical mitogenomes of Lepidoptera. The Ka/Ks ratio shows that cox1 has the slowest evolutionary rate. The secondary structure of trnN lacks the Pseudouracil loop (TψC loop) in most Lethe species. The inferred phylogenetic analyses show that Lethe is a well-supported monophyletic group, and reveal 2 major clades within the genus Lethe, which is consistent with previous morphological classifications.
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| 3. |
- Mitra, S, et al.
(författare)
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Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy
- 2021
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) treatment is constrained due to the inability of peripherally administered therapeutic molecules to cross the blood–brain barrier. Encapsulated cell biodelivery (ECB) devices, a tissue-targeted approach for local drug release, was previously optimized for human mature nerve growth factor (hmNGF) delivery in AD patients but was found to have reduced hmNGF release over time. To understand the reason behind reduced ECB efficacy, we exposed hmNGF-releasing cells (NGC0211) in vitro to human cerebrospinal fluid (CSF) obtained from Subjective Cognitive Impairment (SCI), Lewy Body Dementia (LBD), and AD patients. Subsequently, we exposed NGC0211 cells directly to AD-related factors like amyloid-β peptides (Aβ40/42) or activated astrocyte-conditioned medium (Aβ40/42/IL-1β/TNFα-treated) and evaluated biochemical stress markers, cell death indicators, cell proliferation marker (Ki67), and hmNGF release. We found that all patients’ CSF significantly reduced hmNGF release from NGC0211 cells in vitro. Aβ40/42, inflammatory molecules, and activated astrocytes significantly affected NGC0211 cell proliferation without altering hmNGF release or other parameters important for essential functions of the NGC0211 cells. Long-term constant cell proliferation within the ECB device is critically important to maintain a steady cell population needed for stable mNGF release. These data show hampered proliferation of NGC0211 cells, which may lead to a decline of the NGC0211 cell population in ECBs, thereby reducing hmNGF release. Our study highlights the need for future studies to strengthen ECB-mediated long-term drug delivery approaches.
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| 4. |
- Mitra, S, et al.
(författare)
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Microglia Impairs Proliferation and Induces Senescence In-Vitro in NGF Releasing Cells Used in Encapsulated Cell Biodelivery for Alzheimer's Disease Therapy
- 2022
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 23:16
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Tidskriftsartikel (refereegranskat)abstract
- There is no cure yet available for Alzheimer’s disease (AD). We recently optimized encapsulated cell biodelivery (ECB) devices releasing human mature nerve growth factor (hmNGF), termed ECB-NGF, to the basal forebrain of AD patients. The ECB-NGF delivery resulted in increased CSF cholinergic markers, improved glucose metabolism, and positive effects on cognition in AD patients. However, some ECB-NGF implants showed altered hmNGF release post-explantation. To optimize the ECB-NGF platform for future therapeutic purposes, we initiated in-vitro optimization studies by exposing ECB-NGF devices to physiological factors present within the AD brain. We report here that microglia cells can impair hmNGF release from ECB-NGF devices in-vitro, which can be reversed by transferring the devices to fresh culture medium. Further, we exposed the hmNGF secreting human ARPE-19 cell line (NGC0211) to microglia (HMC3) conditioned medium (MCM; untreated or treated with IL-1β/IFNγ/Aβ40/Aβ42), and evaluated biochemical stress markers (ROS, GSH, ΔΨm, and Alamar Blue assay), cell death indicators (Annexin-V/PI), cell proliferation (CFSE retention and Ki67) and senescence markers (SA-β-gal) in NGC0211 cells. MCMs from activated microglia reduced cell proliferation and induced cell senescence in NGC0211 cells, which otherwise resist biochemical alterations and cell death. These data indicate a critical but reversible impact of activated microglia on NGC0211 cells.
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