Human Cell
·
2022
·Vol. 35
·期 5
·1424-1439
·
IF 4.374
Liu Wen,Li Guojuan,Li Jing,Chen Wei
The long-term treatment of glucocorticoids is a common cause of osteoporosis (OP). This study concentrated on inquiring into the regulatory role and potential mechanisms of TRG-AS1 on dexamethasone (Dex)-induced OP in rats. We adopted Dex to treat rat osteoblasts and rats to simulate in-vitro and in-vivo OP models, respectively. Gain-of-function assays of TRG-AS1, miR-802 and CAB39 were constructed in rat osteoblasts to make certain the influence of TRG-AS1, miR-802 and CAB39 on differentiation, proliferation and apoptosis of rat osteoblasts. TRG-AS1 and CAB39 were down-regulated in the Dex-induced OP model in rats, in contrast to miR-802. Overexpression of TRG-AS1 restrained Dex-induced inhibition of osteogenic differentiation, promoted CAB39/AMPK/SIRT-1 and inhibited NF-κB, while overexpression of miR-802 bridled the inhibitory effect of TRG-AS1 on OP. miR-802 was targeted by TRG-AS1, and inhibited CAB39. Inhibition of either AMPK or SIRT-1 abated the osteogenic differentiation-promoting effect of CAB39. Animal experiments displayed that overexpressing TRG-AS1 alleviated Dex-induced OP in rats. In conclusion, up-regulation of TRG-AS1 protected against glucocorticoid-induced OP in rats by modulating the miR-802-mediated CAB39/AMPK/SIRT-1/NF-κB axis.
研究领域:
分子生物学
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药理学
·
骨科
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CELL CYCLE
·
2022
·
IF 5.173
Tianjiao Lai,Haifeng Qiu,Lulu Si,Yu Zhen,Danxia Chu,Ruixia Guo
Endometrial carcinoma (EC) originates from the endometrium and is one of the most common tumors in female patients, and its incidence has continued to increase in recent decades. LncRNAs are involved in the pathogenesis and metastasis of a variety of malignant tumors, which indicates that lncRNAs can be used as tumor diagnostic markers and potential therapeutic targets. In this study, we analyzed the RNA transcripts of EC cells from The Cancer Genome Atlas (TCGA) and first reported a novel lncRNA, BMPR1B-AS1, that was more highly expressed in endometrial cancer tissues than in adjacent tissues, and BMPR1B-AS1 could promote endometrial cancer cell proliferation and metastasis. Bioinformatics prediction and experimental results both suggested that BMPR1B-AS1 could modulate the malignant behaviors of endometrial cancer cell lines by sponging miR-7-2-3p to modulate DCLK1, and a DCLK1 inhibitor blocked the activation of the PI3K/Akt/NF-κB signaling pathway. Collectively, this study suggests that the BMPR1B-AS1/miR-7-2-3p/DCLK1 axis contributes to the proliferation and metastasis of endometrial cancer cells via the PI3K/Akt/NF-κB pathway.
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2020
·
IF 3.004
Ying Sun,Li Xie,Fulin Feng,Qing Han,Lanlan Wei,Zigang Tang,Xuejun Kang
The determination of the concentrations of urinary biomarkers of oxidative damage to DNA and RNA is difficult due to the low content of targets and the complex matrix of urine. A method using polystyrene/polypyrrole (PS/PPY) electronspun nanofibers as the adsorbent was introduced to the routine urinary treatment and determination of 8-OHdG and 8-oxoG for the first time. And 2-aminoethyl diphenylborate (DPBA) solution was creatively used in the loading and rinsing steps in order to promote the retention of the analytes as well as remove impurities. Under optimal conditions, 8-OHdG, 8-oxoG and IS were separated very well and exhibited a good linearity in the range of 0.5–50 ng mL −1 , with correlation coefficients of R 2 > 0.996. Limits of detection (LOD) were 0.058 ng mL −1 and 0.093 ng mL −1 , and limits of quantification (LOQ) were 0.195 ng mL −1 and 0.309 ng mL −1 , respectively. The recoveries were 88.8–104.9%. The proposed method was so simple and economical that it had the potential to be applied to batch quantitative analysis of 8-OHdG and 8-oxoG in urine. And it was successfully applied to real urine samples of cancer patients.
