Latest ArticlesTo explore the mechanism of regulating reactive oxygen species (ROS)/Nod-like receptor family pyrin domain-contain-ning protein 3 (NLRP3) by Tilianin liposomes improved macrophage pyroptosis.
Macrophage pyroptosis model using lipopolysaccharide (LPS) combined with adenosine triphosphate (ATP) was established. They were divided into control group, model group, and experimental group (RAW 264.7 macrophages). The experimental group was treated with 5 μg·mL-1 Tilianin liposomes for 12 hours, while the control group and model group were cultured normally in complete culture medium without medication for 12 hours. Microplate method was used to detect the release of lactate dehydrogenase (LDH). Enzyme linked immunosorbent assay was used to detect the contents of interleukin (IL)-1β and IL-18. Detection of ROS content in cells was done by flow cytometry. Western blotting was used to detect the relative expression levels of NLRP3.
The LDH release levels in the experimental, control and model groups were (568.54±68.04), (556.05±83.31) and (984.41±138.82) U·L-1; the IL-1β contents were (8.99±2.17), (5.51±0.49) and (38.78±3.33) pg·mL-1; the IL-18 contents were (35.95±5.24), (20.95±2.36) and (64.14±9.73) pg·mL-1; the ROS release levels were 4.00±0.48, 0.68±0.50 and 9.58±0.42; the relative expression levels of NLRP3 protein were 2.44±0.46, 1.00±0.10 and 4.76±0.61, respectively. The above indicators in the experimental and control groups were compared with those in the model group, and there were statistically significant differences (all P<0.01).
Tilianin liposomes can reduce endogenous ROS production and improve LPS/ATP induced RAW 264.7 macrophage pyroptosis, which may be related to the regulation of ROS/NLRP3 inflammasome signaling pathway.
Parkinson’s disease (PD), a highly disabling neurodegenerative disorder, poses significant clinical challenges in both prevention and therapeutic intervention. Butylphthalide (NBP), a small-molecule compound derived from celery seeds, has garnered considerable attention due to its remarkable neuroprotective properties. This article systematically reviews recent studies, demonstrating that NBP not only ameliorates motor and non-motor symptoms in PD patients but also slows disease progression through modulation of neuroinflammation and mitochondrial function. By integrating clinical evidence with advances in molecular mechanism research, it provides a scientific foundation for in-depth investigation of NBP-based PD management and development of novel therapeutics.
To study the effects of carbocisteine on airway inflammation and airway remodeling in mice with Mycoplasma pneumoniae pneumonia and its mechanism.
Mice were randomly divided into control group, model group, experimental group, negative transfection group and positive transfection group, with 12 mice in each group. The control group were inoculated with 0.9% NaCl by nasal drip, the other groups were inoculated with Mycoplasma pneumoniae suspension to establish Mycoplasma pneumoniae pneumonia model. After successful modeling, the experimental group was given 10 mg·kg-1 carbocisteine by intragastric administration; the negative transfection group was given 10 mg·kg-1 carbocisteine by gavage + 1.0×109 PFU of adenovirus containing tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) blank control plasmid in the tail vein, the positive transfection group was given 10 mg·kg-1 carbocisteine by intragastrial + 1.0×109 PFU containing sh-TIPE2 plasmid was injected into the tail vein, the control and model groups were given 0.9% NaCl by intragastric administration. Five groups were treated for 2 weeks with once a day. The levels of inflammatory factors in lung tissue were detected by enzyme-linked immunosorbent assay. Airway remodeling index and p38 mitogen activated protein kinase (p38MAPK) /activated protein-1 (AP-1) signaling pathway related protein expression were detected by Western blot.
