Novel Combination Therapy for Heart Failure: Trimebutine-Methoxsalen Identified through Synergistic Network Virtual Screening and Experimental Validation.

Combination therapy is increasingly favored by pharmaceutical companies and researchers as an effective way to quickly discover new drugs with excellent efficacy, especially in the treatment of complex diseases. Previously, we successfully developed a computational screening method to identify such combinations, although it fell short in elucidating their synergistic mechanisms. In this work, we have transitioned to a highest single agent (HSA) synergy model for network screening, which streamlines the discovery of promising combinations and facilitates the investigation of their synergistic effects.

A Senomorphlytic Three-Drug Combination Discovered in Salsola collina for Delaying Aging Phenotypes and Extending Healthspan.

The pursuit of pharmacological interventions in aging aims focuses on maximizing safety and efficacy, prompting an exploration of natural products endowed with inherent medicinal properties. Subsequently, this work establishes a unique library of plant extracts sourced from Yunnan Province, China. Screening of this herbal library herein revealed that Salsola collina (JM10001) notably enhances both lifespan and healthspan in C.

Characterization of cellular senescence in doxorubicin-induced aging mice.

With a rise in the need to develop anti-aging drugs, a growing number of in vivo studies evaluating the efficacy of potential drug candidates have used doxorubicin-induced aging mice. However, changes in the biomarkers of senescent cells have not been reported in detail in these animals. To lay a foundation for the use of doxorubicin-induced aging mice, we examined the biomarkers of hepatic and renal senescent cells in these mice.

Identification of Guaifenesin-Andrographolide as a Novel Combinatorial Drug Therapy for Epilepsy Using Network Virtual Screening and Experimental Validation.

Combinatorial drug therapy has attracted substantial attention as an emerging strategy for the treatment of diseases with complex pathological mechanisms. We previously developed a potentially universal computational screening approach for combination drugs and used this approach to successfully identify some beneficial combinations for the treatment of heart failure. Herein, this screening approach was used to identify novel combination drugs for the treatment of epilepsy in an approved drug library.

Antiaging Effects of Root Extract on and Doxorubicin-Induced Premature Aging in Adult Mice.

The roots of are a kind of Chinese herb with homology of medicine and food. This is the first report showing the property of the extract of roots (HLB01) to extend the lifespan as well as promote the healthy parameters in (). For doxorubicin- (Doxo-) induced premature aging in adult mice, HLB01 counteracted the senescence-associated biomarkers, including P21 and H2AX.

Rapid Repurposing of Novel Combination Drugs for the Treatment of Heart Failure via a Computationally Guided Network Screening Approach.

Combination drugs, characterized by high efficacy and few side effects, have received extensive attention from pharmaceutical companies and researchers for the treatment of complex diseases such as heart failure (HF). Traditional combination drug discovery depends on large-scale high-throughput experimental approaches that are time-consuming and costly. Herein we developed a novel, rapid, and potentially universal computer-guided combination drug-network-screening approach based on a set of databases and web services that are easy for individuals to obtain and operate, and we discovered for the first time that the menthol-allethrin combination screened by this approach exhibited a significant synergistic cardioprotective effect .

Cardiac metallothionein overexpression rescues diabetic cardiomyopathy in Akt2-knockout mice.

To efficiently prevent diabetic cardiomyopathy (DCM), we have explored and confirmed that metallothionein (MT) prevents DCM by attenuating oxidative stress, and increasing expression of proteins associated with glucose metabolism. To determine whether Akt2 expression is critical to MT prevention of DCM, mice with either global Akt2 gene deletion (Akt2-KO), or cardiomyocyte-specific overexpressing MT gene (MT-TG) or both combined (MT-TG/Akt2-KO) were used. Akt2-KO mice exhibited symptoms of DCM (cardiac remodelling and dysfunction), and reduced expression of glycogen and glucose metabolism-related proteins, despite an increase in total Akt (t-Akt) phosphorylation.

Graphene Oxide and Reduced Graphene Oxide Exhibit Cardiotoxicity Through the Regulation of Lipid Peroxidation, Oxidative Stress, and Mitochondrial Dysfunction.

