OBJECTIVE: Myocardial ischemia/reperfusion injury (MIRI) is an obstacle to the success of cardiac reperfusion therapy. This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway. METHODS: Model mice were subjected to a temporary surgical ligation of the left anterior descending coronary artery, and administered luteolin. The myocardial infarct size, myocardial enzyme levels, and cardiac function were measured. Latent targets and signaling pathways were screened using network pharmacology and molecular docking. Then, proteins related to the p53 signaling pathway, apoptosis and oxidative stress were measured. Hypoxia/reoxygenation (HR)-incubated HL1 cells were used to validate the effects of luteolin in vitro. In addition, a p53 agonist and an inhibitor were used to investigate the mechanism. RESULTS: Luteolin reduced the myocardial infarcted size and myocardial enzymes, and restored cardiac function in MIRI mice. Network pharmacology identified p53 as a hub target. The bioinformatic analyses showed that luteolin had anti-apoptotic and anti-oxidative properties. Additionally, luteolin halted the activation of p53, and prevented both apoptosis and oxidative stress in myocardial tissue in vivo. Furthermore, luteolin inhibited cell apoptosis, JC-1 monomer formation, and reactive oxygen species elevation in HR-incubated HL1 cells in vitro. Finally, the p53 agonist NSC319726 downregulated the protective attributes of luteolin in the MIRI mouse model, and both luteolin and the p53 inhibitor pifithrin-α demonstrated a similar therapeutic effect in the MIRI mice. CONCLUSION Luteolin effectively treats MIRI and may ameliorate myocardial damage by regulating apoptosis and oxidative stress through its targeting of the p53 signaling pathway. Please cite this article as: Zhai P, Ouyang XH, Yang ML, Lin L, Li JY, Li YM, Cheng X, Zhu R, Hu DS. Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway. J Integr Med. 2024; 22(6): 652-664.
Luteolin/pharmacology* ; Animals ; Myocardial Reperfusion Injury/metabolism* ; Oxidative Stress/drug effects* ; Tumor Suppressor Protein p53/genetics* ; Apoptosis/drug effects* ; Mice ; Signal Transduction/drug effects* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Myocardial Infarction/prevention & control* ; Reactive Oxygen Species/metabolism*

Squalene epoxidase (SQLE) is a potential target for the treatment of liver cancer. Bioinformatics analysis indicated that the high expression of SQLE was closely related to the clinical stage and poor prognosis of patients with liver cancer. However, the existing inhibitors against SQLE 195 tyrosine residue (Y195) cannot be used clinically due to severe side effects. In this study, 35 small-molecule compounds targeting SQLE 335 tyrosine residue (Y335) were selected by computer virtual screening. Combined with MTT assay, 3 candidate compounds (19^#, 31^# and 35^#) with significant inhibitory effects on the proliferation of Huh7 cell line were obtained. Further studies showed that these 3 compounds could inhibit the migration of Huh7 cells, reduce the contents of total and free cholesterol, up-regulate the expression of tumor suppressor gene PTEN, and down-regulate the expression of PI3K and AKT proteins. The results showed that the novel inhibitors 19^#, 31^# and 35^# targeting SQLE Y335 could reduce cholesterol content, inhibit the proliferation and migration of Huh7, thus playing an anti-liver cancer role.

Betacoronavirus ; Communication ; Coronavirus Infections ; epidemiology ; prevention & control ; therapy ; Disease Outbreaks ; Humans ; Medical Staff ; Pandemics ; prevention & control ; Patient Care Team ; Personal Protective Equipment ; Pneumonia, Viral ; epidemiology ; prevention & control ; therapy

Animals ; Apoptosis ; Biflavonoids ; pharmacology ; Catechin ; pharmacology ; Grape Seed Extract ; pharmacology ; Kidney ; drug effects ; Male ; Oxidative Stress ; Proanthocyanidins ; pharmacology ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sodium Fluoride ; adverse effects

OBJECTIVETo compare the enhanced recovery program after surgery (ERAS) with conventional perioperative management in patients undergoing radical resection for colorectal cancer.

METHODSThe ERAS protocol included a combination of evidence-based and consensus methodology. A total of 597 consecutive patients undergoing elective colorectal resection were randomized to either the ERAS(n=299) or the control group(n=298). Outcomes related to nutrition and metabolism index, stress index, and recovery index were measured and recorded.

RESULTSDemographics and operative parameters were similar between the two groups(P>0.05). The nutritional status of patients in the ERAS group was improved after surgery compared with that of the control group. On postoperative day (POD) 1, the HOMA-IR in the ERAS group was significantly lower than that in the control group(P<0.01). The cortisol level in the control group was elevated on both POD 1(P<0.01) and POD 5(P<0.01) compared to the preoperative level. However, the cortisol level was not increased until POD 5(P<0.01) in the ERAS group. The levels of TNF-α, IL-1β, IL-6, and IFN-γ were reduced in the ERAS group, indicating less postoperative stress responses compared with the control group. In addition, ERAS group was associated with accelerated recovery of gastrointestinal function. The postoperative length of stay [(5.7±1.6) d vs. (6.6±2.4) d, P<0.01] and expense[(15 998±2655) RMB vs. (17 763±3059) RMB, P<0.01] were reduced in the ERAS group. Twenty-eight patients(9.4%) in the control group and 29(9.7%) in the ERAS group developed complications, while the difference was not statistically significant(P>0.05).

CONCLUSIONERAS protocol alleviates surgical stress response and accelerates postoperative recovery without compromising patient safety.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; surgery ; Female ; Humans ; Male ; Middle Aged ; Perioperative Care ; methods ; Prospective Studies ; Young Adult

OBJECTIVETo describe the prevalence of body overweight and obesity and its changes among Chinese people during 1992-2002, and to provide scientific basis for developing intervention strategies for obesity in China.

METHODSThe data from "1992 China third National Nutrition Survey" (78,704 subjects, 38,323 male and 40,381 female) and from "2002 China National Nutrition and Health Survey" (209,849 subjects, 101,377 male and 108,472 female) were used in this study. The overweight and obesity were defined by using WHO Z-score criteria for children younger than 7 years old, Chinese age-, sex-specific BMI criteria for children aged 7-17 years, and Chinese BMI criteria for adults.

RESULTSThe overall prevalence of overweight and obesity of Chinese people was increased by 38.6% and 80.6%, respectively during the period of 1992-2002. The prevalence of overweight and obesity of Chinese people aged 0-6 years, 7-17 years, 18-44 years, 45-59 years and above 60 years was increased 31.7%, 17.9%, 66.7%, 45.2% and 43.7%, respectively. The increase of the prevalence of overweight and obesity was higher in girls younger than 6 years than their male counterparts, while among other age groups, that were higher in boys than girls. The prevalence of overweight and obesity among people living in rural areas was lower than that of their urban counterparts, while the increment of overweight and obesity prevalence among rural people was greater than that of their urban counterparts. It was estimated that another 70 million overweight and 30 million obese Chinese people emerged in China from 1992 to 2002.

CONCLUSIONThe prevalence of overweight and obesity of Chinese people was increased rapidly in the past decade, which had affected 260 million Chinese people. It would continue to increase in the near future if effective intervention measures have not been taken.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Body Mass Index ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Obesity ; epidemiology ; Overweight ; epidemiology ; Prevalence ; Rural Population ; statistics & numerical data ; Urban Population ; statistics & numerical data ; Young Adult