Probing the interaction of hesperidin showing antiproliferative activity in colorectal cancer cells and human hemoglobin.

Hesperidin, a flavanone glycoside abundant in citrus is known to possess anti-carcinogenic properties. However, its main interaction with cancer cells and blood proteins is not well-studied yet. Here we have explored the interactions of hesperidin with human colorectal cancer cells, HCT116, and human hemoglobin (HHb) with several experimental and theoretical studies. Cellular assays showed that hesperidin interacted with colorectal cancer cells and induced membrane damage, colony formation inhibition, oxidative stress, mitochondrial dysfunction, Bax/Bcl-2, caspase-9, and caspase-3 upregulation, and cytochrome c release determined by cellular, qPCR and ELISA assays. The interaction of the hesperidin with HHb indicated the formation of a static complex mainly with the assistance of hydrogen bonds which lead to partial folding of protein determined by spectroscopy, molecular docking, and molecular dynamic studies. In conclusion, these findings show that hesperidin with potential biding affinity with plasma protein model and slight induced conformational changes can also show promising anticancer activities against colorectal cancer cells.

Plasma Proteome, Metabolome Mendelian Randomization Identifies Sepsis Therapeutic Targets.

BACKGROUND: The interrelation between the plasma proteome and plasma metabolome with sepsis presents a multifaceted dynamic that necessitates further research to elucidate the underlying causal mechanisms. METHODS: Our investigation used public genome-wide association study (GWAS) data to explore the relationships among the plasma proteome, metabolome, and sepsis, considering different sepsis subgroup. Initially, two-sample MR established causal connections between the plasma proteome and metabolome with sepsis. Subsequently, multivariate and iterative MR analyses were performed to understand the complex interactions in plasma during sepsis. The validity of these findings was supported by thorough sensitivity analyses. RESULT: The study identified 25 plasma proteins that enhance risk and 34 that act as protective agents in sepsis. Post p-value adjustment (0.05/1306), ICAM5 emerged with a positive correlation to sepsis susceptibility (p-value = 2.14E-05, OR = 1.10, 95% CI = 1.05-1.15), with this significance preserved across three sepsis subgroup examined. Additionally, 29 plasma metabolites were recognized as risk factors, and 15 as protective factors for sepsis outcomes. Following p-value adjustment (0.05/997), elevated levels of 1,2,3-benzenetriol sulfate (2) was significantly associated with increased sepsis risk (p-value = 3.37E-05, OR = 1.18, 95% CI = 1.09-1.28). Further scrutiny revealed that this plasma metabolite notably augments the abundance of ICAM5 protein (p-value = 3.52E-04, OR = 1.11, 95% CI = 1.04-1.17), devoid of any detected heterogeneity, pleiotropy, or reverse causality. Mediated MR revealed ICAM5 mediated 11.9% of 1,2,3-benzenetriol sulfate (2)'s total effect on sepsis progression. CONCLUSION: This study details the causal link between the plasma proteome and metabolome with sepsis, highlighting the roles of ICAM5 and 1,2,3-benzenetriol sulfate (2) in sepsis progression, both independently and through crosstalk.

Clinical Application of Different Doses of Hydromorphone Slow-Release Analgesia in Lumbar Fusion in Elderly Patients.

INTRODUCTION: The aim of this study is to examine the analgesic efficacy of varying doses of hydromorphone hydrochloride in conjunction with absorbable gelatin sponge for postoperative pain management in elderly individuals undergoing lumbar fusion surgery. Additionally, the study aims to assess the sustained release analgesic properties of this combination and to determine the optimal dosage of hydromorphone hydrochloride for effective pain relief. METHODS: A total of 113 elderly patients (aged ≥ 65 years old) meeting the criteria for 1-2-level posterior lumbar fusion surgery at Ganzhou City People's Hospital between July 2022 and August 2023 were randomly assigned to four groups: group A (0.2 mg hydromorphone hydrochloride 1 ml), group B (0.3 mg hydromorphone hydrochloride 1.5 ml), group C (0.4 mg hydromorphone hydrochloride 2 ml), and group D (0.9% normal saline 2 ml) for standard anesthesia induction and maintenance. Prior to suturing the incision, gelfoam was utilized to administer epidural analgesia to each group. Following the surgical procedure, an intravenous analgesia pump was utilized for pain management. The baseline infusion rate was set at 0.5 ml/h. Patient-controlled analgesia (PCA) was administered at a dose of 2 ml, with a lockout interval of 20 min, allowing the patient to self-administer as needed. Pain relief was assessed using the visual analogue scale (VAS) prior to surgery, as well as at 1 day and 3 days post-operation. The frequency of PCA requests within the initial 48-h postoperative period, the remedial analgesia with dezocine, postoperative adverse reactions, and duration of hospitalization were documented for analysis. RESULTS: The VAS scores of groups B and C were found to be significantly lower than those of group D 1 day after the operation. Additionally, VAS scores at 3 days post-operation, remedial rate of dezocine and PCA follow-up times at 48 h in groups A, B, and C were significantly lower compared to group D (P < 0.001). There was no statistically significant difference between group B and group C in VAS scores at 1 day and 3 days post-operation, as well as PCA follow-up times at 48 h post-operation (P < 0.001). Furthermore, the VAS scores of groups B and C were lower than those of group A at 1 day and 3 days post-operation (P < 0.05). The PCA frequency of group C was also lower than that of group A at 48 h post-operation (P < 0.05). CONCLUSION: The combination of hydromorphone hydrochloride and absorbable gelatin sponge epidural analgesia has been shown to enhance postoperative pain management. A dosage of 0.4 mg of hydromorphone hydrochloride may be considered an appropriate analgesic dose, as it can provide effective pain relief without eliciting adverse reactions. TRIAL REGISTRATION: ChiCTR.org.cn(ChiCTR2200064863). Registered on October 20, 2022.

