CFNC, a neocryptolepine derivative, inhibited the growth of gastric cancer AGS cells by inhibiting PI3K/AKT signaling pathway.

Gastric cancer is highly heterogeneous and there is still a lack of efficient, low-toxicity small molecule compounds for the treatment of gastric cancer. Natural products are important sources for the development of antitumor compounds. Therefore, it is promising strategy to find the lead compound of anti-gastric cancer agents by structural modification of natural products. The aim of this study was to synthesize a novel neocryptolepine derivative CFNC and explore its potential anti-gastric cancer effect and molecular mechanism. The MTT assay showed that the IC50 of CFNC on AGS cells reached 148 nM. CFNC arrested AGS cells in the G2/M phase of the cell cycle. Furthermore, CFNC inhibited cell proliferation and migration, leading to the loss of membrane potential by causing mitochondrial dysfunction, which induced the apoptosis of AGS cells. Western blot assay suggested that CFNC could inhibit the expression of important proteins in the PI3K/AKT/mTOR signaling pathway. These results showed that CFNC exhibited strong cytotoxic activity in gastric cancer cell lines by regulating the PI3K/AKT/mTOR signaling pathway. Taken together, CFNC could be a promising lead compound for the clinical treatment of gastric cancer.

Design, Synthesis and Biological Evaluation of Neocryptolepine Derivatives as Potential Anti-Gastric Cancer Agents.

Natural products play an important role in drug development and lead compound synthesis. Neocryptolepine is a polycyclic quinoline compound isolated from Cryptolepis sanguinolent. The cytotoxicity of neocryptolepine to gastric cancer cells AGS, MKN45, HGC27, and SGC7901 was not very strong, and it also had certain toxicity to gastric mucosa cells GES-1. Therefore, a series of neocryptolepine derivatives were synthesized by the modification of the structure of neocryptolepine, and their cytotoxicity was evaluated. The results showed that compounds C5 and C8 exhibited strong cytotoxicity to AGS cells. The cell colony formation and cell migration experiments suggested that compounds C5 and C8 could inhibit the proliferation and cell migration of AGS and HGC27 cells. Cell cycle and apoptosis experiments showed that compounds C5 and C8 did not cause the apoptosis of AGS and HGC27 cells but, mainly, caused cell necrosis. Compound C5 had no significant effect on AGS and HGC27 cell cycles at low concentration. After treatment with AGS cells for 24 h at high concentration, compound C5 could significantly arrest the AGS cell cycle in the G2/M phase. Compound C8 had no significant effect on the AGS and HGC27 cell cycles. The results of molecular docking and Western blot showed that compounds C5 and C8 might induce cytotoxicity through the PI3K/AKT signaling pathway. Therefore, compounds C5 and C8 may be promising lead compounds for the treatment of gastric cancer.

Retrospective Study of Aging and Sex-Specific Risk Factors of COVID-19 with Hypertension in China.

Background: Coronavirus disease 2019 (COVID-19) has been a global threat that pushes healthcare to its limits. Hypertension is one of the most common risk factors for cardiovascular complications in COVID-19 and is strongly associated with disease severity and mortality. To date, clinical mechanisms by which hypertension leads to increased risk in COVID-19 are still unclear. Furthermore, additional factors might increase these risks, such as the consideration of age and sex, which are of interest when in search of personalized treatments for hypertensive COVID-19 patients. Methods: We conducted a retrospective cohort study of 543 COVID-19 patients in seven provinces of China to examine the epidemiological and clinical characteristics of COVID-19 in this population and to determine risk factors of hypertensive COVID-19 patients. We also used univariable and multivariable logistic regression methods to explore the risk factors associated with hypertensive COVID-19 patients in different age and sex subgroups. Results: Among the enrolled COVID-19 patients, the median age was 47 years (interquartile range (IQR) 34.0-57.0), and 99 patients (18.23%) were over 60 years old. With regard to comorbidities, 91 patients (16.75%) were diagnosed with hypertension, followed by diabetes, coronary disease, and cerebrovascular disease. Of the hypertensive COVID-19 patients, 51 (56.04%) were male. Multivariable analysis showed that old age, comorbid diabetes or coronary heart disease on admission, increased D-dimer, increased glucose, and decreased lymphocyte count were independent risk factors associated with hypertensive COVID-19 patients. Elevated total bilirubin (odds ratio [OR]: 1.014, 95% confidence interval [CI]: 0.23-1.05; p = 0.043) and triglycerides (OR: 1.173, 95% CI: 0.049-1.617; p = 0.007) were found to be associated with elderly hypertensive COVID-19 patients. In addition, we found that decreased lymphocytes, basophil, high-density lipoprotein, and increased fibrinogen and creatinine were related to a higher risk of disease severity in male patients. The most common abnormal clinical findings pertaining to female hypertensive COVID-19 patients were hemoglobin, total bile acid, total protein, and low-density lipoprotein. Conclusions: Factors associated with increased risk of hypertensive COVID-19 patients were identified. Results to the different age and sex subgroups in our study will allow for better possible personalized care and also provide new insights into specific risk stratification, disease management, and treatment strategies for COVID-19 patients with hypertension in the future.