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JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Jihua Wei,Zichun Song,Jiuying Cui,Yuanxun Gong,Qianli Tang,Kai Zhang,Xinlei Song,Xianjiu Liao
In this study, we introduce an electrochemiluminescence (ECL) sensing platform based on the "Entropy-driven triggered T7 amplification-CRISPR/Cas13a system" (EDT-Cas). This platform combines a programmable entropy-driven cycling strategy, T7 RNA polymerase, and the CRISPR/Cas13a system to amplify the determination of the SARS-CoV-2 RdRp gene. The Ti 3 C 2 T x -compliant ECL signaling molecule offers unique benefits when used with the ECL sensing platform to increase the assay sensitivity and the electrode surface modifiability. To obtain the T7 promoter, the SARS-CoV-2 RdRp gene may first initiate an entropy-driven cyclic amplification response. Then, after recognizing the T7 promoter sequence on the newly created dsDNA, T7 RNA polymerase starts transcription, resulting in the production of many single-stranded RNAs (ssRNAs), which in turn trigger the action of CRISPR/Cas13a. Finally, Cas13a/crRNA identifies the transcribed ssRNA. When it cleaves the ssRNA, many DNA reporter probes carrying -U-U- are cleaved on the electrode surface, increasing the ECL signal and allowing for the rapid and highly sensitive detection of SARS-CoV-2. With a detection limit of 7.39 aM, our method enables us to locate the SARS-CoV-2 RdRp gene in clinical samples. The detection method also demonstrates excellent repeatability and stability. The SARS-CoV-2 RdRp gene was discovered using the "Entropy-driven triggered T7 amplification-CRISPR/Cas13a system" (EDT-Cas). The developed ECL test had excellent recoveries in pharyngeal swabs and environmental samples. It is anticipated to offer an early clinical diagnosis of SARS-CoV-2 and further control the spread of the pandemic.
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ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Pengchen Chen,Yali Song,Li Tang,Zhuolin Qiu,Junhui Chen,Siyu Xia,Ashok Iyaswamy,Jing Cai,Yan Sun,Chuanbin Yang,Jigang Wang
Tri (2-Ethylhexyl) phosphate (TEHP), widely used as a fire retardant and plasticizer, has been commonly found in the environment. Its potential health-related risks, especially reproductive toxicity, have aroused concern. However, the potential cellular mechanisms remain unexplored. In this study, we aimed to investigate the molecular mechanisms underlying TEHP-caused cell damage in Sertoli cells, which play a crucial role in supporting spermatogenesis. Our findings indicate that TEHP induces apoptosis in 15P-1 mouse Sertoli cells. Subsequently, we conducted RNA sequencing analyses, which suggested that ER stress, autophagy, and MAPK-related pathways may participate in TEHP-induced cytotoxicity. Furthermore, we demonstrated that TEHP triggers ER stress, activates p38 MAPK, and inhibits autophagy flux. Then, we showed that the inhibition of ER stress or p38 MAPK activation attenuates TEHP-induced apoptosis, while the inhibition of autophagy flux is responsible for TEHP-induced apoptosis. These results collectively reveal that TEHP induces ER stress, activates p38, and inhibits autophagy flux, ultimately leading to apoptosis in Sertoli cells. These shed light on the molecular mechanisms underlying TEHP-associated testicular toxicity.
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American Journal of Translational Research
·
2021
·
IF 4.06
Shan Jiang,Chonghe Wang,Jingyao Zhu,Xuezhu Huang
Objective: To investigate the regulatory mechanism of sevoflurane-induced neuronal apoptosis through analyzing the expression of glial cell-derived neurotrophic factor (GDNF) mediated by miR-133, sponged by long non-coding RNA (lncRNA) CDKN2B-AS1. Methods: An in vitro cell injury model was established by using different concentrations of sevoflurane and primary hippocampal neurons. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8); caspase-3 and caspase-9 activities were detected by colorimetry, and apoptotic cells were determined by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Fluorescence in situ hybridization (FISH) analysis was used to detect localized expression of CDKN2B antisense RNA 1 (CDKN2B-AS1), and dual-luciferase reporter assay was employed to verify the correlation of CDKN2B-AS1 and miR-133, and of miR-133 and GDNF. The expression of CDKN2B-AS1, miR-133, and GDNF mRNA in the cell injury model were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot was utilized to detect the expression of GDNF protein in the cell injury model. Results: In the cell injury model, CDKN2B-AS1 was highly expressed in the cytoplasm, and CDKN2B-AS1 and GDNF were downregulated and miR-133 was upregulated as detected by qRT-PCR (all P<0.05). The connections between CDKN2B-AS1 and miR-133, and between miR-133 and GDNF were confirmed. That is, CDKN2B-AS1 regulated the expression of GDNF by adsorbing miR-133 (all P<0.05). In cells treated with sevoflurane, overexpression of CDKN2B-AS1 could inhibit caspase-3 and caspase-9 activities and the degree of apoptosis. miR-133 could partially alleviate the effect of overexpressing CDKN2B-AS1 on cells, and si-GDNF the effect of miR-133 inhibitor (all P<0.05). Conclusion: lncRNA CDKN2B-AS1 can up-regulate the expression of GDNF, inhibit neuronal apoptosis, and ease the toxic effect of sevoflurane on neural cells by acting as a sponge to adsorb miR-133.
