Optimization of the Extraction Strategy for Polyphenols from Pieris Japonica and Evaluation of Its Antioxidant Activity.

Pieris Japonica, belonging to the Rhododendron family, is known for its anti-insect and analgesic properties. Despite previous research, the components and antioxidant activity of Pieris Japonica extract remain unclear. This study aims to identify the optimal extraction process for Pieris Japonica, determine its components, and evaluate its antioxidant capacity. An L9 (34) orthogonal method was employed to optimize the Pieris Japonica extraction process, with the polyphenol content serving as the extraction efficiency index. The extracted components were identified by high-performance liquid chromatography-mass spectrometry (HPLC/MS-MS). Antioxidant activity was assessed via the DPPH test, ABTS radical scavenging test, and FRAP reduction ability test. The optimal extraction process involved soaking Pieris Japonica powder in 60% ethanol with a weight-to-volume ratio of 1:20 (g/mL), followed by eight hours of reflux at 50°C. Under these conditions, the total polyphenol content was 11.2 ± 0.6 mg/g. HPLC/MS-MS revealed that flavonoids were the primary components in the Pieris Japonica extract. The FRAP method determined the total antioxidant capacity to be 1.00 ± 0.05 µmol/mL, while the DPPH method showed a radical scavenging rate of 42.21 ± 4.02%, and the ABTS method yielded a 85.74% scavenging rate, indicating a strong antioxidant activity. The primary components of Pieris Japonica extract were flavonoids, and the extracted plant material exhibited potent antioxidant activity.

Effects of ultrasonic treatment on the structural, functional properties and beany flavor of soy protein isolate: Comparison with traditional thermal treatment.

This research explored the influences of ultrasonic and thermal treatments on the structure, functional properties, and beany flavor of soy protein isolate (SPI). In comparison with traditional thermal treatment, ultrasonic treatment effectively induced protein structural unfolding and exposure of hydrophobic groups, which reduced relative content of α-helix, increased relative content of ß-turn, ß-sheet and random coil, and improved the solubility, emulsifying and foaming properties of SPI. Both treatments significantly decreased the species and contents of flavor compounds, such as hexanal, (E)-2-nonenal, (Z)-2-heptenal and (E)-2-hexenal in SPI. The relative content of hexanal in the major beany flavor compound decreased from 11.69% to 6.13% and 5.99% at 350 W ultrasonic power and 150 s thermal treatment procedure, respectively. After ultrasonic treatment, structural changes in SPI were significantly correlated with functional properties but showed a weak correlation with flavor. Conversely, the opposite trend was observed for thermal treatment. Thus, using ultrasonic treatment to induce and stabilise the denatured state of proteins is feasible to improve the functional properties and beany flavor of SPI.

Electroacupuncture activates angiogenesis by regulating the PI3K/Pten/Thbs1 signaling pathway to promote the browning of adipose tissue in HFD-induced obese mice.

This study investigated the effect of electroacupuncture (EA) on the browning of white adipose tissue (WAT) via angiogenesis and its potential mechanism in obese mice. Four-week-old male C56BL/6 mice were randomly divided into a high-fat diet (HFD) and a normal chow diet (ND) group. After 12 weeks, HFD mice were randomly divided into two groups to receive or not receive EA for 3 weeks. After EA treatment, body weight, adipocyte size, serum glucose (GLU), triacylglycerol (TG), cholesterol (CHO), leptin (Lep), monocyte chemoattractant protein-1 (MCP-1), WAT browning-related genes, angiogenesis-related genes, and the PI3K/Pten/Thbs1 signaling pathway were evaluated. The results indicated that EA significantly reduced body weight, adipocyte size, and serum concentrations of GLU, TG, CHO, Lep and MCP-1 and promoted WAT browning. Angiogenesis and the PI3K/Pten/Thbs1 signaling pathway were all activated by EA intervention. The expression levels were consistent with the results of RNA-seq and confirmed via qRTPCR and WB. Our study showed that EA may activate angiogenesis via the PI3K/Pten/Thbs1 signaling pathway in WAT, thereby promoting the browning and thermogenesis of adipose tissue.

