Viral vectors and extracellular vesicles: innate delivery systems utilized in CRISPR/Cas-mediated cancer therapy.

Gene editing-based therapeutic strategies grant the power to override cell machinery and alter faulty genes contributing to disease development like cancer. Nowadays, the principal tool for gene editing is the clustered regularly interspaced short palindromic repeats-associated nuclease 9 (CRISPR/Cas9) system. In order to bring this gene-editing system from the bench to the bedside, a significant hurdle remains, and that is the delivery of CRISPR/Cas to various target cells in vivo and in vitro. The CRISPR-Cas system can be delivered into mammalian cells using various strategies; among all, we have reviewed recent research around two natural gene delivery systems that have been proven to be compatible with human cells. Herein, we have discussed the advantages and limitations of viral vectors, and extracellular vesicles (EVs) in delivering the CRISPR/Cas system for cancer therapy purposes.

Exogenous glutathione protects against gentamicin-induced acute kidney injury by inhibiting NF-κB pathway, oxidative stress, and apoptosis and regulating PCNA.

This study was designed, for the first time, to examine the possible nephroprotective effects of exogenous glutathione (EGSH) (100 mg/kg, intraperitoneally) on gentamicin-induced acute kidney injury (GM-induced AKI). EGSH reduced renal histopathological changes, inflammatory cell infiltration, and improved renal dysfunction in rats with AKI. EGSH ameliorated GM-induced renal oxidative stress by promoting the renal activities of catalase, glutathione peroxidase, and superoxide dismutase and diminishing renal malondialdehyde and serum nitric oxide levels. Interestingly, EGSH inhibited intrinsic apoptosis by downregulating Bax and caspase-3 and upregulating Bcl2 in the kidney of rats with AKI. EGSH decreased GM-induced inflammatory response as reflected by a remarkable decrease in the protein expressions of NF-κB-p65, IL-6, TNF-α, and iNOS and a considerable diminish in myeloperoxidase activity. Finally, EGSH markedly declined proliferative cell nuclear antigen (PCNA) protein expression in the animals with AKI. In summary, EGSH alleviated AKI in rats intoxicated with GM, partially by inhibiting oxidative stress, NF-κB pathway, and intrinsic apoptosis and regulating PCNA.

The Roles of microRNA miR-185 in Digestive Tract Cancers.

Digestive tract cancers represent a serious public health issue. In recent years, evidence has accumulated that microRNA miR-185 is implicated in the pathogenesis of this group of highly malignant tumors. Its expression variations correlate with clinical features, such as tumor size, lymph node metastasis, tumor node metastatic stage, survival, recurrence and response to adjuvant therapy, and have diagnostic and prognostic potential. In this review, we compile, evaluate and discuss the current knowledge about the roles of miR-185 in digestive tract cancers. Interestingly, miR-185 is apparently involved in regulating both tumor suppressive and oncogenic processes. We look at downstream effects as well as upstream regulation. In addition, we discuss the utility of miR-185 for diagnosis and its potential concerning novel therapeutic approaches.

D-Limonene Alleviates Acute Kidney Injury Following Gentamicin Administration in Rats: Role of NF-κB Pathway, Mitochondrial Apoptosis, Oxidative Stress, and PCNA.

Clinical application of gentamicin (GM) is well known to be associated with the development of acute kidney injury (AKI). This study was the first to investigate the possible protective effects of D-limonene (D-lim) on AKI following GM administration in rats. 32 rats arranged in four groups (n = 8): (1) the control group received saline intraperitoneally (0.5 ml/day) and orally (0.5 ml/day), (2) the D-lim group received D-lim (100 mg/kg) orally and saline (0.5 ml/day) intraperitoneally, (3) the GM group received GM (100 mg/kg/day) intraperitoneally and saline (0.5 ml/day) orally, and (4) the treated group received intraperitoneal GM (100 mg/kg) and oral D-lim (100 mg/kg). All treatments were performed daily for 12 consecutive days. Results revealed that D-lim ameliorated GM-induced AKI, oxidative stress, mitochondrial apoptosis, and inflammation. D-lim showed nephroprotective effects as reflected by the decrease in serum urea and creatinine and improvement of renal histopathological changes. D-lim alleviated GM-induced oxidative stress by increasing the activities of renal catalase, serum and renal glutathione peroxidase, and renal superoxide dismutase and decreasing renal malondialdehyde and serum nitric oxide levels. Intriguingly, D-lim suppressed mitochondrial apoptosis by considerably downregulating Bax and caspase-3 (Casp-3) mRNA and protein expressions and markedly enhancing Bcl2 mRNA and protein expressions. Furthermore, D-lim significantly decreases GM-induced inflammatory response through downregulation of NF-κB, IL-6, and TNF-α mRNA and/or protein expressions and decrease in renal myeloperoxidase activity. Finally, D-lim remarkably downregulated PCNA protein expression in the treated group compared with the GM group. In brief, this study showed that D-lim alleviated AKI following GM administration in rats, partially through its antioxidant, anti-inflammatory, and antiapoptotic activities as well as downregulation of PCNA expression.