A risk prediction nomogram for resistant hypertension in patients with obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) are liable to have resistant hypertension (RH) associated with unfavorable cardiovascular events. It is of necessity to predict OSA patients who are susceptible to resistant hypertension. Hence, we conducted a retrospective study based on the clinical records of OSA patients admitted to Yixing Hospital Affiliated to Jiangsu University from January 2018 to December 2022. According to different time periods, patients diagnosed between January 2018 and December 2021 were included in the training set (n = 539) for modeling, and those diagnosed between January 2022 and December 2022 were enrolled into the validation set (n = 259) for further assessment. The incidence of RH in the training set and external validation set was comparable (P = 0.396). The related clinical data of patients enrolled were collected and analyzed through univariate analysis and least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a nomogram. Finally, five variables were confirmed as independent risk factors for OSA patients with RH, including smoking, heart disease, neck circumference, AHI and T90. The nomogram established on the basis of variables above was shown to have good discrimination and calibration in both the training set and validation set. Decision curve analysis indicated that the nomogram was useful for a majority of OSA patients. Therefore, our nomogram might be useful to identify OSA patients at high risk of developing RH and facilitate the individualized management of OSA patients in clinical practice.

Aggregation-induced signal amplification strategy based on peptide self-assembly for ultrasensitive electrochemical detection of melanoma biomarker.

The detection of melanoma circulating biomarker in liquid biopsies is current under evaluation for being potentially utilized for earlier cancer diagnosis and its metastasis. Herein, we developed a non-invasive electrochemical approach for ultrasensitive detection of the S100B, serving as a potential promising blood circulating biomarker of melanoma, based on an aggregation-induced signal amplification (AISA) strategy via in-situ peptide self-assembly. The fundamental principle of this assay is that the designed amphiphilic peptides (C16-Pep-Fc), fulfilling multiple functions, feature both a recognition region for specific binding to S100B and an aggregation (self-assembly) region for the formation of peptide nanomicelles under mild conditions. The C16 tails were encapsulated within the hydrophobic core of the aggregates, while the relatively hydrophilic recognition fragment Pep and Fc tag were exposed on the outer surface for subsequent recognition of S100B and signal output. AISA provided remarkable accumulation of electroactive Fc moieties that enabled ultrasensitive S100B detection of as low as 0.02 nM, which was 10-fold lower than un-amplified approach and better than previously reported assays. As a proof-of-concept study, further experiments also highlighted the good reproducibility and stability of AISA and demonstrated its usability when applied to simulated serum samples. Hence, this work not only presented a valuable assay tool for ultrasensitive detecting protein biomarker, but also advocated for the utilization of aggregation-induced signal amplification in electrochemical biosensing system, given its considerable potential for future practical applications.

Analysis of Correlation Between Serum Hypoxia-Inducible Factor-1α, Uric Acid, and Inflammatory Factor Levels and Lung Function in Patients with AECOPD.

Objective: To investigate the correlation between the serum hypoxia-inducible factor-1α, uric acid, inflammatory factor levels, and lung function in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: The clinical data of patients with chronic obstructive pulmonary disease (40 cases) from March 2020 to March 2021 were retrospectively analyzed. According to the disease condition in patients with chronic obstructive pulmonary disease, they were divided into acute exacerbation stage (observation group, 20 cases) and stable stage (control group, 20 cases). All patients' basic data such as age, sex, and course of disease were collected and sorted out, and the serum hypoxia-inducible factor-1α, uric acid, inflammatory factor levels (procalcitonin, interleukin-6, and high-sensitivity C-reactive protein), and the index of their pulmonary function were measured. The profiles of serum hypoxia-inducible factor-1 alpha and uric acid, levels of inflammatory factors, and pulmonary function indices were measured and compared between the observation and control groups. The correlation between patients' serum hypoxia-inducible factor-1α, uric acid, and inflammatory factors and lung function was analyzed. Results: There was no difference in basic data between the observation group and the control group, P > .05. Serum hypoxia-inducible factor-1α, uric acid, and levels of inflammatory factors were all higher in the observation group than the control group, and the differences are significant (P < .05). There was significant difference in lung function indexes between the observation group and the control group (P < .05). Serum hypoxia-inducible factor-1α, uric acid, and inflammatory factor levels were negatively associated with pulmonary function indices. Conclusion: The more serious the condition of AECOPD patients is, the levels of serum hypoxia inducible factor -1α, uric acid and inflammatory factors gradually increase, and the lung function tends to decline.