Integrated network pharmacology, transcriptomics, and metabolomics analysis to reveal the mechanism of salt Eucommiae cortex in the treatment of chronic kidney disease mineral bone disorders via the PPARG/AMPK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The skeletal complications associated with chronic kidney diseases from stages 3-5 in individuals are called Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD), which increases the incidence of cardiovascular diseases drastically and affects the quality of life of patients seriously. Eucommiae cortex has the effect of tonifying kidneys and strengthening bones, and salt Eucommiae cortex is one of the most commonly used traditional Chinese medicines in the clinical treatment of CKD-MBD instead of Eucommiae cortex. However, its mechanism still remains unexplored. AIM OF THE STUDY: The aim of this study was to investigate the effects and mechanisms of salt Eucommiae cortex on CKD-MBD by integrating network pharmacology, transcriptomics, and metabolomics. MATERIALS AND METHODS: The CKD-MBD mice induced by 5/6 nephrectomy and low calcium/high phosphorus diet were treated with salt Eucommiae cortex. The renal functions and bone injuries were evaluated by serum biochemical detection, histopathological analyses, and femur Micro-CT examinations. Differentially expressed genes (DEGs) between the control group and model group, model group and high-dose Eucommiae cortex group, model group and high-dose salt Eucommiae cortex group were analyzed by transcriptomic analysis. The differentially expressed metabolites (DEMs) between the control group and model group, model group and high-dose Eucommiae cortex group, model group and high-dose salt Eucommiae cortex group were analyzed by metabolomics analysis. The common targets and pathways were obtained by integrating transcriptomics, metabolomics, and network pharmacology, which were identified and verified by in vivo experiments. RESULTS: The negative impacts on the renal functions and bone injuries were alleviated with salt Eucommiae cortex treatment effectively. Compared with CKD-MBD model mice, the levels of serum BUN, Ca, and urine Upr were significantly decreased in the salt Eucommiae cortex group. And the Integrated network pharmacology, transcriptomics, and metabolomics analysis revealed that Peroxisome Proliferative Activated Receptor, Gamma (PPARG) was the only common target, mainly involved by AMP-activated Protein Kinase (AMPK) signaling pathways. The activation of PPARG in the kidney tissue was significantly decreased in CKD-MBD mice but increased in the salt Eucommiae cortex treatment. The AMPK signaling pathway was verified and the AMPK expression levels were found to decrease in CKD-MBD mice but increase given salt Eucommiae cortex treatment. CONCLUSIONS: Our study presented that salt Eucommiae cortex alleviated the negative impact of CKD-MBD on the renal injury and bone injury of mice induced by 5/6 nephrectomy with the low calcium/high phosphorus diet effectively, which is highly likely achieved through the PPARG/AMPK signaling pathway.

[Research progress on the effects and mechanisms of electroacupuncture on radiation-induced brain injury].

Radiation-induced brain injury is a serious complication after cranio-cerebral radiotherapy, which affects the patient's quality of life and survival. A large number of studies have shown that various mechanisms such as neuronal apoptosis, blood-brain barrier damage, and synaptic dysfunction may be related to radiation-induced brain injury. Acupuncture has an important role in clinical rehabilitation of various brain injuries. As a new type of acupuncture, electroacupuncture has the characteristics of strong control ability, uniform and long-lasting stimulation, and is widely used in clinic. This article reviews the effects and mechanisms of electroacupuncture on radiation-induced brain injury, in order to provide a theoretical basis and experimental support for reasonable clinical application.

[Progress in the application of evaluation criteria for clinical efficacy of acupuncture in the treatment of knee osteoarthritis].

Knee osteoarthritis is a chronic joint disease characterized by degeneration of knee cartilage and secondary osteoproliferation, pain and dysfunction, with a high morbidity.Clinical evaluation of efficacy was mainly based on scales, including pain scales, knee function scales, quality of life scales. In order to fully present comprehensive evaluation criteria of acupuncture effect of knee osteoarthritis, this paper reviewed the scales, contrasted their characteristics and scope of application, analyzed the existing problems, and offered proposals to develop and choose efficacy evaluation criteria. Expecting to provide refe-rence frame to evaluate the clinical efficacy of acupuncture in treating knee osteoarthritis in the future.

