Progresses, Challenges, and Prospects of CRISPR/Cas9 Gene-Editing in Glioma Studies.

Glioma refers to a tumor that is derived from brain glial stem cells or progenitor cells and is the most common primary intracranial tumor. Due to its complex cellular components, as well as the aggressiveness and specificity of the pathogenic site of glioma, most patients with malignant glioma have poor prognoses following surgeries, radiotherapies, and chemotherapies. In recent years, an increasing amount of research has focused on the use of CRISPR/Cas9 gene-editing technology in the treatment of glioma. As an emerging gene-editing technology, CRISPR/Cas9 utilizes the expression of certain functional proteins to repair tissues or treat gene-deficient diseases and could be applied to immunotherapies through the expression of antigens, antibodies, or receptors. In addition, some research also utilized CRISPR/Cas9 to establish tumor models so as to study tumor pathogenesis and screen tumor prognostic targets. This paper mainly discusses the roles of CRISPR/Cas9 in the treatment of glioma patients, the exploration of the pathogenesis of neuroglioma, and the screening targets for clinical prognosis. This paper also raises the future research prospects of CRISPR/Cas9 in glioma, as well as the opportunities and challenges that it will face in clinical treatment in the future.

Therapeutic Effects of Retinoic Acid in Lipopolysaccharide-Induced Cardiac Dysfunction: Network Pharmacology and Experimental Validation.

Purpose: Sepsis, which is deemed as a systemic inflammation reaction syndrome in the face of infectious stimuli, is the primary cause of death in ICUs. Sepsis-induced cardiomyopathy (SIC) may derive from systemic inflammation reaction and oxidative stress. Retinoic acid (RA) is recognized by its beneficial roles in terms of the immunoresponse to infections and antioxygen actions. However, the treatment efficacy and potential causal links of RA in SIC are still elusive. Methods: By virtue of the STITCH database, we identified the targets of RA. Differentially expressed genes in SIC were acquired from the GEO database. The PPI network of intersected targets was established. GO and KEGG pathway enrichment analysis was completed. Hub genes were analyzed by cytoHubba plug-in. In the process of experimental validation, a mouse sepsis model was established by lipopolysaccharide (LPS), and the treated mice were intraperitoneally injected with RA or Dexamethasone (DEX) 60 min prior to LPS injections. Survival conditions, cardiac functions and antioxidant levels of the mice were assessed. Cardiac inflammation and injury were detected by HE and TUNEL. The levels of key genes and signal pathway expression were analyzed by RT-PCR and Western blot. Results: PPARA, ITGAM, VCAM-1, IGF-1 and IL-6 were identified as key therapeutic targets of RA by network pharmacology. PI3K-Akt signaling pathway is the main regulatory pathway of RA. In vivo researches unraveled that RA can improve the survival rate and cardiac function of LPS-treated mice, inhibit inflammatory factors and myocardial injury, and regulate the expression of key therapeutic targets and key pathways, which is PI3K-Akt signaling pathway. Conclusion: Network pharmacological method offers a predicative strategy to explore the treatment efficacy and causal links of RA in endotoxemic myocarditis. Through experimental verification, we discover that RA can reduce lipopolysaccharide-induced cardiac dysfunction by regulating the PI3K-Akt signaling pathway and key genes.

MK8722, an AMPK activator, inhibiting carcinoma proliferation, invasion and migration in human pancreatic cancer cells.

