The genus Tulotis has been classified into the genus Platanthera in the present taxonomic studies since the morphological characteristics of this genus is very similar to that of Platanthera. ...Platanthera ussuriensis, formerly named as Tulotis ussuriensis, is a small terrestrial orchid species and has been listed as wild plant under State protection (category II) in China. An improved understanding of the genomic information will enable future applications of conservation strategy as well as phylogenetic studies for this rare orchid species. The objective of this research was to characterize and compare the chloroplast genome of P. ussuriensis with other closely related species of Orchidaceae.
The chloroplast genome sequence of P. ussuriensis is 155,016 bp in length, which included a pair of inverted repeats (IRs) of 26,548 bp that separated a large single copy (LSC) region of 83,984 bp and a small single copy (SSC) region of 17,936 bp. The annotation contained a total of 132 genes, including 86 protein-coding genes, 38 tRNA genes and 8 rRNA genes. The simple sequence repeat (SSR) analysis showed that there were 104 SSRs in the chloroplast genome of P. ussuriensis. RNA editing sites recognition indicated 72 RNA editing events occurred, and all codon changes were C to T conversions. Comparative genomics showed that the chloroplast sequence of Platanthera related species were relatively conserved, while there were still some high variation regions that could be used as molecular markers. Moreover, Platanthera related species showed similar IR/SSC and IR/LSC borders. The phylogenetic analysis suggested that P. ussuriensis had a closer evolutionary relationship with P. japonica followed by the remaining Platanthera species.
Orchidaceae is a key group of biodiversity protection and also a hot spot group in the plant taxonomy and evolution studies due to their characteristics of high specialization and rapid evolution. This research determined the complete chloroplast genome of P. ussuriensis for the first time, and compared the sequence with other closely related orchid species. These results provide a foundation for future genomic and molecular evolution of the Orchidaceae species, and provide insights into the development of conservation strategy for Platanthera species.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neuropathic pain (NP) is chronic, intractable, and typically not alleviated using analgesics. Ferroptosis is a new type of cell death characterized by mitochondrial damage, oxidative stress, and ...mitochondrial dysfunction, affecting specific types of synaptic plasticity in the spinal cord. Here, we evaluated the role of ferroptosis in NP using chronic contractile injury (CCI) in rats. The CCI and control groups were subjected to sciatic nerve ligation. The mechanical withdrawal threshold and thermal withdrawal reflex latency were used to detect changes in mechanical pain threshold and thermal pain threshold in rats, respectively. Notably, CCI caused mechanical and thermal stimulation of the injured hind paw, reduced levels of glutathione peroxidase 4 (GPX4), and increased acyl-CoA synthetase long-chain family member 4 (ACSL4). Treatment with the ferroptosis inhibitor ferrostatin-1 (10 mg/kg) 1 h after surgery upregulated GPX4 expression and downregulated ACSL4 expression, whereas the ferroptosis inducer, erastin (10 mg/kg), exerted opposite effects. Treatment with ferrostatin-1 upregulated NeuN expression and downregulated GPX4 expression, whereas erastin reversed these effects. CCI increased the number of damaged mitochondria and decreased the mean planar mitochondrial area, and treatment with erastin further exacerbated these effects. The iron ion content in the spinal cords of CCI-induced rats increased. Treatment with ferrostatin-1 decreased, whereas treatment with erastin increased iron ion content in the CCI-induced rat model. Taken together, our results showed that ferroptosis is involved in the development of NP in male rats by blocking neuron and astrocyte activation in the spinal dorsal horn.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Polymer-based substrate with patterned microstructures has been widely utilized for the development of cell chip in tissue engineering and/or flexible sensors in robotics. The key challenge is to ...fabricate the polymer-based substrate with the localized patterned microstructures. In this study, we presented a method to fabricate localized microstructures by standing surface acoustic wave (SSAW) and user-defined waveguides. To investigate the working mechanism, we developed a 3D numerical model to analyze the induced acoustic pressure distribution and final generated microstructures. Results demonstrated that the utilized waveguide could localize the acoustic pressure field in a specified region within the prepared photosensitive fluid film based on Rayleigh’s radiation theory and capillary wave motion. By adjusting the SSAW driven modes and using different shaped waveguides, both numerical modeling and experimental tests showed that the localized microstructures can form on the liquid film and then successfully fabricated using ultraviolet (UV) solidification. Therefore, our developed method by using the SSAW and waveguide provides a promising alternative process to fabricate the polymer-based microstructure with localized patterns, and the fabricated polymer-based microstructures could be used for the development of flexible sensors, actuator, and/or soft robotics in future applications.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Study on the expression of miRNA‐22 in serum of Alzheimer's disease (AD) patients and the mechanism of neuroinflammation regulation.
