Latest ArticlesTo study the effect and mechanism of galangin in improving depression-like behavior in vascular dementia (VD) mice through microRNA-134 (miRNA-134).
Seventy C57BL/6J mice were randomly divided into sham group (0.9% NaCl), model group (0.9% NaCl), low-dose group (25 mg·kg-1 galangin), medium-dose group (50 mg·kg-1 galangin), high-dose group (100 mg·kg-1 galangin), and mimic NC group (100 mg·kg-1 galangin and mimic NC 15 nmol), miRNA-134 mimic group (100 mg·kg-1 galangin and miRNA-134 mimic 15 nmol). The degree of depression was detected by tail suspension test and forced swimming test; the level of corticosterone was detected by enzyme-linked immunosorbent assay; the level of miRNA-134 was detected by quantitative real time polymerase chain reaction; the apoptosis rate of brain tissue cells was detected by TdT-mediated dUTP nick-end labeling; and the level of synaptic plasticity related protein was detected by Western blot.
The suspension time of the sham group, the model group and the high-dose group were (105.32±15.22), (185.32±24.62) and (112.65±15.08) s, respectively; the swimming time were (86.52±13.25), (152.32±22.22) and (96.22±16.35) s respectively; the levels of corticosterone were (32.65±5.02), (86.62±14.32) and (48.52±5.55) ng·L-1, respectively; the levels of miRNA-134 were 1.00±0.12, 2.32±0.35 and 1.21±0.18, respectively. The apoptosis rates of the sham group, model group, high group, mimic NC group and miRNA-134 mimic group were (5.32±0.62)%, (62.33±8.65)%, (14.32±1.78)%, (15.85±2.22)% and (43.21±7.05)%, respectively; synaptophysin protein levels were 1.00±0.18, 0.32±0.05, 0.88±0.12, 0.82±0.11 and 0.30±0.05, respectively; the postsynaptic density protein-95 protein levels were 1.00±0.14, 0.61±0.07, 0.72±0.09, 0.70±0.08 and 0.45±0.06, respectively. The above indexes in the model group were compared with those in the sham group, those in the high-dose group were compared with those in the model group, and those in the miRNA-134 mimic group were compared with those in the mimic NC group, and the differences were statistically significant (all P<0.05).
Galangin may improve the depression-like behavior of VD mice by inhibiting the expression of miRNA-134, improving synaptic plasticity and inhibiting cell apoptosis.
To observe the clinical efficacy and safety of evolocumab injection combined with pitavastatin calcium tablets in the treatment of patients with acute coronary syndrome after percutaneous coronary intervention (PCI).
According to cohort method, the patients with acute coronary syndrome after PCI were divided into control group and treatment group. Two groups were treated with routine treatment (anti-platelet, anti-coagulation, reducing myocardial oxygen consumption, improving myocardial ischemia). On the routine treatment, control group was treated with pitavastatin calcium 2 mg per time, once a day, orally before bedtime. On the basis of control group, treatment group was given evolocumab 140 mg per time, once every 2 weeks, subcutaneous injection. Two groups were treated for 6 months. The clinical efficay, blood lipid, myocardial injury indexes, serum levels of amyloid A1 (SAA1) and Gla-rich protein (GRP), major adverse cardiovascular events (MACEs) and safety were compared between two groups.
Fifty-two patients were enrolled in the treatment group and 58 patients were enrolled in the control group. After treatment, the total effective rates of treatment and control groups were 94.23% (49 cases/52 cases) and 75.86% (44 cases/58 cases), and the difference was statistically significant (P<0.05). After treatment, the total cholesterol levels of treatment and control groups were (1.17±0.22) and (1.35±0.25) mmol·L-1, triglyceride levels were (2.63±0.76) and (3.89±0.92) mmol·L-1, high-density lipoprotein cholesterol levels were (1.41±0.30) and (1.26±0.28) mmol·L-1, low-density lipoprotein cholesterol levels were (1.23±0.46) and (1.58±0.55) mmol·L-1, cardiac troponin I levels were (0.03±0.01) and (0.05±0.02) ng·mL-1, creatine kinase isoenzyme levels were (12.35±2.38) and (14.23±2.89) U·L-1, SAA1 levels were (213.92±41.58) and (274.18±43.36) μg·mL-1, GRP levels were (21.32±3.50) and (19.35±3.27) ng·mL-1, incidences of MACEs were 9.62% and 24.14%, the differences were statistically significant between two groups (all P<0.05). The adverse drug reactions of two groups were fatigue, pruritus, abdominal pain and elevated aminotransferase. There was no significant difference in total incidences of adverse drug reactions between treatment group and control group (11.54% vs 13.79%, P>0.05).