Exosomal Long Noncoding RNAs in NSCLC: Dysfunctions and Clinical Potential.

Exosomes are a typical subset of extracellular vesicles (EVs) that can be transmitted from parent cells to recipient cells via human bodily fluids. Exosomes perform a vital role in mediating intercellular communication by shuttling bioactive cargos, such as nucleic acids, proteins and lipids. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides without protein translation ability and can be selectively packaged into exosomes. Accumulating evidence indicates that exosomal lncRNAs have a critical role in tumor initiation and progression through regulating tumor proliferation, apoptosis, invasion, metastasis, angiogenesis, treatment resistance and tumor microenvironment. Increasing studies suggest that exosomal lncRNAs have great potential to be served as novel targets and non-invasive biomarkers for diagnosis and prognosis in non-small cell lung cancer (NSCLC). In this review, we provide an overview of current research on the disordered functions of exosomal lncRNAs in NSCLC and summarize their potential clinical applications as diagnostic and prognostic biomarkers and therapeutic targets for NSCLC.

Risk Factors of Readmission Within 90 Days for Chronic Obstructive Pulmonary Disease Patients with Frailty and Construction of an Early Warning Model.

Objective: This study aimed to explore the risk factors for readmission within 90 d in Chronic Obstructive Pulmonary Disease (COPD) patients with frailty and construct a clinical warning model. Methods: COPD patients with frailty hospitalized in the Department of Respiratory and Critical Care Medicine of Yixing Hospital, Affiliated to Jiangsu University, were retrospectively collected from January 1, 2020, to June 30, 2022. Patients were divided into readmission and control groups according to readmission within 90 d. The clinical data of the two groups were evaluated by univariate and multivariate logistic regression analyses to identify readmission risk factors within 90 d in COPD patients with frailty. Then, a risk quantitative early warning model was constructed. Finally, the model's prediction efficiency was evaluated, and external verification was carried out. Results: The multivariate logistic regression analysis showed that BMI, number of hospitalizations in the past year ≥ 2, CCI, REFS, and 4MGS were independent risk factors for readmission within 90 d in COPD patients with frailty. The early warning model for these patients was established as follows: Logit (p) = -1.896 + (-0.166 × BMI) + (0.969 × number of hospitalizations in the past year ≥ 2) + (0.265 × CCI) + (0.405 × REFS) + (-3.209 × 4MGS), and presented an area under the ROC curve (AUC) of 0.744 [95% CI: 0.687-0.801]. The AUC of the external validation cohort was 0.737 (95% CI: 0.648-0.826), and the AUC of the LACE warning model was 0.657 (95% CI:0.552-0.762). Conclusion: The BMI, number of hospitalizations in the past year ≥ 2, CCI, REFS, and 4MGS were independent risk factors for readmission within 90 d in COPD patients with frailty. The early warning model presented a moderate predictive value for assessing the risk of readmission within 90 d in these patients.