BACKGROUND: MK8722 is a potent and systemic pan-AMPK activator. It is an effective, direct, allosteric activator of AMPK complex in many mammals. This study tried to explore the underlying anti-cancer molecular mechanism of MK8722 in human pancreatic cancer cells (PCCs). METHODS: The anti-proliferation, invasion and migration functions of MK8722 in human pancreatic cancer analyzed by real time cellular analysis, colony formation assay, cell migration assay, transwell assay and flow cytometery analysis. Moreover, the potential targeted signaling pathway was tested via RNA-seq and pathway enrichment analysis. RESULTS: In the present study, we investigated the anti-PCCs effects of MK8722 on two different human pancreatic cancer cell lines (PANC-1 and Patu8988). The results showed that MK8722 significantly inhibited human tumor cells proliferation and migration/invasion in a dose-dependent manner. Additionally, the influence of MK8722 was examined by analyzing the expression of potential key genes and pathways, which may provide novel insights to the mechanism of MK8722. CONCLUSION: The inhibition of pancreatic cancer by MK8722 through a number of pathways that inhibit carcinoma proliferation, invasion and migration. The potential effect of MK8722 might be determined by regulating the expression of AL162151, IER2, REPIN1, KRT80 to inhibit cycle arrest and migration.

Association of Sleep Duration and Screen Time With Anxiety of Pregnant Women During the COVID-19 Pandemic.

The COVID-19 pandemic has dramatically changed the patterns of lifestyle and posed psychological stress on pregnant women. However, the association of sleep duration and screen time with anxiety among pregnant women under the backdrop of the COVID-19 pandemic scenario has been poorly addressed. We conducted one large-scale, multicenter cross-sectional study which recruited 1794 pregnant women across middle and west China. Self-reported demographic characteristics, lifestyle, and mental health status were collected from 6th February to 8th May 2020. We investigated the association of sleep duration and screen time with the risk of anxiety by multivariable logistic regression analysis and linear regression analysis after adjusting potential confounders. The dose-response relationship of sleep duration and screen time with anxiety was visualized using a cubic spline plot. Our data revealed that almost 35% of pregnant women suffered from anxiety during the COVID-19 pandemic. Sleep duration was dose-dependently associated with a lower risk of anxiety among pregnant women (OR = 0.41, 95% CI: 0.27-0.63), while screen time exhibited a conversed effect (OR = 2.01, 95% CI:1.00-4.39). Notably, sleep duration (≥8 h/day) synergistically combined with screen time (3-7 h/day) to diminish the risk of anxiety (OR = 0.70, 95% CI: 0.50-0.99). Taken together, sleep duration and screen time were independently and jointly associated with anxiety (P < 0.05). Therefore, promoting a more active lifestyle and maintaining higher sleep quality could improve the mental health of pregnant women, especially under public health emergency.

The role of mRNA in the development, diagnosis, treatment and prognosis of neural tumors.

Neural tumors can generally be divided into central nervous system tumors and peripheral nervous tumors. Because this type of tumor is located in the nerve, even benign tumors are often difficult to remove by surgery. In addition, the majority of neural tumors are malignant, and it is particular the same for the central nervous system tumors. Even treated with the means such as chemotherapy and radiotherapy, they are also difficult to completely cure. In recent years, an increasingly number of studies have focused on the use of mRNA to treat tumors, representing an emerging gene therapy. The use of mRNA can use the expression of some functional proteins for the treatment of genetic disorders or tissue repair, and it can also be applied to immunotherapy through the expression of antigens, antibodies or receptors. Therefore, although these therapies are not fully-fledged enough, they have a broad research prospect. In addition, there are many ways to treat tumors using mRNA vaccines and exosomes carrying mRNA, which have drawn much attention. In this study, we reviewed the current research on the role of mRNA in the development, diagnosis, treatment and prognosis of neural tumors, and examine the future research prospects of mRNA in neural tumors and the opportunities and challenges that will arise in the future application of clinical treatment.

The long noncoding RNA TPTE2P1 promotes the viability of colorectal cancer cells.