[Effect of electroacupuncture on proliferation of hippocampal neural stem cells in young mice with Alzheimer's disease].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the proliferation of endogenous neural stem cells in the hippocampus of young mice with Alzheimer's disease (AD), so as to explore its mechanisms underlying improvement of AD. METHODS: Forty 1.5-month-old APP/PS1 transgenic male mice were randomly divided into an EA group and a model group, 20 mice in each group, and other 20 C57BL/6J male mice of the same age were used as the normal control group. EA (intermittment wave 10 Hz, 2 mA) was applied to "Baihui" (GV 20), "Fengfu" (GV 16) and "Shenshu" (BL 23) for 20 min, once a day, 6 days a week for 16 weeks. H.E. staining was used to assess histopathological changes of neurons of the hippocampal dentate gyrus. Immunohistochemical stain was used to detect the expression of 5-bromodeoxyuridine (BrdU)-positive in the hippocampus, and immunofluorescence double-labeled technique was used to detect the number of proliferated positive neurons of hippocampal neural stem cells. The expression levels of brain derived neurotrophic factor (BDNF) and Nestin mRNA and protein were detected by using real-time PCR and Western blot, separately. RESULTS: The immunoactivity of BrdU, and the expression levels of BDNF and Nestin mRNA and protein in the hippocampus in the model group were significantly lower than in the normal control group (P<0.01, P<0.05), and considerably higher in the EA group than in the model group (P<0.01, P<0.05). The number of BrdU/NeuN dual labeled neurons was slightly increased in the model group than in the normal control group (P>0.05), and evidently increased in the EA group relevant to the model group (P<0.05), suggesting a proliferation of hippocampal neural stem cells. After modeling, the neurons of hippocampal dentate gyrus were arranged loosely and irregularly and their structure was fuzzy, with an appearance of different degrees of nuclear pyknosis, whereas in the EA group, the neuronal contour was clear and the nuclear structure was relatively distinct. CONCLUSION: EA can activate the proliferation of neural stem cells in the hippocampus in AD mice, which may contribute to its function in improving the neuronal structure by upregulating the expression of BDNF.

[Effects of electroacupuncture with different courses on the synaptic structure and synaptic function-related proteins in mice with radiation-induced brain injury].

The aim of the present study was to investigate the effects of different courses of electroacupuncture on synaptic structure and synaptic function-related proteins expression in the hippocampal CA1 region of radiation-induced brain injury mice. Sixty C57BL/6J male mice were randomly divided into control group, radiation-induced brain injury model group, 1-week electroacupuncture group (EA1), 2-week electroacupuncture group (EA2), 3-week electroacupuncture group (EA3), and electroacupuncture-control (EA-Ctrl) group. The mice in model group were exposed to X-ray irradiation (8 Gy, 10 min) to establish radiation-induced brain injury model. The mice in EA groups were acupunctured at electroacupuncture points (Baihui, Fengfu and bilateral Shenshu) for 1 week, 2 weeks and 3 weeks respectively after radiation. Immunohistochemistry was used to observe synaptic structure in hippocampal CA1 region. The expressions of brain-derived neurotrophic factor (BDNF), synapsin-1 and postsynaptic density 95 (PSD95) in the hippocampal CA1 region of each group were detected by RT-PCR and Western blotting. The results showed that the nuclear gap in model and EA-Ctrl groups was significantly decreased compared to control group, however nucleus to cytoplasm ratio was significantly increased. The synaptic cleft, postsynaptic density (PSD) thickness, the mitochondrial surface density, volume density and specific surface area were significantly reduced. Compared with model group, the nucleus to cytoplasm ratio of EA2 group was significantly decreased, the PSD thickness and mitochondrial volume density were significantly increased; the nuclear gap of EA3 group was significantly increased, nucleus to cytoplasm ratio was significantly decreased, synaptic cleft and PSD thickness were significantly increased, and the mitochondrial surface density and specific surface area were all increased significantly. In addition, compared with the control group, the gene and protein expressions of BDNF, synapsin-1 and PSD95 in the hippocampal CA1 region of the model group and EA-Ctrl group were significantly decreased. However, compared with the model group, the gene expression of synapsin-1 in EA groups was significantly up-regulated, the gene expression of BDNF in EA1 and EA2 groups was significantly up-regulated, and the gene expression of PSD95 in EA2 group was significantly up-regulated. Moreover, the protein expressions of BDNF, synapsin-1 and PSD95 of EA groups were significantly up-regulated compared with the model group. These results indicate that the synaptic structure and the expression of synaptic function-related proteins in hippocampal CA1 region were injured by radiation exposure, whereas electroacupuncture intervention can significantly improve the synaptic structure and function damage caused by radiation.

[Current state about researches on selection of experimental indexs mechanisms of acupuncture underlying improvement of chronic fatigue syndrome].