Methods
ELISA assay was used to detect the serum level ...of inflammatory factors, including interleukin‐1β (IL‐1β), interleukin‐18 (IL‐18), and tumor necrosis factor‐α in AD patients. TargetScan database and luciferase reporter gene assay indicated that gasdermin D (GSDMD) was the target gene of miRNA‐22. miRNA‐22 mimic was transfected into microglia, followed by administration of LPS and Nigericin to induce pyroptosis.
Results
In this study, we found that the expression level of miRNA‐22 in peripheral blood was lower in AD patients than that in healthy population. The expression of inflammatory factors was higher in AD patients than that in healthy people, which was negatively correlated with miRNA‐22. miRNA‐22 mimic could significantly inhibit pyroptosis, the expression of GSDMD and p30‐GSDMD was down‐regulated, the release of inflammatory factor was decreased, and the expression of NLRP3 inflammasome was down‐regulated as feedback. In the APP/PS1 double transgenic mouse model, the injection of miRNA‐22 mimic significantly improved the memory ability and behavior of mice. In addition, the expression of the vital protein of pyroptosis in mouse brain tissue, including GSDMD and p30‐GSDMD, was down‐regulated, and the expression of inflammatory factors was also decreased.
Conclusion
miRNA‐22 was negatively correlated with the expression of inflammatory factors in AD patients, and miRNA‐22 could inhibit the release of inflammatory cytokines by regulating the inflammatory pyroptosis of glial cells via targeting GSDMD, thereby improving cognitive ability in AD mice. miRNA‐22 and pyroptosis are potential novel therapeutic targets in the treatment of AD.
miRNA‐22 was negatively correlated with the expression of inflammatory factors in Alzheimer's disease (AD) patients, and miRNA‐22 could inhibit the release of inflammatory cytokines by regulating the inflammatory pyroptosis of glial cells via targeting GSDMD, thereby improving cognitive ability in AD mice. miRNA‐22 and pyroptosis are potential novel therapeutic targets in the treatment of AD.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
We investigate the mechanism whereby chlorpyrifos (CHI), an environmental toxin, causes liver injury by inducing ferroptosis in hepatocytes.
The toxic dose (LD50 = 50 μM) of CHI for inducing AML12 ...injury in normal mouse hepatocytes was determined, and the ferroptosis-related indices were measured, including the levels of SOD, MDA and GSH-Px, as well as the cellular content of iron ions. JC-1 and DCFH-DA assays were employed to detect the mtROS levels, the levels of mitochondrial proteins (GSDMD, NT-GSDMD), as well as the cellular levels of ferroptosis-related proteins (P53, GPX4, MDM2, SLC7A11). We knocked out the GSDMD and P53 in AML12 and observed the CHI-induced ferroptosis of ALM12 after applying YGC063, an ROS inhibitor. In animal experiments, we explored the effect of CHI on liver injury by using conditional GSDMD-knockout mice (C57BL/6 N-GSDMDem1(flox)Cya) and ferroptosis inhibitor Fer-1. Small molecule-protein docking and Pull-down assay were employed to verify the association between CHI and GSDMD.
We found that CHI could induce ferroptosis of AML12. CHI promoted the cleavage of GSDMD, leading to upregulation of mitochondrial NT-GSDMD expression, as well as ROS levels. P53 activation promoted the ferroptosis. Knock out of GSDMD and P53 could inhibit the CHI-induced ferroptosis, and YGC063 could also inhibit ferroptosis. In mice experiments, GSDMD knockout or Fer-1 intervention could significantly inhibit the CHI-induced liver injury. CHI promoted the cleavage of GSDMD by binding to its SER234 site.
