Electroacupuncture stimulation modulates functional brain connectivity in the treatment of pediatric cerebral palsy: a case report.

Background: Pediatric cerebral palsy (CP) is a non-progressive brain injury syndrome characterized by central motor dysfunction and insufficient brain coordination ability. The etiology of CP is complex and often accompanied by diverse complications such as intellectual disability and language disorders, making clinical treatment difficult. Despite the availability of pharmacological interventions, rehabilitation programs, and spasticity relief surgery as treatment options for CP, their effectiveness is still constrained. Electroacupuncture (EA) stimulation has demonstrated great improvements in motor function, but its comprehensive, objective therapeutic effects on pediatric CP remain to be clarified. Methods: We present a case of a 5-year-old Chinese female child who was diagnosed with CP at the age of 4. The patient exhibited severe impairments in motor, language, social, and cognitive functions. We performed a 3-month period of EA rehabilitation, obtaining resting state functional magnetic resonance imaging (rs-fMRI) of the patient at 0 month, 3 months and 5 months since treatment started, then characterized brain functional connectivity patterns in each phase for comparison. Results: After a 12-month follow-up, notable advancements were observed in the patient's language and social symptoms. Changes of functional connectivity patterns confirmed this therapeutic effect and showed specific benefits for different recovery phase: starting from language functions then modulating social participation and other developmental behaviors. Conclusion: This is a pioneering report demonstrating the longitudinal effect of EA stimulation on functional brain connectivity in CP patients, suggesting EA an effective intervention for developmental disabilities (especially language and social dysfunctions) associated with pediatric CP.

Genetic and phenotypic profiling of single living circulating tumor cells from patients with microfluidics.

Accurate prediction of the efficacy of immunotherapy for cancer patients through the characterization of both genetic and phenotypic heterogeneity in individual patient cells holds great promise in informing targeted treatments, and ultimately in improving care pathways and clinical outcomes. Here, we describe the nanoplatform for interrogating living cell host-gene and (micro-)environment (NICHE) relationships, that integrates micro- and nanofluidics to enable highly efficient capture of circulating tumor cells (CTCs) from blood samples. The platform uses a unique nanopore-enhanced electrodelivery system that efficiently and rapidly integrates stable multichannel fluorescence probes into living CTCs for in situ quantification of target gene expression, while on-chip coculturing of CTCs with immune cells allows for the real-time correlative quantification of their phenotypic heterogeneities in response to immune checkpoint inhibitors (ICI). The NICHE microfluidic device provides a unique ability to perform both gene expression and phenotypic analysis on the same single cells in situ, allowing us to generate a predictive index for screening patients who could benefit from ICI. This index, which simultaneously integrates the heterogeneity of single cellular responses for both gene expression and phenotype, was validated by clinically tracing 80 non-small cell lung cancer patients, demonstrating significantly higher AUC (area under the curve) (0.906) than current clinical reference for immunotherapy prediction.

Synthesis of an ordered macroporous metal-organic framework for efficient solid-phase extraction of aflatoxins from milk products.

Aflatoxins (AFs) exhibit hepatotoxicity, immunotoxicity, and carcinogenicity, and their detection in food has attracted widespread concern. An ordered macroporous metal-organic framework (OM-ZIF-8) based on solid-phase extraction (SPE) was used to extract six AFs from milk products. The SPE conditions, including eluting solvent, eluting volume, amounts of OM-ZIF-8, pH of loading solution, loading solvent, ionic strength, loading flow rate, and elution flow rate, were exhaustively optimized. Under optimal parameters, the six AFs were detected by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The OM-ZIF-8 exhibited satisfactory AFs extraction performance through ordered macropore structure, π-π interaction, coordination interaction, and electrostatic interaction. Furthermore, linearity in the range of 0.01-100 ng mL-1 with low detection limits of 0.002-0.0150 ng mL-1 was obtained, and the relative recoveries of AFs were 80.3-110 % with relative standard deviation ≤8.7 %. Thus, this research provides a promising platform for the analysis of trace AFs in complex foods.