Acupuncture therapy is effective in the treatment of chronic fatigue syndrome (CFS) and has its own unique advantages. In the present paper, we reviewed the progress of experimental researches on the underlying mechanisms of acupuncture treatment of CFS in recent 10 years from: 1) regulating the immune system including the peripheral immune organ, immune cells and immune cytokines, proinflammatory and anti-inflammatory cytokines, and lowering the increase of positive rate of multiple mycoplasma infection; 2) regulating the neuroendocrine system including the hypothalamus-pituitary-adrenal axis and stress hormones, monoamine neurotransmitters, and opioid peptides; 3)raising the anti- oxidative stress ability by reducing malondiadehyde, and upregulating activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase; and 4) regulating multiple cellular molecule signaling pathways revealed by genomic and proteomic technologies. In conclusion, acupuncture can relieve CFS through multiple ways and systems, which may provide some ideas for further studies on the biological mechanisms.

Polymerization and coordination synergistically constructed photothermal agents for macrophages-mediated tumor targeting diagnosis and therapy.

Developing an ideal photothermal agent is one of the challenges for effective photothermal therapy (PTT). Herein, a green and simple yet versatile method is developed to construct a novel poly-(iron-dopamine coordination complexes) nanoparticles (P[Fe-DA]-NPs) based on polymerization and coordination synergistically by using Fe3+ ions and dopamine (DA) in aqueous solution, and simultaneously poly(vinylpyrrolidone) (PVP) is applied to improve dispersion stability. P[Fe-DA]-NPs can be laden into macrophages directly with no further purification required to target tumor tissue to perform cell-mediated strategy. P[Fe-DA]-laden macrophages as an ideal photothermal agent has the advantages of good biocompatibility, simple preparation process, high photothermal performance, and effective tumor targeting. Furthermore, the P[Fe-DA]-laden macrophages possess excellent photoacoustic imaging (PAI) capacity for guiding the precise PTT. The results show that the tumors are significantly suppressed after PTT with the help of the accurate PAI diagnosis. This cell-mediated strategy may be the most promising avenue for the future clinical cancer therapy.

Microwave assisted chitosan-polyethylene glycol hydrogel membrane synthesis of curcumin for open incision wound healing.

Chitosan and polyethylene glycol hydrogel membranes containing curcumin were synthesized using microwave technology at fixed frequency, power and time of 2450 MHz, 500 Watt and 120 s. Polymers were solubilized separately, combined with drug and mixed in two different ratios i.e. F1=80:20 and F2=85:15. The untreated and microwave treated hydrogel membranes were analyzed for degree of swelling, degree of degradation, tensile strength, surface morphology, vibrational and thermal analysis and in vitro drug release. Results indicated that F2(micro) showed a significantly high degree of swelling (96.49±1.21 %), low degradation (9.88±1.68 %), sustained drug release through slow erosion (55.1±3.11 %) via non-Fickian diffusion. The vibrational and thermal analysis revealed rigidification of hydrophilic domains of the polymers by formation of hydrogen bonds between chitosan and PEG moieties (OH/NH) and elasticity of hydrophobic domains (asymmetric and symmetric CH moieties and/or C=O moieties) which not only significantly increased the transition temperature and enthalpy (297.2±3.2 °C and 4.24±1.4 J/g) of the chitosan moiety but also resulted in enhanced tensile strength (18.2±1.3 Mpa). In vivo wound healing study revealed significantly faster wound healing in the F2(micro) treated animal group in comparison to a control animal group where at day 14, a significant re-epithelization (87.26 %) with smaller wound size was observed. Hence microwave assisted chitosan-PEG hydrogel membrane of curcumin is advocated to be a suitable plate form for wound healing applications.

A glutathione-depleting chemodynamic therapy agent with photothermal and photoacoustic properties for tumor theranostics.

Nowadays, Fenton reaction-based chemodynamic therapy (CDT) strategies have drawn extensive attention as tumor-specific nanomedicine-based therapy. Nevertheless, current existing CDTs normally suffer from therapeutic bottlenecks such as the scavenging of hydroxyl radical (˙OH) by intracellular antioxidants and unideal therapeutic outcome of single treatment modality. Herein, we constructed novel all-in-one AFP nanoparticles (NPs) as CDT agents through a one-pot process for multifunctional nanotheranostics. The as-constructed AFP NPs could simultaneously produce ˙OH through the Fenton reaction and scavenge intracellular glutathione, functioning as self-reinforced CDT agents to achieve tumor-triggered enhanced CDT (ECDT). In addition, the AFP NPs possessed the capability of H2O2 and acid-boosted photoacoustic imaging and photothermal therapy, enabling a precise and effective tumor therapeutic outcome with minimal nonspecific damage in combination with ECDT. Our novel nanoplatform would open new perspectives on multi-functional CDT agents for accurate and non-invasive tumor theranostics.

