cellular apoptosis
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2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Dinggui Lu ◽  
Jihua Wei ◽  
Jian Chen ◽  
Jingjie Zhao ◽  
Jiajia Wang ◽  
...  

Osteoarthritis (OA) is a degenerative disease characterized by articular cartilage and/or chondrocyte destruction, and although it has long been considered as a primary disease, the importance of meniscus endothelial cell modulation in the subchondral microenvironment has recently drawn attention. Previous studies have shown that apelin could potentially inhibit cellular apoptosis; however, it remains unclear whether apelin could play a protective role in protecting the endothelium in the OA meniscus. In this study, with the advantages of single-cell RNA sequencing (scRNA-seq) data, in combination with flow cytometry, we identified two endothelial subclusters in the meniscus, featured by high expression of Homeobox A13 (HOXA13) and Ras Protein-Specific Guanine Nucleotide Releasing Factor 2 (RASGRF2), respectively. Compared with control patients, both subclusters decreased in absolute cell numbers and exhibited downregulated APJ endogenous ligand (APLN, coding for apelin) and upregulated apelin receptor (APLNR, coding apelin receptor). Furthermore, we confirmed that in OA, decreased endothelial cell numbers, including both subclusters, were related to intrinsic apoptosis factors: one more relevant to caspase 3 (CASP3) and the other to BH3-Interacting Domain Death agonist (BID). In vitro culturing of meniscal endothelial cells purified from patients proved that apelin could significantly inhibit apoptosis by downregulating these two factors in endothelial cell subclusters, suggesting that apelin could potentially serve as a therapeutic target for patients with OA.


2022 ◽  
Author(s):  
Jei Hyoung Park ◽  
Kyoung Jin Nho ◽  
Ji Young Lee ◽  
Yung Joon Yoo ◽  
Woo Jin Park ◽  
...  

Abstract Oxidative stress, caused by the accumulation of reactive oxygen species (ROS) during acute myocardial infarction (AMI), is one of the main factors leading to myocardial cell damage and programmed cell death. Phosphatidylinositol-3-kinase -AKT (PI3K-AKT) signaling is essential for regulating cell proliferation, differentiation, and apoptosis. Phosphoinositide-3-kinase (PI3K)-interacting protein 1 (PIK3IP1) is an intrinsic inhibitor of PI3K in various tissues, but its functional role during AMI remains unknown. In this study, the anti-ischemic role of PIK3IP1 in an in vitro AMI setting was evaluated using H9c2 cells. The MTT assay demonstrated that cell viability decreased significantly with treatment of H2O2 (200 -500 µM). The TUNEL assay results revealed substantial cellular apoptosis following treatment with 200 µM H2O2. Under the same conditions, the expression levels of hypoxia-inducible factor (HIF-1α), endothelin-1 (ET-1), bcl-2-like protein 4 (BAX), and cleaved caspase–3, were elevated, whereas those of PIK3IP1 and Bcl-2 decreased significantly. PIK3IP1 overexpression inhibited H2O2-induced, and PI3K-mediated, apoptosis; however, PIK3IP1 knockdown reversed this effect, suggesting that PIK3IP1 functions as an anti-apoptotic molecule. To identify both the upstream and downstream molecules associated with PIK3IP1, ET-1 receptor type-specific antagonists (BQ-123 and BQ-788) and PI3K subtype-specific antagonists (LY294002 and IPI-549) were used to determine the participating isoforms. Co-immunoprecipitation was performed to identify the binding partners of PIK3IP1. Our results demonstrated that ROS-induced cardiac cell death may occur through the ETA-PI3Kγ-AKT axis, and that PIK3IP1 inhibits binding with both ETA and PI3Kγ. Taken together, these findings reveal that PIK3IP1 plays an anti-ischemic role by reducing the likelihood of programmed cell death via interacting with the ETA-PI3Kr-AKT axis.


2022 ◽  
Vol 4 (01) ◽  
Author(s):  
Danran Li ◽  
Nina Wang ◽  
Tianyang Zhang ◽  
Guangxing Wu ◽  
Yifeng Xiong ◽  
...  

