1.Pharmacotherapy in patients with heart failure with reduced ejection fraction: A systematic review and meta-analysis.
Jia TANG ; Ping WANG ; Chenxi LIU ; Jia PENG ; Yubo LIU ; Qilin MA
Chinese Medical Journal 2025;138(8):925-933
BACKGROUND:
Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated.
METHODS:
PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI).
RESULTS:
We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI + BB + MRA + SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI + BB + MRA + SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI + BB + MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle ACEI + BB + MRA in improving LVEF. ACEI + BB + MRA + SGLT-2i was better than ACEI + BB + MRA (-8.05 mL/m 2 , 95% CI: -14.88 to -1.23 mL/m 2 ) and ACEI + BB + SGLT-2i (-18.94 mL/m 2 , 95% CI: -36.97 to -0.61 mL/m 2 ) in improving LVEDVI. ACEI + BB + MRA + SGLT-2i (-3254.21 pg/mL, 95% CI: -6242.19 to -560.47 pg/mL) was superior to ARB + BB + MRA in reducing NT-proBNP.
CONCLUSIONS:
Adding SGLT-2i to ARNI/ACEI + BB + MRA is beneficial for reversing cardiac remodeling. The new quadruple drug "ARNI + BB + MRA + SGLT-2i" is superior to the golden triangle "ACEI + BB + MRA" in improving LVEF.
REGISTRATION
PROSPERO; No. CRD42022354792.
Humans
;
Heart Failure/physiopathology*
;
Stroke Volume/physiology*
;
Angiotensin Receptor Antagonists/therapeutic use*
;
Angiotensin-Converting Enzyme Inhibitors/therapeutic use*
;
Sodium-Glucose Transporter 2 Inhibitors/therapeutic use*
;
Randomized Controlled Trials as Topic
;
Mineralocorticoid Receptor Antagonists/therapeutic use*
;
Adrenergic beta-Antagonists/therapeutic use*
2.Comparison of glucose fluctuation between metformin combined with acarbose or sitagliptin in Chinese patients with type 2 diabetes: A multicenter, randomized, active-controlled, open-label, parallel design clinical trial.
Xiaoling CAI ; Suiyuan HU ; Chu LIN ; Jing WU ; Junfen WANG ; Zhufeng WANG ; Xiaomei ZHANG ; Xirui WANG ; Fengmei XU ; Ling CHEN ; Wenjia YANG ; Lin NIE ; Linong JI
Chinese Medical Journal 2025;138(9):1116-1125
BACKGROUND:
Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM).
METHODS:
This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data.
RESULTS:
A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV.
CONCLUSIONS:
Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia.
TRIAL REGISTRATION
Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans
;
Metformin/therapeutic use*
;
Sitagliptin Phosphate/therapeutic use*
;
Acarbose/therapeutic use*
;
Diabetes Mellitus, Type 2/blood*
;
Middle Aged
;
Male
;
Female
;
Adult
;
Blood Glucose/drug effects*
;
Hypoglycemic Agents/therapeutic use*
;
Aged
;
Glycated Hemoglobin/metabolism*
;
Adolescent
;
Young Adult
;
China
;
East Asian People
3.Systematic review and Meta-analysis of efficacy and safety of Wumei Pills in treatment of type 2 diabetes mellitus.