The levels of tumor necrosis factor-α in control, model, experimental, negative transfection and positive transfection groups were (9.18±1.92), (134.32±24.56), (42.20±8.61), (39.95±7.77) and (74.03±13.59) pg·mL-1; the levels of interleukin-6 were (5.80±1.21), (65.12±11.81), (22.94±4.47), (26.11±5.08) and (42.67±7.97) pg·mL-1; the relative protein expression levels of matrix metallopeptidase 9 were 1.00±0.16, 3.64±0.62, 1.45±0.22, 1.39±0.20 and 2.16±0.38; the relative protein expression levels of tissue inhibitor of metalloproteinases 1 were 1.00±0.14, 0.52±0.11, 0.89±0.16, 0.84±0.15 and 0.65±0.13; the phospho-p38MAPK/p38MAPK ratios were 1.00±0.16, 2.74±0.48, 1.57±0.29, 1.54±0.27 and 2.31±0.36; the relative protein expression levels of cellular proto-oncogene Jun were 1.00±0.14, 2.25±0.38, 1.34±0.21, 1.37±0.22 and 1.98±0.32; the relative protein expression levels of cellular proto-oncogene Fos were 1.00±0.18, 3.07±0.56, 1.86±0.32, 1.91±0.35 and 2.51±0.44, respectively. The above indexes in the model group were compared with the experimental and control groups, the above indexes in the positive transfection group were compared with the negative transfection group, and the differences were statistically significant (all P<0.05).
Carbocisteine inhibits airway inflammation and airway remodeling in mice with Mycoplasma pneumoniae pneumonia by inhibiting the p38MAPK/AP-1 signaling pathway.
To observe the clinical efficacy and safety of evolocumab injection combined with rosuvastatin tablets in the treatment of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).
The AMI patients were randomly divided into control group and treatment group. The control group was given oral rosuvastatin at an initial dose of 10 mg daily, if the level of low-density lipoprotein cholesterol (LDL-C) >1.4 mmol·L-1, the dose was increased to 20 mg daily. On the basis of control group, the treatment group received evolocumab 140 mg, subcutaneous injection of the abdomen, once every 2 weeks. Two groups were treated for 6 months. The clinical efficacy, myocardial injury markers, lipid metabolism parameters, overall incidence of cardiovascular events and safety were compared between two groups.
Treatment group were enrolled 55 cases, 2 cases dropped out, and 53 cases were finally included in the statistical analysis. Control group were enrolled 53 cases, 1 case dropped out, and 52 cases were finally included in the statistical analysis. After treatment, the total effective rates of treatment and control groups were 92.45% (49 cases/53 cases) and 78.85% (41 cases / 52 cases), with statistically significant difference (P<0.05). After treatment, the levels of high-sensitivity cardiac troponin were (2.02±0.61) and (2.78±0.73) ng·L-1, the levels of creatine kinase-MB were (38.90±6.47) and (50.05±6.15) U·L-1, the levels of total cholesterol were (2.27±0.15) and (3.15±0.19) mmol·L-1, the levels of triglycerides were (1.61±0.12) and (1.77±0.17) mmol·L-1, the levels of LDL-C were (1.25±0.15) and (2.08±0.13) mmol·L-1, the overall incidences of cardiovascular events were 5.77% and 16.98%, respectively. The differences of above indexes were statistically significant (all P<0.05). The adverse drug reactions of treatment group were skin rash, elevated creatine kinase and liver injury, while those in the control group were nausea and vomiting, skin rash and liver injury. The total incidences of adverse drug reactions in treatment and control groups were 9.43% and 5.77%, without statistically significant difference (P>0.05).
Evolocumab injection combined with rosuvastatin tablets has a definitive clinical efficacy in the treatment of patients with AMI after PCI, which can significantly improve cardiac function, reduce the risk of myocardial injury and cardiovascular events, with good safety.
To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying 16 bioactive constituents of Gardenia jasminoides Eills in various murine tissues.
The ileum, colon, stomach, liver, kidney and brain tissues of mice were collected following intragastric administration of Gardenia jasminoides Ellis. Subsequently, the samples were processed by precipitating protein. The analysis was performed using the Waters CORTECS C18 column (4.6 mm×150.0 mm, 2.7 μm) with mobile phase gradient elution consisting of a methanol-water solution, and specnuezhenide was used as the internal standard; the flow rate was set at 0.4 mL·min-1 while maintaining a column temperature of 40 ℃; detection was performed in negative ion mode utilizing an electrospray ion source. Furthermore, the method was evaluated for its specificity, standard curve and lower limit of quantification, precision and recovery, stability and reproducibility. Additionally, the tissue distribution characteristics of the active components of Gardenia jasminoides Ellis in mice were investigated.
This study established a method for the analysis of 16 bioactive constituents in Gardenia jasminoides Ellis within complex matrices. The linear range spanned from 0.98 to 6.00×104 ng·mL-1, with a limit of quantitation ranging from 0.92 to 11.72 ng·mL-1, and the RSD values for intra-day and inter-day precision as well as recovery were all below 15%. Amongst the examined tissues, ileum tissue exhibited the highest levels of these active components, followed by gastric tissue. Iridoid components demonstrated extensive distribution across various tissues. The diterpenoid constituent crocetin was predominantly found in the liver and brain, while crocin Ⅱ showed higher distribution in the colon.