2022 ◽  
Vol 2022 ◽  
pp. 1-18
Author(s):  
Wei Chen ◽  
Wenhui Huang ◽  
Yu Yang ◽  
Keshen Li

Cerebral endothelial cells play an essential role in brain angiogenesis, and their function has been found to be impaired in diabetes. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite of glucose formed mainly during glycolysis, and its levels can be elevated in hyperglycemic conditions. MG is a potent precursor of AGEs (advanced glycation end-products). In this study, we investigated if MG can induce angiogenesis dysfunction and whether MG scavengers can ameliorate angiogenesis dysfunction induced by MG. Here, we used cultured human brain microvascular endothelial cells (HBMECs) treated with MG and oxygen-glucose deprivation (OGD) to mimic diabetic stroke in vitro. We also used the MG challenged chicken embryo chorioallantoic membrane (CAM) to study angiogenesis in vivo. Interestingly, administration of MG significantly impaired cell proliferation, cell migration, and tube formation and decreased protein expression of angiogenesis-related factors, which was rescued by three different MG scavengers, glyoxalase 1 (GLO1), aminoguanidine (AG), and N-acetyl cysteine (NAC). In cultured CAM, MG exposure significantly reduced angiogenesis and the angiogenesis-related dysfunction could be attenuated by pretreatment with AG or NAC. Treatment of cultured HBMECs with MG plus OGD increased cellular apoptosis significantly, which could be prevented by exposure to GLO1, AG, or NAC. We also noted that administration of MG increased cellular oxidative stress as measured by reactive oxygen species (ROS) generation, enhanced AGE accumulation, and receptor for advanced glycation end-product (RAGE) expression in the cultured HBMECs, which were partially reversed by GLO1, AG, or NAC. Taken together, our findings demonstrated that GLO1, AG, or NAC administration can ameliorate MG-induced angiogenesis dysfunction, and this can be mainly attributed to attenuated ROS production, reduced cellular apoptosis, and increased levels of angiogenic factors. Overall, this study suggested that GLO1, AG, or NAC may be promising candidate compounds for the treatment of angiogenesis dysfunction caused by hyperglycemia in diabetic ischemic stroke.


2021 ◽  
Vol 10 ◽  
pp. e2342
Author(s):  
Shabnam Zarei Moradi ◽  
Seyed Abdolhamid Angaji ◽  
Mitra Salehi ◽  
Mehrdad Hashemi

Background: Testicular torsion is one cause of infertility without proper treatment. In this study, we investigate the effects of NiO2 nanoparticles (NPs) and curcumin on sperm parameters in rats and the expressions of genes involved in the apoptotic pathway, as well as expressions of miR-34 and circRNA 0001518. Materials and Methods: Forty-eight rats were randomly divided into eight groups: control (healthy rats), control rats that received NiO2-NPs, healthy rats that received curcumin, rats that received simultaneous NiO2-NPs and curcumin, untreated testicular ischemia/reperfusion (I/R) rats, testicular I/R rats that received NiO2-NPs, testicular I/R rats that received curcumin, and testicular I/R rats that received NiO2-NPs and curcumin. Then, sperms were extracted from the rats’ epididymides to analyze concentration, viability, morphology, and motility. The cellular apoptosis level was studied using flow cytometry. Also, Bad and Bcl-X gene expressions, as well as miR-34 and circRNA 0001518 levels were measured. Results: We observed improved sperm parameters in the testicular I/R) rats that received curcumin and NiO2-NPs. Administration of NiO2-NPs to healthy rats increased both apoptosis and the Bad/Bcl-X expression ratio. However, its administration to testicular I/R rats alone or in combination with curcumin decreased apoptosis and the Bad/Bcl-X expression ratio and increased expressions of miR-34 and circRNA 0001518. Conclusion: Administration of NiO2-NPs and curcumin, alone or in combination, can have therapeutic effects in testicular I/R conditions by altering the expressions of genes in the mitochondrial apoptotic pathway and their regulatory elements.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yunyun Zhuo ◽  
Haoming Wang ◽  
Luetao Zou ◽  
Yiyang Wang ◽  
Yanzhu Hu ◽  
...  