Targeting NF-κB in Hepatic Ischemia-Reperfusion Alleviation: from Signaling Networks to Therapeutic Targeting.

Hepatic ischemia-reperfusion injury (HIRI) is a major complication of liver trauma, resection, and transplantation that can lead to liver dysfunction and failure. Scholars have proposed a variety of liver protection methods aimed at reducing ischemia-reperfusion damage, but there is still a lack of effective treatment methods, which urgently needs to find new effective treatment methods for patients. Many studies have reported that signaling pathway plays a key role in HIRI pathological process and liver function recovery mechanism, among which nuclear transfer factor-κB (NF-κB) signaling pathway is one of the signal transduction closely related to disease. NF-κB pathway is closely related to HIRI pathologic process, and inhibition of this pathway can delay oxidative stress, inflammatory response, cell death, and mitochondrial dysfunction. In addition, NF-κB can also interact with PI3K/Akt, MAPK, and Nrf2 signaling pathways to participate in HIRI regulation. Based on the role of NF-κB pathway in HIRI, it may be a potential target pathway for HIRI. This review emphasizes the role of inhibiting the NF-κB signaling pathway in oxidative stress, inflammatory response, cell death, and mitochondrial dysfunction in HIRI, as well as the effects of related drugs or inhibitors targeting NF-κB on HIRI. The objective of this review is to elucidate the role and mechanism of NF-κB pathway in HIRI, emphasize the important role of NF-κB pathway in the prevention and treatment of HIRI, and provide a theoretical basis for the target NF-κB pathway as a therapy for HIRI.

The role of PI3K/AKT signaling pathway in myocardial ischemia-reperfusion injury.

Myocardial ischemia has a high incidence and mortality rate, and reperfusion is currently the standard intervention. However, reperfusion may lead to further myocardial damage, known as myocardial ischemia/reperfusion injury (MIRI). There are currently no effective clinical treatments for MIRI. The PI3K/Akt signaling pathway is involved in cardiovascular health and disease and plays an important role in reducing myocardial infarct size and restoring cardiac function after MIRI. Activation of the PI3K/Akt pathway provides myocardial protection through synergistic upregulation of antioxidant, anti-inflammatory, and autophagy activities and inhibition of mitochondrial dysfunction and cardiomyocyte apoptosis. Many studies have shown that PI3K/Akt has a significant protective effect against MIRI. Here, we reviewed the molecular regulation of PI3K/Akt in MIRI and summarized the molecular mechanism by which PI3K/Akt affects MIRI, the effects of ischemic preconditioning and ischemic postconditioning, and the role of related drugs or activators targeting PI3K/Akt in MIRI, providing novel insights for the formulation of myocardial protection strategies. This review provides evidence of the role of PI3K/Akt activation in MIRI and supports its use as a therapeutic target.

Effects of perioperative dextrose infusion on preventing postoperative nausea and vomiting in patients undergoing laparoscopic surgery: a meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this study was to systematically examine the literature and assess the effects of perioperative dextrose infusion on the prevention of postoperative nausea and vomiting (PONV) in patients following laparoscopic surgery under general anesthesia. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Studies were eligible for inclusion if they evaluated the prevention of PONV with perioperative intravenous dextrose. Studies listed in PUBMED, Web of Science, and EMBASE databases published up to December 2020 were identified. Data were extracted and analyzed independently using a fixed-effects or random-effects model according to the heterogeneity. RESULTS: Six RCTs involving 526 patients were included. Our results showed that perioperative dextrose infusion not only reduced the incidence of PONV (risk ratio [RR] = 0.61, 95% confidence interval [CI]: 0.39-0.95; I2 = 59%) but also decreased the requirement for antiemetics compared with the control (RR = 0.53, 95% CI: 0.42-0.66; I2 = 32%). Furthermore, perioperative glucose infusion did not increase blood glucose levels compared with the control (mean difference [95% CI] = 74.55 [-20.64 to 169.73] mg/dL; I2 = 100%). CONCLUSION: Our study reveals that perioperative dextrose infusion may reduce the risk of PONV after laparoscopic surgery. However, additional population-based RCTs are needed to confirm this finding.

Comparison of Percutaneous Nephrolithotomy Under Regional versus General Anesthesia: A Meta-Analysis of Randomized Controlled Trials.

The aim of the present meta-analysis was to systematically examine the literature and to identify of the results of randomized controlled trials (RCTs) comparing the efficacy and safety of regional anesthesia (RA) versus general anesthesia (GA) for percutaneous nephrolithotomy (PCNL). An exhaustive electronic literature search of PubMed, Embase, and Web of science was performed until March 2018. Nine prospective RCTs concluding 858 patients comparing the use of RA to GA for PCNL were included. Combined results demonstrated that PCNL under RA could reduce operative time (mean difference [MD] -6.20; 95% CI -10.39 to -2.01), hospital stay (MD -0.59; 95% CI -0.74 to -0.45), visual analgesic score on the first and third postoperative day (MD -2.62, 95% CI -3.04 to -2.19 and MD -0.38; 95% CI -0.58 to -0.18) , analgesic requirements (MD -36.84; 95% CI -55.23 to -18.45), and nausea and/or vomiting (relative risk [RR] 0.28; 95% CI 0.13-0.61). There were no significant differences between RA and GA groups in terms of stone-free rate, blood transfusion, and postoperative fever rate. The results of subgroup analysis were basically consistent with the overall findings. Current evidence suggests that RA is an available and safe option in carefully evaluated and selected patients.