Objective: Graphene has been widely used for various biological and biomedical applications due to its unique physiochemical properties. This study aimed to evaluate the cardiotoxicity of graphene oxide (GO) and reduced GO (rGO) and , as well as to investigate the underlying toxicity mechanisms.

Methods: GO was reduced by gamma irradiation to prepare rGO and then characterized by UV/visible light absorption spectroscopy.

Cardiac injury prediction and lymphocyte immunity and inflammation analysis in hospitalized patients with coronavirus disease 2019 (COVID-19).

Background: Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic. The ability to predict cardiac injury and analyze lymphocyte immunity and inflammation of cardiac damage in patients with COVID-19 is limited. We aimed to determine the risk factors and predictive markers of cardiac injury in these patients.

Combination of Broccoli Sprout Extract and Zinc Provides Better Protection against Intermittent Hypoxia-Induced Cardiomyopathy Than Monotherapy in Mice.

Nuclear factor-E2-related factor 2 (Nrf2) and metallothionein have each been reported to protect against chronic intermittent hypoxia- (IH-) induced cardiomyopathy. Sulforaphane-rich broccoli sprout extract (BSE) and zinc can effectively induce Nrf2 and metallothionein, respectively, to protect against IH-induced cardiomyopathy via antioxidative stress. However, whether the cardiac protective effects of the combination of BSE and zinc can be synergistic or the same has not been evaluated.

Protective Effect of Lactobacillus rhamnosus GG and its Supernatant against Myocardial Dysfunction in Obese Mice Exposed to Intermittent Hypoxia is Associated with the Activation of Nrf2 Pathway.

Prolonged intermittent hypoxia (IH) has been shown to impair myocardial function (mainly via oxidative stress and inflammation) and modify gut microbiota in mice. Gut microbiota plays an important role in health and disease, including obesity and cardiovascular disease (CVD). Probiotics refer to live microorganisms that confer health benefits on the host after administration in adequate amounts.

Effects of Breast Cancer Genes 1 and 2 on Cardiovascular Diseases.

Carriers of mutations of breast cancer gene 1 and/or 2 (BRCA1/2) have a higher risk of developing breast and ovarian cancers at a relatively young age. Recently, a causative role for BRCA1/2 in cardiovascular diseases has been emerging. In this review, we summarize currently available evidence obtained from studies on animal models and human BRCA1/2 mutation carriers that shows a correlation of BRCA1/2 deficiency with various cardiovascular diseases, including ischemic heart disease, atherosclerosis, and chemotherapy-linked cardiac muscle disorders.

Protection against diabetic cardiomyopathy is achieved using a combination of sulforaphane and zinc in type 1 diabetic OVE26 mice.

Sulforaphane (SFN) can effectively induce nuclear factor E2-related factor 2 (Nrf2), and zinc (Zn) can effectively induce metallothionein (MT), both of which have been shown to protect against diabetic cardiomyopathy (DCM). However, it is unclear whether combined treatment with SFN and Zn offers better cardiac protection than either one alone. Here, we treated 5-week-old OVE mice that spontaneously develop type 1 diabetes with SFN and/or Zn for 18 weeks.

Nrf2 expression and function, but not MT expression, is indispensable for sulforaphane-mediated protection against intermittent hypoxia-induced cardiomyopathy in mice.

We reported previously that nuclear factor erythroid 2-related factor 2 (Nrf2) and metallothionein (MT) play critical roles in preventing intermittent hypoxia (IH)-induced cardiomyopathy. In addition, positive feedback regulation between Nrf2 and MT is required for the efficient compensative responses of the heart to IH. As an activator of Nrf2, sulforaphane (SFN) has attracted attention as a potential protective agent against cardiovascular disease.

miRNAS in cardiovascular diseases: potential biomarkers, therapeutic targets and challenges.

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the world. Although considerable progress has been made in the diagnosis, treatment and prognosis of CVD, there is still a critical need for novel diagnostic biomarkers and new therapeutic interventions to decrease the incidence of this disease. Recently, there is increasing evidence that circulating miRNAs (miRNAs), i.

Analysis of metabolism-related indicators and MTHFR gene polymorphism in patients with H-type hypertension.