Wei-Jin HUANG ; Yun-Yi YANG ; Jia-Yuan CAI ; Xiao-Xiao QU ; Yan-Ming HE ; Hong-Jie YANG
China Journal of Chinese Materia Medica 2025;50(12):3441-3451
Wumei Pills, a classic traditional Chinese medicine(TCM) formula, are widely used in the treatment of biliary ascariasis and diarrhea. In recent years, studies have shown that Wumei Pills have advantages in the treatment of type 2 diabetes mellitus(T2DM), while there are no relevant reports that systematically evaluate the efficacy of Wumei Pills in the treatment of T2DM. This study addresses this issue by systematically evaluating the efficacy and safety of Wumei Pills, aiming to provide an evidence-based basis for clinical practice. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, and VIP were researched for the randomized controlled trial(RCT) involving Wumei Pills for the treatment of T2DM that were published from inception to September 2024. RevMan 5.3 was used for the Meta-analysis of the data. A total of 18 RCTs were included, with a total of 1 437 patients. Meta-analysis produced the following results.(1)Treatment group outperformed control group in terms of overall response rate(RR=1.28, 95%CI[1.14, 1.43], P<0.000 1), fasting blood glucose(FPG)(WMD=-0.69, 95%CI[-0.93,-0.46], P<0.000 01), two-hour postprandial plasma glucose(2hPG)(WMD=-0.74, 95%CI[-1.17,-0.31], P<0.000 7), glycated hemoglobin(HbA1c)(WMD=-0.39, 95%CI[-0.60,-0.18], P=0.000 3), high-density lipoprotein(HDL)(WMD=0.38, 95%CI[0.28, 0.48], P<0.000 01), and body mass index(BMI)(WMD=-1.41, 95%CI[-2.40,-0.42], P=0.005).(2)The two groups had comparable effects regarding total cholesterol(TC)(WMD=-0.53, 95%CI[-1.13, 0.08], P=0.09) and low-density lipoprotein(LDL)(WMD=-0.25, 95%CI[-0.56, 0.06], P=0.12).(3)Triglycerides(TG)(WMD=-0.28,95%CI [-0.59,0.03],P=0.08), sensitivity analysis showed potential reduction effect(WMD=-0.20,95%CI[-0.36,-0.04],P=0.01). Occurrence of adverse drug reaction(RR=0.43,95%CI [0.23,0.80],P=0.007), sensitivity analysis showed significant disappearance(RR=0.56,95%CI[0.26,1.22],P=0.14), suggesting that the efficacy of treatment group was not better than that of control group. The results indicate that the treatment of T2DM with Wumei Pills is greatly related to the improvement of glucose metabolism, lipid metabolism, and clinical efficacy. The findings provide a basis for clinical application of Wumei Pills in treating T2DM, while the conclusion remains to be verified by clinical studies with higher quality.
Humans
;
Diabetes Mellitus, Type 2/blood*
;
Drugs, Chinese Herbal/administration & dosage*
;
Randomized Controlled Trials as Topic
;
Blood Glucose/metabolism*
;
Hypoglycemic Agents/therapeutic use*
;
Treatment Outcome
;
Glycated Hemoglobin/metabolism*
;
Female
4.Qishen Granules Modulate Metabolism Flexibility Against Myocardial Infarction via HIF-1 α-Dependent Mechanisms in Rats.
Xiao-Qian SUN ; Xuan LI ; Yan-Qin LI ; Xiang-Yu LU ; Xiang-Ning LIU ; Ling-Wen CUI ; Gang WANG ; Man ZHANG ; Chun LI ; Wei WANG
Chinese journal of integrative medicine 2025;31(3):215-227
OBJECTIVE:
To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation.
METHODS:
In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions.
RESULTS:
QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism.
CONCLUSIONS
QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals
;
Myocardial Infarction/physiopathology*
;
Male
;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
;
Rats, Sprague-Dawley
;
Glucose/metabolism*
;
Drugs, Chinese Herbal/therapeutic use*
;
Energy Metabolism/drug effects*
;
Rats
;
Fatty Acids/metabolism*
;
Myocardium/pathology*
5.Hesperidin Suppressed Colorectal Cancer through Inhibition of Glycolysis.
Ke-Xiang SUN ; Wei-Shan TAN ; Hao-Yue WANG ; Jia-Min GAO ; Shu-Yun WANG ; Man-Li XIE ; Wan-Li DENG
Chinese journal of integrative medicine 2025;31(6):529-540
OBJECTIVE:
To explore the role of the natural compound hesperidin in glycolysis, the key ratelimiting enzyme, in colorectal cancer (CRC) cell lines.