Light-driven micro/nanomotors in biomedical applications.

Nanotechnology brings hope for targeted drug delivery. However, most current drug delivery systems use passive delivery strategies with limited therapeutic efficiency. Over the past two decades, research on micro/nanomotors (MNMs) has flourished in the biomedical field. Compared with other driven methods, light-driven MNMs have the advantages of being reversible, simple to control, clean, and efficient. Under light irradiation, the MNMs can overcome several barriers in the body and show great potential in the treatment of various diseases, such as tumors, and gastrointestinal, cardiovascular and cerebrovascular diseases. Herein, the classification and mechanism of light-driven MNMs are introduced briefly. Subsequently, the applications of light-driven MNMs in overcoming physiological and pathological barriers in the past five years are highlighted. Finally, the future prospects and challenges of light-driven MNMs are discussed as well. This review will provide inspiration and direction for light-driven MNMs to overcome biological barriers in vivo and promote the clinical application of light-driven MNMs in the biomedical field.

An Extended NIR-II Superior Imaging Window from 1500 to 1900†nm for High-Resolution In Vivo Multiplexed Imaging Based on Lanthanide Nanocrystals.

High-resolution in vivo optical multiplexing in second near-infrared window (NIR-II, 1000-1700 nm) is vital to biomedical research. Presently, limited by bio-tissue scattering, only luminescent probes located at NIR-IIb (1500-1700 nm) window can provide high-resolution in vivo multiplexed imaging. However, the number of available luminescent probes in this narrow NIR-IIb region is limited, which hampers the available multiplexed channels of in vivo imaging. To overcome the above challenges, through theoretical simulation we expanded the conventional NIR-IIb window to NIR-II long-wavelength (NIR-II-L, 1500-1900 nm) window on the basis of photon-scattering and water-absorption. We developed a series of novel lanthanide luminescent nanoprobes with emission wavelengths from 1852 nm to 2842 nm. NIR-II-L nanoprobes enabled high-resolution in vivo dynamic multiplexed imaging on blood vessels and intestines, and provided multi-channels imaging on lymph tubes, tumors and intestines. The proposed NIR-II-L probes without mutual interference are powerful tools for high-contrast in vivo multiplexed detection, which holds promise for revealing physiological process in living body.

Recent progress of micro/nanomotors to overcome physiological barriers in the gastrointestinal tract.

Oral administration is a convenient administration route for gastrointestinal disease therapy with good patient compliance. But the nonspecific distribution of the oral drugs may cause serious side effects. In recent years, oral drug delivery systems (ODDS) have been applied to deliver the drugs to the gastrointestinal disease sites with decreased side effects. However, the delivery efficiency of ODDS is tremendously limited by physiological barriers in the gastrointestinal sites, such as the long and complex gastrointestinal tract, mucus layer, and epithelial barrier. Micro/nanomotors (MNMs) are micro/nanoscale devices that transfer various energy sources into autonomous motion. The outstanding motion characteristics of MNMs inspired the development of targeted drug delivery, especially the oral drug delivery. However, a comprehensive review of oral MNMs for the gastrointestinal diseases therapy is still lacking. Herein, the physiological barriers of ODDS were comprehensively reviewed. Afterward, the applications of MNMs in ODDS for overcoming the physiological barriers in the past 5 years were highlighted. Finally, future perspectives and challenges of MNMs in ODDS are discussed as well. This review will provide inspiration and direction of MNMs for the therapy of gastrointestinal diseases, pushing forward the clinical application of MNMs in oral drug delivery.

Sensitive Interrogation of Enhancer Activity in Living Cells on a Nanoelectroporation-Probing Platform.