Emerging roles of tRNA-derived fragments in cancer.

tRNA-derived fragments (tRFs) are an emerging category of small non-coding RNAs that are generated from cleavage of mature tRNAs or tRNA precursors. The advance in high-throughput sequencing has contributed to the identification of increasing number of tRFs with critical functions in distinct physiological and pathophysiological processes. tRFs can regulate cell viability, differentiation, and homeostasis through multiple mechanisms and are thus considered as critical regulators of human diseases including cancer. In addition, increasing evidence suggest the extracellular tRFs may be utilized as promising diagnostic and prognostic biomarkers for cancer liquid biopsy. In this review, we focus on the biogenesis, classification and modification of tRFs, and summarize the multifaceted functions of tRFs with an emphasis on the current research status and perspectives of tRFs in cancer.

In vitro electrochemical detection of the degradation of amyloid-ß oligomers.

The clearance of overloaded amyloid ß (Aß) oligomers is thought to be an attractive and potential strategy for the therapy of Alzheimer's disease (AD). A variety of strategies have already been utilized to study Aß degradation in vitro. Here, the electrochemical detection based on direct electrooxidation of specific Tyr residues within Aß peptide has been developed as a simple and robust approach for monitoring the oligomers' degradation. C60 was employed for photodegrading Aß oligomers due to the generated ROS under light irradiation. The oxidation current of Tyr residues by square wave voltammetry (SWV) increased upon the Aß degradation, confirming that the structure variation of Aß peptide indeed influenced the exposure of those redox species to the electrode surface and final signal output. Chronoamperometric assay also found the electrooxidation of Tyr undergone an irreversible process. Additionally, the direct electrochemistry was capable of detecting the aggregation with rapid test and better sensitivity in compared with dynamic light scattering (DLS), atomic force microscopy (AFM) and thioflavin T (ThT) based fluorescence assay. Thus, this work indicated the potential application of direct electrochemistry in the in vitro measurement of Aß degradation and clearance, providing new insights and a complementary means into the AD theranostics.

Extracellular Vesicles in Cancer Drug Resistance: Roles, Mechanisms, and Implications.

Extracellular vesicles (EVs) are cell-derived nanosized vesicles that mediate cell-to-cell communication via transporting bioactive molecules and thus are critically involved in various physiological and pathological conditions. EVs contribute to different aspects of cancer progression, such as cancer growth, angiogenesis, metastasis, immune evasion, and drug resistance. EVs induce the resistance of cancer cells to chemotherapy, radiotherapy, targeted therapy, antiangiogenesis therapy, and immunotherapy by transferring specific cargos that affect drug efflux and regulate signaling pathways associated with epithelial-mesenchymal transition, autophagy, metabolism, and cancer stemness. In addition, EVs modulate the reciprocal interaction between cancer cells and noncancer cells in the tumor microenvironment (TME) to develop therapy resistance. EVs are detectable in many biofluids of cancer patients, and thus are regarded as novel biomarkers for monitoring therapy response and predicting prognosis. Moreover, EVs are suggested as promising targets and engineered as nanovehicles to deliver drugs for overcoming drug resistance in cancer therapy. In this review, the biological roles of EVs and their mechanisms of action in cancer drug resistance are summarized. The preclinical studies on using EVs in monitoring and overcoming cancer drug resistance are also discussed.

Associations of Clinical Characteristics and Intestinal Flora Imbalance in Stable Chronic Obstructive Pulmonary Disease (COPD) Patients and the Construction of an Early Warning Model.

OBJECTIVE: Establish a simple predictive model and scoring rule that is suitable for clinical medical staff in respiratory departments to assess intestinal flora imbalance occurrence in stable chronic obstructive pulmonary disease (COPD) patients. METHODS: From January 1, 2019, to December 31, 2020, COPD patients (195 cases) - who attended the Outpatient Department, Respiratory and Critical Care, Yixing Hospital, Jiangsu University - were enrolled in a cross-sectional study. Based on stool examination results, patients were divided into experimental (41 cases) and control (154 cases) groups. Single-factor and logistic regression analyses were performed with the baseline data of the two groups to obtain a new predictive model, which was further simplified. RESULTS: Five predictive factors composed the model: body mass index (BMI), serum albumin (ALB), Charlson's Comorbidity Index (CCI), gastrointestinal symptom score (GSRs), and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. The model to predict intestinal flora imbalance in stable COPD patients had an area under the ROC curve (AUC) of 0.953 [95% CI (0.924, 0.982)]. After simplifying the scoring rules, the AUC was 0.767 [95% CI (0.676, 0.858)]. CONCLUSION: In the current study, we obtained a model that could effectively predict intestinal flora imbalance risk in stable COPD patients, being suitable for implementation in early treatments to improve the prognosis. Moreover, all indicators can be easily and simply obtained.

