Genetic susceptibility in pneumoconiosis in China: a systematic review.

OBJECTIVE: Pneumoconiosis, encompassing coal workers' pneumoconiosis (CWP), silicosis and asbestosis, is one of the most common occupational diseases in China. Previous studies revealed significant associations between genetic variations and pneumoconiosis risk among individuals in different countries. With the known variability of genetic makeup between ethnicities, susceptibility to pneumoconiosis due to genetic differences is likely to be ethnicity-specific. The present review aimed at providing a comprehensive overview on the association between genetic polymorphisms and susceptibility of pneumoconiosis, specifically among people in China. METHODS: The literature search was performed in seven English and Chinese databases using keywords related to the review aim. An appraisal of the methodological quality of the included studies was conducted using the assessment tool derived from the Strengthening the Reporting of Genetic Association Studies (STREGA) statement. RESULTS: Forty-five studies were included in this review. Genotypes of specific genes which are associated with the risk of CWP, silicosis and asbestosis were reported. Our findings showed that genes encoding inflammatory cytokines have been examined extensively, and they demonstrated an association between these genes and pneumoconiosis risk. Gene-environment interactions in pneumoconiosis susceptibility were also reported by a number of studies. CONCLUSIONS: This review summarised the evidence demonstrating the association between genetic polymorphisms and pneumoconiosis susceptibility among people in China, and that various genotypes could modify their risk to develop pneumoconiosis. The findings prompt that identification of individuals at high pneumoconiosis risk through genetic screening and strategies limiting their exposure to dust could be a potential strategy for the control of this occupational disease in China.

Association between genetic polymorphisms in cytochrome P450 enzymes and survivals in women with breast cancer receiving adjuvant endocrine therapy: a systematic review and meta-analysis.

Tamoxifen is commonly prescribed for preventing recurrence in patients with breast cancer. However, the responses of the patients on tamoxifen treatment are variable. Cytochrome P450 genetic variants have been reported to have a significant impact on the clinical outcomes of tamoxifen treatment but no tangible conclusion can be made up till now. The present review attempts to provide a comprehensive review on the associative relationship between genetic polymorphisms in cytochrome P450 enzymes and survival in breast cancer patients on adjuvant tamoxifen therapy. The literature search was conducted using five databases, resulting in the inclusion of 58 studies in the review. An appraisal of the reporting quality of the included studies was conducted using the assessment tool from the Effective Public Health Practice Project (EPHPP). Meta-analyses were performed on CYP2D6 studies using Review Manager 5.3 software. For other studies, descriptive analyses were performed. The results of meta-analyses demonstrated that shorter overall survival, disease-free survival and relapse-free survival were found in the patients with decreased metabolisers when compared to normal metabolisers. The findings also showed that varying and conflicting results were reported by the included studies. The possible explanations for the variable results are discussed in this review.

Hypericin and Pheophorbide a Mediated Photodynamic Therapy Fighting MRSA Wound Infections: A Translational Study from In Vitro to In Vivo.

High prevalence rates of methicillin-resistant Staphylococcus aureus (MRSA) and lack of effective antibacterial treatments urge discovery of alternative therapeutic modalities. The advent of antibacterial photodynamic therapy (aPDT) is a promising alternative, composing rapid, nonselective cell destruction without generating resistance. We used a panel of clinically relevant MRSA to evaluate hypericin (Hy) and pheophobide a (Pa)-mediated PDT with clinically approved methylene blue (MB). We translated the promising in vitro anti-MRSA activity of selected compounds to a full-thick MRSA wound infection model in mice (in vivo) and the interaction of aPDT innate immune system (cytotoxicity towards neutrophils). Hy-PDT consistently displayed lower minimum bactericidal concentration (MBC) values (0.625-10 µM) against ATCC RN4220/pUL5054 and a whole panel of community-associated (CA)-MRSA compared to Pa or MB. Interestingly, Pa-PDT and Hy-PDT topical application demonstrated encouraging in vivo anti-MRSA activity (>1 log10 CFU reduction). Furthermore, histological analysis showed wound healing via re-epithelization was best in the Hy-PDT group. Importantly, the dark toxicity of Hy was significantly lower (p < 0.05) on neutrophils compared to Pa or MB. Overall, Hy-mediated PDT is a promising alternative to treat MRSA wound infections, and further rigorous mechanistic studies are warranted.

Exploration of Potential Genetic Biomarkers for Heart Failure: A Systematic Review.