Enhancers involved in the upregulation of multiple oncogenes play a fundamental role in tumorigenesis and immortalization. Exploring the activity of enhancers in living cells has emerged as a critical path to a deep understanding of cancer properties, further providing important clues to targeted therapy. However, identifying enhancer activity in living cells is challenging due to the double biological barriers of a cell cytoplasmic membrane and a nuclear membrane, limiting the sensitivity and responsiveness of conventional probing methods. In this work, we developed a nanoelectroporation-probing (NP) platform, which enables intranuclear probe delivery for sensitive interrogation of enhancer activity in living cells. The nanoelectroporation biochip achieved highly focused perforation of the cell cytoplasmic membrane and brought about additional driving force to expedite the delivery of probes into the nucleus. The probes targeting enhancer activity (named "PH probe") are programmed with a cyclic amplification strategy and enable an increase in the fluorescence signals over 100-fold within 1 h. The platform was leveraged to detect the activity of CCAT1 enhancers (CCAT1, colon cancer-associated transcript-1, a long noncoding RNA that functions in tumor invasion and metastasis) in cell samples from clinical lung cancer patients, as well as reveal the heterogeneity of enhancers among different patients. The observations may extend the linkages between enhancers and cancer cells while validating the robustness and reliability of the platform for the assay of enhancer activity. This platform will be a promising toolbox with wide applicable potential for the intranuclear study of living cells.

Superoxide dismutase 2 ameliorates mitochondrial dysfunction in skin fibroblasts of Leber's hereditary optic neuropathy patients.

Background: In Leber's hereditary optic neuropathy (LHON), mtDNA mutations mediate mitochondrial dysfunction and apoptosis of retinal ganglion cells. Mitochondrial superoxide dismutase 2 (SOD2) is a crucial antioxidase against reactive oxygen species (ROS). This study aims to investigate whether SOD2 could ameliorate mtDNA mutation mediated mitochondrial dysfunction in skin fibroblasts of LHON patients and explore the underlying mechanisms. Methods: The skin of normal healthy subjects and severe LHON patients harboring m.11778G > A mutation was taken to prepare immortalized skin fibroblast cell lines (control-iFB and LHON-iFB). LHON-iFB cells were transfected with SOD2 plasmid or negative control plasmid, respectively. In addition, human neuroblastoma SH-SY5Y cells and human primary retinal pigmental epithelium (hRPE) cells were stimulated by H2O2 after gene transfection. The oxygen consumption rate (OCR) was measured with a Seahorse extracellular flux analyzer. The level of ATP production, mitochondrial membrane potential, ROS and malondialdehyde (MDA) were measured separately with the corresponding assay kits. The expression level of SOD2, inflammatory cytokines and p-IκBα/IκBα was evaluated by western-blot. Assessment of apoptosis was performed by TUNEL assay. Results: LHON-iFB exhibited lower OCR, ATP production, mitochondrial membrane potential but higher level of ROS and MDA than control-iFB. Western-blot revealed a significantly increased expression of IL-6 and p-IκBα/IκBα in LHON-iFB. Compared with the negative control, SOD2 overexpression increased OCR, ATP production and elevated mitochondrial membrane potential, but impaired ROS and MDA production. Besides, western-blot demonstrated exogenous SOD2 reduced the protein level of IL-6 and p-IκBα/IκBα. TUNEL assays suggested SOD2 inhibited cells apoptosis. Analogously, in SH-SY5Y and hRPE cells, SOD2 overexpression increased ATP production and mitochondrial membrane potential, but decreased ROS, MDA levels and suppressed apoptosis. Conclusion: SOD2 upregulation inhibited cells apoptosis through ameliorating mitochondrial dysfunction and reducing NF-κB associated inflammatory response. This study further support exogenous SOD2 may be a promising therapy for the treatment of LHON.

Knockdown of PAR2 alleviates cancer-induced bone pain by inhibiting the activation of astrocytes and the ERK pathway.