The method exhibits high specificity, excellent sensitivity, reproducibility, and stability. Moreover, the matrix effect can be controlled effectively, rendering it suitable for analyzing Gardenia jasminoides Ellis in complex matrices. The intestine is the major tissue for the distribution of Gardenia jasminoides Ellis, which may be an important part for its efficacy. Furthermore, the extensive pharmacological effects of Gardenia jasminoides Ellis may be related to the component tendency to different tissues.
To observe the clinical efficacy and safety of ropivacaine for erector spinae plane block (ESPB) combined with total intravenous anesthesia (TIVA) in patients undergoing colorectal cancer surgery.
Patients with colorectal cancer were randomly divided into treatment and control groups. Before the general anesthesia induction, treatment group received deep injection of 0.375% ropivacaine solution (25 mL) for local anesthesia in the erector spinae plane. Two groups received anesthesia induction with 0.05 mg·kg-1 midazolam + 0.4 μg·kg-1 sufentanil + 1.5 mg·kg-1 propofol + 0.15 mg·kg-1 cisatracurium, and anesthesia maintenance with 3-4 mg·L-1 propofol + 0.5-1.0 μg·kg-1 sufentanil + 0.05-0.10 mg·kg-1 cisatracurium. The sufentanil dosage, hemodynamics, visual analogue scale (VAS) and Ramsay sedation scores, interleukin (IL)-6 and cortisol levels and safety were compared between two groups.
Treatment group were enrolled 57 cases, 5 cases dropped out, and 52 cases were finally included in the statistical analysis. Control group were enrolled 55 cases, 3 cases dropped out, and 52 cases were finally included in the statistical analysis. At extubation, heart rates of treatment and control groups were (89.54±5.41) and (101.98±8.58) beat·min-1, mean arterial pressures were (83.60±7.48) and (93.12±7.35) mmHg, and the differences were statistically significant (all P<0.05). Intraoperative sufentanil dosages of treatment and control groups were (16.35±2.54) and (23.77±3.02) μg, VAS scores at 24 h after operation were (2.98±0.42) and (3.67±0.58) points, IL-6 levels at 24 h after operation were (17.92±2.41) and (28.12±3.81) ng·L-1, cortisol levels at 24 h after operation were (154.88±24.06) and (187.46±27.51) ng·mL-1, respectively; the differences were statistically significant (all P<0.05). Ramsay scores at 1 and 24 h postoperatively showed no statistically significant differences between and within groups (all P>0.05). The adverse drug reactions of treatment group were block site hematoma, nausea and vomiting, while those in control group were nausea and vomiting, hypotension and delirium. The incidences of total adverse drug reactions in the treatment and control groups were 11.54% and 21.15%, without significant difference (P>0.05).
Ropivacaine ESPB combined with TIVA can help the patients undergoing colorectal cancer surgery to maintain stable intraoperative hemodynamics, reduce sufentanil consumption and pain, decrease postoperative inflammatory and stress responses, without increasing the incidence of adverse drug reactions.
To investigate the effects of long non-coding RNA (lncRNA) MAGI1-IT1 on the proliferation, invasion, migration and epithelial mesenchymal transformation (EMT) of breast cancer cells by regulating the miR-485-5p/actin gamma 1 (ACTG1) axis.
HCC1937 cells were cultured in vitro and randomly divided into control, si-MAGI1-IT1, miR-485-5p mimics, negative cotransfection and positive cotransfection groups. Control group was cultured normally without transfection; si-MAGI1-IT1 group was transfected with si-MAGI1-IT1; miR-485-5p mimics group was transfected with miR-485-5p mimics; negative cotransfection group was transfected with si-NC and NC-miR-485-5p; positive cotransfection group was given si-MAGI1-IT1 and miR-485-5p inhibitor combined transfection. Cell proliferation was detected by cell counting kit-8 method, cell migration was detected by cell scratch assay, cell invasion was detected by Transwell assay, and expression levels of lncRNA MAGI1-IT1, miR-485-5p and ACTG1 were detected by real-time fluorescence quantitative polymerase chain reaction method. The expression of proliferation and EMT-related proteins were detected by immunohistochemical staining.