Patients with heart failure (HF) often present with signs and symptoms that are often nonspecific and with a wide differential diagnosis, making diagnosis and prognosis of HF by clinical presentation alone challenging. Our knowledge on genetic diversity is rapidly evolving with high-throughput DNA sequencing technology, which makes a great potential for genetic biomarker development. The present review attempts to provide a comprehensive review on the modification of major genetic components in HF patients and to explore the potential application of these components as clinical biomarkers in the diagnosis and in monitoring the progress of HF. The literature search was conducted using six databases, resulting in the inclusion of eighteen studies in the review. The findings of these studies were summarized narratively. An appraisal of the reporting quality of the included studies was conducted using a twelve-item checklist adapted from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. The findings showed that changes in genetic components in patients with HF compared to healthy controls could be noninvasive diagnostic or prognostic tools for HF with higher specificity and sensitivity in comparison with the traditional biomarkers. This review provided evidence for the potential of developing genetic biomarkers of HF.

Association of early-life gut microbiome and lifestyle factors in the development of eczema in Hong Kong infants.

Childhood eczema is common but its prevalence is variable in different regions of the world. In this study, we explore the associations of various risk factors such as the microbiome, environment, lifestyle, diet and maternal stress with the development of eczema among infants in Hong Kong. Upon enrolment in the study, the infants' parents provided demographic data by self-reporting. At enrolment and 1 year after birth, the infants' allergic conditions, lifestyles and dietary factors and the degree of maternal stress were assessed using various questionnaires. The infants' gut microbiomes were analysed by 16S RNA sequencing, and the longitudinal changes in various bacterial strains were compared between control and eczema-affected groups. Multivariate analyses (after adjustment for other significant factors) revealed that the changes in the abundance of Hungatella hathewayi in the gut were significantly associated with the development of eczema (p = 0.005). In conclusion, the increased abundance of Hungatella hathewayi was associated with an increased risk of developing eczema by 1 year of age. This study thus explored the potential risk factors for the development of eczema in Hong Kong infants, and sheds light on the possible association between early-life gut microbiome and other environmental factors.

Effects of gut microbiome and environment on the development of eczema in Chinese infants.

BACKGROUND: Eczema is a relapsing and persistent inflammatory skin disease affecting about one-fifth of children worldwide. As in other developed countries, the prevalence of this chronic disease in Hong Kong is approximately 30%. Moreover, the number of local cases reported has been on a rising trend since 1995. Eczema frequently starts in early infancy. A total of 45% of all cases begin within the first six months of life, 60% during the first year and 85% before the age of 5. The pathophysiology of eczema is multi-factorial and is a complex inter-relationship between skin barrier, genetic predisposition, immunologic development, microbiome, environment, nutrition, and pharmacological and psychological factors. OBJECTIVE: To characterize the longitudinal changes of gut microbial profile in early childhood and to examine the association between gut microbiome diversity, environmental factors and the development of eczema in early childhood. METHOD: We will conduct a longitudinal cohort study that follows 1250 Hong Kong Chinese infants for 2 years and assess the gut microbiome and other potential environmental factors in the aetiology of eczema. Parents will be asked to provide demographic data, their infant birth data, allergy condition, diet, environmental conditions as well as the data on maternal stress. Stool specimen will be collected for gut microbiome diversity analysis. We will examine newborn infants at enrollment, at 4 months, 1 year and 2 years after birth. EXPECTED RESULTS: This study will evaluate the association between gut microbiome, environmental factors and the development of eczema in Chinese infants. Findings from this study may be used to develop a predictive path model to guide effective health promotion, disease prevention and management.

Tamoxifen-related endocrine symptoms in Chinese patients with breast cancer: Study protocol clinical trial (SPIRIT Compliant).