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Advanced Science
·
2022
·Vol. 9
·期 30
·2201425
·
IF 17.521
Huan Lei,Daidi Fan
In addition to oxidative stress and impaired angiogenesis, the overexpression of metalloproteinases (MMPs) and proinflammatory cytokines, which are promoted by hyperglycemia, causes chronic inflammation in diabetic wounds. Herein, TA-siRNA nanogels are prepared for the first time on the basis of the self-assembling interaction between tannic acid (TA) and short interfering RNA (siRNA). The efficient, biodegradable nanogels are cross-linked with poly(vinyl alcohol) (PVA), human-like collagen (HLC), TA, and borax to prepare adaptive, conductive PHTB (TA-siRNA) hydrogels. In response to high levels of reactive oxygen species (ROS), the ROS-responsive borate ester bonds in the hydrogels are oxidized and broken, and TA-siRNA nanogels are released into cells to reduce the expression of the MMP-9. Moreover, the TA and HLC promote collagen expression, reduce inflammation, and ROS level. It is found that electrical stimulation (ES) promotes the in vivo release of TA-siRNA nanogels from PHTB (TA-siRNA) hydrogels and endocytosis of the nanogels. The combination therapy using ES and PHTB (TA-siRNA) hydrogels accelerates the healing of diabetic wounds by reducing the levels of ROS and MMP-9 and promoting the polarization of macrophages, production of collagen, and angiogenesis. This study provides insights on the design of functional gene-delivery and efficient therapeutic strategies to promote the repair of diabetic chronic wounds.
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ANALYTICAL CHEMISTRY
·
2016
·
IF 5.886
Dongqing Kong,Sai Bi,Zonghua Wang,Jianfei Xia,Feifei Zhang
In this work, an in situ growth protocol is introduced to fabricate three-dimensional graphene films (3D GFs) on gold substrates, which are successfully utilized as working electrode for electrochemical detection of nucleic acid (microRNA) and protein (lysozyme) based on a signal-on sensing mechanism. To realize the bridge between the gold substrate and graphene film, a monolayer of 4-aminothiophenol is self-assembled on the substrate, which is then served as connectors for the growth of 3D GFs on the gold substrate by the hydrothermal reduction (HR) technique. Moreover, given the excellent properties, such as enlarged surface area, strong binding strength between 3D GFs and gold substrate, and improved conductivity, the proposed 3D GF-fabricated gold substrate is readily employed to the construction of electrochemical biosensing platforms through introduction of magnetic nanoparticles (MNPs) as probe carriers. On the basis of the strand displacement reaction and specific binding between aptamer and its target, the developed biosensors achieve signal-on detection of microRNA-155 (miR-155) and lysozyme (Lyz) with high sensitivity and selectivity and further successfully applied to human serum assay. Overall, the proposed strategy for in situ growth of 3D GFs provides a powerful tool for a wide range of applications, which is not limited to electrochemical biosensors and can be extended to other areas, such as electrocatalysis and electronic energy-related systems.