A smartphone-integrated multicolor fluorescence probe of bacterial spore biomarker: The combination of natural clay material and metal-organic frameworks.

The metal-organic frameworks (MOFs) functionalized palygorskite (Pal) hybrid as a novel multicolor fluorescence probe for the detection of bacterial spore biomarker-dipicolinic acid (DPA), had been prepared via in-situ growth. The MOFs can effectively encapsulate dye molecules on the surface of Pal, and the rich carboxyl groups on its surface can coordinate with europium ions (Eu3+), forming a highly sensitive recognition group. The results indicated that the limit of detection (LOD) of this multicolor fluorescence probe was as low as 9.3 nM and was obviously lower than the amount of anthrax spores infecting the human body (60 µM). Moreover, a wide linear range from 0 to 35 µM was obtained. The high specific surface area of Pal, as well as the permanent porosity and suitable binding sites of Eu3+-doped MOFs may play a major role in the sensitivity and linear detection range. The multicolor fluorescence strategy made full use of the diversity of fluorescence signals collected by dye molecules and lanthanide ions, which can realize the real-time and on-site detection through the smartphone with a color-scanning application (APP). The practicability of this probe was further verified by detecting DPA released by non-infectious Bacillus subtilis.

Exosome-transmitted lncRNA UFC1 promotes non-small-cell lung cancer progression by EZH2-mediated epigenetic silencing of PTEN expression.

Long non-coding RNAs (LncRNAs) have been suggested as important regulators of cancer development and progression in non-small cell lung cancer (NSCLC). Nevertheless, the biological roles and clinical significance of lncRNA UFC1 in NSCLC remain unclear. We detected the expression of UFC1 in tumor tissues, serum, and serum exosomes of NSCLC patients by qRT-PCR. Gene overexpression or silencing were used to examine the biological roles of UFC1 in NSCLC. RNA immunoprecipitation and ChIP assays were performed to evaluate the interaction between UFC1 and enhancer of zeste homolog 2 (EZH2) and the binding of EZH2 to PTEN gene promoter. Rescue study was used to access the importance of PTEN regulation by UFC1 in NSCLC progression. UFC1 expression was upregulated in tumor tissues, serum, and serum exosomes of NSCLC patients and high level of UFC1 was associated with tumor infiltration. UFC1 knockdown inhibited NSCLC cell proliferation, migration and invasion while promoted cell cycle arrest and apoptosis. UFC1 overexpression led to the opposite effects. Mechanistically, UFC1 bound to EZH2 and mediated its accumulation at the promoter region of PTEN gene, resulting in the trimethylation of H3K27 and the inhibition of PTEN expression. UFC1 knockdown inhibited NSCLC growth in mouse xenograft tumor models while the simultaneous depletion of PTEN reversed this effect. NSCLC cells derived exosomes could promote NSCLC cell proliferation, migration and invasion through the transfer of UFC1. Moreover, Exosome-transmitted UFC1 promotes NSCLC progression by inhibiting PTEN expression via EZH2-mediated epigenetic silencing. Exosome-mediated transmit of UFC1 may represent a new mechanism for NSCLC progression and provide a potential marker for NSCLC diagnosis.

GdPO4-Based Nanoprobe for Bioimaging and Selective Recognition of Dipicolinic Acid and Cysteine by a Sensing Ensemble Approach.