BACKGROUND: Breast cancer is the most prevalent cancer in females and disease recurrence remains a significant problem. To prevent recurrence, tamoxifen is prescribed for at least 5 years. However, among patients who receive tamoxifen, individual responses are highly variable. These responses are affected by the type, frequency, and severity of endocrine symptoms, as well as adherence rates. Polymorphisms in genes involved in the metabolism of tamoxifen (ie, CYP3A4, CYP2D6) may influence responses to tamoxifen. In this study, the inter-relationships among endocrine symptoms, drug adherence, and genetic polymorphisms in Chinese breast cancer patients receiving tamoxifen therapy will be examined. We hypothesize that patients with more severe endocrine symptoms will be less likely to adhere to tamoxifen treatment. In addition, we hypothesize that a relationship will exist between the severity of tamoxifen-induced symptoms and allelic variations in tamoxifen metabolism-related genes. Although many association studies have determined that select genotypes influence the efficacy of tamoxifen, very few studies have investigated for associations between tamoxifen-induced endocrine symptoms and these polymorphisms. OBJECTIVES: The aim of this study was to characterize genetic polymorphisms in tamoxifen metabolism-associated genes in Chinese women with breast cancer and to explore the inter-relationships between genetic polymorphisms, endocrine symptoms, and adherence to tamoxifen. METHOD: We will conduct a prospective cohort study that follows 200 Chinese women over 18 months and assess treatment-related symptoms and genetic variations. Endocrine symptoms and drug adherence will be determined through interview-administered standardized questionnaires. Polymorphisms in drug metabolism genes will be determined using real-time polymerase chain reaction based genotyping method. Data will be analyzed to determine associations between allelic variations, endocrine symptoms, and adherence. DISCUSSION: The proposed study will evaluate for polymorphisms in gene(s) that are associated with tamoxifen-related endocrine symptoms and adherence with tamoxifen. We will explore the relationships between genotypes, endocrine symptoms, and drug adherence in Chinese breast cancer patients. Findings from this study may assist clinicians to identify patients at higher risk for a worse symptom experience and lower adherence rates and enable them to initiate appropriate interventions. In the long term, the findings from this study may be used to develop and test tailored symptom management interventions for these patients.

Trimethylamine-N-oxide as One Hypothetical Link for the Relationship between Intestinal Microbiota and Cancer - Where We Are and Where Shall We Go?

Previous epidemiological studies had provided evidence for a link between the microbial dysbiosis and cancer, particularly colorectal cancer (CRC), yet the molecular basis of this link remains elusive. Recently, the association between plasma levels of trimethylamine-N-oxide (TMAO), an oxidised form of trimethylamine (TMA), and risks of various cancers was demonstrated. The discovery could potentially provide an alternative explanation for the aforementioned link, as TMA production is attributed to intestinal bacteria. Current evidence suggests that inflammation could be a potential molecular mechanism to explain the link between TMAO and cancer, although other mechanisms such as oxidative stress, DNA damage and disruption in protein folding might also play a role. This mini-review article first provides an overview of the current evidence for the association between TMAO and certain cancer types, and the potential mechanisms that could explain their association. Thereafter, the direction of further research on the connection between the intestinal microbiota, TMAO and cancer is suggested.

Regulation of TLR4 in silica-induced inflammation: An underlying mechanism of silicosis.

Silicosis is an incurable lung disease affecting millions of workers in hazardous occupations. It is caused by chronic exposure to the dust that contains free crystalline silica. Silica-induced lung damage occurs by several main mechanisms including cell death by apoptosis, fibrosis and production of cytokines. However, the signal pathways involved in these mechanisms are not fully characterized. In this study, the toll-like receptor 4 (TLR4)-related signal pathway was examined in silica-treated U937-differentiated macrophages. The expression level of TLR4 was measured by both quantitative PCR and Western blot. Confirmation of the involvement of MyD88/TIRAP and NFκB p65 cascade was performed by Western blot. The secretion of cytokines IL-1ß, IL-6, IL-10 and TNFα was measured by enzyme-linked immunosorbent assay. Our results showed that TLR4 and related MyD88/TIRAP pathway was associated with silica-exposure in U937-differentiated macrophages. Protein expression of TLR4, MyD88 and TIRAP was upregulated when the U937-differentiated macrophages were exposed to silica. However, the upregulation was attenuated when TLR4 inhibitor, TAK-242 was present. At different incubation times of silica exposure, it was found that NFκB p65 cascade was activated at 10-60 minutes. Release of cytokines IL-1ß, IL-6, IL-10 and TNFα was induced by silica exposure and the induction of IL-1ß, IL-6 and TNFα was suppressed by the addition of TAK-242. In conclusion, our study demonstrated that TLR4 and related MyD88/TIRAP pathway was involved in silica-induced inflammation in U937-differentiated macrophages. Downstream NFκB p65 cascade was activated within 1 hour when the U937-differentiated macrophages were exposed to silica. The better understanding of early stage of silica-induced inflammatory process may help to develop earlier diagnosis of silicosis.

Novel Kunitz-like Peptides Discovered in the Zoanthid Palythoa caribaeorum through Transcriptome Sequencing.

