Ultrasensitive PEC cytosensor for breast cancer cells detection and inhibitor screening based on plum-branched CdS/Bi2S3 heterostructures.

Breast cancer is the most common malignant tumor in women, which seriously threatens the life and health of patients. Therefore, facile and sensitive detection of human breast cancer cells is crucial for cancer diagnosis. In this work, plum-branched CdS/Bi2S3 heterostructures (CdS/Bi2S3 HSs) were synthesized under hydrothermal condition, whose photoelectrochemical (PEC) property and biocompatibility were scrutinously investigated. In parallel, a signal amplification strategy was designed based on immune recognition between epidermal growth factor receptor (EGFR) overexpressed on membrane of breast cancer cells MDA-MB-231 and its aptamer. Integration of the above together, a highly sensitive PEC cytosensor was developed for analysis of target MDA-MB-231 cells, exhibiting a wider linear range of 1 × 102 âˆ¼ 3 × 105 cells mL-1 with a limit of detection (LOD) down to 6 cells mL-1 (S/N = 3). Further, the biosensor was explored for anticancer drug (e.g., dacomitinib) screening by monitoring the variations in the PEC signals of the expressed EGFR upon drug stimulation. The obtained CdS/Bi2S3 HSs are identified as promising and feasible photoactive material for determination of cancer cells and drug screening in clinic and related research.

Ultrasensitive photoelectrochemical aptasensor for detecting telomerase activity based on Ag2S/Ag decorated ZnIn2S4/C3N4 3D/2D Z-scheme heterostructures and amplified by Au/Cu2+-boron-nitride nanozyme.

Enzyme-mediated signal amplification strategies have gained substantial attention in photoelectrochemical (PEC) biosensing, while natural enzyme on the photoelectrode inevitably obstructs the interfacial electron transfer, in turn deteriorating the photocurrent responses. Herein, Au nanoparticles and Cu2+-modified boron nitride nanosheets (AuNPs/Cu2+-BNNS) behaved as nanozyme to achieve remarkable magnification in the PEC signals from a novel signal-off aptasensor for ultra-sensitive assay of telomerase (TE) activity based on Ag2S/Ag nanoparticles decorated ZnIn2S4/C3N4 Z-scheme heterostructures (termed as Ag2S/Ag/ZnIn2S4/C3N4, synthesized by hydrothermal treatment). Specifically, telomerase primer sequences (TS) were extended by TE in the presence of deoxyribonucleoside triphosphates (dNTPs), which was directly bond with the thiol modified complementary DNA (cDNA), achieving efficient linkage with the nanozyme via Au-S bond. The immobilized nanoenzyme catalyzed the oxidation between 4-chloro-1-naphthol (4-CN) and H2O2 to generate insoluble precipitation on the photo-electrode. By virtue of the inhibited PEC signals with the TE-enabled TS extension, an aptasensor for assay of TE activity was developed, showing the wide linear range of 50-5×105 cell mL-1 and a low detection limit of 19 cell mL-1. This work provides some valuable guidelines for developing advanced nanozyme-based PEC bioanalysis of diverse cancer cells.

Anticancer Properties of Phyllanthus emblica (Indian Gooseberry).

There is a wealth of information emanating from both in vitro and in vivo studies indicating fruit extract of the Phyllanthus emblica tree, commonly referred to as Indian Gooseberries, has potent anticancer properties. The bioactivity in this extract is thought to be principally mediated by polyphenols, especially tannins and flavonoids. It remains unclear how polyphenols from Phyllanthus emblica can incorporate both cancer-preventative and antitumor properties. The antioxidant function of Phyllanthus emblica can account for some of the anticancer activity, but clearly other mechanisms are equally important. Herein, we provide a brief overview of the evidence supporting anticancer activity of Indian Gooseberry extracts, suggest possible mechanisms for these actions, and provide future directions that might be taken to translate these findings clinically.

Effect of ermiao fang with xixin (herba asari mandshurici) on bone marrow stem cell directional homing to a focal zone in an osteoarthritis rat model.

