A newly synthesized flavone avoids COMT-catalyzed methylation and mitigates myocardial ischemia/reperfusion injury in H9C2 cells via JNK and P38 pathways.

Objectives: Luteolin is a flavone that provides defense against myocardial ischemia/reperfusion (I/R) injury. However, this compound is subjected to methylation mediated by catechol-O-methyltransferase (COMT), thus influencing its pharmacological effect. To synthesize a new flavone from luteolin that avoids COMT-catalyzed methylation and find out the protective mechanism of LUA in myocardial I/R injury. Materials and Methods: Luteolin and 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) were used to synthesize the new flavone known as LUAAPH-1 (LUA). Then, the myocardial ischemia/reperfusion injury cell model was established using H9c2 cells to detect the effect in myocardial ischemia/reperfusion regulation and to identify the underlying mechanism. Results: Pretreatment with LUA (20 µmol/l) substantially increased cell viability while reducing cell apoptosis rate and caspase-3 expression induced by I/R, and the protective effect of LUA on cell viability was stronger than diosmetin, which is the major methylated metabolite of luteolin. In addition, intracellular reactive oxygen species (ROS) production and calcium accumulation were both inhibited by LUA. Furthermore, we identified that LUA markedly relieved the promotive effects of I/R stimulation upon JNK and p38 phosphorylation. Conclusion: LUT pretreatment conveys significant cardioprotective effects after myocardial I/R injury, and JNK and p38 MAPK signaling pathway may be involved.

Psychosocial adaptation and influencing factors among patients with chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and long-lasting side effect caused by various anticancer agents that damage sensory, motor and autonomic nerves. It can cause maladaptive behaviors, including disease severity, anxiety, depression, sleep disorders, falls, and social impairment. These disorders have physical, psychological and social effects on patients and can seriously influence their quality of life. AIM: To investigate the current situation of psychosocial adaptation to the disease and its influencing factor in patients with CIPN. METHODS: A convenience sampling method was used to select 233 patients with CIPN in our hospital from February to August 2021. In addition, a cross-sectional survey was conducted using a sociodemographic questionnaire, the Self-Report Psychosocial Adjustment to Illness Scale, and the European Organisation for the Research and Treatment of Cancer Quality of Life CIPN20 (QLQ-CIPN20). Factors influencing psychosocial adaptation in patients with CIPN were analyzed by t-test or one-way analysis of variance, correlation analysis, multiple stepwise regression analysis, and structural equation models. RESULTS: The psychosocial adaptation score of patients with CIPN was 52.51 ± 13.18. Multivariate analysis showed that autonomic nerves, tumor stage, motor nerves, education level, availability of caregivers, semi-retirement status, CIPN grade were independent risk factors for patients with CIPN (P < 0.05). Structural equation models showed that QLQ-CIPN20 mediated the relationship between CIPN grade, tumor stage, and psychosocial adaptation. CONCLUSION: Patients with CIPN have poor psychosocial adaptation and are affected by a variety of physiological, psychological, and social factors. Patients' adaptive responses should be assessed, and targeted interventions implemented.

A Newly Synthesized Flavone from Luteolin Escapes from COMT-Catalyzed Methylation and Inhibits Lipopolysaccharide-Induced Inflammation in RAW264.7 Macrophages via JNK, p38 and NF-κB Signaling Pathways.

Luteolin is a common dietary flavone possessing potent anti-inflammatory activities. However, when administrated in vivo, luteolin becomes methylated by catechol-O-methyltransferases (COMT) owing to the catechol ring in the chemical structure, which largely diminishes its anti-inflammatory effect. In this study, we made a modification on luteolin, named LUA, which was generated by the chemical reaction between luteolin and 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). Without a catechol ring in the chemical structure, this new flavone could escape from the COMT-catalyzed methylation, thus affording the potential to exert its functions in the original form when administrated in the organism. Moreover, an LPS-stimulated RAW cell model was applied to detect the anti-inflammatory properties. LUA showed much more superior inhibitory effect on LPS-induced production of NO than diosmetin (a major methylated form of luteolin) and significantly suppressed upregulation of iNOS and COX-2 in macrophages. LUA treatment dramatically reduced LPS-stimulated reactive oxygen species (ROS) and mRNA levels of pro-inflammatory mediators such as IL-1ß, IL-6, IL-8 and IFN-ß. Furthermore, LUA significantly reduced the phosphorylation of JNK and p38 without affecting that of ERK. LUA also inhibited the activation of NF-κB through suppression of p65 phosphorylation and nuclear translocation.

Metabolomic analysis of biochemical changes in the tissue and urine of proteoglycan-induced spondylitis in mice after treatment with moxibustion.