Palythoa caribaeorum (class Anthozoa) is a zoanthid that together jellyfishes, hydra, and sea anemones, which are venomous and predatory, belongs to the Phyllum Cnidaria. The distinguished feature in these marine animals is the cnidocytes in the body tissues, responsible for toxin production and injection that are used majorly for prey capture and defense. With exception for other anthozoans, the toxin cocktails of zoanthids have been scarcely studied and are poorly known. Here, on the basis of the analysis of P. caribaeorum transcriptome, numerous predicted venom-featured polypeptides were identified including allergens, neurotoxins, membrane-active, and Kunitz-like peptides (PcKuz). The three predicted PcKuz isotoxins (1-3) were selected for functional studies. Through computational processing comprising structural phylogenetic analysis, molecular docking, and dynamics simulation, PcKuz3 was shown to be a potential voltage gated potassium-channel inhibitor. PcKuz3 fitted well as new functional Kunitz-type toxins with strong antilocomotor activity as in vivo assessed in zebrafish larvae, with weak inhibitory effect toward proteases, as evaluated in vitro. Notably, PcKuz3 can suppress, at low concentration, the 6-OHDA-induced neurotoxicity on the locomotive behavior of zebrafish, which indicated PcKuz3 may have a neuroprotective effect. Taken together, PcKuz3 figures as a novel neurotoxin structure, which differs from known homologous peptides expressed in sea anemone. Moreover, the novel PcKuz3 provides an insightful hint for biodrug development for prospective neurodegenerative disease treatment.

Evaluation in zebrafish model of the toxicity of rhodamine B-conjugated crotamine, a peptide potentially useful for diagnostics and therapeutics.

Crotamine is defensin-like cationic peptide from rattlesnake venom that possesses anticancer, antimicrobial, and antifungal properties. Despite these promising biological activities, toxicity is a major concern associated with the development of venom-derived peptides as therapeutic agents. In the present study, we used zebrafish as a system model to evaluate the toxicity of rhodamine B-conjugated (RhoB) crotamine derivative. The lethal toxic concentration of RhoB-crotamine was as low as 4 µM, which effectively kill zebrafish larvae in less than 10 min. With non-lethal concentrations (<1 µM), crotamine caused malformation in zebrafish embryos, delayed or completely halted hatching, adversely affected embryonic developmental programming, decreased the cardiac functions, and attenuated the swimming distance of zebrafish. The RhoB-crotamine translocated across vitelline membrane and accumulated in zebrafish yolk sac. These results demonstrate the sensitive responsivity of zebrafish to trial crotamine analogues for the development of novel therapeutic peptides with improved safety, bioavailability, and efficacy profiles.

Evaluating Efficacy and Safety of Combination Medication of Atorvastatin and a Herbal Formula Containing Salvia miltiorrhiza and Pueraria lobata on Hyperlipidemia.

Despite being a potent hypolipidemic drug, atorvastatin (AS) possesses certain adverse effects. Using AS and an herbal formula (Danshen and Gegen, DG) in combination may achieve potentiated hypolipidemic effects and also reduce its adverse effects. Hence, this study aimed to investigate the efficacy and safety of an AS and DG combination on high-fat diet-induced hyperlipidemia. Treatment outcomes were assessed by measuring parameters including body weight, adipose tissue, liver, total cholesterol, triglyceride, and low-density and high-density lipoprotein cholesterol. Measurements of adverse effects were achieved by determining aspartate aminotransferase (AST), alanine transaminase (ALT), and creatine kinase (CK). Danshen and Gegen, as well as AS alone, reduced body weight, adipose tissue, liver weight, liver fat vacuoles, total liver lipids, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in high-fat diet-fed mice but increased AST, ALT, and CK. A combination of AS and DG was able to enhance reduced effects on the aforementioned parameters in relation to hyperlipidemia over AS or DG alone. It also reduced the elevation of AST, ALT, and CK induced than by AS or DG alone. Results demonstrated that an AS and DG combination resulted in stronger hypolipidemic effects than with AS or DG alone. Additionally, DG might attenuate adverse effects of AS on the liver and skeletal muscle. Copyright © 2017 John Wiley & Sons, Ltd.

An andrographolide derivative AGP-26b exhibiting anti-angiogenic activity in HUVECs and zebrafish via blocking the VEGFA/VEGFR2 signaling pathway.

