To the present study aimed to investigate the protective effects of Erlong Zuoci Pills on oxidative stress induced by hydrogen peroxide (H2O2) in House Ear Institute-Organ of Corti 1 (HEI-OC1) and to explore the mechanism by cellular metabolomics. There were 6 groups in the experiment: the control group, model group, three dose groups of ELZC (low, medium, and high), and positive control ascorbic acid group. The oxidative stress injury model was established in the HEI-OC1 by inducing 0.9 mmol/L H2O2 for 12 h. The proliferation of HEI-OC1 cells was observed by CCK-8 assay; the contents and activity of lactate hydrogenase (LDH), reactive oxygen species (ROS), and superoxide dismutase (SOD) in HEI-OC1 cells were detected by corresponding kits. Finally, the endogenous substances of cells were analyzed from the perspective of metabolomics. Compared with the model group, ELZC groups could significantly increase the cell proliferation rate after administration. Moreover, they could also ameliorate the increase of ROS and LDH content and the decrease of antioxidant enzyme SOD caused by H2O2. Metabolomic results revealed significant differences among multiple groups in the scores of partial least squares discriminant analysis. The ELZC group could relocate the model group back to the control group. The metabolic regulation of ELZC on oxidative stress in HEI-OC1 cells mainly affects nucleotide metabolism and amino acid metabolism. In summary, the results indicate that ELZC exhibits protective effects on H2O2-induced oxidative stress in HEI-OC1 cells. Additionally, this protective effect may be produced by increasing the content of amino acids such as uridine and phenylalanine, thereby regulating pathways such as pyrimidine metabolism, phenylalanine metabolism, biosynthesis of phenylalanine, tyrosine, and tryptophan, and histidine metabolism.

Due to its synergistic effects and reduced side effects, combination therapy has become an important strategy for treating complex diseases. In traditional Chinese medicine (TCM), the "monarch, minister, assistant, envoy" compatibilities theory provides a systematic framework for drug compatibility and has guided the formation of a large number of classic formulas. However, due to the complex compositions and diverse mechanisms of action of TCM, it is difficult to comprehensively reveal its potential synergistic patterns using traditional methods. Synergistic prediction based on molecular compatibility theory provides new ideas for identifying combinations of active compounds in TCM. Compared to resource-intensive traditional experimental methods, artificial intelligence possesses the ability to mine synergistic patterns from multi-omics and structural data, providing an efficient means for modeling and optimizing TCM combinations. This paper systematically reviews the application progress of AI in the synergistic prediction of TCM active compounds and explores the challenges and prospects of its application in modeling combination relationships, thereby contributing to the modernization of TCM theory and methodological innovation.
Artificial Intelligence ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Drug Synergism

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

: Bacteroides, as one of the most abundant and diverse genera in the human gut, is regarded as a window into the study of gut microbiota-host interactions. Currently, CRISPR/Cas-based gene editing systems targeting Bacteroides have been widely applied, while the large size of Cas nucleases limits their potential application scenarios (such as in situ gut Bacteroides editing based on phage delivery). Therefore, this study aims to develop a compact and highly efficient genetic editing tool in Bacteroides., We developed a miniaturized CRISPR/Cas gene editing system for human gut Bacteroides. First, the editing capabilities of different miniaturized CRISPR/Cas systems, including AsCas12f, CasΦ2, and ISDge10, were evaluated in Bacteroides fragilis. Subsequently, the editing capability of AsCas12f was assessed across various Bacteroides species, and the size of this system was further optimized. The results demonstrated that the CRISPR/AsCas12f genome editing system exhibited the highest editing efficiency in B. fragilis. The CRISPR/AsCas12f system achieved efficient genome editing in B. fragilis, Bacteroides thetaiotaomicron, and Phocaeicola vulgatus. Furthermore, with a repair template of 500 bp homologous arms, the editing efficiency remained as high as 94.7%. In conclusion, CRISPR/AsCas12f can serve as a chassis tool enzyme for the development of Bacteroides-based miniature gene editors and derivative technologies, laying a foundation for the further development of gene editing technology for Bacteroides.
CRISPR-Cas Systems/genetics* ; Gene Editing/methods* ; Bacteroides/genetics* ; Humans ; Gastrointestinal Microbiome/genetics* ; Bacteroides fragilis/genetics*

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Objective:To investigate whether repeated tirofiban injections can continuously inhibit platelet aggregation in the arterial duct and affect its closure in neonatal canines.Methods:Four 24-month-old pregnant beagles underwent cesarean sections in two batches (two dogs per batch) 1-2 days before the expected delivery date at the Xuzhou Medical University Animal Experiment Center. The first litter of 21 neonates served as the control group (receiving 10 ml/kg normal saline) and were randomly divided into 1-h ( n=7, injected immediately after birth), 4-h ( n=7, injected at 0 h and 2 h after birth), and 12-h subgroups ( n=7, injected at 0 h, 2 h, 4 h, 6 h, 8 h, and 10 h after birth). The second litter of 18 neonates served as the experimental group (receiving 10 ml/kg tirofiban) with identical subgroup assignments ( n=6 per subgroup). Echocardiography was performed at 1 h, 4 h, and 12 h after birth to measure arterial duct inner diameter, maximum shunt velocity, and left atrial diameter/aortic root diameter (LA/Ao) ratio. Plasma platelet-derived growth factor (PDGF) was detected by enzyme-linked immunosorbent assay, while platelet membrane glycoprotein Ⅱb-Ⅲa in the arterial duct was assessed by Western blot and immunohistochemistry. Data were analyzed using t-tests, one-way ANOVA, Chi square tests, or Fisher's exact test. Results:No significant bleeding tendency occurred in either group. Two control neonates (one each in the 4-h and 12-h subgroups) died. In both control and experimental 1-h subgroups, all arterial ducts remained open, with no significant differences in ductal diameter, shunt velocity, or LA/Ao between groups (all P>0.05). In the 4-h subgroups, all experimental neonates had patent ducts arteriosus, while two controls exhibited closure; the experimental group had larger ductal diameters [(1.05±0.05) vs. (0.55±0.44) mm, t=－2.75, P<0.05)] and higher LA/Ao ratios (1.31±0.09 vs. 1.14±0.03, t=－4.90, P<0.05), but lower maximum shunt velocities [(107.06±17.47) vs. (153.74±12.78) cm/s, t=4.54, P=0.002). In the 12-h subgroups, all the controls had closed arterial ducts, while four of six experimental neonates exhibited closure, though the difference in closure rate was not statistically significant (6/6 vs. 4/6, Fisher's exact test, P=0.455). Plasma PDGF and glycoprotein Ⅱb-Ⅲa levels did not differ between two 1-h subgroups (all P>0.05). However, the 4-h and 12-h experimental subgroups showed lower PDGF levels [(373.5±13.1) vs. (880.3±80.2) pg/ml, t=10.81; (356.7±35.0) vs. (1 111.2±125.3) pg/ml, t=9.74; both P<0.05] and reduced glycoprotein Ⅱb-Ⅲa expression (0.32±0.07 vs. 0.80±0.23, t=3.29; 0.42±0.07 vs. 0.92±0.26, t=3.24; both P<0.05) compared to controls. Conclusion:Repeated tirofiban injections sustainably inhibit platelet aggregation in the arterial duct of neonatal canines and delay ductal closure, suggesting that intraductal platelet aggregation may be one factor influencing this process.