Papers by Thuzar Hla Shwe
International Immunopharmacology
Biomedicines
Sesamin, a major phytochemical in sesame seeds and oil, has been reported to have effects on phys... more Sesamin, a major phytochemical in sesame seeds and oil, has been reported to have effects on physiological and pathological angiogenesis in several studies. Nevertheless, the underlying mechanisms of sesamin’s effect on angiogenesis are not understood well enough. This study aimed to investigate its effect on both physiological and pathological angiogenesis using the in vivo chick chorioallantoic membrane (CAM) model and the in vitro human endothelial cell line, EA.hy926, model. Sesamin inhibited the VEGFA-induced pathological angiogenesis significantly, although no effect was seen on angiogenesis without induction. It reduced the formation of vascular branches in the VEGFA-treated CAMs and also the proliferation and migration of EA.hy926 endothelial cells induced by VEGFA. Sesamin impeded the VEGF-mediated activation of Src and FAK signaling proteins, which may be responsible for sesamin-mediated reduction of pathological angiogenesis. Moreover, the effect of sesamin on the express...
Scientific Reports
Diabetes mellitus (DM), one of the principal causes of morbidity and mortality worldwide, is impl... more Diabetes mellitus (DM), one of the principal causes of morbidity and mortality worldwide, is implicated in the progression of age-related neurodegenerative diseases (NDDs), in which microglial activation is a crucial mediator. Sesamin, a kind of phytochemical, shows inhibitory effects on microglial activation. The present study studied whether sesamin protects against neurotoxicity triggered by high glucose-induced microglial activation. We firstly demonstrated that high doses of glucose, which mimics hyperglycemia in DM, did induce the activation of murine BV2 microglial cells, increasing inflammatory responses such as the production of ROS or inflammatory mediators like IL-1β, TNF-⍺, and nitric oxide, through activation of p38 and JNK signaling pathways. Next, conditioned medium (CM) collected from high glucose-activated BV2 cell culture was used to show aggravated neurotoxicity in differentiated PC12 cells, indicating that high glucose-activated microglia could induce neurotoxici...
International Journal of Molecular Sciences, 2021
Liver cancer is the sixth most common cancer worldwide with high morbidity and mortality. Program... more Liver cancer is the sixth most common cancer worldwide with high morbidity and mortality. Programmed death ligand 1 (PD-L1) is a major ligand of programmed death 1 receptor (PD1), and PD1/PD-L1 checkpoint acts as a negative regulator of the immune system. Cancers evade the host’s immune defense via PD-L1 expression. This study aimed to investigate the effects of tumor-related cytokines, interferon gamma (IFNγ), and tumor necrosis factor alpha (TNFα) on PD-L1 expression in human hepatocellular carcinoma cells, HepG2. Furthermore, as atorvastatin, a cholesterol-lowering agent, is documented for its immunomodulatory properties, its effect on PD-L1 expression was investigated. In this study, through real-time RT-PCR, Western blot, and immunocytochemistry methods, PD-L1 expression in both mRNA and protein levels was found to be synergistically upregulated in HepG2 by a combination of IFNγ and TNFα, and STAT1 activation was mainly responsible for that synergistic effect. Next, atorvastati...
Brain Research Bulletin, 2021
Neuroinflammation-mediated microglial reactivity is a major process, which explains the increased... more Neuroinflammation-mediated microglial reactivity is a major process, which explains the increased risk of Alzheimer's disease (AD) development in patients with Type 2 diabetes mellitus (T2DM). Advanced glycation end products (AGEs), formed by hyperglycemic condition in diabetes, is characterized as an intermediary of brain injury with diabetes through induction of microglial reactivity. Here, we explored the effect of AGEs on microglial reactivity using BV2 as a model. The NF-κB, p38 and JNK pathways were found to be important mechanism in AGEs-induced BV2 microglial reactivity. NF-κB inhibitor (BAY-11-7082), p38 inhibitor (SB203580) and JNK inhibitor (SP600125) exhibited the potential inhibition of AGEs-induced NO production. We also found that the sesamin, a major lignan found in sesame seed oils, exerts an anti-inflammatory effect under AGEs-induced microglial reactivity via suppressing the phosphorylation of NF-κB, p38 and JNK pathways. Moreover, sesamin also ameliorated AGEs-induced-receptor for advanced glycation end products (RAGE) expression. Taken together, sesamin may be a promising phytochemical compound to delay inflammatory progress by AGEs microglia function. Similarly, inhibition of AGEs-induced microglial reactivity might be potential therapeutic targets of neuroinflammation-based mechanisms in T2DM link progressive AD.