The aim of this study is to investigate the anti-angiogenic properties of andrographolide derivatives AGP-26a (12ß-isomer), AGP-26b (12α-isomer) and AGP-26 (4 : 1 mixture of AGP-26a and AGP-26b) in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) and the Tg(fli-1a:EGFP)y1 zebrafish model were used to identify the anti-angiogenic activities of AGP-26, AGP-26a, and AGP-26b. The results showed that AGP-26b exhibits the strongest inhibitory effect on VEGF-induced proliferation, migration, invasion and formation of capillary-like structures in HUVECs. In the zebrafish model, AGP-26b also showed the strongest suppression of ISV development. Further studies showed that the underlying mechanism of the anti-angiogenic effects of AGP-26b was at least partly through the blockage of the VEGF/VEGFR2 signaling pathways. AGP-26b blocked the activation of VEGFR2. Consequently, the phosphorylation of key intracellular proangiogenic kinases such as Src family kinase (Src), focal adhesion kinase (Fak), mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase 1 and 2 (Erk1/2) and Akt induced by VEGF was suppressed by treatment with AGP-26b. Moreover, AGP-26b reduced the protein expression of matrix metalloproteinases (MMP-9 but not MMP-2) in HUVECs. These results provide evidence supporting the notion that AGP-26b may serve as a potential therapeutic anti-angiogenic agent.

A new cycloartane-type triterpenoid from the roots of Dianella ensifolia (L.) DC.

A new cycloartane-type triterpenoid, named 22-hydroxy-cyclolaudenol (1), together with two known cycloartane-type triterpenoids were isolated from the roots of Dianella ensifolia. Their structures were determined based on spectroscopic methods, including UV, IR, HR-ESI-MS, NMR and X-ray diffraction. Compound 1 displayed cytotoxic effects against cancer cell lines B16-F10, A549 and MDA-MB-231.

Synergistic effect of fenretinide and curcumin for treatment of non-small cell lung cancer.

Curcumin and fenretinide are 2 well-known and promising chemotherapeutic compounds via various molecular mechanisms. However, the anticancer capacity of either curcumin or fenretinide is limited. This prompted us to examine the combined anticancer effects of curcumin and fenretinide. Our results demonstrate for the first time that there is synergistic anticancer effect of combined treatment with these 2 agents, leading to enhanced cytotoxicity and enhanced expression level of pro-apoptotic protein cleaved PARP in non-small cell lung cancer (NSCLC) cells while showed little toxicity to rat cardiomyoblast normal cells. The combination treatment was also demonstrated to inhibit lung carcinoma growth in vivo. Furthermore, we show that fenretinide or the ER stress inhibitor 4-PBA decreased curcumin-induced Glucose-regulated protein 78 (GRP78) upregulation, and produced a similar enhanced cytotoxic effect. In addition, GRP78 knockdown by siRNA also enhanced the cytotoxic effect of curcumin in A549 and H1299 cells. Our findings suggest that the 2 small molecules, when used in combination, can potentially be effective therapeutic agents for treating NSCLC, at least in part, by regulating endoplasmic reticulum (ER) chaperone protein GRP78.

Anti-angiogenic activity of a new andrographolide derivative in zebrafish and HUVECs.

Andrographolide is among the most promising anti-tumor and anti-angiogenic components in Andrographis paniculata but its poor bioavailability and limited efficacy pose difficulties for its therapeutic development. Therefore, improving its pharmaceutical features and potency, by modifying its chemical structure, is desirable. In the present study, a new andrographolide derivative (AGP-40) was synthesized and characterized for its anti-angiogenic properties. Human umbilical vein endothelial cells (HUVECs) and zebrafish models were used to identify the anti-angiogenic activity of AGP-40. AGP-40 significantly suppressed the formation of blood vessels in zebrafish and inhibited proliferation, migration and tube formation in vitro. The anti-angiogenic effects of AGP-40 are at least partially mediated via the PI3K/Akt and MEK/Erk(1/2) signaling pathways. Furthermore, AGP-40 exhibited stronger anti-proliferative effects than andrographolide against A549, HepG2, Hela cancer cell lines. This study is the first to demonstrate the promising anti-angiogenic activity of the new andrographolide derivative AGP-40. Our results indicate that AGP-40 could serve as a potential therapeutic agent for the treatment and prevention of diseases associated with excessive angiogenesis.

Complexation of clofazimine by macrocyclic cucurbit[7]uril reduced its cardiotoxicity without affecting the antimycobacterial efficacy.

