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Li-Xia Hu,1,* Hong Wang,1,* Meng Rao,1,* Xiao-Ling Zhao,1 Jing Yang,1 Shi-Fu Hu,1 Jing He,1,2 Wei Xia,1 Hefang Liu,1 Bo Zhen,1 Haihong Di,1 Changsheng Xie,3 Xianping Xia,3 Changhong Zhu,11Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China; 2Central Hospital of Wuhan, Wuhan, People's Republic of China; 3Department of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, People's Republic of China *These authors contributed equally to this work Abstract: A copper/low-density polyethylene nanocomposite (nano-Cu/LDPE), a potential intrauterine device component material, has been developed from our research. A logical extension of our previous work, this study was conducted to investigate the expression of plasminogen activator inhibitor 1 (PAI-1), substance P (SP), and substance P receptor (SP-R) in the endometrium of Sprague Dawley rats, New Zealand White rabbits, and Macaca mulatta implanted with nano-Cu/LDPE composite. The influence of the nano-Cu/LDPE composite on the morphology of the endometrium was also investigated. Animals were randomly divided into five groups: the sham-operated control group (SO group), bulk copper group (Cu group), LDPE group, and nano-Cu/LDPE groups I and II. An expression of PAI-1, SP, and SP-R in the endometrial tissues was examined by immunohistochemistry at day 30, 60, 90, and 180 postimplantation. The significant difference for PAI-1, SP, and SP-R between the nano-Cu/LDPE groups and the SO group (P

Purpose: To determine how low inorganic phosphate stress (LIPS) induced by sevelamer transartieral embolization (S-TAE) affects immune regulation and angiogenesis in hepatocellular carcinoma (HCC)., Material and Methods: Transcatheter arterial embolization (TAE) using conventional lipiodol plus Poly (vinyl alcohol) (PVA) microsphere and S-TAE were conducted on a McA-RH7777 orthotopic liver tumor model in rats, followed by the assessment of alterations in immunity- and angiogenesis-related factors. The cells were cultured under hypoxic conditions and stimulated with LIPS to analyze the modulation of programmed cell death 1 ligand 1 (PD-L1), vascular endothelial growth factor (VEGFα), and transforming growth factor-β1 (TGF-β1) expression through Western blotting, qRT‒PCR, and immunofluorescence assays. Cell migratory capacity and angiogenesis were also evaluated., Results: TAE increased the expression of neoplastic PD-L1 and VEGFα, and S-TAE, which depletes intratumoral Pi, downregulated the expression of PD-L1, VEGFα and TGF-β1, and augmented the infiltration of CD8+ T-cells, thereby inhibited angiogenesis and activated anticancer immunity. In vitro, the study demonstrated that LIPS inhibits hypoxia-induced upregulation of PD-L1 expression and the HIF-1α/VEGFα axis. Moreover, LIPS inhibited the tube formation ability of Human Umbilical Vein Endothelial Cells (HUVECs) and the migration ability and epithelial-mesenchymal transition (EMT) process of cancer cells under hypoxic conditions., Conclusions: S-TAE inhibited the expression of PD-L1 and VEGFα, thereby activated anti-tumor immunity and suppressing tumor angiogenesis. All the findings reveal the biology of tumors under low Pi stress and suggest the potential therapeutic value of S-TAE., (Copyright © 2024. Published by Elsevier Inc.)