Mechanical overloading-induced nucleus pulposus cell (NPC) apoptosis plays a core role in the pathogenesis of intervertebral disc degeneration. In this study, we investigated the involvement of mammalian silent information regulator 2 homolog (SIRT1) in NPC apoptosis under high-magnitude compression. Our results showed that high-magnitude compression aggravated cellular apoptosis and attenuated the expression levels of SIRT1 and microtubule-associated protein-1 light chain-3B (LC3B) in rat NPCs in a three-dimensional (3D) cell culture model and an in vivo rat tail compression model, whereas SIRT1 overexpression in NPCs partially reversed these indicators. Moreover, SIRT1 overexpression increased the formation of the LC3B/Fas complex, alleviated activation of the NF-κB pathway, and reduced NPC apoptosis. Finally, downregulation of LC3B partially activated the NF-κB pathway and aggravated NPC apoptosis. Overall, upregulation of SIRT1 increases formation of the LC3B/Fas complex, which contributes to suppression of NPC apoptosis by inhibiting the NF-κB pathway under high compressive stress.


2021 ◽  
Author(s):  
Shynggys Sergazy ◽  
Anastassiya Vetrova ◽  
Ilkay Erdogan Orhan ◽  
Fatma Sezer Senol Deniz ◽  
Ahmet Kahraman ◽  
...  

Aim: To determine the antiproliferative and cytotoxic activities of Geranium and Erodium species against human cancer and noncancer cell lines, respectively. Methods: Twenty-one species of Geranium and Erodium were extracted and screened against cancerous and noncancerous human cell lines. Results: In a dose-response manner, G. glaberrimum, G. asphodeloides, E. brandianum and E. leucanthum were able, with variable potency, to inhibit cellular proliferation. Except for  E. brandianum, all extracts induced cellular autophagy in tumor cells with similar levels to that of rapamycin; but, only E. brandianum induced cellular apoptosis, likely through Bcl2 and BAX protein expressions. Discussion: This is the first study to report the potential antiproliferative effects of ethanol extracts of several Geraniaceae species.


2021 ◽  
Vol 12 ◽  
Author(s):  
Terence Peter Scott ◽  
Louis Hendrik Nel

Lyssaviruses cause the disease rabies, which is a fatal encephalitic disease resulting in approximately 59,000 human deaths annually. The prototype species, rabies lyssavirus, is the most prevalent of all lyssaviruses and poses the greatest public health threat. In Africa, six confirmed and one putative species of lyssavirus have been identified. Rabies lyssavirus remains endemic throughout mainland Africa, where the domestic dog is the primary reservoir – resulting in the highest per capita death rate from rabies globally. Rabies is typically transmitted through the injection of virus-laden saliva through a bite or scratch from an infected animal. Due to the inhibition of specific immune responses by multifunctional viral proteins, the virus usually replicates at low levels in the muscle tissue and subsequently enters the peripheral nervous system at the neuromuscular junction. Pathogenic rabies lyssavirus strains inhibit innate immune signaling and induce cellular apoptosis as the virus progresses to the central nervous system and brain using viral protein facilitated retrograde axonal transport. Rabies manifests in two different forms - the encephalitic and the paralytic form - with differing clinical manifestations and survival times. Disease symptoms are thought to be due mitochondrial dysfunction, rather than neuronal apoptosis. While much is known about rabies, there remain many gaps in knowledge about the neuropathology of the disease. It should be emphasized however, that rabies is vaccine preventable and dog-mediated human rabies has been eliminated in various countries. The global elimination of dog-mediated human rabies in the foreseeable future is therefore an entirely feasible goal.


2021 ◽  
pp. 118749
Author(s):  
Jianping Tang ◽  
Qianqian Su ◽  
Zhenkun Guo ◽  
Jinfu Zhou ◽  
Fuli Zheng ◽  
...  

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