Porphyrin-based covalent organic framework nanoparticles for photoacoustic imaging-guided photodynamic and photothermal combination cancer therapy.

Combination of photodynamic therapy (PDT) and photothermal therapy (PTT) generally requires different components to build a composite irradiated with different excitation lights. One component photoactive agent for enhanced combination of PDT and PTT under the excitation of a single wavelength light source is more urgent in tumor phototherapy via adjusting spatial arrangement of photoactive units. Herein, porphyrin-based covalent organic framework nanoparticles (COF-366 NPs) were synthesized to control the orderly spatial arrangement of the photoactive building units and firstly used for antitumor therapy in vivo. COF-366 NPs provide the simultaneous therapy of PDT and PTT under a single wavelength light source with the monitoring of photoacoustic (PA) imaging, which makes the operation simpler and more convenient. COF-366 NPs had achieved good phototherapy effect even in the face of large tumors. The prepared multifunctional COF-366 NPs open up a new avenue to phototherapeutic materials and expand the application range of covalent organic framework.

Pterostilbene, an active component of the dragon's blood extract, acts as an antidepressant in adult rats.

BACKGROUND: Hippocampal neurogenesis has been widely considered as one of the potential biological mechanisms for the treatment of depression caused by chronic stress. Many natural products have been reported to be beneficial for neurogenesis. OBJECTIVES: The present study is designed to investigate the effect of dragon's blood extract (DBE) and its biologically active compound, pterostilbene (PTE), on hippocampal neurogenesis. METHODS: The male Sprague-Dawley (SD) rats were used in this study, which were maintained on the normal, DBE and PTE diet groups for 4 weeks before dissection in the normal rat model and behavioral testing in the CUS depression rat model. Meanwhile, DMI-treated rats are subcutaneously injected with DMI (10 mg/kg, i.p.). RESULTS: Results revealed that DBE and PTE have the ability to promote hippocampal neurogenesis. DBE and PTE also promoted the proliferation of neural stem cells isolated from the brain of suckling rats. Oral administration of DBE and PTE induced the proliferation, migration, and differentiation of neural progenitor cells (NPCs) in chronic unexpected stressed (CUS) model rats, and improved the behavioral ability and alleviated depress-like symptoms of CUS rats. It was also observed that PTE treatment significantly induced the expression of neurogenesis-related factors, including BDNF, pERK, and pCREB. CONCLUSION: Oral administration of PTE could affect neurogenesis and it is likely to be achieved via BDNF/ERK/CREB-associated signaling pathways.

Study on MgxSr3-x(PO4)2 bioceramics as potential bone grafts.

Magnesium (Mg) and strontium (Sr), which are essential nutrient elements in the natural bone, positively affect the osteogenic activity even in wide ranges of ion concentrations. However, it remains unknown whether magnesium-strontium phosphates [MgxSr3-x(PO4)2] are potential bone grafts for accelerating bone regeneration. Herein, a serial of MgxSr3-x(PO4)2, including Mg3(PO4)2, Mg2Sr(PO4)2, Mg1.5Sr1.5(PO4)2, MgSr2(PO4)2 and Sr3(PO4)2, were synthesized using a solid-state reaction approach. The physicochemical properties and cell behaviors of MgxSr3-x(PO4)2 bioceramics were characterized and compared with the common bone graft ß-tricalcium phosphate (ß-TCP). The results indicated that various MgxSr3-x(PO4)2 bioceramics differed in compressive strength and in vitro degradation rate. All the MgxSr3-x(PO4)2 bioceramics had excellent biocompatibility. In contrast to ß-TCP, the MgxSr3-x(PO4)2 enhanced alkaline phosphatase activity of mouse bone mesenchymal stem cells (mBMSCs), and inhibited osteoclastogenesis-related gene expression of RAW264.7 cells, but did not enhance osteogenesis-related gene expression of mBMSCs which were treated with osteogenesis induction supplements. However, Mg3(PO4)2 stimulated osteogenesis-related gene expression of mBMSCs without the treatment of osteogenesis induction supplements. This work contributes to the design of bone graft and may open a new avenue for the bone regeneration field.