BACKGROUND: Moxibustion is widely used in East Asian countries to manage the symptom of rheumatic diseases. The aim of this study was to identify potential metabolic profiles of moxibustion on relieving ankylosing spondylitis (AS) mice through UHPLC-Q-TOF/MS metabolomic study. METHODS: Thirty-two female Balb/c mice were randomized into healthy control (HC), AS model, moxibustion at acupuncture points (MA) in AS model, and moxibustion at non-acupuncture points (MNA) AS model groups. Moxibustion was administered daily at GV4, bilateral BL23 and bilateral ST36 acupuncture points for four weeks in the MA group. The overall health status, the thickness of hind paws and the tissue concentrations of IL-1ß, PGE2, IL-6 and TNF-α were assessed. The UHPLC-Q-TOF/MS was used to explore the perturbations of endogenous metabolites in tissue and urine of AS model mice intervened by moxibustion. RESULTS: Compared with the AS group, the overall health status was significantly improved after 4-week moxibustion intervention (p < 0.05). The results also showed that MA significantly reduced the levels of paw thickness and decreased the levels of four cytokines in the tissue (p < 0.01). Thirty-seven endogenous metabolites identified by the OPLS-DA were considered to be contributing to therapeutic effects of moxibustion. Moreover, metabolic pathway analysis further revealed that the identified metabolites were mainly involved in TCA cycle, Lipid metabolism, Amino Acid metabolism, Intestinal flora metabolism and Purine metabolism. CONCLUSIONS: UHPLC-Q-TOF/MS based metabolomics approach, as a novel and powerful tool, can help us to gain the insights into potential mechanisms of action of moxibustion for AS.

Effect of Trimetazidine on Diabetic Patients with Coronary Heart Diseases: A Meta-Analysis of Randomized, Controlled Trials.

Objective To explore the therapeutic effects of trimetazidine (TMZ) on diabetic patients with coronary heart diseases.Methods We conducted a comprehensive electronic search of PubMed, EMBASE, and Cochrane databases between the inception dates of databases and May 2019 (last search conducted on 30 May 2019) to identify randomized controlled trials. The evaluation method recommended by Cochrane Collaboration for bias risk assessment was employed for quality assessment. Random or fixed models were used to investigate pooled mean differences in left ventricular function, serum glucose metabolism, serum lipid profile, myocardial ischemia episodes and exercise tolerance with effect size indicated by the 95% confidence interval (CI).Results Additional TMZ treatment contributed to considerable improvement of left ventricular ejection fraction (WMD=4.39, 95%CI: 3.83, 4.95, P<0.00001), left ventricular end diastolic diameter (WMD=-3.17, 95%CI: -4.90, -1.44, P=0.0003) and left ventricular end systolic diameter (WMD=-4.69, 95%CI: -8.66, -0.72, P=0.02). TMZ administration also significantly decreased fasting blood glucose (SMD=-0.43, 95%CI: -0.70, -0.17, P=0.001), glycosylated hemoglobin level (WMD=-0.59, 95%CI: -0.95, -0.24, P=0.001), serum level of total cholesterol (WMD=-20.36, 95%CI: -39.80, -0.92, P=0.04), low-density lipoprotein cholesterol (WMD=-20.12, 95%CI: -32.95, -7.30, P=0.002) and incidence of myocardial ischemia episodes (SMD=-0.84, 95%CI: -1.50, -0.18, P=0.01). However, there were no significant differences in serum triglyceride level, high-density lipoprotein cholesterol, exercise tolerance between the TMZ group and the control group. Conclusion TMZ treatment in diabetic patients with coronary heart disease is effective to improve cardiac function, serum glucose and lipid metabolism and clinical symptoms.

Theory of mind deficits in patients with esophageal cancer combined with depression.

AIM: To characterize the two components of theory of mind (ToM) in patients with esophageal cancer combined with depression. METHODS: Sixty-five patients with esophageal cancer combined with depression (depressed group) and 62 normal controls (control group) were assessed using reading the mind in the eyes test, faux pas task, verbal fluency test, digit span test and WAIS IQ test. The depressed group was divided into two subgroups including psychotic depressed (PD) group (32 cases) and nonpsychotic depressed (NPD) group (33 cases). The clinical symptoms of patients were assessed using Beck depression inventory version II and brief psychiatric reacting scale (BPRS). RESULTS: There was a significant difference between the depressed group and the control group on tasks involving ToM social perceptual components (mind reading: t = 7.39, P < 0.01) and tests involving ToM social cognitive components (faux pas questions: t = 13.75, P < 0.01), respectively. A significant difference was also found among the PD group, the NPD group and the control group on mind reading (F = 32.98, P < 0.01) and faux pas questions (χ² = 78.15, P < 0.01), respectively. The PD group and NPD group performed worse than normal group controls both on mind reading and faux pas questions (P < 0.05). The PD group performed significantly worse than the NPD group on tasks involving ToM (mind reading: F = 18.99, P < 0.01; faux pas questions: F = 36.01, P < 0.01). In the depressed group, there was a negative correlation between ToM performances and BPRS total score (mind reading: r = -0.35, P < 0.01; faux pas questions: r = -0.51, P < 0.01), and between ToM performances and hostile suspiciousness factor score (mind reading: r = -0.75, P < 0.01; faux pas questions: r = -0.73, P < 0.01), respectively. CONCLUSION: The two components of ToM are both impaired in patients with esophageal cancer combined with depression. This indicates that there may be an association between ToM deficits and psychotic symptoms in clinical depression.