OBJECTIVE: Cancer-induced bone pain (CIBP) is a kind of pain with complex pathophysiology. Proteinase-activated receptor 2 (PAR-2) is involved in CIBP. This study explored the effects of PAR-2 on CIBP rats. METHODS: CIBP rat model was established by injecting Walker 256 rat breast cancer cells into the left tibia of female Sprague-Dawley rats and verified by tibial morphology observation, HE staining, and mechanical hyperalgesia assay. CIBP rats were injected with PAR-2 inhibitor, ERK activator, and CREB inhibitor through the spinal cord sheath on the 13th day after operation. CIBP behaviors were measured by mechanical hyperalgesia assay. On the 14th day after operation, L4-5 spinal cord tissues were obtained. PAR-2 expression, co-expression of PAR-2 and astrocyte marker GFAP, GFAP mRNA and protein levels and the ERK pathway-related protein levels were detected by Western blot, immunofluorescence double staining, RT-qPCR, and Western blot. RESULTS: CIBP rats had obvious mechanical hyperalgesia and thermal hyperalgesia from the 7th day after modeling; mechanical hyperalgesia threshold and thermal threshold were decreased; PAR-2 was increased in spinal cord tissues and was co-expressed with GFAP. PAR-2 silencing alleviated rat CIBP by inhibiting astrocyte activation. p-ERK/t-ERK and p-CREB/t-CREB levels in CIBP spinal cord were elevated, the ERK/CREB pathway was activated, while the ERK/CREB pathway was inhibited by PAR-2 silencing. The alleviating effect of PAR-2 inhibitor on hyperalgesia behaviors in CIBP rats were weakened by ERK activator, while were partially restored by CREB inhibitor. CONCLUSIONS: PAR-2 knockdown inhibited the ERK/CREB pathway activation and astrocyte activation, thus alleviating CIBP in rats.

Wave-shaped microfluidic chip assisted point-of-care testing for accurate and rapid diagnosis of infections.

BACKGROUND: Early diagnosis and classification of infections increase the cure rate while decreasing complications, which is significant for severe infections, especially for war surgery. However, traditional methods rely on laborious operations and bulky devices. On the other hand, point-of-care (POC) methods suffer from limited robustness and accuracy. Therefore, it is of urgent demand to develop POC devices for rapid and accurate diagnosis of infections to fulfill on-site militarized requirements. METHODS: We developed a wave-shaped microfluidic chip (WMC) assisted multiplexed detection platform (WMC-MDP). WMC-MDP reduces detection time and improves repeatability through premixing of the samples and reaction of the reagents. We further combined the detection platform with the streptavidin-biotin (SA-B) amplified system to enhance the sensitivity while using chemiluminescence (CL) intensity as signal readout. We realized simultaneous detection of C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) on the detection platform and evaluated the sensitivity, linear range, selectivity, and repeatability. Finally, we finished detecting 15 samples from volunteers and compared the results with commercial ELISA kits. RESULTS: Detection of CRP, PCT, and IL-6 exhibited good linear relationships between CL intensities and concentrations in the range of 1.25-40 µg/ml, 0.4-12.8 ng/ml, and 50-1600 pg/ml, respectively. The limit of detection of CRP, PCT, and IL-6 were 0.54 µg/ml, 0.11 ng/ml, and 16.25 pg/ml, respectively. WMC-MDP is capable of good adequate selectivity and repeatability. The whole detection procedure takes only 22 min that meets the requirements of a POC device. Results of 15 samples from volunteers were consistent with the results detected by commercial ELISA kits. CONCLUSIONS: WMC-MDP allows simultaneous, rapid, and sensitive detection of CRP, PCT, and IL-6 with satisfactory selectivity and repeatability, requiring minimal manipulation. However, WMC-MDP takes advantage of being a microfluidic device showing the coefficients of variation less than 10% enabling WMC-MDP to be a type of point-of-care testing (POCT). Therefore, WMC-MDP provides a promising alternative to POCT of multiple biomarkers. We believe the practical application of WMC-MDP in militarized fields will revolutionize infection diagnosis for soldiers.

P2X7 Receptor Antagonist Attenuates Retinal Inflammation and Neovascularization Induced by Oxidized Low-Density Lipoprotein.

