Hypoxia plays a significant role in solid tumors by the increased expression of hypoxia-inducible factor-1α (HIF-1α), which is known to promote cancer invasion and metastasis. Cancer-cell invasion dynamically begins with the degradation of the extracellular matrix (ECM) via invadopodia formation. The chemical substrates that are utilized by hypoxic cells as fuel to drive invadopodia formation are still not fully understood. Therefore, the aim of the study was to maintain MDA-MB-231 cells under hypoxia conditions to allow cells to form a large number of invadopodia as a model, followed by identifying their nutrient utilization. The results of the study revealed an increase in the number of cells forming invadopodia under hypoxia conditions. Moreover, Western blot analysis confirmed that essential proteins for hypoxia and invadopodia, including HIF-1α, vascular endothelial growth factor (VEGF), metallopeptidase-2 (MMP-2), and Rho guanine nucleotide exchange factor 7 (β-PIX), significantly increased under hypoxia. Interestingly, phenotype microarray showed that only 11 chemical substrates from 367 types of substrates were significantly metabolized in hypoxia compared to in normoxia. This is thought to be fuel for hypoxia to drive the invasion process. In conclusion, we found 11 chemical substrates that could have potential energy sources for hypoxia-induced invadopodia formation of these cells. This may in part be a target in the hypoxic tumor and invadopodia formation. Additionally, these findings can be used as potential carrier targets in cancer-drug discovery, such as the usage of dextrin.
The COVID-19 pandemic has emerged as a significant event of the current century, introducing substantial transformations in economic and social activities worldwide. The primary objective of this study is to investigate the relationship between daily COVID-19 cases and Pakistan stock market (PSX) return volatility. To assess the relationship between daily COVID-19 cases and the PSX return volatility, we collected secondary data from the World Health Organization (WHO) and the PSX website, specifically focusing on the PSX 100 index, spanning from March 15, 2020, to March 31, 2021. We used the GARCH family models for measuring the volatility and the COVID-19 impact on the stock market performance. Our E-GARCH findings show that there is long-term persistence in the return volatility of the stock market of Pakistan in the period of the COVID-19 timeline because ARCH alpha (ω1) and GARCH beta (ω2) are significant. Moreover, is asymmetrical effect is found in the stock market of Pakistan during the COVID-19 period due to Gamma (ѱ) being significant for PSX. Our DCC-GARCH results show that the COVID-19 active cases have a long-term spillover impact on the Pakistan stock market. Therefore, the need of strong planning and alternative platform should be needed in the distress period to promote the stock market and investor should advised to make diversified international portfolio by investing in high and low volatility stock market to save their income. This study advocated the implications for investors to invest in low volatility stock especially during the period of pandemics to protect their return on investment. Moreover, policy makers and the regulators can make effective policies to maintain financial stability during pandemics that is very important for the country's economic development.
The approach of drug delivery systems emphasizes the use of nanoparticles as a vehicle, offering the optional property of delivering drugs as a single dose rather than in multiple doses. The current study aims to improve antioxidant and drug release properties of curcumin loaded gum Arabic-sodium alginate nanoparticles (Cur/ALG-GANPs). The Cur/ALG-GANPs were prepared using the ionotropic gelation technique and further subjected to physico-chemical characterization using attenuated total reflectance-Fourier transform infrared (ATR-FTIR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), size distribution, and transmission electron microscopy (TEM). The size of Cur/ALG-GANPs ranged between 10 ± 0.3 nm and 190 ± 0.1 nm and the zeta potential was -15 ± 0.2 mV. The antioxidant study of Cur/ALG-GANPs exhibited effective radical scavenging capacity for 1,1-diphenyl-2-picrylhydrazyl (DPPH) at concentrations that ranged between 30 and 500µg/mL. Cytotoxicity was performed using MTT assay to measure their potential in inhibiting the cell growth and the result demonstrated a significant anticancer activity of Cur/ALG-GANPs against human liver cancer cells (HepG2) than in colon cancer (HT29), lung cancer (A549) and breast cancer (MCF7) cells. Thus, this study indicates that Cur/ALG-GANPs have promising anticancer properties that might aid in future cancer therapy.
Exosomes are extracellular vesicles with a diameter ranging from 40 to 160 nm. They are produced by hepatocytes, cholangiocytes, hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs) and Kupffer cells in liver tissue. The secretion of exosomes might vary in quantity and composition in reaction to multiple triggers and various stages of disease. They transport various payloads, such as proteins, DNAs, and RNAs, and enable cell interaction to regulate myriad physiological and pathological processes in liver tissue. Long non-coding RNAs (lncRNAs) are a crucial component of exosomes with an excellent capability to regulate multiple cellular activities such as differentiation, development, metabolism, proliferation, apoptosis, and activation. With the advancements in transcriptomic and genomic study methods and database management technology, the functions and mechanisms of exosomal lncRNAs in liver diseases have been well-studied. This article delves into the detailed role of exosomal lncRNAs in liver disease onset and progression, ranging from hepatocellular carcinoma (HCC) to liver fibrosis drug-induced liver damage (DILI) and steatotic liver diseases.