International Immunopharmacology, 2020
Programmed death ligand 1 (PD-L1) is overexpressed in some metastatic breast cancer subtypes, spe... more Programmed death ligand 1 (PD-L1) is overexpressed in some metastatic breast cancer subtypes, specifically triple-negative breast cancer (TNBC). This feature can assist in the eradication of anti-tumor immunity, thereby enhancing the survival of the tumor. This study aims to explore how sesamin affects PD-L1 expression in breast cancer cells and its related molecular mechanisms. We found high levels of expression of PD-L1 in both mRNA and protein levels in the TNBC cell line, MDA-MB231, but not in the luminal type-breast cancer cell line, MCF-7. We then demonstrated the tumor suppressive effect of sesamin, which induced the inhibition of cell proliferation in MDA-MB231 cells. Additionally, sesamin triggered PD-L1 downregulation (both mRNA and protein) through the inhibition of AKT, NF-κB and JAK/Stat signaling in MDA-MB231 cells. Moreover, the migration ability of MDA-MB231 cells was effectively diminished by sesamin via inhibition of the activation of MMP-9 and MMP-2. In summary, this study demonstrated that sesamin suppresses MDA-MB231 breast cancer cells' proliferation and migration; and decreases the expression of PD-L1 via the downregulation of AKT, NF-κB, and JAK/Stat signaling. Therefore, sesamin may be an effective alternative and novel therapeutic option for immunotherapy in breast cancer cells with high PD-L1 expression.
Toxicon, 2020
Green pit viper (Trimeresurus sp.) bite occurred throughout Myanmar, but there is no specific ant... more Green pit viper (Trimeresurus sp.) bite occurred throughout Myanmar, but there is no specific antivenom produced in the country for related envenomation. Instead, Myanmar Russell's viper antivenom (Anti-MRV) was often misused because of prolonged clotting time was observed from both species. Thai green pit viper antivenom (Anti-TGPV) raised against Trimeresurus albolabris was found to be effective against venoms of more than ten Trimeresurus sp. from Thailand, Malaysia and Indonesia. The present study compared the neutralization capacities of Anti-TGPV and Anti-MRV towards the venom from T. erythrurus from Myanmar. Anti-TGPV was more efficacious than Anti-MRV in cross-neutralizing the lethal and haemorrhagic activities of the venom by a potency of a least 1.4 times higher. Although Anti-TGPV effectively cross-neutralized the coagulation activity of the venom, Anti-MRV failed to do so. Immunodiffusion and immunoblot experiments showed that Anti-TGPV cross-reacted with more protein components of the venom than Anti-MRV. In conclusion, Anti-TGPV is a better choice for patients bitten by Myanmar green pit viper, but further clinical investigation is required. The current findings highlight the development of a specific antivenom against Myanmar green pit viper venom.
Molecules, 2020
Programmed death ligand 1 (PD-L1) is overexpressed in the most aggressive breast cancer subtype, ... more Programmed death ligand 1 (PD-L1) is overexpressed in the most aggressive breast cancer subtype, triple-negative breast cancer (TNBC), assisting the eradication of antitumor immunity, and thereby enhancing the survival of the tumor. This study explored how hesperidin affects PD-L1 expression, and thereby cancer progression in breast cancer cells. We found that MDA-MB231, the triple-negative breast adenocarcinoma cancer cell line, (high aggressiveness) has higher expression, in both mRNA and protein, of PD-L1 than that of the other breast cancer cell line, MCF-7 (low aggressiveness). Hesperidin inhibited cell proliferation in MDA-MB231 cells. Additionally, high expression of PD-L1 (both mRNA and protein) in aggressive cancer cells was strongly inhibited by hesperidin through inhibition of Akt and NF-κB signaling. Moreover, hesperidin treatment, by inhibiting activation of matrix metalloproteinases such as MMP-9 and MMP-2, suppressed the metastatic phenotype and cell migration in the ...
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Papers by Thuzar Hla Shwe