Multiple functions incorporated in one single-component nanoplatform pave the way for important biomedicine applications. Herein, a multifunctional terbium-doped gadolinium orthophosphate (GdPO4:Tb-EDTA) nanoplatform was prepared through a simple, ecofriendly, one-step hydrothermal method. Results showed that dipicolinic acid (DPA), the biomarker of bacterial spores, significantly increased the fluorescence intensity of this nanoplatform and conferred it with rapid response and excellent selectivity. Subsequently, the fluorescence of the ensemble GdPO4:Tb-EDTA-DPA can be remarkably quenched by Cu2+, which led to a rewritable nanosensor used in the detection of cysteine (Cys) with excellent sensitivity. In addition, GdPO4:Tb-EDTA can also be a potential T1-weighted magnetic resonance imaging (MRI) contrast agent, which indicated a satisfactory in vitro MRI with r1 relaxivity values of 13.9 mM-1 s-1 and in vivo MRI through intravenous administration on a rat model. Overall, the proposed assay may have great theoretical and practical significance for designing multifunctional biomaterials.

A novel visual ratiometric fluorescent sensing platform for highly-sensitive visual detection of tetracyclines by a lanthanide- functionalized palygorskite nanomaterial.

A palygorskite (Pal)-based ratiometric fluorescent nanoprobe is designed in order to establish a real time, on-site visual, and highly sensitive detection method for tetracyclines (TCs). The nanoprobe comprises the green emissive dye molecules embedded in the natural Pal, which serve as the internal reference signal. The potential red-emissive seed-europium (Eu3+) ions are covalently bound on the surface of modified Pal, and they can act as the specific recognition element. The emission intensity of Eu3+ ions significantly increases upon TC addition. The nanoprobe fluorescence changes from green to yellow, orange, or red, thereby accomplishing the visual ratiometric fluorescent detection. This nanoprobe exhibits a high sensitivity with a detection limit of 7.1nM and an excellent selectivity in monitoring the levels of TCs in milk samples. In addition, this nanoprobe is useful for quantitative determination of TCs, and it is not affected with intensity fluctuations due to instrumental or environmental factors. The nanoprobe-immobilized test paper realizes real-time TCs analysis by using a smartphone with an easy-to-access color-scanning APP as the detection platform. Moreover, the reported construction of visual ratiometric detection system follows the sustainable development idea, that is, from nature, for nature, and into the nature.

Synthesis, characterization and antitumor activity of Ln(III) complexes with hydrazone Schiff base derived from 2-acetylpyridine and isonicotinohydrazone.

In the present study, two isostructural lanthanide (Ln)(III) complexes, namely Ln(HL)2(NO3)(CH3OH)2)·CH3OH, where Ln = La in complex 1 and Ce in complex 2, and hydrogen ligand (HL) = (E)-N'-[1-(2-pyridinyl)ethylidene]isonicotinohydrazone, have been isolated and characterized by elemental analysis, infrared spectra and single-crystal X-ray diffraction analysis. The results revealed that the acylhydrazone ligand HL in each complex was deprotonated as an anionic ligand and coordinated to the central La(III) ion via enolization of oxygen and nitrogen atoms. Furthermore, the antitumor effects and potential mechanisms of the two complexes were explored in the human lung cancer cell line A549 and in the human gastric cancer cell lines BGC823 and SGC7901. In the present study, the roles the two complexes on the proliferation and apoptosis of the above tumor cell lines were determined by MTT assay and Annexin V/propidium iodide flow cytometry, respectively. Furthermore, various apoptosis-associated key genes, including caspase 3, B cell lymphoma (Bcl)-2-associated X protein (Bax) and Bcl-2, were detected by western blotting to explore the possible antitumor mechanisms of the two complexes. The results revealed that the two complexes had comparable antitumor activities in terms of inhibiting proliferation and inducing apoptosis in tumor cell lines. The changes in the protein expression levels of caspase 3, Bax and Bcl-2 further verified the apoptosis-promoting mechanisms of the two complexes in tumor cell lines. These findings have a great potential in biomedical applications of novel Ln(III) complexes.