A Novel Isaindigotone Derivative Displays Better Anti-Proliferation Activities and Induces Apoptosis in Gastric Cancer Cells.

Isaindigotone is an alkaloid containing a pyrrolo-[2,1-b]quinazoline moiety conjugated with a benzylidene group and isolated from the root of Isatis indigotca Fort. However, further anticancer activities of this alkaloid and its derivatives have not been fully explored. In this work, a novel isaindigotone derivative was synthesized and three different gastric cell lines and one human epithelial gastric cell line were used to study the anti-proliferation effects of the novel isaindigotone derivative BLG26. HGC27 cells and AGS cells were used to further explore the potential mechanisms. BLG26 exhibited better anti-proliferation activities in AGS cells with a half-maximal inhibitory concentration (IC50) of 1.45 µM. BLG26 caused mitochondrial membrane potential loss and induced apoptosis in both HGC27 cells and AGS cells by suppressing mitochondrial apoptotic pathway and PI3K/AKT/mTOR axis. Acute toxicity experiment showed that LD50 (median lethal dose) of BLG26 was above 1000.0 mg/kg. This research suggested that BLG26 can be a potential candidate for the treatment of gastric cancer.

Natural Environmental Variation Determines Microbial Diversity Patterns in Serofluid Dish, a Traditional Chinese Fermented Vegetable Food.

Serofluid dish is a traditional fermented food that contains rich microbial populations. To gain insight into the environmental variables shaping the microbial diversity patterns, serofluid dish samples were collected from different areas, and 16S rRNA sequencing was performed. Analyses revealed both species and community diversity, including phylotype richness, Shannon index and phylogenetic diversity, were mostly influenced by pH. Additionally, such effects were corroborated by the Mantel test of pairwise UniFrac distances and variable selection of multiple linear regression models. Eventually, correlations between dominant lineages and the pH of serofluid dish other than geographical distance explained a large portion of the changes in microbial composition and diversity. Lactobacillus and related genera, Pediococcus and Acetobacter were largely driven by the variability of pH, and higher richness was observed under moderate pH ranges. Collectively, the results demonstrated that a microbial diversity pattern in serofluid dish is predictable by natural environmental variation and can be better understood through pH conditions.

Anti-Gastric Cancer Activity of the Cell-free Culture Supernatant of Serofluid Dish and Lactiplantibacillus plantarum YT013.

Cancer is second only to heart disease as a cause of death, despite improvements in its early diagnosis and precision medicine. Due to the limitations of commonly used anticancer methods such as surgery, radiotherapy and chemotherapy, biological therapy, especially probiotics such as lactic acid bacteria, has received widespread attention. Lactobacillus has been proven to inhibit the proliferation of a variety of cancer cells. In this work, the effects of the cell-free culture supernatant of serofluid dish (CCS1) and the cell-free culture supernatant of Lactiplantibacillus plantarum YT013 (CCS2) isolated from serofluid dish on AGS, HCT116, HepG2 and PANC-1 cells were investigated. Based on the CCK-8 assay, CCS1 and CCS2 were shown to suppress the growth of cancer cells in a concentration-dependent manner. The IC50 values of CCS2 of AGS, HCT116, HepG2 and PANC-1 cells were 346.51 ± 35.28, 1207.69 ± 333.18, 650.94 ± 123.78 and 808.96 ± 126.27 µg/ml, respectively. In addition, the results of fluorescence microscopy showed that CCS2 changed cell morphology and treated with CCS2 (200, 400 and 800 µg/ml) for 48 h, AGS cell apoptosis was quantitatively surveyed by flow cytometry, showing 25.0, 34.1, and 42.6% total apoptotic cells. Moreover, western blotting confirmed that BAX, BAD and Caspase-3/8/9 were significantly upregulated and that BCL-2 was significantly downregulated in AGS cells treated with CCS2. These results indicated that CCS2 might lead to apoptosis via the endogenous mitochondrial apoptotic pathway. In summary, Lactiplantibacillus plantarum YT013 may be considered a good candidate for anticancer therapies.