研究领域:
材料科学
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分析化学
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生物医学工程
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FISH & SHELLFISH IMMUNOLOGY
·
2025
·
IF 3.9
Meiqin Mao,Zhixia Zhuang,Xiaoru Wang,Huabin Huang,Jiaonan Zhang,Jiaolin Zhang,Qingpi Yan
Pseudomonas plecoglossicida is a significant pathogen in aquaculture, capable of infecting various teleost fish and causing visceral white spot disease, which leads to substantial economic losses. The PhoP/PhoQ two-component system plays a central role in virulence regulation in Gram-negative bacteria; however, its specific function in P. plecoglossicida remains unclear. To elucidate the role of the phoP gene in the pathogenicity of this bacterium, we used hybrid grouper ( Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) as an infection model to compare the pathogenicity and host immune responses among the wild-type (NZBD9), phoP deletion (Δ phoP ), and complemented (C-Δ phoP ) strains. In artificial infection experiments, the Δ phoP strain exhibited significantly attenuated virulence, with an LD 50 value of 4.082 × 10 4 , which was 13.7 times higher than that of the wild-type strain. Furthermore, the deletion of phoP reduced bacterial load in the spleen and alleviated histopathological damage in the spleen, head kidney, and intestine. RNA-seq analysis of spleen tissue at 4 days post-infection identified 1768 differentially expressed genes (DEGs), including 704 up-regulated and 1064 down-regulated genes. GO and KEGG enrichment analyses revealed that these DEGs were primarily involved in immune-related processes and pathways, including TLR signaling, NF-κB activation, PI3K-Akt signaling, cytokine-cytokine receptor interaction, and cell adhesion molecules. Temporal expression profiling via qRT-PCR demonstrated that key immune genes (including tlr1, tlr5 , tlr13 , traf5 , nf-κb , mcp1 , cd3 , and il10 ) were generally down-regulated or exhibited delayed and weakened activation in Δ phoP -infected fish, indicating a subdued and dysregulated immune response. These results suggest that the phoP gene is essential for maintaining full virulence in P. plecoglossicida , modulating host immunity by suppressing critical inflammatory and immune signaling pathways. Our study provides novel insights into the role of the PhoP/PhoQ system in host–pathogen interactions and lays a theoretical foundation for developing targeted control strategies against P. plecoglossicida infection in aquaculture.
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ZOOLOGICAL RESEARCH
·
2023
·
IF 4.9
Cong Li,Rui Bi,Lin Wang,Yu-Hua Ma,Yong-Gang Yao,Ping Zheng
Tree shrews ( Tupaia belangeri chinensis ) share a close relationship to primates and have been widely used in biomedical research. We previously established a spermatogonial stem cell (SSC)-based gene editing platform to generate transgenic tree shrews. However, the influences of long-term expansion on tree shrew SSC spermatogenesis potential remain unclear. Here, we examined the in vivo spermatogenesis potential of tree shrew SSCs cultured across different passages. We found that SSCs lost spermatogenesis ability after long-term expansion (>50 passages), as indicated by the failure to colonize the seminiferous epithelium and generate donor spermatogonia (SPG)-derived spermatocytes or spermatids marking spermatogenesis. RNA sequencing (RNA-seq) analysis of undifferentiated SPGs across different passages revealed significant gene expression changes after sub-culturing primary SPG lines for more than 40 passages on feeder layers. Specifically, DNA damage response and repair genes (e.g., MRE11 , SMC3 , BLM , and GEN1 ) were down-regulated, whereas genes associated with mitochondrial function (e.g., NDUFA9 , NDUFA8 , NDUFA13 , and NDUFB8 ) were up-regulated after expansion. The DNA damage accumulation and mitochondrial dysfunction were experimentally validated in high-passage cells. Supplementation with nicotinamide adenine dinucleotide (NAD + ) precursor nicotinamide riboside (NR) exhibited beneficial effects by reducing DNA damage accumulation and mitochondrial dysfunction in SPG elicited by long-term culture. Our research presents a comprehensive analysis of the genetic and physiological attributes critical for the sustained expansion of undifferentiated SSCs in tree shrews and proposes an effective strategy for extended in vitro maintenance.