Evolocumab injection combined with pitavastatin calcium tablets has a definitive clinical efficacy in the treatment of patients with acute coronary syndrome after PCI, which can effectively reduce the blood lipid levels, the incidence of MACEs and myocardial injury, regulate the serum levels of SAA1 and GRP, without increasing the incidence of adverse drug reactions.
To investigate the effect and mechanism of ursodeoxycholic acid on bronchial epithelial cell injury induced by toluene diisocyanate (TDI).
BEAS-2B cells were randomly divided into control group (conventional culture), TDI-human serum albumin (HSA) group (120.00 mg·L-1 TDI-HSA), low-dose group (100 μmol·L-1 ursodeoxycholic acid+120.00 mg·L-1 TDI-HSA), high-dose group (200 μmol·L-1 ursodeoxycholic acid+120.00 mg·L-1 TDI-HSA) and rapamycin group (25 nmol·L-1 rapamycin+120.00 mg·L-1 TDI-HSA). The expression of inflammatory factors was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA); the level of reactive oxygen species (ROS) was detected by DCFH-DA; and the protein expression of each cell was detected by Western blot.
The mRNA levels of interleukin (IL)-6 in control group, TDI-HSA group, low-dose group and high-dose group were 1.00±0.13, 2.20±0.24, 1.87±0.12, 1.48±0.14, respectively; IL-8 levels were (22.65±1.96), (81.42±6.35), (56.36±5.88), (38.28±3.25) pg·mL-1, respectively; ROS levels were (100.00±3.47)%, (351.25±22.52)%, (312.80±26.59)%, (242.15±13.60)%, respectively; the protein levels of dynamic associated protein 1 (DRP1) were 0.23±0.03, 0.82±0.08, 0.69±0.10, 0.55±0.05, respectively; benzyl chloride 1 (Beclin1) protein expression levels were 0.23±0.04, 0.60±0.07, 0.44±0.04, 0.37±0.03, respectively; phosphorylated adenylate activates protein kinase (p-AMPK) protein expression levels were 0.20±0.05, 0.49±0.05, 0.40±0.03, 0.34±0.04, respectively. Beclin1 protein expression levels in high-dose group and rapamycin group were 0.35±0.04 and 0.69±0.07, respectively; IL-6 levels were (17.63±1.36) and (29.52±3.49) pg·mL-1, respectively; IL-18 levels were (65.22±5.30) and (95.58±6.80) pg·mL-1, respectively. The above indexes: TDI-HSA group was compared with control group, low- dose group and high- dose group were compared with TDI-HSA group, rapamycin group compared with high dose group, the differences were significant (all P<0.05).
Ursodeoxycholic acid may mediate ROS/AMPK/ autophagy pathway to improve the inflammatory response and mitochondrial dysfunction induced by TDI-HSA.
To investigate the cardioprotective mechanism of Ilexin A in ameliorating hyperlipidemia through the regulation of microRNA-133a-3p (miR-133a-3p) and uncoupling protein 2 (UCP2).
Rats were randomly divided into control group (gavage with an equal volume of distilled water as the experimental group), model group (gavage with an equal volume of distilled water as the experimental group), experimental group (gavage with 40 mg·kg-1 Ilexin A), miR-133a-3p inhibitor group (gavage with 40 mg·kg-1 Ilexin A + tail vein injection of 1.95×1012 vg·mL-1 adenovirus containing miR-133a-3p inhibitor), and OE-UCP2 group (gavage with 40 mg·kg-1 Ilexin A + tail vein injection of 1.95×1012 vg·mL-1 adenovirus containing both miR-133a-3p inhibitor and OE-UCP2). Blood lipid levels, including low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), were measured by enzyme-linked immunosorbent assay. Cardiac function parameters, such as the mitral inflow peak early diastolic velocity to late diastolic velocities (E/A) and left ventricular ejection fraction (LVEF), were assessed via echocardiography. The relative expression levels of mRNA were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR), while protein levels were detected by Western blot.