Reversing effects of ginsenosides on LPS-induced hepatic CYP3A11/3A4 dysfunction through the pregnane X receptor.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng C. A. Meyer), a traditional Chinese medicine, is widely used in the adjunctive therapy of the liver diseases. AIM OF THE STUDY: Ginsenosides are one kind of the main active ingredients in ginseng. Although hepatoprotective mechanisms of ginsenosides, such as anti-oxidation, anti-inflammation and anti-apoptosis, have been well studies, little is known about the effect of ginsenosides on drug metabolism in liver. Since CYP3A11/3A4 is a major enzyme catalyzing the drug metabolism in liver, an investigation of the enzyme's expression during the progression of a liver disease will gain valuable information about the hepatic drug metabolism. The purpose of this study was to determine the effect of ginsenosides on the expression of hepatic CYP3A11/3A4 in the lipopolysaccharides (LPS) injured human HepG2 cells and mice. We hypothesize that ginsenosides are important to stabilize CYP3A11/3A4 expression in an injured liver. MATERIALS AND METHODS: In this study, LPS was intraperitoneally intermittently injected to induce the liver injury in mice. Ginsenosides were intragastrically administered to mice for 7 days to treat the liver injury. Serum biochemical analysis and histopathological study were taken to evaluate the hepatoprotective effect of ginsenosides. The effect of ginsenosides was also evaluated in human HepG2 cells in the presence and absence of LPS. Real-time PCR and western blotting method were used to detect the mRNA and protein levels of CYP3A11/3A4 in mouse liver tissue and human HepG2 cells. The reporter gene-transfected cells were used to identify upstream targets in HepG2 cells. RESULTS: LPS injection in mice resulted in the up-regulation of pro-inflammatory cytokines such as IL-1ß, IL-6 and TNF-α in liver, up-regulation of hepatic enzymes such as Tbil, ALT, AST and ALP in serum, and down-regulation of CYP3A11/3A4 expression in liver. Ginsenosides treatment reversed the up-regulation of pro-inflammatory cytokines and serum hepatic enzymes elicited by LPS. Pathological results suggest that ginsenosides reduced liver damage. Moreover, ginsenosides reversed the decrease of CYP3A11/3A4 expression in the liver of LPS-injured mouse and in LPS-treated HepG2 cells. To further investigate the regulatory mechanisms, we found that ginsenosides enhanced the rifampicin-induced pregnane X receptor (PXR) transactivation of the CYP3A4 promoter. Treatment of hPXR-over-expressed cells with ginsenosides increased the rifampicin-inducible expression of CYP3A4 in a concentration-dependent manner. CONCLUSION: Ginsenosides reverse the effects of LPS-induced hepatic CYP3A11/3A4 dysfunction, suggesting that the stabilization of the CYP3A11/3A4 expression in an injured liver appears a novel hepatoprotective mechanism of ginsenosides.

Targeted and NIR light-controlled delivery of nitric oxide combined with a platinum(iv) prodrug for enhanced anticancer therapy.

This study reports a strategy of combining a Pt(iv) prodrug and a ruthenium nitrosyl (Ru-NO) donor into a single nanoplatform {N-GQDs@Ru-NO-Pt@FA} in which the platinum(iv) prodrug is conjugated onto a photoactivatable NO donor (Ru-NO) through a covalent bond and the nitric oxide-releasing platinum prodrug and folate groups are decorated on N-doped graphene quantum dots (N-GQDs). After cellular uptake of the nanoplatform, the platinum(iv) prodrug was reduced to an active anti-cancer Pt(ii) species inside the cancerous cells, and simultaneously, near-infrared (NIR) light illumination induced the release of NO, accompanied by a prominent photothermal effect. This nanoplatform is capable of targeting intracellular co-delivery of Pt(ii) and NO under 808 nm NIR light irradiation, accompanied by photothermal therapy, thereby leading to a significant synergistic therapeutic effect.

Electrophysiological characteristics and radiofrequency ablation of sustained monomorphic ventricular tachycardia in adult patients with isolated ventricular noncompaction.