CHI can bind to GSDMD to promote its cleavage, while NT-GSDMD can open mitochondrial membrane to promote the mtROS release. Cytoplasmic upregulation of ROS levels can facilitate the P53-mediated ferroptosis. GSDMD-mtROS is the primary mechanism whereby CHI induces ferroptosis in hepatocytes.
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•We have explored the role and mechanism of liver injury caused by CHI.•CHI can induce iron death and lead to liver injury through mtROS.•GSDMD-mtROS is the primary mechanism whereby CHI induces ferroptosis in hepatocytes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Triptolide (TRI) is an active diterpenoid lactone compound isolated from Tripterygium wilfordii,We focused on investigating the effect and mechanism of Triptolide (TRI) on liver injury.
The toxic ...dose (LD50 = 100 μM) of TRI on liver Kupffer cells was explored, and network pharmacological analysis was performed to identify Caspase-3 as the target of TRI-induced liver injury. Regarding the pyroptosis research, we examined the level of TRI-induced pyroptosis in Kupffer cells, including inflammatory cytokine detection, protein assay, microscopic cell observation and LDH toxicity test. The effect of TRI on pyroptosis was assessed after knocking out GSDMD, GSDME and Caspase-3 in cells, respectively. We also investigated the liver injury-inducing action of TRI at the animal level.
Our experimental results were consistent with those predicted by network pharmacology, indicating that TRI could bind to Caspase-3-VAL27 site to promote the cleavage of Caspase-3, and Cleaved-Caspase-3 induced pyroptosis of Kupffer cells through GSDME cleavage. GSDMD was not involved in TRI’s action. TRI could promote Kupffer cell pyroptosis, elevate the inflammatory cytokine levels, and facilitate the expressions of N-GSDME and Cleaved-Capase 3. After the mutation of VAL27, TRI could not bind to Caspase-3. Animal-level results showed that TRI could induce liver injury in mice, while Caspase-3 knockout or Caspase-3 inhibitors could antagonize the action of TRI.
We find that the TRI-induced liver injury occurs primarily through the Caspase-3-GSDME pyroptosis signal. TRI can promote Caspase − 3 maturation and regulate kupffer cell pyroptosis. The present findings offer a new idea for the safe use of TRI.
•TRI can promote Caspase-3 maturation and regulate kupffer cell pyroptosis.•The binding of TRI, a Caspase-3 activator, to VAL27 site promoted the maturation and cleavage of Cleaved-Caspase-3.•TRI activated Caspase-3-GSDME in tissues and elevated the levels of N-GSDME and Cleaved-Caspase-3.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We investigated the toxicological mechanism by which perfluorooctane sulfonate (PFOS) induces liver injury via ferroptosis.
Primary mouse hepatocytes were treated with LD50 = 55M PFOS. Their ...cytotoxicity was detected by CCK-8 and LDH assays, while JC-1 staining was used to identify their mitochondrial membrane potential. GSH-Px, MDA, and SOD levels were determined using kits, and Fe2+ levels were determined using the FerroOrange probe and iron ion assay kit. The DCFH-DA probe was used to examine ROS levels, while Western blot was used to examine protein expressions. After treatment with the ferroptosis inhibitor YL939 and the ROS inhibitor BABTA, the ability of PFOS to induce ferroptosis was observed. In animal experiments, we examined the liver function and the degree of hepatic ferroptosis of mice treated with PFOS as well as their histopathological changes.
PFOS could induce hepatocyte ferroptosis, while YL939 and BABTA treatment could inhibit PFOS-induced ferroptosis. PFOS could induce liver injury and increase ferroptosis levels in tissue, while treatment with YL939 and BABTA could inhibit liver injury.
PFOS can induce ferroptosis in hepatocytes and cause liver injury in mice, which is its toxicological mechanism.
•PFOS can induce ferroptosis in hepatocytes•PFOS can cause liver injury in mice, which is its toxicological mechanism•PFOS can trigger hepatocyte injury through ROS-mediated ferroptosis, thereby causing liver injury
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
This study was mainly conducted to explore the expression changes of GSDMD and conventional markers (including T‐Tau, Tau181p, and Aβ1–42) in the cerebrospinal fluid among patients with ...Alzheimer's disease (AD) and vascular dementia (VD), followed by determination of role of GSDMD in diagnosing and identifying AD and VD.