Age-related macular degeneration (AMD) is a common and severe blinding disease among people worldwide. Retinal inflammation and neovascularization are two fundamental pathological processes in AMD. Recent studies showed that P2X7 receptor was closely involved in the inflammatory response. Here, we aim to investigate whether A740003, a P2X7 receptor antagonist, could prevent retinal inflammation and neovascularization induced by oxidized low-density lipoprotein (ox-LDL) and explore the underlying mechanisms. ARPE-19 cells and C57BL/6 mice were treated with ox-LDL and A740003 successively for in vitro and in vivo studies. In this research, we found that A740003 suppressed reactive oxygen species (ROS) generation and inhibited the activation of Nod-like receptor pyrin-domain protein 3 (NLRP3) inflammasome and nuclear factor-κB (NF-κB) pathway. A740003 also inhibited the generation of angiogenic factors in ARPE-19 cells and angiogenesis in mice. The inflammatory cytokines and phosphorylation of inhibitor of nuclear factor-κB alpha (IKBα) were repressed by A740003. Besides, ERG assessment showed that retinal functions were remarkably preserved in A740003-treated mice. In summary, our results revealed that the P2X7 receptor antagonist reduced retinal inflammation and neovascularization and protected retinal function. The protective effects were associated with regulation of NLRP3 inflammasome and the NF-κB pathway, as well as inhibition of angiogenic factors.

Intravitreal Injection of an Exosome-Associated Adeno-Associated Viral Vector Enhances Retinoschisin 1 Gene Transduction in the Mouse Retina.

To investigate whether exosome-associated adeno-associated virus (AAV) retinoschisin 1 (RS1) vector improved the transduction efficiency of RS1 in the mouse retina. pAAV2-RS1-ZsGreen plasmid was constructed by homologous recombination. Exosome-associated AAV vectors containing human RS1 gene (exosome-associated AAV [exo-AAV]2-RS1-ZsGreen) were isolated from producer cells' supernatant, and confirmed by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. In vitro, HEK-293T cells were transduced with AAV2-RS1-ZsGreen and exo-AAV2-RS1-ZsGreen. In vivo, 1 µL of AAV2-RS1-ZsGreen or 1 µL exo-AAV2-RS1-ZsGreen (2 × 108 genome copies/µL) was injected intravitreally into the C57BL/6J mouse eyes. Phosphate buffer saline was injected as controls. The mRNA and the protein expression in the retina were detected. Exo-AAV2-RS1-ZsGreen possessed lipid bilayers, a saucer-like structures and an average of 120 nm particle size. The expression of RS1 and ZsGreen in exo-AAV2-RS1-ZsGreen group were 7.6 times and 5.7 times that of AAV2-RS1-ZsGreen group in HEK-293T cells, respectively. Furthermore, RS1 protein expression increased by 11.8 times in HEK-293T cells. Intravitreal injection of exo-AAV significantly increased the transduction efficiency of RS1 than AAV. Exo-AAV may be a powerful gene delivery system for gene therapy of X-link retinoschisis as well as other inherited retina degenerations.

The Protective Effects of VVN001 on LPS-Induced Inflammatory Responses in Human RPE Cells and in a Mouse Model of EIU.