The cell activities (optical density) of the control, si-MAGI1-IT1, miR-485-5p mimics, negative cotransfection and positive cotransfection groups were 0.89±0.12, 0.36±0.05, 0.32±0.03, 0.89±0.10 and 0.85±0.11; the migration rates were (91.82±11.13)%, (38.40±7.64)%, (33.17±6.03)%, (92.43±10.87)% and (86.10±10.76)%; the number of invasions was 296.50±23.48, 93.00±17.36, 76.50±15.01, 302.50±25.32 and 269.00±24.92; the relative expression levels of lncRNA MAGI1-IT1 were 0.98±0.11, 0.29±0.06, 0.96±0.10, 1.00±0.12 and 0.30±0.07; the relative expression levels of miR-485-5p were 0.99±0.13, 2.12±0.16, 2.20±0.18, 0.98±0.15 and 1.04±0.16; the relative expression levels of ACTG1 were 1.01±0.12, 0.34±0.05, 0.31±0.07, 1.02±0.14 and 0.97±0.11; the positive expression levels of proliferating cell nuclear antigen (optical density) were 1.65±0.16, 0.53±0.12, 0.45±0.08, 1.64±0.14 and 1.60±0.17; the positive expression levels of Cyclin D1 (optical density) were 1.53±0.15, 0.46±0.11, 0.40±0.06, 1.52±0.14 and 1.48±0.13; the positive expression levels of Vimentin (optical density) were 1.49±0.14, 0.45±0.07, 0.39±0.06, 1.50±0.12 and 1.45±0.13, respectively. The above indexes in the si-MAGI1-IT1 group were compared with the control group, the above indexes in the miR-485-5p mimics group (except lncRNA MAGI1-IT1) were compared with the control group, the above indexes in the positive cotransfection group (except lncRNA MAGI1-IT1) were compared with the si-MAGI1-IT1 group, the differences were statistically significant (all P<0.05).
Knockdown of lncRNA MAGI1-IT1 can reduce the expression of ACTG1 by up-regulating miR-485-5p, thereby inhibiting the proliferation, migration, invasion and EMT of breast cancer cells.
To investigate the effects of etomidate on the expression of mammalian sirolimus like target protein (mTOR)/silencing information regulatory factor 1 (SIRT1) gene to inhibit the proliferation, invasion and migration of bladder cancer BIU-87 cells.
The BIU-87 cells were divided into normal group, positive control group and experimental -L, -M, -H groups. The normal group was given normal culture; the positive control group was treated with MEM medium containing paclitaxel at a final concentration of 15 mg·mL-1; the experimental -L, -M, -H groups were treated with MEM medium containing etomidate at final concentrations of 112.50, 225.00 and 450.00 mg·L-1, respectively. After 24 hours of intervention, the migration ability of cells was detected using the cell scratching method, the invasion ability of cells was detected using the Transwell method, the levels of glucose and lactate in cells were detected using enzyme-linked immunosorbent assay, and the expression levels of mTOR, SIRT1 and matrix metalloproteinase (MMP) proteins were detected using Western blotting.
The number of invasive cells in the experimental -M, -H groups, positive control group and normal group was 248.56±5.67, 117.37±16.72, 76.54±8.23 and 376.40±53.41; the migration distances were (22.30±2.89), (13.67±5.46), (8.63±2.07) and (38.24±5.24) μm; the glucose levels were (38.97±2.43), (29.75±3.58), (21.52±4.20) and (64.26±7.26) μmol·L-1; the lactate levels were (37.36±3.29), (20.32±5.67), (14.76±2.37) and (51.52±3.10) μmol·L-1; the phosphorylated mTOR/mTOR ratios were 0.26±0.05, 0.20±0.04, 0.15±0.03 and 0.47±0.07; the relative expression levels of SIRT1 protein were 0.23±0.01, 0.18±0.02, 0.09±0.02 and 0.72±0.13; the relative expression levels of MMP-9 protein were 0.19±0.05, 0.14±0.01, 0.10±0.01 and 0.28±0.04, respectively. Compared with positive control group and normal group, the differences of above indexes in experimental -M, -H groups were statistically significant (all P<0.05).
Etomidate can effectively inhibit the proliferation, invasion and migration of BIU-87 cells by suppressing the expression of mTOR/SIRT1.