Methods
In this study, 60 patients with VD, 60 patients with AD, and 50 healthy controls were enrolled. Lumbar puncture was performed to collect cerebrospinal fluid samples. Patients with VD and patients with AD were evaluated using the Mini‐Mental State Examination (MMSE) scale, Montreal Cognitive Assessment (MoCA) scale, Clinical Dementia Rating (CDR) scale, Activity of Daily Living (ADL) scale, and Neuropsychiatric Inventory (NPI) questionnaire, aiming to determine the behavioral ability of patients. ELISA kit was purchased to determine the levels of GSDMD, T‐Tau, Tau181p, and Aβ1–42 in cerebrospinal fluid, and the expression of inflammatory factors, IL‐1β and IL‐6, was also detected.
Results
(1) The levels of GSDMD, T‐Tau, and Tau181p in the cerebrospinal fluid were higher in patients with AD than those of patients with VD and healthy controls, while the levels of Aβ1‐42 in the cerebrospinal fluid were lower in patients with AD than that in healthy controls and patients with VD. (2) GSDMD had good diagnostic accuracy in AD. Additionally, GSDMD, T‐Tau, Tau181p, and Aβ1‐42 had good discrimination accuracy in distinguishing AD and VD. (3) The expression levels of inflammatory factors (IL‐1β and IL‐6) in cerebrospinal fluid were higher in patients with AD than those of healthy controls and patients with VD, which were positively correlated with GSDMD expression.
Conclusion
The expression of GSDMD was increased in patients with AD, which could be used as a biomarker for AD diagnosis and identification from VD.
The expression of GSDMD was increased in AD patients, which could be used as a biomarker for AD diagnosis and identification from VD.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The study was designed to assess the expression of long non-coding RNA HOTAIR (lncRNA HOTAIR) in tissues and peripheral blood of patients with advanced hepatocellular carcinoma (HCC). In addition, we ...also investigated the prognostic correlation between the expression level of lncRNA HOTAIR in tumour tissues and peripheral blood of patients with advanced HCC and sunitinib monotherapy.
A total of 60 patients with advanced HCC who received sunitinib monotherapy and another 60 healthy individuals who were examined at the physical examination centre during the same period were included in the study. Real-time quantitative PCR (RT-QPCR) was used to determine the relative expression of lncRNA HOTAIR in tumour tissue, adjacent tissue, and peripheral blood of HCC patients as well as peripheral blood of healthy controls. Moreover, the clinicopathological information, overall survival (OS), and progression-free survival (PFS) were collected, followed by correlation analysis with lncRNA HOTAIR expression.
The expression of lncRNA HOTAIR was significantly higher in tumour tissues compared to that in adjacent tissues (
= 9.03,
< 0.001). The expression of lncRNA HOTAIR in peripheral blood of HCC patients was higher than that in healthy controls (
= 8.04,
< 0.001). There was a correlation between the expression of lncRNA HOTAIR in tumour tissue and peripheral blood in HCC patients (
= 0.638,
< 0.001). Patients with low lncRNA HOTAIR expression in tumour tissues harboured significantly longer OS (13.4 vs. 9.5,
< 0.001) and PFS (8.4 vs. 6.2,
< 0.001) compared to those with high expression. Consistently, patients with low lncRNA HOTAIR expression in peripheral blood had significantly prolonged OS (12.8 vs. 9.1,
< 0.001) and PFS (8.9 vs. 6.4,
< 0.001) compared to those with high expression. Patients with low expression both in tumour tissue and peripheral blood had prolonged OS (14.3 vs. 8.8,
< 0.001) and PFS (10.6 vs. 6.0,
< 0.001) compared to the rest of the patients. Cox regression analysis indicated that the expression level of lncRNA HOTAIR in tumour tissue and peripheral blood was an independent predictive factor of OS and PFS in patients with advanced HCC treated by sunitinib.
The expression of lncRNA HOTAIR was up-regulated in tumour tissue and peripheral blood in patients with advanced HCC. In addition, the expression level of lncRNA HOTAIR was one of the indicators predicting the effectiveness of sunitinib therapy.
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