In the model and experimental groups, LDL-C levels were (0.92±0.12) and (0.76±0.09) mmol·L-1; HDL-C levels were (0.82±0.10) and (1.14±0.13) mmol·L-1; E/A ratios were 0.89±0.11 and 1.17±0.14; LVEF values were (41.31±5.07)% and (59.92±7.86)%; the relative expression levels of miR-133a-3p were 0.33±0.06 and 1.22±0.18; uncoupling protein 2 (UCP2) mRNA levels were 0.57±0.08 and 0.79±0.09; cleaved caspase-3 protein levels were 1.00±0.15 and 0.71±0.09; B-cell lymphoma-2 (Bcl-2) protein levels were 1.00±0.17 and 1.94±0.27, respectively. The differences between the model and experimental groups for these parameters were statistically significant (all P<0.05).
Ilexin A ameliorates hyperlipidemia by regulating miR-133a-3p and UCP2. Its mechanism may involve downregulating Bcl-2 and activating cleaved caspase-3 to induce apoptosis, thereby exerting cardioprotective effects and improving cardiac function.
To investigate the clinical effect of cinacalcet in the treatment of secondary hyperparathyroidism (SHPT) in patients undergoing hemodialysis for chronic kidney disease (CKD).
Patients who underwent hemodialysis for CKD and had SHPT were divided into the control group and the treatment group according to the cohort method. The control group was treated with 0.25 μg of calcitriol capsules once a day via oral administration. On this basis, the treatment group was treated with 25 mg of cinacalcet tablets once a day via oral administration. Patients in both groups were treated for 12 weeks. Clinical efficacy, parathyroid volume, parathyroid function [serum phosphorus, serum calcium, alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH)], and cardiovascular function [creatine kinase-MB (CK-MB), hypersensitive troponin Ⅰ (hs-cTnⅠ) and myoglobin (MYO)]were compared between the two groups. Safety was evaluated.
Sixty-two cases were enrolled in the treatment group and fifty-eight cases in the control group. After treatment, the total effective rates in the treatment group and the control group were 93.55% (58 cases/62 cases) and 77.59% (45 cases/58 cases), with statistically significant difference (P<0.05). After treatment, serum phosphorus levels in the treatment group and the control group were (1.31±0.16) and (1.50±0.34) mmol·L-1; serum calcium levels were (2.63±0.91) and (2.25±0.72) mmol·L-1; ALP levels were (83.28±8.40) and (126.46±12.39) U·L-1; iPTH levels were (215.32±16.69) and (307.65±20.14) pg·mL-1. The differences were statistically significant (all P<0.05). After treatment, the length of the parathyroid gland in the treatment group and the control group were (0.58±0.10) and (0.77±0.19) cm; width were (0.34±0.08) and (0.45±0.16) cm; thickness were (0.25±0.05) and (0.33±0.15) cm; volume were (0.82±0.15) and (1.13±0.22) cm3. The differences were statistically significant (all P<0.05). After treatment, serum CK-MB levels in the treatment group and the control group were (4.18±0.73) and (6.53±1.26) ng·mL-1; hs-cTnⅠ levels were (0.04±0.01) and (0.07±0.03) ng·mL-1; MYO levels were (70.69±9.41) and (112.39±12.60) ng·mL-1. The differences were statistically significant (all P<0.05). The adverse drug reactions in the treatment group and the control group mainly included nausea and vomiting, increased blood pressure, and myalgia. The total incidence of adverse drug reactions in the treatment group and the control group were 8.06 % (5 cases / 62 cases) and 22.41% (13 cases / 58 cases), respectively, and the difference was statistically significant (P<0.05).
Cinacalcet is effective in the treatment of SHPT in patients undergoing hemodialysis for CKD. It can reduce parathyroid gland volume, maintain calcium and phosphorus metabolism, and protect cardiovascular function, with high safety.
To investigate the effects of circCSPP1 mediated autophagy on the proliferation and metastasis ability of gastric cancer cells.
