Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications.

(R, S)- and (S)-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) and have become a research focus in recent years. However, they both have risks of psychomimetic effects, dissociative effects, and abuse liability, which limit their clinical use. Recent preclinical and clinical studies have shown that (R)-ketamine has a more efficient and lasting antidepressant effect with fewer side effects compared to (R, S)- and (S)-ketamine. However, a recent small-sample randomized controlled trial found that although (R)-ketamine has a lower incidence of adverse reactions in adult TRD treatment, its antidepressant efficacy is not superior to the placebo group, indicating its antidepressant advantage still needs further verification and clarification. Moreover, an increasing body of research suggests that (R)-ketamine might also have significant applications in the prevention and treatment of medical fields or diseases such as cognitive disorders, perioperative anesthesia, ischemic stroke, Parkinson's disease, multiple sclerosis, osteoporosis, substance use disorders, inflammatory diseases, COVID-19, and organophosphate poisoning. This article briefly reviews the mechanism of action and research on antidepressants related to (R)-ketamine, fully revealing its application potential and development prospects, and providing some references and assistance for subsequent expanded research.

Circular RNA MTO1 intercorrelates with microRNA-630, both associate with Enneking stage and/or pathological fracture as well as prognosis in osteosarcoma patients.

OBJECTIVE: Circular RNA-mitochondrial tRNA translation optimization 1 (circ-MTO1) not only involves in bioprocess of various cancers, but also regulates osteosarcoma progression by regulating microRNA-630 (miR-630). However, the clinical role of circ-MTO1 and miR-630 in osteosarcoma is still obscure. This study aimed to assess the correlation of circ-MTO1 and miR-630 with disease features and prognosis and to explore their association with each other in osteosarcoma patients. METHODS: Forty-four osteosarcoma patients who received neoadjuvant chemotherapy to surgical resection were analyzed in this retrospective study. Then, circ-MTO1 and miR-630 expressions were evaluated in tumor and adjacent non-tumor specimens by reverse transcription quantitative polymerase chain reaction. RESULTS: Circ-MTO1 was lower in tumor than in non-tumor tissues (p<0.001); meanwhile, its elevated tumor expression was correlated with less advanced Enneking stage (p=0.049), good neoadjuvant chemotherapy response (p=0.029), and longer disease-free survival (DFS) (p=0.047). However, no association was found between circ-MTO1 and overall survival (OS) (p=0.122). Additionally, miR-630 in tumor was higher than in non-tumor tissues (p<0.001), while its raised tumor expression was associated with pathological fracture occurrence (p=0.003), advanced Enneking stage (p=0.036), poor neoadjuvant chemotherapy response (p=0.035), and shorter DFS (p=0.011). However, no association was found between miR-630 and OS (p=0.066). In addition, tumor circ-MTO1 was negatively associated with miR-630 (r=-0.323, p=0.032). CONCLUSION: Circ-MTO1 and miR-630 expressions are inter-correlated and dysregulated in osteosarcoma patients. Besides, they associate with Enneking stage and/or pathological fracture, as well as neoadjuvant treatment response and accumulating DFS in these patients.

Clinical significance of sirtuin 1 level in sepsis: correlation with disease risk, severity, and mortality risk

This study aimed to investigate the value of sirtuin 1 (SIRT1) in differentiating sepsis patients from healthy controls (HCs), and its correlation with inflammation, disease severity, as well as prognosis in sepsis patients. Serum samples were collected from 180 sepsis patients and 180 age- and gender-matched HCs. The SIRT1 level in the serum samples was detected by enzyme-linked immunoassay. The clinical data of the sepsis patients were documented, and their disease severity scores and 28-day mortality rate were assessed. SIRT1 was decreased in sepsis patients compared with HCs, and the receiver operating characteristic curve (ROC) showed that SIRT1 distinguished sepsis patients from HCs (area under the curve (AUC): 0.901; 95% confidence interval (CI): 0.868-0.934). In sepsis patients, SIRT1 negatively correlated with serum creatinine (Scr), white blood cells (WBC), C-reactive protein (CRP), acute physiology, and chronic health evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score, while it positively correlated with albumin. No correlation of SIRT1 with primary infection site or primary organism was observed. Furthermore, SIRT1 was reduced in 28-day non-survivors compared with 28-day survivors, and subsequent ROC showed that SIRT1 predicted 28-day mortality of sepsis patients (AUC: 0.725; 95% CI: 0.651-0.800), and its prognostic value was not inferior to Scr, albumin, WBC, and CRP, but was less than SOFA score and APACHE II score. In conclusion, measurement of serum SIRT1 might assist with the optimization of disease assessment, management strategies, and survival surveillance in sepsis patients.

Clinical significance of sirtuin 1 level in sepsis: correlation with disease risk, severity, and mortality risk.

This study aimed to investigate the value of sirtuin 1 (SIRT1) in differentiating sepsis patients from healthy controls (HCs), and its correlation with inflammation, disease severity, as well as prognosis in sepsis patients. Serum samples were collected from 180 sepsis patients and 180 age- and gender-matched HCs. The SIRT1 level in the serum samples was detected by enzyme-linked immunoassay. The clinical data of the sepsis patients were documented, and their disease severity scores and 28-day mortality rate were assessed. SIRT1 was decreased in sepsis patients compared with HCs, and the receiver operating characteristic curve (ROC) showed that SIRT1 distinguished sepsis patients from HCs (area under the curve (AUC): 0.901; 95% confidence interval (CI): 0.868-0.934). In sepsis patients, SIRT1 negatively correlated with serum creatinine (Scr), white blood cells (WBC), C-reactive protein (CRP), acute physiology, and chronic health evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score, while it positively correlated with albumin. No correlation of SIRT1 with primary infection site or primary organism was observed. Furthermore, SIRT1 was reduced in 28-day non-survivors compared with 28-day survivors, and subsequent ROC showed that SIRT1 predicted 28-day mortality of sepsis patients (AUC: 0.725; 95% CI: 0.651-0.800), and its prognostic value was not inferior to Scr, albumin, WBC, and CRP, but was less than SOFA score and APACHE II score. In conclusion, measurement of serum SIRT1 might assist with the optimization of disease assessment, management strategies, and survival surveillance in sepsis patients.