The role of γδT lymphocytes in atherosclerosis.

Atherosclerosis poses a significant threat to human health, impacting overall well-being and imposing substantial financial burdens. Current treatment strategies mainly focus on managing low-density lipids (LDL) and optimizing liver functions. However, it's crucial to recognize that Atherosclerosis involves more than just lipid accumulation; it entails a complex interplay of immune responses. Research highlights the pivotal role of lipid-laden macrophages in the formation of atherosclerotic plaques. These macrophages attract lymphocytes like CD4 and CD8 to the inflamed site, potentially intensifying the inflammatory response. γδ T lymphocytes, with their diverse functions in innate and adaptive immune responses, pathogen defense, antigen presentation, and inflammation regulation, have been implicated in the early stages of Atherosclerosis. However, our understanding of the roles of γδ T cells in Atherosclerosis remains limited. This mini-review aims to shed light on the characteristics and functions of γδ T cells in Atherosclerosis. By gaining insights into the roles of γδ T cells, we may uncover a promising strategy to mitigate plaque buildup and dampen the inflammatory response, thereby opening new avenues for effectively managing this condition.

Diterpenoid honatisine overcomes temozolomide resistance in glioblastoma by inducing mitonuclear protein imbalance through disruption of TFAM-mediated mtDNA transcription.

BACKGROUND: Glioblastoma (GBM) represents as the most formidable intracranial malignancy. The systematic exploration of natural compounds for their potential applications in GBM therapy has emerged as a pivotal and fruitful avenue of research. PURPOSE: In the present study, a panel of 96 diterpenoids was systematically evaluated as a repository of potential antitumour agents. The primary objective was to discern their potency in overcoming resistance to temozolomide (TMZ). Through an extensive screening process, honatisine, a heptacyclic diterpenoid alkaloid, emerged as the most robust candidate. Notably, honatisine exhibited remarkable efficacy in patient-derived primary and recurrent GBM strains. Subsequently, we subjected this compound to comprehensive scrutiny, encompassing GBM cultured spheres, GBM organoids (GBOs), TMZ-resistant GBM cell lines, and orthotopic xenograft mouse models of GBM cells. RESULTS: Our investigative efforts delved into the mechanistic underpinnings of honatisine's impact. It was discerned that honatisine prompted mitonuclear protein imbalance and elicited the mitochondrial unfolded protein response (UPRmt). This effect was mediated through the selective depletion of mitochondrial DNA (mtDNA)-encoded subunits, with a particular emphasis on the diminution of mitochondrial transcription factor A (TFAM). The ultimate outcome was the instigation of deleterious mitochondrial dysfunction, culminating in apoptosis. Molecular docking and surface plasmon resonance (SPR) experiments validated honatisine's binding affinity to TFAM within its HMG-box B domain. This binding may promote phosphorylation of TFAM and obstruct the interaction of TFAM bound to heavy strand promoter 1 (HSP1), thereby enhancing Lon-mediated TFAM degradation. Finally, in vivo experiments confirmed honatisine's antiglioma properties. Our comprehensive toxicological assessments underscored its mild toxicity profile, emphasizing the necessity for a thorough evaluation of honatisine as a novel antiglioma agent. CONCLUSION: In summary, our data provide new insights into the therapeutic mechanisms underlying honatisine's selective inducetion of apoptosis and its ability to overcome chemotherapy resistance in GBM. These actions are mediated through the disruption of mitochondrial proteostasis and function, achieved by the inhibition of TFAM-mediated mtDNA transcription. This study highlights honatisine's potential as a promising agent for glioblastoma therapy, underscoring the need for further exploration and investigation.

Development and external validation of a novel score for predicting postoperative 30­day mortality in tumor craniotomy patients: A cross­sectional diagnostic study.

The identification of patients with craniotomy at high risk for postoperative 30-day mortality may contribute to achieving targeted delivery of interventions. The present study aimed to develop a personalized nomogram and scoring system for predicting the risk of postoperative 30-day mortality in such patients. In this retrospective cross-sectional study, 18,642 patients with craniotomy were stratified into a training cohort (n=7,800; year of surgery, 2012-2013) and an external validation cohort (n=10,842; year of surgery, 2014-2015). The least absolute shrinkage and selection operator (LASSO) model was used to select the most important variables among the candidate variables. Furthermore, a stepwise logistic regression model was established to screen out the risk factors based on the predictors chosen by the LASSO model. The model and a nomogram were constructed. The area under the receiver operating characteristic (ROC) curve (AUC) and calibration plot analysis were used to assess the model's discrimination ability and accuracy. The associated risk factors were categorized according to clinical cutoff points to create a scoring model for postoperative 30-day mortality. The total score was divided into four risk categories: Extremely high, high, intermediate and low risk. The postoperative 30-day mortality rates were 2.43 and 2.58% in the training and validation cohort, respectively. A simple nomogram and scoring system were developed for predicting the risk of postoperative 30-day mortality according to the white blood cell count; hematocrit and blood urea nitrogen levels; age range; functional health status; and incidence of disseminated cancer cells. The ROC AUC of the nomogram was 0.795 (95% CI: 0.764 to 0.826) in the training cohort and it was 0.738 (95% CI: 0.7091 to 0.7674) in the validation cohort. The calibration demonstrated a perfect fit between the predicted 30-day mortality risk and the observed 30-day mortality risk. Low, intermediate, high and extremely high risk statuses for 30-day mortality were associated with total scores of (-1.5 to -1), (-0.5 to 0.5), (1 to 2) and (2.5 to 9), respectively. A personalized nomogram and scoring system for predicting postoperative 30-day mortality in adult patients who underwent craniotomy were developed and validated, and individuals at high risk of 30-day mortality were able to be identified.

Toxicity study of rats treated by plasma-activated solution.

Background: Cold atmospheric plasma (CAP) is an effective treatment for various skin diseases. Plasma-activated solution (PAS) is an indirect method of CAP treatment that produces biological effects similar to those of direct treatment with plasma devices. The anticancer and bacteriostatic effects of PAS have been demonstrated in vitro experiments; however, on the basis of the lack of toxicological studies on PAS, its effects on living mammals when administered by subcutaneous injection is poorly known. Purpose: The purpose of this study was to evaluate the effects of PAS on local skin tissue cells, blood system, heart, liver, lungs, kidneys and other vital organs of the rat when injected subcutaneously. Methods: PAS was prepared by CAP irradiation of phosphate-buffered saline (PBS). PBS and different PBS groups (CAP irradiation for 1, 3, or 5 min) were injected subcutaneously once every 48 h. The rats were euthanized immediately after 10 cycles of therapy. Results: No adverse effects were observed during the entire period of the experiment. Histopathological examination of organs and tissues revealed no structural changes. Moreover, no obvious structural changes were observed in skin tissue. DNA damage and cancerous proliferative changes were not detected in skin tissue treated with PAS. Subsequently, RNA sequencing and western blotting were performed. The results showed that PAS increased the expression of growth factors like transforming growth factor beta (TGF-ß) and vascular endothelial growth factor A (VEGFA). These results might be directly linked to the role of PAS in stimulating TGF-ß receptor signaling pathway and angiogenesis. Conclusion: The results showed that multiple subcutaneous injections of PAS did not show significant toxic side effects on local skin tissues and some vital organs in rats, providing a scientific basis to support the future treatment of skin diseases with PAS.