Design and synthesis of novel N()-substituted thiosemicarbazones bearing a pyrrole unit as potential anticancer agents.

A series of N(4)-substituted thiosemicarbazones (TSCs) bearing pyrrole unit (1a-1e) were synthesized and fully characterized by elemental analyses, infrared spectra, 1H nuclear magnetic resonance and single crystal X-ray diffraction. The compounds were assessed as potential chemotherapeutic agents. All newly synthesized compounds were screened for their anticancer activity against lung cancer PC-9, esophageal cancer Eca-109 and gastric cancer SGC-7901 cell lines. The results of MTT, Terminal deoxynucleotidyl transferase dUTP nick end labeling and fluorescence-activated cell sorting assays indicated that all the prepared compounds exhibited cytotoxicity against PC-9, Eca-109 and SGC-7901 cells in vitro. All the compounds significantly induced cancer cell apoptosis accompanied by increasing the Bax/Bcl-2 ratio and activation of caspase-3. The structure-activity association was discussed and the potential pre-clinical trials may be conducted. The present findings have a great potential in biomedical applications of novel N(4)-substituted TSCs.

Synthesis, characterization and anticancer activities of transition metal complexes with a nicotinohydrazone ligand.

The reaction of divalent transition metal salts and (E)-N'-(1-(pyridin-2-yl)ethylidene)nicotinohydrazide (penh) led to the formation of [Mn(penh)2] (complex 1), [Co(penh)2] (complex 2), [Cu(penh)2] (complex 3) and [Cd (penh)2] (complex 4) complexes. The four complexes were characterized using elemental analyses, infrared spectra and single-crystal X-ray diffraction analyses. Subsequently, the complexes were used for in vitro cell level experiments to determine potential antitumor effects. The results demonstrated that the complexes exhibited a similar structure; however, they were crystallized with distinct space groups. In comparison with the uncomplexed penh ligand, all four complexes were able to markedly decrease the proliferation rate of various types of tumor cell, including the human lung cancer cell line A549, human gastric cancer cell line BGC823 and human esophageal cancer cell line Eca109, in a concentration-dependent manner. Furthermore, the complexes promoted tumor cell apoptosis, as demonstrated in the apoptosis assay, and this was confirmed using electrophoresis.

Using fluorescently-labeled magnetic nanocomposites as a dual contrast agent for optical and magnetic resonance imaging.

Dual-modality imaging probes synergistically combine magnetic resonance (MR) and fluorescence into a single nanocomposite. This promising technique affords a new level of flexibility for molecular imaging uses in biomedical research. In this study, we report a new strategy for the synthesis of a novel attapulgite nanorod-based atta@Fe3O4@[Ru(bpy)2(fmp)]Cl2 nanocomposite (atta@Fe3O4@Ru NC). Our synthesized NC has both photoluminescent and magnetic properties, bright fluorescence, as well as significant magnetic resonance. Transmission electron microscopy, energy dispersive spectroscopy, fluorescence spectrometry, and magnetization measurements were all used to validate its properties. In vitro studies showed that our functionalized NC had high cellular biocompatibility and was successfully used to label living cells through endocytosis of cells. Moreover, a CCK8 assay showed that even high concentrations of the atta@Fe3O4@Ru NC had low toxicity. Finally, the intravenous administration of the atta@Fe3O4@Ru NC to a rabbit model of hepatic carcinoma resulted in a marked and negatively enhanced T2-weighted MRI in both normal liver and tumor, which can further enhance the visibility of the liver cancer tissue and normal liver tissue. Collectively, these results suggest that the atta@Fe3O4@Ru NC can be used for tumor discovery and diagnosis.