Synthesis and anticancer evaluations of novel 1H-imidazole [4,5-f][1,10] phenanthroline derivative for the treatment of colorectal cancer.

1H-imidazole [4,5-f][1,10] phenanthroline is a promising chemical structure for cancer treatment. Herein, we synthesized a novel 1H-imidazole [4,5-f][1,10] phenanthroline derivative named IPM714 and found it exhibited selectively colorectal cancer (CRC) cells inhibitory activities, with half maximal inhibitory concentration (IC50) of 1.74 µM and 2 µM in HCT116 cells and SW480 cells, respectively. The present study is intended to explore the cytotoxicity of IPM714 in cancer cells of various types and its anticancer mechanism in vitro. Cellular functional analyses indicated IPM714 can arrest HCT116 cell cycle in S phase and induce apoptosis in HCT116 and SW480 cells. Western blot and molecular docking showed that IPM714 may suppress PI3K/AKT/mTOR pathway to inhibit cell proliferation and regulate cell cycle as well as apoptosis. This study proved IPM714 to be a promising drug in CRC therapy.

Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents.

A series of novel derivatives of isaindigotone, which comes from the root of isaits indinatca Fort, were synthesised (Compound 1-26). Four human gastrointestinal cancer cells (HCT116, PANC-1, SMMC-7721, and AGS) were employed to evaluate the anti-proliferative activity. Among them, Compound 6 displayed the most effective inhibitory activity on AGS cells with an IC50 (50% inhibitory concentration) value of 2.2 µM. The potential mechanism study suggested that Compound 6 induced apoptosis in AGS cells. The collapse of mitochondrial membrane potential (MMP) in AGS cells was proved. In docking analysis, good affinity interaction between Compound 6 and AKT1 was discovered. Treatment of AGS cells with Compound 6 also resulted in significant suppression of PI3K/AKT/mTOR signal pathway. The collapse of MMP and suppression of PI3K/AKT/mTOR signal pathway may be responsible for induction of apoptosis. This derivative Compound 6 could be useful as an underlying anti-tumour agent for treatment of gastric cancer.

Vanillin Derivatives Reverse Fusobacterium nucleatum-Induced Proliferation and Migration of Colorectal Cancer Through E-Cadherin/ß-Catenin Pathway.

Colorectal cancer (CRC) is a common clinical malignant tumor and closely related to intestinal microbiome disorders. Especially, Fusobacterium nucleatum (F. nucleatum) is one of the most prevalent pathogens in CRC. However, its change in CRC patients of Northwest China, an area with a high incidence of gastrointestinal tumors, is unclear, and therapeutic strategies targeting F. nucleatum remain unresolved. Here, fecal samples of healthy people and CRC patients were studied using 16S rRNA sequencing to explore microbial community alterations. Additionally, vanillin derivate (IPM711 and IPM712) intervention by coculture with CRC cells and potential mechanism were investigated. Results showed that intestinal microbial homeostasis was gradually dysregulated, and the abundance of Fusobacterium was higher in CRC patients. Moreover, IPM711 and IPM712 showed better anti-F. nucleatum activity than vanillin by increasing cell membrane permeability and destroying bacterial integrity. In addition, IPM711 and IPM712 could downregulate the expression of E-cadherin and ß-catenin, thus, suppressing the migration of HCT116. Collectively, IPM711 and IPM712 have both anticolorectal cancer and anti-F. nucleatum activities, providing potential natural product drug candidates for microbe-targeted strategies for the treatment of CRC.

Synthesis of 8-Fluoroneocryptolepine and Evaluation for Cytotoxic Activity against AGS Cancer Cells.