The human gastric cancer cells NCI-N87 were divided into Vector group (transfected with Vector), circCSPP1 group (transfected with circCSPP1) and inhibitor group (transfected with circCSPP1 and incubated with 10 μmol·L-1 chloroquine). The MKN-45 cells were divided into sh-NC group (transfected with circCSPP1 shRNA-NC), sh-circCSPP1 group (transfected with circCSPP1 shRNA) and agonist group (transfected with circCSPP1 shRNA + 1 μmol·L-1 sirolimus). Flow cytometry was used to detect cell apoptosis. Transwell was used to detect cell migration and invasion. Western blot were used to detect the expression levels of microtubule associated protein light chain 3-Ⅱ (LC3-Ⅱ) and p62 protein.
In NCI-N87 cells: the apoptosis rates of Vector, circCSPP1 and inhibitor groups were (7.95±0.66)%, (3.93±0.62)% and (7.37±0.85)%; the number of cell migrations were 122.50±12.25, 169.40±16.09 and 109.00±8.22; the number of cell invasions were 73.38±12.33, 117.30±12.78 and 55.25±8.73; the relative expression levels of LC3-Ⅱ protein were 0.40±0.06, 1.13±0.11 and 0.44±0.08; the relative expression levels of p62 protein were 1.62±0.15, 0.21±0.08 and 1.43±0.16. The differences of above indexes were statistically significant between the circCSPP1 group and the inhibitor and Vector groups (all P<0.05). In MKN-45 cells: the cell apoptosis rates of sh-NC, sh-circCSPP1 and agonist groups were (6.81±0.68)%, (12.02±0.78)% and (5.76±1.21)%; the number of cell migrations were 191.60±21.43, 87.50±10.76 and 155.60±10.36; the number of cell invasions were 150.00±11.55, 61.63±11.39 and 154.50±17.99; the relative expression levels of LC3-Ⅱ protein were 1.08±0.05, 0.13±0.03 and 1.18±0.06; the relative expression levels of p62 protein were 0.15±0.03, 1.29±0.08 and 0.19±0.04. Compared with the sh-circCSPP1 group, the differences of above indicators in the agonist and sh-NC groups were statistically significant (all P<0.05).
circCSPP1 can improve the proliferation and metastasis ability of gastric cancer cells by inducing autophagy.
Liver fibrosis is caused by various chronic injuries and metabolic disorders. Cirrhosis is the end stage of progressive liver fibrosis, which is estimated to affect 1% - 2% of the global population and cause more than 1 million deaths worldwide every year. Activation and maintenance of hepatic stellate cells (HSCs) are the main driving factors in liver fibrosis. At the same time, the process of trans-differentiation of HSCs involves reprogramming of energy metabolism, which is a key metabolic feature necessary to promote cell growth. Current studies found that Sirtuin protein family plays an important role in the progress of liver fibrosis, and further found that in the progress of liver fibrosis, especially after HSCs activation. Energy metabolism reprogramming involves various cells, including liver cells, HSCs, and immune cells. Targeting intracellular metabolism to limit fibrosis progression is currently a research hotspot. This article reviews the regulatory role of the Sirtuin protein family in energy metabolism in HSCs.
To evaluate the in vitro antibacterial activity of cefteram against common clinically isolated bacteria in the past three years.
The clinical isolates were collected and the minimal inhibitory concentration (MICs) were determined by the microdilution method.
A total of 484 pathogenic bacteria over the period 2021-2023 were studied. The results show that cefteram has good antibacterial activity against Streptococcus spp other than penicillin-resistant Streptococcus pneumoniae (MICs of penicillin ≥ 2 mg·L-1), MIC90 value of cefteram was less than or equal 1 mg·L-1, and the susceptibility rate was 100.0%, which was similar to penicillin, slightly better than cefpodoxime, better than cefuroxime, cefixime, cefaclor and cefalexin. Against gram-negative bacteria, cefteram also showed better antibacterial activity, especially against β-lactamase (ESBLs) negative Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Haemophilus influenzae, and Moraxella catarrhalis. The MIC90 value of cefteram was ≤ 2 mg·L-1, and the susceptibility rate was 100.0%. Especially for Hemophilus influenzae, cefteram was better than all comparator agents, were comparable to cefpodoxime, better than cefuroxime, cefaclor and cefalexin. For Peptostreptococcus spp., cefteram was comparable to cefuroxime, better than all compared agents.