PURPOSE: This study examined electrophysiological characteristics and outcomes of patients with sustained ventricular tachycardia (VT) in the setting of isolated ventricular noncompaction (IVNC). BACKGROUND: In patients with IVNC, VT has been associated with sudden cardiac death. However, the electrophysiological characteristics and optimal management of these VTs are only incompletely understood. METHODS: This retrospective cohort study assessed arrhythmia characteristics and outcomes in IVNC patients with sustained monomorphic VTs. Data were obtained from five academic centers covering the time period from January 1, 2006, to December 31, 2016, with a median follow-up of 40 months. RESULTS: Eighteen consecutive IVNC patients with sustained VTs (12 males [66%], mean age of 44.4 ± 16.9 years) were enrolled. Seven (39%) patients underwent VT ablation (five males, mean age of 43.3 ± 15.5 years) and nine (50%) patients received ICD therapy. Six of 18 patients (33%) died during a median follow-up of 40 months. Of these, three had ICDs, two had undergone VT ablation, and one had received only antiarrhythmic drugs. Among the seven patients with prior VT ablation, five VTs in the RV (three RVOT and one tricuspid annulus) and two LV VTs (one anterolateral papillary muscle and one inferolateral wall) were localized by 3-D mapping and successfully ablated. In six of seven ablation cases (85.7%), the VTs were distant from the noncompaction zone. VTs appeared to be focal in 57% (4/7) and macro-reentry in 43% (3/7) of patients based on 3-D mapping and entrainment studies. The success rate of VT ablation was 85.7% with one VT recurrence and two deaths during the mean follow-up of 54 (28-115) months. CONCLUSIONS: IVNC Patients with sustained VTs appear to have a poor prognosis despite receiving ICD or apparently successful VT ablation therapy. Further, most VTs appear to arise remote from the noncompaction zone. Whether these VTs were "idiopathic" or related to IVNC was uncertain.

Kernel differential subgraph reveals dynamic changes in biomolecular networks.

Many major diseases, including various types of cancer, are increasingly threatening human health. However, the mechanisms of the dynamic processes underlying these diseases remain ambiguous. From the holistic perspective of systems science, complex biological networks can reveal biological phenomena. Changes among networks in different states influence the direction of living organisms. The identification of the kernel differential subgraph (KDS) that leads to drastic changes is critical. The existing studies contribute to the identification of a KDS in networks with the same nodes; however, networks in different states involve the disappearance of some nodes or the appearance of some new nodes. In this paper, we propose a new topology-based KDS (TKDS) method to explore the core module from gene regulatory networks with different nodes in this process. For the common nodes, the TKDS method considers the differential value (D-value) of the topological change. For the different nodes, TKDS identifies the most similar gene pairs and computes the D-value. Hence, TKDS discovers the essential KDS, which considers the relationships between the same nodes as well as different nodes. After applying this method to non-small cell lung cancer (NSCLC), we identified 30 genes that are most likely related to NSCLC and extracted the KDSs in both the cancer and normal states. Two significance functional modules were revealed, and gene ontology (GO) analyses and literature mining indicated that the KDSs are essential to the processes in NSCLC. In addition, compared with existing methods, TKDS provides a unique perspective in identifying particular genes and KDSs related to NSCLC. Moreover, TKDS has the potential to predict other critical disease-related genes and modules.

A ruthenium-nitrosyl-functionalized nanoplatform for the targeting of liver cancer cells and NIR-light-controlled delivery of nitric oxide combined with photothermal therapy.

The development of light-controlled nitric oxide (NO)-releasing nanoplatforms that are capable of specifically targeting liver cancer cell lines and delivering an optimal amount of NO can significantly affect liver cancer therapy. In this study, a multifunctional nanoplatform {N-GQDs@Ru-NO@Gal} (1) for the near-infrared (NIR) light-responsive release of NO, consisting of a NO donor (Ru-NO) and a liver-targeting galactose derivative (Gal) covalently attached to N-doped graphene quantum dots (N-GQDs), was reported. Nanoplatform 1 preferentially targeted liver cancer cells over normal cells and instantly released NO as well as exhibited a prominent photothermal effect upon NIR irradiation at 808 nm, thereby leading to efficient anti-tumor efficacy. {N-GQDs@Ru-NO@Gal} with a small size (<10 nm), good biocompatibility, and fluorescent-tracing properties represents a unique example of a multifunctional NO-releasing nanoplatform that combines photodynamic and photothermal therapies for the targeted treatment of liver cancer. Hence, the developed nanoplatform demonstrates potential for applications in NO-mediated multimodal phototherapy in the near future.