METHODS:
In vitro, HCT116 and SW620 were treated with different doses of hesperidin (0-500 µmol/L), cell counting kit-8 and colone formation assays were utilized to detected inhibition effect of hesperidin on CRC cell lines. Transwell and wound healing assays were performed to detect the ability of hesperidin (0, 25, 50 and 75 µmol/L) to migrate CRC cells. To confirm the apoptotic-inducing effect of hesperidin, apoptosis and cycle assays were employed. Western blot, glucose uptake, and lactate production determination measurements were applied to determine inhibitory effects of hesperidin (0, 25 and 50 µmol/L) on glycolysis. In vivo, according to the random number table method, nude mice with successful tumor loading were randomly divided into vehicle, low-dose hesperidin (20 mg/kg) and high-dose hesperidin (60 mg/kg) groups, with 6 mice in each group. The body weights and tumor volumes of mice were recorded during 4-week treatment. The expression of key glycolysis rate-limiting enzymes was determined using Western blot, and glucose uptake and lactate production were assessed. Finally, protein interactions were probed with DirectDIA Quantitative Proteomics, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.
RESULTS:
Hesperidin could inhibit CRC cell line growth (P<0.05 or P<0.01). Moreover, hesperidin presented an inhibitory effect on the migrating abilities of CRC cells. Hesperidin also promoted apoptosis and cell cycle alterations (P<0.05). The immunoblotting results manifested that hesperidin decreased the levels of hexokinase 2, glucose transporter protein 1 (GLUT1), GLUT3, L-lactate dehydrogenase A, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), PFKFB3, and pyruvate kinase isozymes M2 (P<0.01). It remarkably suppressed tumor xenograft growth in nude mice. GO and KEGG analyses showed that hesperidin treatment altered metabolic function.
CONCLUSION
Hesperidin inhibits glycolysis and is a potential therapeutic choice for CRC treatment.
Hesperidin/therapeutic use*
;
Colorectal Neoplasms/metabolism*
;
Glycolysis/drug effects*
;
Animals
;
Humans
;
Apoptosis/drug effects*
;
Mice, Nude
;
Cell Movement/drug effects*
;
Cell Line, Tumor
;
Cell Proliferation/drug effects*
;
Glucose/metabolism*
;
Cell Cycle/drug effects*
;
Mice, Inbred BALB C
;
Mice
;
HCT116 Cells
;
Lactic Acid
6.Role of acitretin in regulating glucose and lipid homeostasis in an imiquimod-induced psoriasis model mouse.
Kexin LONG ; Wangqing CHEN ; Manyun MAO ; Wu ZHU
Journal of Central South University(Medical Sciences) 2025;50(3):344-357
OBJECTIVES:
Psoriasis is a chronic inflammatory skin disease often accompanied by comorbidities such as hyperglycemia, insulin resistance, and obesity. Acitretin, as a second-generation retinoid, is used in the treatment of psoriasis. This study aims to explore the role of acitretin on glucose and lipid metabolism in psoriasis.
METHODS:
HepG2 cells were treated with acitretin under high- or low-glucose conditions. mRNA and protein expression levels of glucose transport-related genes were evaluated using real-time reverse transcription PCR (real-time RT-PCR) and Western blotting. Glucose uptake was analyzed by flow cytometry, and intracellular lipid droplet formation was assessed via Oil Red O staining. Healthy adult female BALB/C mice were randomly divided into 3 groups: a control group, an imiquimod (IMQ)-induced psoriasis model group (IMQ group), and an acitretin treatment group. Skin lesions and inflammatory markers were examined, along with changes in body weight, plasma glucose/lipid levels, and transcription of metabolic genes. Islets were isolated from normal and psoriasis-induced mice, and the effect of acitretin on insulin secretion was evaluated in vitro.
RESULTS:
Acitretin treatment increased glucose uptake and lipid droplet synthesis of HepG2 in high-glucose environment, with elevated transcription levels of glucose transport-related genes GLUT1 and GLUT4. Transcription of gluconeogenesis-related gene G6pase decreased, while transcription levels of glycogen synthesis-related genes AKT1 and GSY2 increased (all P<0.05), while acitretin inhibits glucose uptake and promotes gluconeogenesis in low-glucose environment. In vivo experiments revealed that compared with the control group, the blood glucose level in the IMQ group was significantly decreased (P<0.05), while acitretin treatment partially restored glucose homeostasis and alleviated weight loss. Ex vivo culture of islets from psoriatic mice revealed that acitretin reduced elevated insulin secretion and downregulated PDX-1 expression, while upregulating glucose homeostasis gene SIRT1 and insulin sensitivity gene PPARγ (all P<0.05). These findings suggest that acitretin plays a critical role in improving islet function and restoring islet homeostasis.
