Toxicity and Hepatoprotective Effects of ZnO Nanoparticles on Normal and High-Fat Diet-Fed Rat Livers: Mechanism of Action.

This experiment aimed to evaluate the beneficial and toxic properties of synthetic zinc oxide nanoparticles (ZnO NPs) on the liver of normal and high-fat diet (HFD) fed-rats. The ZnO NPs were synthesized and, its characterizations were determined by different techniques. Effect of ZnO NP on cell viability, liver enzymes and lipid accumulation were measured in HepG2 cells after 24 h. After that, rats orally received various dosages of ZnO NPs for period of 4 weeks. Toxicity tests were done to determine the appropriate dose. In the subsequent step, the hepatoprotective effects of 5 mg/kg ZnO NPs were determined in HFD-fed rats (experiment 2). The oxidative stress, NLRP3 inflammasome, inflammatory, and apoptosis pathways were measured. Additionally, the activity of caspase 3, nitric oxide levels, antioxidant capacity, and various biochemical factors were measured. Morphological changes in the rat livers were also evaluated by hematoxylin and eosin (H & E) and Masson trichrome. Liver apoptosis rate was also approved by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Treatment of animals with 5 mg/ZnO NPs revealed potential hepatoprotective properties, while ZnO NPs at the doses of above 10 mg/kg showed toxic effects. Antioxidant enzyme gene expression and activity were significantly augmented, while apoptosis, NLRP3 inflammasome, and inflammation pathways were significantly reduced by 5 mg/kg ZnO NPs. Liver histopathological alterations were restored by 5 mg/kg ZnO NPs in HFD. Our study highlights the hepatoprotective effects of ZnO NPs against the HFD-induced liver damage, involving antioxidant, anti-inflammatory, and anti-apoptotic pathways, indicating their promising therapeutic potential.

AS1411 aptamer-functionalized exosomes in the targeted delivery of doxorubicin in fighting colorectal cancer.

Severe side effects of chemotherapy agents on vital organs are the major causes of cancer-related mortality, not merely cancer disease. Encapsulating chemotherapeutic molecules in nanocarriers is a justifiable solution in decreasing the risk of their side effects and boosting the efficiency of treatment. The present study has developed the doxorubicin (DOX)-loaded AS1411 (anti-nucleolin) aptamer surface-functionalized exosome (DOX-Apt-Exo) to treat colorectal cancer in both in-vitro and in-vivo experimental models. HEK293-derived exosomes were loaded with DOX through the incubation method with a nearly 13% encapsulation efficiency. Afterwards, the 5-terminal carboxyl group of AS1411-aptamer was converted into amine-reactive NHS esters with EDC/NHS amide coupling chemistry before being conjugated to the amine groups on the exosome surface. DLS and TEM estimated the designed formulation (DOX-Apt-Exo) size of about 200 nm. Aptamer-binding affinity and cellular uptake of DOX-Apt-Exo by nucleolin-overexpressing cancer cells were depicted through fluorescence microscopy. Comparing the in-vitro cytotoxicity impact of DOX-loaded exosomes, either targeted or non-targeted by MTT assay, clearly verified a high effectiveness of ligand-receptor mediated target therapy. Subsequently, in-vivo experiments which were conducted on four groups of ectopic mouse models of colon cancer (5 in each group) demonstrated the tumor growth suppression through professional long-term accumulation and retention of DOX-Apt-Exo at the tumor site by ligand-receptor interaction. The results suggested that AS1411 aptamer-functionalized exosomes can be recommended as a safe and effective system to site-specific drug delivery in possible clinical applications of colon cancer.

Stem cells or their exosomes: which is preferred in COVID-19 treatment?

It only took 8 months for the pneumonia caused by a previously unknown coronavirus to turn into a global pandemic of unprecedentedly far-reaching implications. Failure of the already discovered treatment measures opened up a new opportunity to evaluate the potentials of mesenchymal stem cells and their extracellular vesicles (EVs), exosomes in particular. Eventually, the initial success experienced after the use of MSCs in treating the new pneumonia by Lnge and his team backed up the idea of MSC-based therapies and pushed them closer to becoming a reality. However, MSC-related concerns regarding safety such as abnormal differentiation, spontaneous malignant and the formation of ectopic tissues have triggered the replacement of MSCs by their secreted exosomes. The issue has been further strengthened by the fact that the exosomes leave similar treatment impacts when compared to their parental cells. In recent years, much attention has been paid to the use of MSC-derived exosomes in the treatment of a variety of diseases. With a primary focus on COVID-19 and its current treatment methods, the present review looks into the potentials of MSCs and MSC-derived exosomes in battling the ongoing pandemic. Finally, the research will draw an analogy between exosomes and their parental cells, when it comes to the progresses and challenges in using exosomes as a large-scale treatment method.

DLX6-AS1: a putative lncRNA candidate in multiple human cancers.

Long non-coding RNAs (lncRNAs) have important roles in regulating the expression of genes and act as biomarkers in the initial development of different cancers. Increasing research studies have verified that dysregulation of lncRNAs occurs in various pathological processes including tumorigenesis and cancer progression. Among the different lncRNAs, DLX6-AS1 has been reported to act as an oncogene in the development and prognoses of different cancers, by affecting many different signalling pathways. This review summarises and analyses the recent research studies describing the biological functions of DLX6-AS1, its overall effect on signalling pathways and the molecular mechanisms underlying its action on the expression of genes in multiple human cancers. Our critical analysis suggests that different signalling pathways associated to this lncRNA may be used as a biomarker for diagnosis, or targets of treatment in cancers.

The Functional Role of Long Non-coding RNA UCA1 in Human Multiple Cancers: a Review Study.

In various cancers, high-grade tumor and poor survival rate in patients with upregulated lncRNAs UCA1 have been confirmed. Urothelial carcinoma associated 1 (UCA1) is an oncogenic non-coding RNA with a length of more than 200 nucleotides. The UCA1 regulate critical biological processes that are involved in cancer progression, including cancer cell growth, invasion, migration, metastasis, and angiogenesis. So It should not surprise that UCA1 overexpresses in variety of cancers type, including pancreatic cancer, ovarian cancer, gastric cancer, colorectal cancer, breast cancer, prostate cancer, endometrial cancer, cervical cancer, bladder cancer, adrenal cancer, hypopharyngeal cancer, oral cancer, gallbladder cancer, nasopharyngeal cancer, laryngeal cancer, osteosarcoma, esophageal squamous cell carcinoma, renal cell carcinoma, cholangiocarcinoma, leukemia, glioma, thyroid cancer, medulloblastoma, hepatocellular carcinoma and multiple myeloma. In this article, we review the biological function and regulatory mechanism of UCA1 in several cancers and also, we will discuss the potential of its as cancer biomarker and cancer treatment.