Multifunctional nanocomposite based on halloysite nanotubes for efficient luminescent bioimaging and magnetic resonance imaging.

A novel multifunctional halloysite nanotube (HNT)-based Fe3O4@HNT-polyethyleneimine-Tip-Eu(dibenzoylmethane)3 nanocomposite (Fe-HNT-Eu NC) with both photoluminescent and magnetic properties was fabricated by a simple one-step hydrothermal process combined with the coupling grafting method, which exhibited high suspension stability and excellent photophysical behavior. The as-prepared multifunctional Fe-HNT-Eu NC was characterized using various techniques. The results of cell viability assay, cell morphological observation, and in vivo toxicity assay indicated that the NC exhibited excellent biocompatibility over the studied concentration range, suggesting that the obtained Fe-HNT-Eu NC was a suitable material for bioimaging and biological applications in human hepatic adenocarcinoma cells. Furthermore, the biocompatible Fe-HNT-Eu NC displayed superparamagnetic behavior with high saturation magnetization and also functioned as a magnetic resonance imaging (MRI) contrast agent in vitro and in vivo. The results of the MRI tests indicated that the Fe-HNT-Eu NC can significantly decrease the T2 signal intensity values of the normal liver tissue and thus make the boundary between the normal liver and transplanted cancer more distinct, thus effectively improving the diagnosis effect of cancers.

Synthesis, characterization, and antitumor activity of three ternary dinuclear copper (II) complexes with a reduced Schiff base ligand and diimine coligands in vitro and in vivo.

Three ternary copper (II) complexes containing 1,10-phenanthroline (phen, 1), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 2) and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 3), with the formulation [Cu2(NCL)2(H4PASP)]·4.5H2O (1-3) (where NCL=the diimine coligand, H4PASP=N,N'-(p-xylylene)di-2-aminosuccinic acid), were isolated and characterized. The binding of these complexes with calf thymus DNA was studied using UV-visible absorption titration, emission, and circular dichroism spectroscopy, among other methods. The changes in physicochemical properties that occurred upon binding of these complexes with DNA indicate that binding occurs primarily through intercalative interactions. Human tumor cell lines HeLa, PC3, and HepG2 were treated with the copper(II) complexes in vitro and cell survival rate was assessed by 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay and crystal violet survival assay. Flow cytometry was performed on treated cells labeled with AnnexinV/Propidium Iodide staining to determine rates of apoptosis. Western blot was performed to determine the expression levels of the apoptotic markers p53, Bax, and Bcl-2. The complexes reduced cell viability and induced apoptosis in cells of human tumor cell lines in a dose-dependent manner. In addition, using a nude mouse xenograft model, we found that the three ternary copper (II) complexes inhibited human tumor cell growth in vivo. In conclusion, these novel synthetic copper complexes have profound antitumor effects on human tumor cells and are promising therapeutic agents for human tumors.

Ternary Dinuclear Copper(II) Complexes of a Reduced Schiff Base Ligand with Diimine Coligands: DNA Binding, Cytotoxic Cell Apoptosis, and Apoptotic Mechanism.

A serial of mixed-ligand Cu(II) complexes of the type [Cu(phens)(H2 PDILeu)]H2 O (1-4) containing phens as 2,2'-bipyridyl (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3), and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 4) have been isolated and characterized. The interaction of the complexes with calf-thymus DNA has been explored by physical methods to propose modes of DNA binding of the complexes, which indicate that 4 interacts with DNA more strongly than all of the other complexes through intercalation interaction. Furthermore, cell apoptosis was detected by AnnexinV/PI flow cytometry and TUNEL assay and by Western blotting to detect the protein expression of p53, Bax, and Bcl-2. All the three copper complexes can effectively induce apoptosis of the three human tumor cells, which was accompanied with upregulation of the expression of p53 and Bax, while Bcl-2 decreased.