Neocryptolepine derivatives have attracted great interest because of their unique cytotoxic activity. 8-Fluoroneocryptolepine (8FNC) was synthesized, and its cytotoxicity was evaluated by MTT assay in AGS gastric cancer cells and gastric mucosa GES-1 cells. 8-Fluoroneocryptolepine showed greater selectivity and cytotoxicity to AGS cells than the cisplatin (CIS) and fluorouracil (5-Fu) commonly used in clinical treatment of gastric cancer. Most importantly, we significantly improved the cytotoxic effect of 8FNC against AGS cells by structural modification and reduced the cytotoxicity against GES-1 cells compared with neocryptolepine. We further evaluated the activity of 8FNC against AGS cells in vitro. Our results indicate that 8FNC arrests the AGS cell cycle in the G2/M phase, reduces the mitochondrial membrane potential of AGS cells, and drives the initiation of apoptotic body formation in 8FNC-induced apoptosis. Moreover, 8FNC exhibits strong inhibitory effects on AGS cell migration. Studies on the molecular mechanisms of the cytotoxic activities of 8FNC revealed that it may play a significant role in the inhibitory effect on AGS human gastric cancer cells through the PI3K/AKT signaling pathway. In conclusion, 8FNC may become a promising lead compound in the development of potential clinical drug candidates for the treatment of gastric cancer.

Synthesis and biological activity of 1H-imidazo[4,5-f][1,10]phenanthroline as a potential antitumor agent with PI3K/AKT/mTOR signaling.

1H-imidazo[4,5-f][1,10]phenanthroline (IPM713) is a type of tricyclic conjugated rigid planar structure with potential medical applications, but its anticancer activity has not yet been fully studied. In the present research, cells from seven different cancer types were used to study the anticancer effect, and IPM713 was found to inhibit the colorectal cancer cell line HCT116 most significantly, with a half maximal inhibitory concentration (IC50) of 1.7 µM. The mechanisms by which IPM713 exerts anti-colorectal cancer activity were studied. IPM713 blocked the cell cycle in G0/G1 phase and induced apoptosis by suppressing the PI3K/AKT/mTOR axis. In addition, an acute toxicity test showed that the median lethal dose (LD50) was above 5000 mg/kg. The findings of this research suggest that IPM713 can interfere with the PI3K/AKT/mTOR signaling pathway and might be a potential therapeutic candidate for the treatment of colorectal cancer.

The effects of qishen granules for patients with chronic heart failure: A multicenter randomized double-blind placebo-controlled trial.

Background: Despite advancements in chronic heart failure (CHF) treatment, the effect often remains unsatisfactory and unstable. More effective therapies are needed. Qishen granules (QSG) are a novel Chinese botanical drug effective in treating CHF in animal models, but clinical evidence remains inadequate. Objective: This study aims to evaluate the effects of QSG on patients with CHF. Methods: We enrolled CHF patients in this 12-week, randomized, double-blind, placebo-controlled trial and randomly assigned them to the QSG (twice a day, 6.8 g granules at once) or placebo group. The primary endpoint was a change in the plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level after treatment. The secondary outcome consists of the New York Heart Association (NYHA) functional classification, 6-min walking distance (6MWD), TCM syndrome integral scale, quality of life, and echocardiographic index. Results: A total of 191 patients completed the 12-week follow-up period, with 94 in the QSG group and 97 in the placebo group. The Qishen granules group demonstrated a considerably greater reduction in NT-proBNP than the placebo group (50% vs 32% for QSG vs placebo, respectively; p = 0.011). Patients who received QSG performed better in the NYHA functional rank, 6MWD, TCM syndrome integral scale, and quality of life (p < 0.05). The QSG group performed better in HFrEF patients regarding the efficiency of NT-proBNP. There was no statistical significance in the change in evaluated safety parameters, such as blood routine and biochemistry. Conclusion: Based on standard treatment, Qishen granules further reduced the levels of NT-proBNP when compared with placebo. Together with other outcomes, our findings suggest that QSG could be used in combination therapy for CHF. Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT03027375. Registered 9 October 2017.

Potential application of a knowledgebase of iron metabolism of Acidithiobacillus ferrooxidans as an alternative platform

BACKGROUND: Acidithiobacillus ferrooxidans is a facultative anaerobe that depends on ferrous ion oxidation as well as reduced sulfur oxidation to obtain energy and is widely applied in metallurgy, environmental protection, and soil remediation. With the accumulation of experimental data, metabolic mechanisms, kinetic models, and several databases have been established. However, scattered data are not conducive to understanding A. ferrooxidans that necessitates updated information informed by systems biology. RESULTS: Here, we constructed a knowledgebase of iron metabolism of A. ferrooxidans (KIMAf) system by integrating public databases and reviewing the literature, including the database of bioleaching substrates (DBS), the database of bioleaching metallic ion-related proteins (MIRP), the A. ferrooxidans bioinformation database (Af-info), and the database for dynamics model of bioleaching (DDMB). The DBS and MIRP incorporate common bioleaching substrates and metal ion-related proteins. Af-info and DDMB integrate nucleotide, gene, protein, and kinetic model information. Statistical analysis was performed to elucidate the distribution of isolated A. ferrooxidans strains, evolutionary and metabolic advances, and the development of bioleaching models. CONCLUSIONS: This comprehensive system provides researchers with a platform of available iron metabolism-related resources of A. ferrooxidans and facilitates its application.