To investigate protective effects of VVN001 on lipopolysaccharide (LPS)-induced inflammatory response in human retinal pigment epithelial (RPE) cells and in a mouse model of endotoxin-induced uveitis (EIU), and to explore the underlying mechanisms. Human primary RPE (hRPE) and ARPE-19 cells were pretreated with or without VVN001 for 1 h followed by 10 µg/mL LPS stimulation for 24 h. mRNA, and protein levels of inflammatory cytokines were analyzed with real-time PCR, western blotting, and ELISA. EIU was induced by intravitreal injection of 125 ng LPS in female BALB/c mice. VVN001 eye drops (1%) were locally administrated every 4 h for 24 h after LPS injection. Clinical scores were assessed with a slit lamp. mRNA and protein levels of inflammatory cytokines were investigated simultaneously. Compared with the LPS group, VVN001 pretreatment significantly reduced mRNA expressions of intercellular adhesion molecule-1 (ICAM-1), IL-6, IL-8, TNF-α, IL-1ß, IL-18, caspase-1 in hRPE, and ARPE-19 cells. Protein overproduction of ICAM-1, TNF-α, IL-1ß, NLRP3, caspase-1 P20, and p-IκBα/IκBα stimulated by LPS was suppressed by VVN001 pretreatment. In vivo, VVN001 significantly reduced the average clinical score from 5.0 to 1.3 in EIU mice. Furthermore, overproduction of ICAM-1, IL-1ß, NLRP3, caspase-1 P20, and p-IκBα/IκBα at mRNA and protein levels were remarkably suppressed by VVN001. VVN001 alleviated the inflammatory response induced by LPS both in vitro and in vivo. The effect of anti-inflammation is associated with inhibiting the overproduction of ICAM-1 and blocking the activation of NLRP3 inflammasome and the NF-κB signaling pathway.

Comparison of intravitreal dexamethasone implant and anti-VEGF drugs in the treatment of retinal vein occlusion-induced oedema: a meta-analysis and systematic review.

OBJECTIVE: To compare the efficacy and safety of intravitreal dexamethasone (DEX) implant and anti-vascular endothelial growth factor (anti-VEGF) agents in the treatment of macular oedema secondary to retinal vein occlusion (RVO). DESIGN: Systematic review and meta-analysis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE). DATA SOURCES: PubMed, Cochrane Library and ClinicalTrials.gov registry were searched from inception to 10 December 2019, without language restrictions. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) and real-world observation studies comparing the efficacy of DEX implant and anti-VEGF agents for the treatment of patients with RVO, naïve or almost naïve to both arms, were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data for mean changes in best-corrected visual acuity (BCVA), central subfield thickness (CST) and product safety. Review Manager V.5.3 and GRADE were used to synthesise the data and validate the evidence, respectively. RESULTS: Four RCTs and 12 real-world studies were included. An average lower letter gain in BCVA was determined for the DEX implant (mean difference (MD) = -6.59; 95% CI -8.87 to -4.22 letters) administered at a retreatment interval of 5-6 months. Results were similar (MD6 months=-12.68; 95% CI -21.98 to -3.37 letters; MD12 months=-9.69; 95% CI -12.01 to -7.37 letters) at 6 and 12 months. The DEX implant resulted in comparable or marginally less CST reduction at months 6 and 12 but introduced relatively higher risks of elevated intraocular pressure (RR=3.89; 95% CI 2.16 to 7.03) and cataract induction (RR=5.22; 95% CI 1.67 to 16.29). Most real-life studies reported an insignificant numerical gain in letters for anti-VEGF drugs relative to that for DEX implant. However, the latter achieved comparable efficacy with a 4-month dosage interval. CONCLUSION: Compared with anti-VEGF agents, DEX implant required fewer injections but had inferior functional efficacy and safety. Real-life trials supplemented the efficacy data for DEX implant.

FAM46B is a prokaryotic-like cytoplasmic poly(A) polymerase essential in human embryonic stem cells.

Family with sequence similarity (FAM46) proteins are newly identified metazoan-specific poly(A) polymerases (PAPs). Although predicted as Gld-2-like eukaryotic non-canonical PAPs, the detailed architecture of FAM46 proteins is still unclear. Exact biological functions for most of FAM46 proteins also remain largely unknown. Here, we report the first crystal structure of a FAM46 protein, FAM46B. FAM46B is composed of a prominently larger N-terminal catalytic domain as compared to known eukaryotic PAPs, and a C-terminal helical domain. FAM46B resembles prokaryotic PAP/CCA-adding enzymes in overall folding as well as certain inter-domain connections, which distinguishes FAM46B from other eukaryotic non-canonical PAPs. Biochemical analysis reveals that FAM46B is an active PAP, and prefers adenosine-rich substrate RNAs. FAM46B is uniquely and highly expressed in human pre-implantation embryos and pluripotent stem cells, but sharply down-regulated following differentiation. FAM46B is localized to both cell nucleus and cytosol, and is indispensable for the viability of human embryonic stem cells. Knock-out of FAM46B is lethal. Knock-down of FAM46B induces apoptosis and restricts protein synthesis. The identification of the bacterial-like FAM46B, as a pluripotent stem cell-specific PAP involved in the maintenance of translational efficiency, provides important clues for further functional studies of this PAP in the early embryonic development of high eukaryotes.