CONCLUSIONS
Acitretin helps maintain the balance between hepatic glycogenesis and gluconeogenesis, enhances insulin sensitivity, and improves pancreatic islet function, thereby promoting systemic and cellular glucose homeostasis.
Acitretin/therapeutic use*
;
Psoriasis/drug therapy*
;
Animals
;
Imiquimod
;
Humans
;
Glucose/metabolism*
;
Homeostasis/drug effects*
;
Mice
;
Lipid Metabolism/drug effects*
;
Mice, Inbred BALB C
;
Female
;
Hep G2 Cells
;
Disease Models, Animal
7.Impact of PCSK9 Inhibitor Recaticimab on Hyperlipidemia and Plasma Glucose: A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Study.
Ye HU ; Chen CHEN ; Xiao Hui HE ; Shu Yu ZHANG ; Xu Hong WANG
Biomedical and Environmental Sciences 2025;38(10):1246-1254
OBJECTIVE:
Recaticimab (SHR-1209) significantly reduces low-density lipoprotein cholesterol levels. However, its effect on glucose metabolism remains unclear. This study aimed to evaluate its effect on glycemic parameters in a Chinese population.
METHODS:
Recaticimab versus placebo was administered in a 5:1 ratio to 110 hyperlipidemia patients who were followed up for 24 weeks. Glycated hemoglobin (HbA1c) levels were measured at baseline every 12 weeks. Fasting plasma glucose (FPG) levels were measured at baseline at week 1, 3, 5, 8, 12, 16, 20, and 24. Repeated-measures mixed-effects models were used to determine the longitudinal association between reacticimab and FPG and HbA1c levels.
RESULTS:
Among the 81 participants with normal glucose metabolism, HbA1c levels significantly decreased ( F = 4.568, P = 0.036). In the 29 participants with abnormal glucose metabolism, a significant time effect was observed for FPG levels ( F = 2.492, P = 0.016). For participants with normal and abnormal glucose metabolism, no significant group × time interaction effects on FPG or HbA1c levels were identified.
CONCLUSION
Recaticimab showed no adverse glycemic effects in participants with normal or abnormal glucose metabolism, indicating its safety in patients with or without diabetes.
Humans
;
Male
;
Female
;
Blood Glucose/drug effects*
;
Middle Aged
;
Double-Blind Method
;
Hyperlipidemias/blood*
;
Antibodies, Monoclonal, Humanized/therapeutic use*
;
PCSK9 Inhibitors
;
Glycated Hemoglobin
;
Aged
;
Adult
;
Proprotein Convertase 9
8.Systematic review and Meta-analysis of efficacy and safety of Tangmaikang Granules in treatment of diabetic peripheral neuropathy.
Wen-Ying XIE ; Chen ZHANG ; Jing-Yan XIN ; Wen-Hui LI ; Tao-Jing ZHANG
China Journal of Chinese Materia Medica 2023;48(2):542-554
This study aimed to explore the efficacy and safety of Tangmaikang Granules in the treatment of diabetic peripheral neuropathy(DPN). PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang and VIP were retrieved for randomized controlled trial(RCT) of Tangmaikang Granules in the treatment of DPN. Cochrane handbook 5.3 was used to evaluate the quality of the inclu-ded studies, and RevMan 5.4.1 and Stata 15.1 were employed to analyze data and test heterogeneity. GRADEpro was used to assess the quality of each outcome index. Clinical effective rate was the major outcome index, while the improvement in numbness of hands and feet, pain of extremities, sluggishness or regression of sensation, sensory conduction velocity(SCV) and motor conduction velocity(MCV) of median nerve and peroneal nerve, fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), and glycated hemoglobin(HbA1c) and incidence of adverse reactions were considered as the minor outcome indexes. A total of 19 RCTs with 1 602 patients were eventually included. The Meta-analysis showed that the improvements in clinical effective rate(RR=1.45, 95%CI[1.32, 1.61], P<0.000 01), pain of extremities(RR=1.70, 95%CI[1.27, 2.27], P=0.000 3), MCV of peroneal nerve(MD=4.08, 95%CI[3.29, 4.86], P<0.000 01) and HbA1c(SMD=-1.23, 95%CI[-1.80,-0.66], P<0.000 1) of Tangmaikang Granules alone or in combination in the experimental group were better than those in