研究领域:
生物医学研究
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干细胞生物学
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分子遗传学
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生殖生物学
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MOLECULAR NEUROBIOLOGY
·
2025
·Vol. 63
·期 1
·229
·
IF 4.3
Zhang Zhiyang,Xu Nixi,Tao Zean,Liang Yun,Jin Lixia,Li Zhuoxuan,Cao Yuanwu,Jiang Chang,Chen Zixian
Spinal cord injury (SCI) often results in permanent functional loss due to the complexity of the post-SCI microenvironment, but the composition and functional dynamics of the post-SCI microenvironment remain poorly understood. We applied spatial metabolomics to detect metabolites within the spinal cord of SCI rats, revealing the existence of a high-uric acid (hUA) microenvironment. Subsequently, we utilized Bulk-RNA sequencing and single-cell RNA sequencing (scRNA-seq) analysis, identified elevated expression of Cellular communication network factor 1 (Ccn1) and alterations in purine metabolic patterns. To investigate the role of Ccn1 within this hUA microenvironment, PC12 cell line and Sprague–Dawley (SD) rats were used. In vitro , 4 groups were designed: Control ( n = 6), UA (PC12 cells treated with 200 μM UA for 24 h) ( n = 6), siCcn1 ( Ccn1 knockdown using small interfering RNA) ( n = 6), and siCcn1 + UA ( n = 6). In vivo groups: SCI (spinal cord injury only) ( n = 6), hUA (induced hUA microenvironment by gavage with oxonic acid potassium salt 750 mg/kg and and ethambutol 250 mg/kg) ( n = 6), AAV ( Ccn1 knockdown via adeno-associated virus) ( n = 6), and AAV + hUA ( n = 6). Results showed that UA significantly reduced cellular aerobic respiration levels (Control vs UA: 62.87 ± 16.76 vs 17.09 ± 4.91 pmol/min, P < 0.01) and induced pyroptosis, Ccn1 knockdown significantly improved aerobic respiration ( siCcn1 + UA vs UA: 46.45 ± 12.54 vs 17.09 ± 4.91 pmol/min, P < 0.05) and reduced the level of pyroptosis. Total cellular ATP levels, the NAD⁺/NADH ratio, and proliferation capacity were also assessed. In vivo , Ccn1 knockdown significantly increased the Basso, Beattie, and Bresnahan (BBB) locomotor scores of animals on the 7 days post-injury ( AAV + hUA vs hUA: 3.33 ± 0.52 vs 2.00 ± 0.63, P < 0.05) and reduced neuronal pyroptosis. The hUA microenvironment upregulated Ccn1 expression, suppressed aerobic respiration, induced pyroptosis, and disrupted purine metabolism, Ccn1 knockdown reversed these biological processes, suggesting its potential as a therapeutic target for SCI.
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Molecular Biomedicine
·
2025
·Vol. 6
·期 1
·1-18
·
IF 10.1
Zhang Shuqin,Cheng Yajia,Gao Yujia,Xu Feifei,Wang Yuna,Zhang Junling,Shang Yue,Li Deguan,Fan Saijun
With advancements in radiotherapy technologies, the detrimental effects of ionizing radiation on biological systems, particularly the hematopoietic system, have caused significant concern. N 6 -methyladenosine (m 6 A), the most pervasive representative of post-transcriptional modifications, plays critical roles in diverse biological events. Non-coding RNA comprises the vast majority of the human genome. This study aimed to explore the role of long non-coding RNA (lncRNA) m 6 A modification in γ-ray irradiation-induced hematopoietic injury. By using mouse models, it was found that γ-radiation rapidly damaged hematopoietic bone marrow cells (BMCs), triggering apoptosis, oxidative stress and DNA damage, along with up-regulation of m 6 A Reader proteins. We revealed the time-conditioned landscape of lncRNA m 6 A methylome of BMCs in the short term after radiation and found that a dynamic “change-then-recover” trend involved. LncRNA Snhg15 was identified as a key regulator through integration analysis of the methylome and transcriptome data. Its m 6 A modification was closely related to progression of radiation injury in BMCs. Further research demonstrated that the novel m 6 A Reader LRPPRC could interact with the modification site of Snhg15 , stabilize Snhg15 and promote its expression, thereby exacerbating radiation-induced injury to BMCs both in vitro and in vivo. Knockdown of Lrpprc or Snhg15 could alleviate the radiation injury to the hematopoietic system. Additionally, the LRPPRC- Snhg15 axis was involved in the radio-protective efficacy of gut microbiota-derived valeric acid. These findings uncover a novel mechanism by which m 6 A-modified lncRNA Snhg15 is stabilized by LRPPRC modulates γ-irradiation-induced hematopoietic injury, providing potential therapeutic targets for the prevention and treatment of radiation injuries.
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