Background: This study aims to analyze the polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene in patients with hypertension, and explore the correlation between H-type hypertension and metabolic biochemical indicators such as homocysteine (Hcy).

Methods: One hundred patients with H-type hypertension and 100 patients with common hypertension were selected as the study subjects. Plasma Hcy and blood lipids, blood glucose, and other biochemical indicators were detected in the two groups.

[Correlation of VEGF expression with microvessel and microlymphatic density in sinonasal squamous cell carcinoma].

Objective: To study the expression of VEGF in sinonasal squamous cell carcinoma and its correlations with microvessel density (MVD), microlymphatic vessel density (MLVD).

Method: The expression of VEGF, MVD and MLVD in 41 cases of sinonasal squamous cell carcinoma were detected by immunohistochemical technique.

Result: In the sinonasal squamous cell carcinoma, the positive rate of VEGF was 82.

[Nasal bleeding as the first symptom of tsutsugamushi disease: a case report].

A case of 76-years-old male patient with nasal bleeding as the first symptom in our hospital, who was finally diagnosed as tsutsugamushi disease. This old man was bited by insect in farmland 2 days before the symptom occurred. PE: Left thigh and right buttock have eschar, with splenomegaly.

[Study about eye complication of nasopharyngeal carcinoma].

Objective: To explore the eye complication of nasopharyngeal carcinoma (NPC), to analysis the clinical manifestation, CT characteristics and pathological diagnosis of eye complications of NPC and to provide the base for early diagnosis of NPC.

Method: To retrospectively study of 82 cases eye complications in 562 cases NPC, to study their clinical manifestation, CT characteristics and pathological diagnosis.

Result: The clinical studies showed that eye complication cases were occurred in 82 cases of 562 NPC cases (14.

[The significance of the expression of Col IV and LN in nasal and paranasal sinus malignant tumor].

Objective: To study the pathological relationship between the expression of Col IV and LN in nasal and paranasal sinus malignant tumor (NPMT).

Method: The immunohistochemical technique was used to detected the expression of Col IV and LN in NPMT, para-cancer tissues and non-cancer tissues.

Result: There was a significance on the expression of the Col IV and LN in NPMT, para-cancer tissues and non-cancer tissues (P<0.

[Cluster analysis in micrangium detection in malignant nasal and paranasal sinus tumor].

Objective: To study the application of cluster analysis in micrangium detection in malignant nasal and paranasal sinus tumor.

Methods: Microvessel density (MVD) counting and cluster analysis were used to detect the micrangium in patients with malignant nasal and paranasal sinus tumor to assess the association between the malignancy and MVD.

Results: According to cluster analysis, the MVD counting could be clustered into two groups, and the MVD showed significant differences between the tumor tissues, adjacent normal tissue and the control group (P<0.

[Inhibition of growth and proliferation of Hep-2 cells by targeting hTERT gene using small interference RNA technology].

Objective: To investigate the inhibition of hTERT gene to Hep-2 cells of laryngeal neoplasms.

Method: siRNA-hTERT mRNA was designed. Hep-2 cells, cultured in vitro, were transfected with lipofectamine 2000 and the inhibitory effect was detected by reverse transcriptase (RT-PCR), MTT assay, and morphology.

[Clinical significance of the expression of p53, p63 and p73 in nasal and paranasal sinus carcinoma].

Objective: To study the clinical significance of the expression of p53, p63 and p73 protein and the correlation of p53 and p63 in nasal and paranasal sinus carcinoma (NPSC).

Method: The immunohistochemical technique was used to detect the expression of p53, p63 and p73 in 67 cases of NPSC, para-cancer tissues and non-cancer tissues.

Result: The positive rate of p53 and p63 protein in NPSC was significantly higher than that in park cancer tissues and non-cancer tissues (P<0.

[Inhibition of growth and proliferation of Hep-2 cells by targeting c-myc gene using small interference RNA technology].

Objective: To investigate the effect of small interfering RNA (siRNA) targeting c-myc gene in Hep-2 cells.

Method: siRNA targeting c-myc mRNA was designed and synthesized. In vitro cultured Hep-2 cells were transfected with lipofectamine 2000 and the inhibitory effect was detected by MTT, morphology, real time PCR assay.