Intravitreal Injection of Amyloid ß1-42 Activates the Complement System and Induces Retinal Inflammatory Responses and Malfunction in Mouse.

To investigate whether intravitreal injection of amyloid ß1-42 (Aß1-42) activates the complement system and induces retinal inflammatory responses and malfunction, Aß1-42 was applied intravitreally in mice. The expressions of key components of complement system were determined by real-time PCR. Retinal function was assessed by electroretinography. We found interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in Aß1-42 treated mice retinas increased from day 1 to day 7. Compared with control group, mRNA expression of C1qa and C3 in the Aß1-42 treated retinas increased at days 1 and 7. The level of CFB, CFD, or CFH increased at day 4 and day 7. Regulator of membrane attack complex (MAC), CD59a, increased from day 1 to day 7. The expression of the main complement components in Aß1-42 treated eyes increased at days 4 and 7. Therefore, our results suggested that exogenous Aß1-42 activated CP and AP of the complement system in mice retinas, induced retinal inflammatory responses, and caused retinal malfunction.

Highly efficient capture of circulating tumor cells with low background signals by using pyramidal microcavity array.

This report demonstrates that a microfluidic device with integrated silicon filter exhibits outstanding capture efficiency and superior enrichment purity when employed to separate tumor cells from whole blood samples. We fabricate the silicon filter with pyramidal microcavity array (MCA) by microfabrication. We design the structure of the cavity to efficiently enrich tumor cells, while allowing hematologic cells to deform and pass through. The capture efficiency of MCF-7, SW620 and Hela cells spiked in 1 mL of whole blood are approximately 80%. Unwanted white blood cells (WBCs) trapped on the MCA are below 0.003%. In addition, this microfluidic device successfully identifies circulating tumor cells (CTCs) in 5 of 6 patients' blood samples, with a range of 5-86 CTCs per mL. These results reveal that the disposable microfluidic device can effectively enrich tumor cells with different sizes and various morphologies, while maintaining high capture efficiency and purity. Therefore, this label-free technique can serve as a versatile platform to facilitate CTCs analysis in diverse biochemical applications.

Bidirectional regulation of angiogenesis by phytoestrogens through estrogen receptor-mediated signaling networks.

Sex hormone estrogen is one of the most active intrinsic angiogenesis regulators; its therapeutic use has been limited due to its carcinogenic potential. Plant-derived phytoestrogens are attractive alternatives, but reports on their angiogenic activities often lack in-depth analysis and sometimes are controversial. Herein, we report a data-mining study with the existing literature, using IPA system to classify and characterize phytoestrogens based on their angiogenic properties and pharmacological consequences. We found that pro-angiogenic phytoestrogens functioned predominantly as cardiovascular protectors whereas anti-angiogenic phytoestrogens played a role in cancer prevention and therapy. This bidirectional regulation were shown to be target-selective and, for the most part, estrogen-receptor-dependent. The transactivation properties of ERα and ERß by phytoestrogens were examined in the context of angiogenesis-related gene transcription. ERα and ERß were shown to signal in opposite ways when complexed with the phytoestrogen for bidirectional regulation of angiogenesis. With ERα, phytoestrogen activated or inhibited transcription of some angiogenesis-related genes, resulting in the promotion of angiogenesis, whereas, with ERß, phytoestrogen regulated transcription of angiogenesis-related genes, resulting in inhibition of angiogenesis. Therefore, the selectivity of phytoestrogen to ERα and ERß may be critical in the balance of pro- or anti-angiogenesis process.