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Browsing Staff Publication by Author "Abdalkhalig Elkhider"
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- ItemAquaporin 5 promotes tumor migration and angiogenesis in non‑small cell lung cancer cell line H1299(Elkhider, 2020-01-07) Abdalkhalig Elkhider; Bing Wang; Xunli Ouyang; Mahmoud AL‑Azab; Williams Walana; Xiaotong Sun; Han Li; Yawei Tang; Jing Wei; Xia LiNon‑small cell lung cancer (NSCLC) constitutes the majority of all lung‑cancer cases. Aquaporin 5 (AQP5) may be involved in NSCLC by promoting lung‑cancer initiation and progression. The present study aimed to determine the role of AQP5 in migration and angiogenesis using NSCLC cells and HUVECs. AQPs 1, 3, 4, 5, 8 and 9 were screened in the NSCLC cell line H1299, and the present results showed that AQP5 mRNA was upregulated compared with the other AQP genes. At the protein level, AQP5 was significantly increased in H1299 cells compared with 16HBE cells. AQP5 knockdown in H1299 cells significantly decreased cell migration compared with untransfected cells, as demonstrated by both Transwell and wound closure assays. The present study further investigated H1299 ability to promote HUVEC vascularisation. The supernatants of both transfected and untransfected H1299 cells were used as conditioned medium for HUVECs, and tube formation was measured. The supernatant of AQP5‑downregulated cells exhibited significantly low tube formation potential compared with untransfected cells. Similarly, vascular endothelial growth factor was significantly increased in control cells (si‑NC) compared with cells transfected with small interfering RNA targeting AQP5. The present study found that AQP5 downregulation significantly decreased the phosphorylation level of epidermal growth factor receptor and the activity of the ERK1/2 pathway. In summary, the present study suggested that AQP5 influenced migration and angiogenesis in NSCLCs in vitro and may potentially exhibit similar in vivo effects.
- ItemIL-8 analogue CXCL8 (3-72) K11R/G31P, modulates LPS-induced inflammation via AKT1-NF-kβ and ERK1/2-AP-1 pathways in THP-1 monocytes(Elsevier, 2018-08-17) Williams Walana; Jing-Jing Wanga; Iddrisu Baba Yabasinb; Michael Ntim; Sylvanus Kampo; Mahmoud Al-Azab; Abdalkhalig Elkhider; Eugene Dogkotenge Kuugbee; Jya-wei Cheng; John R. Gordon; Fang LiIL-8 is elevated during inflammation, and it initiates cascade of down-stream reactions. Its antagonist, CXCL8 (3–72) K11R/G31P (G31P), represses inflammatory reactions via competitive binding to CXC chemokine family, preferentially G protein-couple receptors (GPCRs) CXCR1/2. This study reports the effect of G31P on the transcription profile of lipopolysaccharide (LPS) induced inflammation in THP-1 monocytes ex-vivo. LPS (1 μg/ ml) induced elevation of IL-8 was significantly reduced by G31P (20 μg/ml and 30 μg/ml), with relatively increased inhibition of CXCR2 than CXCR1. Transcription of IL-1β, IL-6, and TNF-α were significantly inhibited, while IL-10 remained relatively unchanged. G31P treatment also had repressing effect on the inflammatory associated enzymes COX-2, MMP-2, and MMP-9. Significant restriction of c-Fos, and NF-kβ mRNA expression was observed, while that of c-Jun was marginally elevated. Conversely, SP-1 mRNA expression was seen to increase appreciably by G31P treatment. While the translation of pAKT, pERK1/2, and p65- NF-kβ were downregulated by the G31P following THP-1 cells stimulation with LPS, reactive oxygen species (ROS) expression was on the positive trajectory. Collectively, the IL-8 analogue, G31P, modulates the inflammatory profile of LPS induced inflammation in THP-1 monocytes via AKT1-NF-kβ and ERK1/2-AP-1 pathways.
- ItemIndian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway(2020-04-01) Mahmoud Al-Azab; Bing Wang; Abdalkhalig Elkhider; Williams Walana; Weiping Li1; Bo Yuan; Yunshan Ye; Yawei Tang; Marwan Almoiliqy; Salah Adlat; Jing Wei; Yan Zhang; Xia LiPremature senescence of bone marrow-derived mesenchymal stem cells (BMSC) remains a major concern for their application clinically. Hedgehog signaling has been reported to regulate aging-associated markers and MSC skewed differentiation. Indian Hedgehog (IHH) is a ligand of Hedgehog intracellular pathway considered as an inducer in chondrogenesis of human BMSC. However, the role of IHH in the aging of BMSC is still unclear. This study explored the role IHH in the senescence of BMSC obtained from human samples and senescent mice. Isolated BMSC were transfected with IHH siRNA or incubated with exogenous IHH protein and the mechanisms of aging and differentiation investigated. Moreover, the interactions between IHH, and mammalian target of rapamycin (mTOR) and reactive oxygen species (ROS) were evaluated using the corresponding inhibitors and antioxidants. BMSC transfected with IHH siRNA showed characteristics of senescence-associated features including increased senescence-associated β-galactosidase activity (SA-β-gal), induction of cell cycle inhibitors (p53/p16), development of senescence-associated secretory phenotype (SASP), activation of ROS and mTOR pathways as well as the promotion of skewed differentiation. Interestingly, BMSC treatment with IHH protein reversed the senescence markers and corrected biased differentiation. Moreover, IHH shortage-induced senescence signs were compromised after mTOR and ROS inhibition. Our findings presented anti-aging activity for IHH in BMSC through down-regulation of ROS/mTOR pathways. This discovery might contribute to increasing the therapeutic, immunomodulatory and regenerative potency of BMSC and introduce a novel remedy in the management of aging-related diseases.