To explore the effects of essential oil of Ligusticum chuanxiong (LCEO) on primary dysmenorrhea (PD) and preliminarily its mechanism of action.
Forty-eight female non-pregnant KM mice were randomly divided into blank group, model group, positive control group and experimental -L, -M, -H groups. Except for the blank group, the remaining groups were gavaged with estradiol valerate to establish the PD mouse model. Starting from the 7th day, the blank group and the model group were gavaged with equal volumes of distilled water in the morning, the positive control group was administered 120 mg·kg-1 of ibuprofen solution by gastric lavage, while the low, medium, and high dose experimental groups were gavaged with 22, 44 and 88 mg·kg-1 of LCEO, respectively, for 5 consecutive days. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of oxytocin (OT) and prostaglandin F2α (PGF2α) in mice uterine. Using the oxytocin-induced rat isolated uterine contraction model, the study explored the mechanism of LCEO in relaxing uterine smooth muscle through preincubation with different blocking agents (Indomethacin, phentolamine mesylate, propranolol hydrochloride, atropine sulfate, diphenhydramine hydrochloride, ranitidine hydrochloride and nifedipine).
The OT contents in the blank group, model group, positive control group and experimental -L, -M, -H groups were (3.57±0.81), (5.54±0.60), (4.63±0.75), (4.15±0.76), (4.04±1.19) and (3.67±0.66) pg·mg-1; the PGF2α contents were (1.22±0.38), (2.53±0.45), (1.84±0.52), (1.30±0.31), (1.21±0.35) and (0.48±0.15) pg·mg-1, respectively. The above indexes in the model group were compared with the experimental -L, -M, -H and blank, positive control groups, there were statistically significant differences in all comparisons (P<0.01, P<0.05). After preincubation with indomethacin, phentolamine mesylate, and atropine sulfate, the relaxant effect on uterine smooth muscle of LCEO was significantly weakened. After preincubation with propranolol hydrochloride, diphenhydramine hydrochloride, ranitidine hydrochloride and nifedipine, the relaxant effect on uterine smooth muscle of LCEO did not show any significant changes.
LCEO has a significant effect on primary dysmenorrhea, and its mechanism may be related to inhibiting cyclooxygenase and blocking receptors α and M.
To observe the clinical efficacy and safety of omalizumab injection combined with salmeterol ticasone inhalation powder in the treatment of patients with chest tightness variant asthma (CTVA).
Patients with CTVA were randomly divided into treatment group and control group. Patients in the control group were given salmeterol ticasone inhalation powder one puff each time, twice a day. Treatment group was given subcutaneous injection of omalizumab injection on the basis of control group, 150-600 mg per time according to symptoms, once every 4 weeks, continuous treatment for 12 weeks. Clinical efficacy, improvement of symptoms, airway resistance and lung function and safety were compared between the two groups.
A total of 10 cases dropped out during the trial, and 49 cases and 48 cases were included in the final control group and treatment group, respectively. After treatment, the total effective rates of the control group and treatment group were 79.59% (39 cases/49 cases) and 93.75% (45 cases/48 cases), respectively, with statistical significance (P<0.05). After treatment, the daytime cough scores of the control group and the treatment group were (0.51±0.17) and (0.42±0.13) score, the nighttime cough scores were (0.72±0.20) and (0.54±0.18) score, and the chest tightness scores were (0.44±0.12) and (0.37±0.09) score, forced expiratory volume in one second was (2.44±0.33) and (2.60±0.37) L, peak expiratory flow rates were (4.72±0.45) and (4.95±0.39) L·s-1, total airway resistance measured value/predicted values were 126.34±10.77 and 121.94±9.28, central airway resistance measured value/predicted values were 86.47±6.20 and 82.16±7.33, and the differences were statistically significant (all P<0.05). The adverse drug reactions in the treatment group mainly included mild oropharyngeal edema, headache, swelling at the injection site, and epigastric pain, while those in the control group mainly included mild oropharyngeal edema, subjective palpitation, and headache. The total incidences of adverse drug reactions in the treatment group and the control group were 10.42% (5 cases/48 cases) and 8.16% (4 cases/49 cases), respectively. There was no statistically significant difference (P>0.05).
Omalizumab injection combined with salmeterol ticasone inhalation powder is more effective than monotherapy in the treatment of patients with CTVA, without increasing the incidences of adverse drug reactions.