NUFIP1-engineered exosomes derived from hUMSCs regulate apoptosis and neurological injury induced by propofol in newborn rats.

BACKGROUND: Propofol can increase neurotoxicity in infants but the precise mechanism is still unknown. Our previous study revealed that nuclear FMR1 interacting protein 1 (NUFIP1), a specific ribophagy receptor, can alleviate T cell apoptosis in sepsis. Yet, the effect of NUFIP1-engineered exosomes elicited from human umbilical cord blood mesenchymal stem cells (hUMSCs) on nerve injury induced by propofol remains unclear. This study intended to investigate the effect of NUFIP1-engineered exosomes on propofol-induced nerve damage in neonatal rats. METHODS: Firstly, NUFIP1-engineered exosomes were extracted from hUMSCs serum and their identification was conducted using transmission electron microscopy (TEM), Flow NanoAnalyzer, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB). Subsequently, the optimal exposure duration and concentration of propofol induced apoptosis were determined in SH-SY5Y cell line using WB. Following this, we co-cultured the NUFIP1-engineered exosomes in the knockdown group (NUFIP1-KD) and overexpression group (NUFIP1-OE) with SH-SY5Y cells and assessed their effects on the apoptosis of SH-SY5Y cells using terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay, Hoechst 33258 staining, WB, and flow cytometry, respectively. Finally, NUFIP1-engineered exosomes were intraperitoneally injected into neonatal rats, and their effects on the learning and memory ability of neonatal rats were observed through the righting reflex and Morris water maze (MWM) test. Hippocampi were extracted from different groups for hematoxylin-eosin (HE) staining, immunohistochemistry, immunofluorescence, and WB to observe their effects on apoptosis in neonatal rats. RESULTS: TEM, Flow NanoAnalyzer, qRT-PCR, and WB analyses confirmed that the exosomes extracted from hUMSCs serum exhibited the expected morphology, diameter, surface markers, and expression of target genes. This confirmed the successful construction of NUFIP1-KD and NUFIP1-OE-engineered exosomes. Optimal exposure duration and concentration of propofol were determined to be 24 hours and 100 µg/ml, respectively. Co-culture of NUFIP1 engineered exosomes and SH-SY5Y cells resulted in significant up-regulation of pro-apoptotic proteins Bax and c-Caspase-3 in the KD group, while anti-apoptotic protein Bcl-2 was significantly decreased. The OE group showed the opposite trend. TUNEL apoptosis assay, Hoechst 33258 staining, and flow cytometry yielded consistent results. Animal experiments demonstrated that intraperitoneal injection of NUFIP1-KD engineered exosomes prolonged the righting reflex recovery time of newborn rats, and MWM tests revealed a significant diminution in the time and number of newborn rats entering the platform. HE staining, immunohistochemistry, immunofluorescence, and WB results also indicated a significant enhancement in apoptosis in this group. Conversely, the experimental results of neonatal rats in the OE group revealed a certain degree of anti-apoptotic effect. CONCLUSIONS: NUFIP1-engineered exosomes from hUMSCs have the potential to regulate nerve cell apoptosis and mitigate neurological injury induced by propofol in neonatal rats. Targeting NUFIP1 may hold great significance in ameliorating propofol-induced nerve injury.

Cannabidiol regulates apoptosis and autophagy in inflammation and cancer: A review.

Cannabidiol (CBD) is a terpenoid naturally found in plants. The purified compound is used in the treatment of mental disorders because of its antidepressive, anxiolytic, and antiepileptic effects. CBD can affect the regulation of several pathophysiologic processes, including autophagy, cytokine secretion, apoptosis, and innate and adaptive immune responses. However, several authors have reported contradictory findings concerning the magnitude and direction of CBD-mediated effects. For example, CBD treatment can increase, decrease, or have no significant effect on autophagy and apoptosis. These variable results can be attributed to the differences in the biological models, cell types, and CBD concentration used in these studies. This review focuses on the mechanism of regulation of autophagy and apoptosis in inflammatory response and cancer by CBD. Further, we broadly elaborated on the prospects of using CBD as an anti-inflammatory agent and in cancer therapy in the future.

Global Research Trends and Hotspots of Autophagy in Colorectal Cancer: A 20-year Bibliometric Analysis Based on Web of Science.

BACKGROUND: Autophagy plays a pivotal role in the progression and management of colorectal cancer (CRC). Recently, numerous articles focusing on the role of autophagy in CRC have emerged. The present study was conducted to provide a comprehensive analysis of the current state and changing trends in the relationship of autophagy and CRC over the past 20 years. METHODS: The Web of Science Core Collection (WOSCC) was utilized to extracted all publications with respect to autophagy and CRC during 2002-2021. The contributions of various countries/regions, institutions and journals in this field were analyzed, moreover, research hotspots and promising future trends predicted through keywords were identified by the online platform of bibliometrics, CiteSpace and VOSviewer. RESULTS: A total of 2418 related publications from 2002 to 2021 were identified and collected. China occupied first place with respect to the number of publications, followed by the USA and South Korea. Shanghai Jiao Tong University published the most papers in this field. Most publications were published in Oncotarget. Additionally, analysis of the keywords identified 4 clusters with various research focuses: "mechanism-related research", "clinical-related research", "tumorigenesis research" and "chemotherapy-related research". The three latest hot keywords in this field were epithelial-mesenchymal transition (EMT), promote and invasion. CONCLUSIONS: The number of publications and research interest on autophagy and CRC are increasing annually, and the USA had prominent academic positions in the field. Shanghai Jiao Tong University represents a high level of research and the latest progress in this field can be tracked at Oncotarget. Throughout the research history of autophagy and CRC in the past 20 years, previous studies have mainly concentrated on apoptosis and drug resistance in tumor cells, while EMT in regulating tumorigenesis and development of clinical drugs that inhibit tumor invasion through autophagy may be novel hotspots in the future.

Effect of radical lymphadenectomy in colorectal cancer with para-aortic lymph node metastasis: a systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) with para-aortic lymph node metastasis (PALNM) is an intractable clinical situation, and the role of radical lymphadenectomy in the treatment of CRC with PALNM is still controversial. The aim of the current system review and meta-analysis is to evaluate the clinical efficacy and safety of radical lymphadenectomy in CRC patients with PALAN. METHODS: We performed a systematic search of PubMed, Embase, Cochrane Library and other online databases up to 31 October 2021. The clinical data including overall survival and postoperative complications were screened and analyzed after data extraction. Odds ratios (ORs) were applied to analyze these dichotomous outcomes with a fixed effects model. RESULTS: A total of 7 available retrospective clinical studies involving 327 patients were finally included. CRC patients with PALNM who underwent radical lymphadenectomy showed significantly overall survival (OR: 6.80, 95% CI: 3.46-13.38, P < 0.01; I2 = 0%) when compared to those who did not receive radical lymphadenectomy. Moreover, in terms of postoperative complications (OR: 0.71, 95% CI: 0.35-1.44, P = 0.48; I2 = 0%), there was no statistical difference between radical lymphadenectomy treatment and control groups. CONCLUSIONS: The radical lymphadenectomy treatment has showed the expected clinical efficacy in prolonging overall survival time of CRC patients with PALAN. Moreover, the preemptive radical lymphadenectomy could not cause additional postoperative complications.