Cefteram had a wide and balanced antibacterial against clinical isolatied of gram-negative bacteria, gram-positive bacteria and anaerobic bacteria in China in recent years. Cefteram also showed better antibacterial activity, especially against penicillin intermediate and ampicillin-resistant Hemophilus influenzae, and is a good variety among oral cephalosporins.
To observe the clinical efficacy and safety of recombinant epidermal growth factor (rhEGF) gel combined with gelatin sponge application under ear endoscopy in the treatment of traumatic tympanic membrane perforations.
Patients with traumatic tympanic membrane perforations were divided into control group and treatment group using cohort method. The control group received intravenous infusion of clindamycin phosphate injection (0.9 g, once daily). The treatment group received rhEGF gel (1 drop per dose, twice daily) combined with gelatin sponge application under ear endoscopy. Both groups received treatment for 1 week. The clinical efficacy, inflammatory markers [white blood cell count (WBC), C-reactive protein (CRP)], hearing status, and safety were compared between the two groups.
A total of 37 patients in the control group and 43 patients in the treatment group were enrolled. The overall treatment efficacy in the treatment and control groups were 95.35% (41 cases /43 cases) and 78.38% (29 cases/37 cases), respectively, with statistically significant difference (P<0.05). After treatment, the WBC levels in the treatment and control groups were (7.74±1.47) and (10.68±1.64) × 10·L-1, respectively; the CRP levels were (3.37±0.97) and (6.35±1.01) pg·mL-1, respectively; the air conduction hearing thresholds were (25.64±2.13) and (29.68±2.24) dB HL, respectively; and the air-bone conduction gap were (6.54±1.24) and (12.36±2.47) dB, respectively. The treatment group showed statistically significant differences in all these indicators compared to the control group (all P<0.05). The adverse drug reactions in the treatment group, the main adverse drug reaction was infection, while in the control group mainly included infection and re-perforation. The incidence of adverse drug reactions in the treatment and control groups were 4.65% (2 cases /43 cases) and 10.81% (4 cases /37 cases), respectively, with no significant difference (P>0.05).
The clinical efficacy of treating patients with traumatic tympanic membrane perforation by combining rhEGF gel with absorbable gelatin sponge patch is better than that of conservative treatment. It has a low incidence of adverse drug reactions and high safety.
To study the pharmacokinetic profile of oseltamivir phosphate dry syrup in Chinese healthy subjects and to evaluate the bioequivalence and safety of the test formulation (T) and the reference formulation (R) under fasting and fed conditions.
In a randomized, open, two-agent, two-sequence, two-cycle, double-crossover trial design, 36 healthy subjects were enrolled in the fasting and fed groups, respectively, who received a single oral dose of 2.5 g of oseltamivir phosphate dry syrup of either the T or R. The blood concentrations of oseltamivir were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the pharmacokinetic parameters were calculated by using the WinNonlin (8.2) software and evaluated for bioequivalence and safety.
Under fasting conditions, the Cmax of oseltamivir of the T and R were (64.40±17.50) and (64.10±20.90) ng·mL-1, AUC0-t were (142.76±43.64) and (151.60±35.10) h·ng·mL-1, AUC0-∞ were (147.67±37.60) and (153.05±35.30) h·ng·mL-1, respectively. Under fed conditions, the Cmax of oseltamivir of the T and R were (47.70±18.30) and (46.90±17.20) ng·mL-1, AUC0-t were (170.52±26.28) and (168.70±24.51) h·ng·mL-1, AUC0-∞ were (173.08±26.50) and (171.30±24.59) h·ng·mL-1, respectively. The 90% confidence intervals for the geometric mean ratios of Cmax, AUC0-t and AUC0-∞ for the T and R fell in the range of 80.00% to 125.00% for both the fasting and fed groups. Adverse drug reaction rates were 27.78% and 44.44% in the fasting and fed groups, respectively.
Two kinds of oseltamivir phosphate dry syrups were bioequivalent and had favorable safety profiles in Chinese healthy subjects in both fasted and fed states.