the control group. Compared with the conditions in the control group, numbness of hands and feet(RR=1.42, 95%CI[1.12, 1.80], P=0.003), sluggishness or regression of sensation(RR=1.41, 95%CI[1.05, 1.91], P=0.02), SCV of median nerve(MD=4.59, 95%CI[0.92, 8.27], P=0.01), SCV of peroneal nerve(MD=4.68, 95%CI[3.76, 5.60], P<0.000 01) and MCV of median nerve(MD=5.58, 95%CI[4.05, 7.11], P<0.000 01) of Tangmaikang Granules in combination in the experimental group were improved by subgroup analysis. The levels of FBG(MD=-0.57, 95%CI[-1.27, 0.12], P=0.11) and 2hPBG(MD=-0.69, 95%CI[-1.70, 0.33], P=0.18) in the experimental group were similar to those in the control group after treatment with Tangmaikang Granules alone or in combination. There was no difference in the safety(RR=1.28, 95%CI[0.58, 2.82], P=0.54) of Tangmaikang Granules in the treatment of DPN between the experimental group and the control group. Tangmaikang Granules could significantly increase clinical effective rate and nerve conduction velocity as well as improve symptoms of peripheral nerve and blood glucose level, and no serious adverse reactions were identified yet. Further validation was needed in future in large-sample, multicenter, high-quality RCTs.
Humans
;
Blood Glucose
;
Diabetic Neuropathies/drug therapy*
;
Drugs, Chinese Herbal/therapeutic use*
;
Glycated Hemoglobin
;
Hypesthesia/drug therapy*
;
Multicenter Studies as Topic
;
Pain/etiology*
;
Treatment Outcome
;
Peripheral Nervous System Diseases/etiology*
9.Effect and Mechanism of Atorvastatin on Reversing Drug Resistance in Leukemia by Regulating Glycolysis through PTEN/mTOR Pathway.
Journal of Experimental Hematology 2023;31(1):38-44
OBJECTIVE:
To investigate the influence and mechanism of atorvastatin on glycolysis of adriamycin resistant acute promyelocytic leukemia (APL) cell line HL-60/ADM.
METHODS:
HL-60/ADM cells in logarithmic growth phase were treated with different concentrations of atorvastatin, then the cell proliferation activity was measured by CCK-8 assay, the apoptosis was detected by flow cytometry, the glycolytic activity was checked by glucose consumption test, and the protein expressions of PTEN, p-mTOR, PKM2, HK2, P-gp and MRP1 were detected by Western blot. After transfection of PTEN-siRNA into HL-60/ADM cells, the effects of low expression of PTEN on atorvastatin regulating the behaviors of apoptosis and glycolytic metabolism in HL-60/ADM cells were further detected.
RESULTS:
CCK-8 results showed that atorvastatin could inhibit the proliferation of HL-60/ADM cells in a concentration-dependent and time-dependent manner (r=0.872, r=0.936), and the proliferation activity was inhibited most significantly when treated with 10 μmol/L atorvastatin for 24 h, which was decreased to (32.3±2.18)%. Flow cytometry results showed that atorvastatin induced the apoptosis of HL-60/ADM cells in a concentration-dependent manner (r=0.796), and the apoptosis was induced most notably when treated with 10 μmol/L atorvastatin for 24 h, which reached to (48.78±2.95)%. The results of glucose consumption test showed that atorvastatin significantly inhibited the glycolytic activity of HL-60/ADM cells in a concentration-dependent and time-dependent manner (r=0.915, r=0.748), and this inhibition was most strikingly when treated with 10 μmol/L atorvastatin for 24 h, reducing the relative glucose consumption to (46.53±1.71)%. Western blot indicated that the expressions of p-mTOR, PKM2, HK2, P-gp and MRP1 protein were decreased in a concentration-dependent manner (r=0.737, r=0.695, r=0.829, r=0.781, r=0.632), while the expression of PTEN protein was increased in a concentration-dependent manner (r=0.531), when treated with different concentrations of atorvastatin for 24 h. After PTEN-siRNA transfected into HL-60/ADM cells, it showed that low expression of PTEN had weakened the promoting effect of atorvastatin on apoptosis and inhibitory effect on glycolysis and multidrug resistance.