Risk Factors in Patients with Diabetes Hospitalized for COVID-19: Findings from a Multicenter Retrospective Study.

METHODS: In this multicenter retrospective study, patients with COVID-19 in China were included and classified into two groups according to whether they were complicated with diabetes or not. Demographic symptoms and laboratory data were extracted from medical records. Univariable and multivariable logistic regression methods were used to explore the risk factors. RESULTS: 538 COVID-19 patients were finally included in this study, of whom 492 were nondiabetes and 46 were diabetes. The median age was 47 years (IQR 35.0-56.0). And the elderly patients with diabetes were more likely to have dry cough, and the alanine aminotransferase, lactate dehydrogenase, Ca, and mean hemoglobin recovery rate were higher than the other groups. Furthermore, we also found the liver and kidney function of male patients was worse than that of female patients, while female cases should be paid more attention to the occurrence of bleeding and electrolyte disorders. Moreover, advance age, blood glucose, gender, prothrombin time, and total cholesterol could be considered as risk factors for COVID-19 patients with diabetes through the multivariable logistic regression model in our study. CONCLUSION: The potential risk factors found in our study showed a major piece of the complex puzzle linking diabetes and COVID-19 infection. Meanwhile, focusing on gender and age factors in COVID-19 patients with or without diabetes, specific clinical characteristics, and risk factors should be paid more attention by clinicians to figure out a targeted intervention to improve clinical efficacy worldwide.

Efficacy and safety of Qishen granules for chronic heart failure: A protocol for systematic review and meta-analysis.

BACKGROUND: Qishen granules (QSG) is a famous traditional Chinese Medicine (TCM) formula used to treat chronic heart failure (CHF). The objective of this protocol is to clarify the efficacy and safety of QSG for treating CHF. METHODS: Six databases will be electronically searched up to November 1, 2020 for randomized controlled trials (RCTs) in English and Chinese languages. Two independent reviewers will complete tasks of literature retrieval and data extraction. After that, the Cochrane Collaboration risk of bias tool will be utilized to assess methodological quality. The primary outcomes are left ventricular ejection fraction, left ventricular fractional shortening, and N-terminal B-type natriuretic peptide. The secondary outcomes consist of composite cardiac events, adverse effects, and quality of life. Meta-analysis will be performed using the Revman version 5.3. RESULTS: This study will provide a high-quality synthesis of current evidence of QSG for CHF from primary and secondary outcomes. CONCLUSION: This study will provide evidence for the effectiveness and safety of QSG in the treatment of CHF. PROSPERO REGISTRATION NUMBER: CRD42020150442.

Human Gut Microbiome-Based Knowledgebase as a Biomarker Screening Tool to Improve the Predicted Probability for Colorectal Cancer.

Colorectal cancer (CRC) is a common clinical malignancy globally ranked as the fourth leading cause of cancer mortality. Some microbes are known to contribute to adenoma-carcinoma transition and possess diagnostic potential. Advances in high-throughput sequencing technology and functional studies have provided significant insights into the landscape of the gut microbiome and the fundamental roles of its components in carcinogenesis. Integration of scattered knowledge is highly beneficial for future progress. In this study, literature review and information extraction were performed, with the aim of integrating the available data resources and facilitating comparative research. A knowledgebase of the human CRC microbiome was compiled to facilitate understanding of diagnosis, and the global signatures of CRC microbes, sample types, algorithms, differential microorganisms and various panels of markers plus their diagnostic performance were evaluated based on statistical and phylogenetic analyses. Additionally, prospects about current changelings and solution strategies were outlined for identifying future research directions. This type of data integration strategy presents an effective platform for inquiry and comparison of relevant information, providing a tool for further study about CRC-related microbes and exploration of factors promoting clinical transformation (available at: http://gsbios.com/index/experimental/dts_ mben?id=1).

Clinical features and risk factors for severe inpatients with COVID-19: A retrospective study in China.