Long noncoding RNAs (lncRNAs) have important functions in tumor development and progression, including colorectal cancer (CRC), but their roles are not completely understood. In this study, the roles of the lncRNA transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 pseudogene 1 (TPTE2P1), previously implicated in gallbladder cancer cell migration and invasion, were evaluated in CRC. In particular, quantitative polymerase chain reaction was used to quantify TPTE2P1 levels in tumor tissues and cell lines. The association between TPTE2P1 and survival was analyzed using the online tool OncoLnc. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, colony formation assays, and flow cytometry were used to evaluate the effects of TPTE2P1 on viability, cell cycle progression, and apoptosis. Signaling pathway proteins were quantitated by Western blot analysis. Finally, the role of TPTE2P1 was analyzed in vivo using mouse models. TPTE2P1 levels were significantly higher in CRC tissues than in adjacent normal tissues. Higher expression was associated with a poor survival rate. The silencing of TPTE2P1 led to cell cycle arrest at the S phase and thereby inhibited cell viability. TPTE2P1 knockdown also caused cancer cell apoptosis via the activation of the apoptosis regulator (BCL2)/caspase 3 signaling cascade. In addition, the inhibition of TPTE2P1 had suppressive effects on tumors in vivo. TPTE2P1 is upregulated in CRC and plays essential roles in the regulation of cell viability in vitro and tumor formation in vivo.

Bufalin and 5-fluorouracil synergistically induce apoptosis in colorectal cancer cells.

5-fluorouracil (5-FU) has been used in the treatment of colorectal cancer for >50 years. However, drug resistance remains an obstacle in the application of 5-FU-based chemotherapy. Bufalin, a type of steroid with anti-tumor activity, may be purified from the skin and parotid venom glands of toads. In order to improve the anti-tumor effect of 5-FU, the present study examined the combined effects of bufalin with 5-FU on human colorectal cancer HCT116 cells. Following treatment, cell proliferation was quantified using MTT assay and apoptotic cell percentage was assessed by flow cytometry. The apoptosis-associated protein expression was evaluated by western blotting. It was observed that bufalin enhanced the cytotoxicity of 5-FU in HCT116 cells via the induction of the mitochondrial apoptotic pathway. Additionally, bufalin combined with 5-FU reduced the expression levels of anti-apoptotic proteins, such as Mcl-1, XIAP and Bcl-2 and upregulated the levels of the pro-apoptotic proteins, Bax and Bad. To verify the role of Bax, RNA interference was used to knock-down Bax. It was determined that the synergistic effect between 5-FU and bufalin was diminished following the silencing of Bax. In summary, bufalin in combination with 5-FU may induce a higher level of apoptosis compared with monotherapy, and the combination mat be a potential therapeutic strategy for the treatment of colorectal cancer.

Knockdown of TCTN1 Strongly Decreases Growth of Human Colon Cancer Cells.

BACKGROUND Tectonic family member 1 (TCTN1), a member of the tectonic family, is involved in several developmental processes and is aberrantly expressed in multiple solid tumors. However, the expression and regulation of TCTN1 in human colorectal cancer (CRC) is still not clear. MATERIAL AND METHODS The expression of TCTN1 mRNA was first explored by using Oncomine microarray datasets. TCTN1 expression was silenced in human CRC cell lines HCT116 and SW1116 via RNA interference (RNAi). Furthermore, we investigated the effect of TCTN1 depletion on CRC cell growth by MTT, colony formation, and flow cytometry in vitro. RESULTS In this study, meta-analysis showed that the expressions of TCTN1 mRNA in CRC specimens were significantly higher than that in normal specimens. Knockdown of TCTN1 expression potently inhibited the abilities of cell proliferation and colony formation as determined. Flow cytometry analysis showed that depletion of TCTN1 could cause cell cycle arrest at the G2/M phase. In addition, Annexin V/7-AAD double-staining indicated that TCTN1 silencing promoted cell apoptosis through down-regulation of caspase 3 and Bcl-2 and upregulation of cleaved caspase 3 and PARP. CONCLUSIONS Our results indicate that TCTN1 may be crucial for CRC cell growth, providing a novel alternative to target therapies of CRC. Further research on this topic is warranted.