CONCLUSION
Atorvastatin can inhibit the proliferation, glycolysis, and induce apoptosis of HL-60/ADM cells. It may be related to the mechanism of increasing the expression of PTEN, inhibiting mTOR activation, and decreasing the expressions of PKM2 and HK2, thus reverse drug resistance.
Humans
;
Atorvastatin/pharmacology*
;
PTEN Phosphohydrolase/pharmacology*
;
Sincalide/metabolism*
;
Drug Resistance, Neoplasm/genetics*
;
TOR Serine-Threonine Kinases/metabolism*
;
Leukemia, Promyelocytic, Acute/drug therapy*
;
Doxorubicin/pharmacology*
;
Apoptosis
;
RNA, Small Interfering/pharmacology*
;
Glycolysis
;
Glucose/therapeutic use*
;
Cell Proliferation
10.Network Meta-analysis of oral Chinese patent medicines in treating type 2 diabetes mellitus complicated with angina pectoris of coronary heart disease.
Xu-Ming ZHANG ; Xiao-Xiao ZHAO ; Yi LIU ; Yan-Ming XIE
China Journal of Chinese Materia Medica 2023;48(18):5078-5090
Bayesian network Meta-analysis was employed to compare the efficacy of different oral Chinese patent medicines in treating type 2 diabetes mellitus with angina pectoris of coronary heart disease. Randomized controlled trial(RCT) of oral Chinese patent medicines in treating type 2 diabetes mellitus complicated with angina pectoris of coronary heart disease were retrieved from 8 Chinese and English databases including CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, Cochrane Library, and Web of Science with the time interval from inception to November 2022. The BUGSnet package in R 4.2.1 was used to conduct Meta-analysis. A total of 45 RCTs were included, involving 4 727 patients and 7 oral Chinese patent medicines. Network Meta-analysis showed that the conventio-nal western medicine combined with Chinese patent medicines improved the outcome indicators. Shexiang Baoxin Pills + conventional western medicine had the best effect on reducing the incidence of adverse cardiovascular events, and Yixinshu Capsules + conventional western medicine on reducing the frequency and duration of angina pectoris. The conventional western medicine combined with oral Chinese patent medicines can reduce blood glucose indicators. Yindan Xinnaotong Soft Capsules + conventional western medicine had the best effect on reducing fasting blood glucose(FBG), 2 hours postprandial blood glucose(PBG), and glycosylated hemoglobin(HbA1c). The conventional western medicine combined with oral Chinese patent medicines can reduce blood lipid indicators. Yixinshu Capsules + conventional western medicine had the best effect on reducing total cholesterol(TC) and low density lipoprotein-cholesterol(LDL-C), and Yindan Xinnaotong Soft Capsules + conventional western medicine on reducing triglyceride(TG). Current evidence suggests that the patients with type 2 diabetes mellitus complicated with angina pectoris of coronary heart disease could reasonably choose oral Chinese patent medicines on the basis of routine antiplatelet, anticoagulant, hypoglycemic, and antihypertensive therapies, which could reduce the incidence of adverse cardiovascular events, alleviate the symptoms of angina pectoris, and reduce the glucose and lipid metabolism indicators. Shexiang Baoxin Pills + conventional treatment and Yixinshu Capsules + conventional western medicine have better effect on angina pectoris, Yindan Xinnaotong Soft Capsules + conventional western medicine on lowering blood glucose, and Yindan Xinnaotong Soft Capsules + conventional western medicine and Yixinshu Capsules + conventional western medicine on reducing blood lipid. Due to the lack of direct comparative results between Chinese patent medicines and other factors, high-quality studies remain to be carried out for further verification.
Humans
;
Nonprescription Drugs
;
Network Meta-Analysis
;
Diabetes Mellitus, Type 2/drug therapy*
;
Bayes Theorem
;
Blood Glucose
;
Angina Pectoris/drug therapy*
;
Coronary Disease/drug therapy*
;
Drugs, Chinese Herbal/therapeutic use*
;
Capsules
;
Lipids
;
Cholesterol

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