BACKGROUND: A worldwide outbreak of coronavirus disease (COVID-19), since 2019, has brought a disaster to people all over the world. Many researchers carried out clinical epidemiological studies on patients with COVID-19 previously, but risk factors for patients with different levels of severity are still unclear. METHODS: 562 patients with laboratory-confirmed COVID-19 from 12 hospitals in China were included in this retrospective study. Related clinical information, therapies, and imaging data were extracted from electronic medical records and compared between patients with severe and non-severe status. We explored the risk factors associated with different severity of COVID-19 patients by logistic regression methods. RESULTS: Based on the guideline we cited, 509 patients were classified as non-severe and 53 were severe. The age range of whom was 5-87 years, with a median age of 47 (IQR 35.0-57.0). And the elderly patients (older than 60 years old) in non-severe group were more likely to suffer from fever and asthma, accompanied by higher level of D-dimer, red blood cell distribution width and low-density lipoprotein. Furthermore, we found that the liver and kidney function of male patients was worse than that of female patients in both severe and non-severe groups with different age levels, while the severe females had faster ESR and lower inflammatory markers. Of major laboratory markers in non-severe cases, baseline albumin and the lymphocyte percentage were higher, while the white blood cell and the neutrophil count were lower. In addition, severe patients were more likely to be accompanied by an increase in cystatin C, mean hemoglobin level and a decrease in oxygen saturation. Besides that, advanced age and indicators such as count of white blood cell, glucose were proved to be the most common risk factors preventing COVID-19 patients from aggravating. CONCLUSION: The potential risk factors found in our study have shown great significance to prevent COVID-19 patients from aggravating and turning to critical cases during treatment. Meanwhile, focusing on gender and age factors in groups with different severity of COVID-19, and paying more attention to specific clinical symptoms and characteristics, could improve efficacy of personalized intervention to treat COVID-19 effectively.

IPM712, a vanillin derivative as potential antitumor agents, displays better antitumor activity in colorectal cancers cell lines.

Colorectal cancer (CRC), a major health threat in the world, ranks third in incidence and second in mortality among cancers. Chemotherapy, an important treatment for colorectal cancer, have be limited in the clinic due to the resistance and side effect. Studies have shown that PI3K-related regulatory pathways play a colossal role in colorectal cancer. Therefore, it is a good strategy to find a new drug which works by affecting the PI3K signaling pathway. In this paper, we obtained a new vanillin derivative (IPM712) by modifying the structure of IPM711 and tested its anticancer activity in vitro and toxicity in vivo. Results showed that IPM712 has a better anticancer activity than 5-Fu in HCT116 and SW480 cell lines. Furthermore, IPM712 can inhibit cell proliferation, migration and induce the apoptosis by affecting PI3K-related protein expression. Acute toxicity experiments show that IPM712 has no significant toxicity at therapeutic concentrations. Based on these results, IPM712 is a promising anticancer drug candidate for human colorectal cancer therapy.

Corrigendum to "Antiapoptosis and Antifibrosis Effects of Qishen Granules on Heart Failure Rats via Hippo Pathway".

[This corrects the article DOI: 10.1155/2019/1642575.].

Protective Role of Enalapril in Anthracycline-Induced Cardiotoxicity: A Systematic Review.

BACKGROUND: Evidence of the preventive and therapeutic effects of enalapril on cardiotoxicity caused by chemotherapy needs to be further confirmed and updated. METHODS: We performed a systematic review of studies from electronic databases that were searched from inception to January 29, 2019, and included relevant studies analyzing enalapril as a cardioprotective agent before or during the use of anthracyclines by oncology patients. Homogeneous results from different studies were pooled using RevMan 5.3 software. The Cochrane risk-of-bias tool was used to determine the quality of the studies. RESULTS: We examined and screened 626 studies according to specific criteria and ultimately included seven studies that were relevant to the indicated topic. Among them, three studies reported the incidence of death during 6- and 12-month follow-up periods. Six of the seven included studies showed possible positive results, suggesting that enalapril plays a cardioprotective role, while five of these studies showed that there was a significant difference in the left ventricular ejection fraction (LVEF) between an enalapril group and a control group (weighted mean difference (WMD) = 7.18, 95% CI: 2.49-11.87, I2 = 96%, P < .001). Moreover, enalapril was beneficial in reducing troponin I (TnI), creatine kinase myocardial band (CK-MB) and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels in cancer patients treated with anthracycline. CONCLUSIONS: Although a protective effect of enalapril on myocardial toxicity was observed in terms of the LVEF values and TnI, CK-MB and NT-proBNP levels, its use in the prevention and treatment of cardiotoxicity caused by anthracycline needs to be investigated by more scientific research.