OBJECTIVE: To investigate the effects of Ermiao Fang (EM) with medical guide Xixin (Herba Asari Mandshurici) (HAM) on bone marrow stem cell migration to a focal zone in osteoarthritis (OA) rats. METHODS: OA rats were induced by arthrectomy and assigned to sham-operated, model, EM, or EM plus HAM groups. All rats were injected with recombinant human granulocyte colony-stimulating factor 30 microg x kg(-1) x d(-1) for 7 days and treated with EM or EM plus HAM at 1.6 or 1.9 g x kg(-1) x d(-1) for 3 or 6 weeks, respectively. Chondrocyte apoptosis and cartilage matrix components were tested by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay and special staining. Levels of interleukin-1 beta (IL-1beta) tumor necrosis factor alpha (TNF-alpha) nitric oxide (NO), and inducible nitric oxide synthase (iNOS) in serum were detected by enzyme-linked immunosorbent assay or radioimmunoassay. Matrix metalloproteinases (MMPs)-13, tissue inhibitors of metalloproteinases (TIMPs)-1, Bromodeoxyuridine (BrdU), cluster of differentiation 34 (CD34), and stromal cell-derived factor 1 (SDF-1) were measured by immunohistochemical assay. RESULTS: The EM and EM plus HAM groups had significantly less cartilage damage and synovium inflammation the model group. Moreover, the EM and EM plus HAM groups had less chondrocyte apoptosis and more proteoglycan and collagen content than the model group. The EM and EM plus HAM groups had obviously higher MMPs-13 and TIMPs-1 expression in the cartilage than the model group. Moreover, the two formula groups had less release of IL-1beta, TNF-alpha, NO, and iNOS than model group. Importantly, the expressions of BrdU, CD34, and SDF-1 in cartilage were significantly higher in the EM and EM plus HAM-Medtreated rats than model group. Notably, the EM plus HAM treatment seemed to have the greatest effects. CONCLUSION: HAM improves the therapeutic effects of EM on OA rats by enhancing BMSC directional homing to the focal zone.

BOLD study of stimulation-induced neural activity and resting-state connectivity in medetomidine-sedated rat.

Functional magnetic resonance imaging (fMRI) in anesthetized-animals is critical in studying the mechanisms of fMRI and investigating animal models of various diseases. Medetomidine was recently introduced for independent anesthesia for longitudinal (survival) fMRI studies in rats. Since stimulation-induced fMRI signal is anesthesia-dependent and its characteristics in rats under medetomidine are not fully elucidated, the blood oxygenation level dependent (BOLD) fMRI response to electrical forepaw stimulation under medetomidine was systematically investigated at 9.4 T. Robust activations in contralateral primary somatosensory cortex (SI) and thalamus were observed and peaked at the stimulus frequency of 9 Hz. The response in SI saturates at the stimulus strength of 4 mA while that in thalamus monotonically increases. In addition to fMRI data acquired with the forepaw stimulation, data were also acquired during the resting-state to investigate the synchronization of low frequency fluctuations (LFF) in the BOLD signal (<0.08 Hz) in different brain regions. LFF during resting-state have been observed to be synchronized between functionally related brain regions in human subjects while its origin is not fully understood. LFF have not been extensively studied or widely reported in anesthetized-animals. In our data, synchronized LFF of BOLD signals are found in clustered, bilaterally symmetric regions, including SI and caudate-putamen and the magnitude of the LFF is approximately 1.5%, comparable to the stimulation-induced BOLD signals. Similar to resting-state data reported in human subjects, LFF in rats under medetomidine likely reflect functional connectivity of these brain regions.

Adenovirus with insertion-mutated E1A selectively propagates in liver cancer cells and destroys tumors in vivo.

The adenovirus E1A proteins are involved in the transcriptional activation of viral and cellular genes needed for controlling cell cycle and virus replication. Undifferentiated embryonic carcinoma cells have the ability to produce an E1A-like activity that can induce the expression of E1A-targeted adenoviral and cellular genes in the absence of the E1A products. Differentiated embryonic carcinoma cells lose the ability to produce the E1A-like activity. In this study, we investigated the E1A-like activity in cancer cells with an adenovirus having a mutated E1a gene. The mutation is generated by the insertion of a large DNA fragment in the E1a gene and interrupts the COOH-terminal region of both the E1A 12S and 13S proteins. The E1a-mutated virus can efficiently replicate in HepG2 and Hep3B liver cancer cells and produce high titers of virus. Replication of the E1a-mutated virus inhibits tumor formation and destroys tumors in vivo. The results obtained in this study imply that cancer cells may produce an E1A-like activity to support the selective replication of mutated virus in cancer cells. In addition, we found that although the E1a-mutated virus could not replicate in Huh1.cl2 liver cells, the viral DNA could amplify in the cells. This result suggests that replication of adenoviral DNA is necessary, but not sufficient, for generating infectious viral progeny and destroying tumor cells.