Cucurbit[7]uril (CB[7]) has recently attracted increasing attention in pharmaceutical sciences due to its great potential in improving the physicochemical properties and bioactivity of drug molecules. Herein, we have investigated the influence of CB[7]'s complexation on the solubility, antimycobacterial activity, and cardiotoxicity of a model anti-tuberculosis drug, clofazimine (CFZ), that has poor water-solubility and inherent cardiotoxicity. In our study, CFZ was found to be complexed by CB[7], in a 1 : 1 binding mode with a relatively strong binding affinity (in the order of magnitude of 10(4)-10(5) M(-1)), as determined by the phase solubility method via HPLC-UV analysis and (1)H NMR titration, as well as UV-visible spectroscopic titration, and further confirmed by electrospray ionization mass spectrometry (ESI-MS). Upon complexation, the solubility of virtually insoluble CFZ was significantly increased, reaching a concentration of up to approximately 0.53-fold of the maximum solubility of CB[7]. The inherent cardiotoxicity of CFZ was dramatically reduced to almost nil in the presence of CB[7]. Importantly, on the other hand, such a supramolecular complexation of the drug did not compromise its therapeutic efficacy, as shown by the antimycobacterial activities examined against Mycobacterium smegmatis, demonstrating the significant potential of CB[7] as a functional pharmaceutical excipient.

A novel agent exerts antitumor activity in breast cancer cells by targeting mitochondrial complex II.

The mitochondrial respiratory chain, including mitochondrial complex II, has emerged as a potential target for cancer therapy. In the present study, a novel conjugate of danshensu (DSS) and tetramethylpyrazine (TMP), DT-010, was synthesized. Our results showed that DT-010 is more potent than its parental compounds separately or in combination, in inhibiting the proliferation of MCF-7 and MDA-MB-231 cells by inducing cytotoxicity and promoting cell cycle arrest. It also inhibited the growth of 4T1 breast cancer cells in vivo. DT-010 suppressed the fundamental parameters of mitochondrial function in MCF-7 cells, including basal respiration, ATP turnover, maximal respiration. Treatment with DT-010 in MCF-7 and MDA-MB-231 cells resulted in the loss of mitochondrial membrane potential and decreased ATP production. DT-010 also promoted ROS generation, while treatment with ROS scavenger, NAC (N-acetyl-L-cysteine), reversed DT-010-induced cytotoxicity. Further study showed that DT-010 suppressed succinate-induced mitochondrial respiration and impaired mitochondrial complex II enzyme activity indicating that DT-010 may inhibit mitochondrial complex II. Overall, our results suggested that the antitumor activity of DT-010 is associated with inhibition of mitochondrial complex II, which triggers ROS generation and mitochondrial dysfunction in breast cancer cells.

A Novel Danshensu Derivative Prevents Cardiac Dysfunction and Improves the Chemotherapeutic Efficacy of Doxorubicin in Breast Cancer Cells.

Doxorubicin (Dox) is an anthracycline antibiotic widely used in clinics as an anticancer agent. However, the use of Dox is limited by its cardiotoxicity. We have previously shown that a Danshensu (DSS) derivative, ADTM, displayed strong cardioprotective effects. With improved chemical stability and activity, a novel DSS derivative, D006, based on the structure of ADTM, was synthesized. In the present study, the protective effects of D006, indexed by attenuation of the cardiotoxicity induced by Dox as well as chemosensitizing effects that increase the antitumor activity of Dox, were investigated. Our results showed that D006 was more potent than either parental compound, or their use in combination, in ameliorating Dox-induced toxicity in H9c2 cells. In our zebrafish model, D006, but not DSS, alone significantly preserved the ventricular function of zebrafish after Dox treatment. Moreover, D006 upregulated mitochondrial biogenesis and increased mtDNA copy number after Dox treatment of H9c2 cells. D006 promoted the expression of HO-1 protein in a time-dependent manner while the HO-1 inhibitor, Znpp, reversed the protective effects of D006. In human breast tumor MCF-7 cells, D006 enhanced Dox-induced cytotoxicity by increasing apoptosis. In conclusion, our results indicate that a new DSS derivative exhibits promising protective effects against Dox-induced cardiotoxicity both in vivo and in vitro, an effect at least partially mediated by induction of HO-1 expression and the activation of mitochondrial biogenesis. Meanwhile, D006 also potentiated the anti-cancer effects of Dox in breast tumor cells.