Backgroup: Currently, aromatherapy is being increasingly utilized in clinical practice, particularly in managing the side effects associated with radiotherapy and chemoradiotherapy. However, it remains to be established whether aromatherapy can effectively alleviate these symptoms., Objective: To investigate the effects of aromatherapy on the physical and mental health of patients with cancer undergoing radiotherapy and chemotherapy., Methods: Seven databases were researched from inception until September 29, 2023, including PubMed, Scopus, and Web of Science, Chinese National Knowledge Infrastructure, Wanfang database, China Biology Medicine disc and VIP Chinese Medical Journal Database. Review Manager version 5.3 was utilized for data analysis. The Cochrane Risk of Bias tool RoB2 was employed to evaluate the quality of the literature included in the study. Evidence quality rating was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach through the GRADEpro GDT online tool., Results: Nineteen studies involving 1,541 patients were included. Aromatherapy can alleviate nausea [relative risk (RR)=0.64, 95% confidence interval (CI): 0.53 to 0.78, P<0.05, I 2 =46%; standardized mean difference (SMD)=-0.86, 95% CI: -1.21 to -0.51, P<0.05, I 2 =64%] and vomiting (RR=0.54, 95% CI: 0.42 to 0.69, P<0.05, I 2 =35%; SMD=-1.28, 95% CI: -1.52 to -1.03, P<0.05, I 2 =92%), improve sleep disorders [mean difference (MD)=-3.39, 95% CI: -3.95 to -2.84, P<0.05, I 2 =0%], relieve pain (SMD=-1.58, 95% CI: -1.96 to -1.21, P<0.05, I 2 =0%), mitigate fatigue (SMD=-1.28, 95% CI: -2.44 to -0.11, P<0.05, I 2 =93%) and enhance quality of life (SMD=0.50, 95% CI: 0.22 to 0.79, P<0.05, I 2 =0%) in cancer patients after radiotherapy and chemotherapy, but it may not have a significant effect on anxiety. The risk of bias was high in the included studies using the Cochrane Risk of Bias tool RoB2, and no studies were considered to be of high grade according to the GRADE system., Conclusions: Aromatherapy is an efficacious, safe and economic adjunctive therapy for cancer patients, which can mend the physical symptoms and mental health of cancer patients. However, more high-quality studies are needed to verify it. (PROSPERO registration No. CRD42023390171)., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Liver fibrosis is a chronic liver disease characterized by a progressive wound healing response caused by chronic liver injury. Currently, there are no approved clinical treatments for liver fibrosis. Sevelamer is used clinically to treat hyperphosphatemia and has shown potential therapeutic effects on liver diseases. However, there have been few studies evaluating the therapeutic effects of sevelamer on liver fibrosis, and the specific mechanisms are still unclear. In this study, we investigated the antifibrotic effects of sevelamer-induced low inorganic phosphate (Pi) stress in vitro and in vivo and analyzed the detailed mechanisms. We found that low Pi stress could inhibit the proliferation of activated hepatic stellate cells (HSCs) by promoting apoptosis, effectively suppressing the migration and epithelial-mesenchymal transition (EMT) of hepatic stellate cells. Additionally, low Pi stress significantly increased the antioxidant stress response. It is worth noting that low Pi stress indirectly inhibited the activation and migration of HSCs by suppressing transforming growth factor β (TGF-β) expression in macrophages. In a rat model of liver fibrosis, oral administration of sevelamer significantly decreased blood phosphorus levels, improved liver function, reduced liver inflammation, and increased the antioxidant stress response in the liver. Our study revealed that the key mechanism by which sevelamer inhibited liver fibrosis involved binding to gastrointestinal phosphate, resulting in a decrease in blood phosphorus levels, the downregulation of TGF-β expression in macrophages, and the inhibition of HSC migration and fibrosis-related protein expression. Therefore, our results suggest that sevelamer-induced low Pi stress can attenuate hepatic stellate cell activation and inhibit the progression of liver fibrosis, making it a potential option for the treatment of liver fibrosis and other refractory chronic liver diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Numerous studies have shown the positive correlation between high levels of Pi and tumour progression. A critical goal of macrophage-based cancer therapeutics is to reduce anti-inflammatory macrophages (M2) and increase proinflammatory antitumour macrophages (M1). This study aimed to investigate the relationship between macrophage polarization and low-Pi stress. First, the spatial populations of M2 and M1 macrophages in 22 HCC patient specimens were quantified and correlated with the local Pi concentration. The levels of M2 and M1 macrophage markers expressed in the peritumour area were higher than the intratumour levels, and the expression of M2 markers was positively correlated with Pi concentration. Next, monocytes differentiated from THP-1 cells were polarized against different Pi concentrations to investigate the activation or silencing of the expression of p65, IκB-α and STAT3 as well as their phosphorylation. Results showed that low-Pi stress irreversibly repolarizes tumour-associated macrophages (TAMs) towards the M1 phenotype by silencing stat6 and activating p65. Moreover, HepG-2 and SMCC-7721 cells were cultured in conditioned medium to investigate the innate anticancer immune effects on tumour progression. Both cancer cell lines showed reduced proliferation, migration and invasion, as epithelial-mesenchymal transition (EMT) was inactivated. In vivo therapeutic effect on the innate and adaptive immune processes was validated in a subcutaneous liver cancer model by the intratumoural injection of sevelamer. Tumour growth was significantly inhibited by the partial deprivation of intratumoural Pi as the tumour microenvironment under low-Pi stress is more immunostimulatory. The anticancer immune response, activated by low-Pi stress, suggests a new macrophage-based immunotherapeutic modality., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Sorafenib is a tyrosine kinase inhibitor for the treatment of advanced-stage HCC; however, clinical trials of sorafenib failed to demonstrate long-term survival benefits due to drug resistance. Low Pi stress has been shown to inhibit tumor growth and the expression of multidrug resistance-associated proteins. In this study, we investigated the sensitivity of HCC to sorafenib under conditions of low Pi stress. As a result, we found that low Pi stress facilitated sorafenib-mediated suppression of migration and invasion of HepG-2 and Hepa1-6 cells by decreasing the phosphorylation or expression of AKT, Erk and MMP-9. Angiogenesis was inhibited due to decreased expression of PDGFR under low Pi stress. Low Pi stress also decreased the viability of sorafenib-resistant cells by directly regulating the expression of AKT, HIF-1a and P62. In vivo drug sensitivity analysis in the four animal models showed a similar tendency that low Pi stress enhances sorafenib sensitivity in both the normal and drug-resistant models. Altogether, low Pi stress enhances the sensitivity of hepatocellular carcinoma to sorafenib and expands the indications for sevelamer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

As the most efficient method to treat hepatocellular carcinoma in the immediate or advanced stage, transarterial chemoembolization (TACE) is coming into the era of microsphere (MP). Drug-eluting beads have shown their huge potential as an embolic agent and drug carrier for chemoembolization, but their sizes are strictly limited to be above 40 μm, which was considered to occlude vessels in a safe mode. microsphere smaller than 40 µm is easy to be washed out and transported to the normal liver lobe or other organs, causing severe adverse events and failed embolization. To determine whether sevelamer ultrafine particle (0.2-0.5 µm) is qualified as a safe and efficient embolic agent, we investigated the safety and therapeutic efficiency of transarterial sevelamer embolization (TASE) in the VX2 rabbit liver cancer model, aiming to challenge the "40 µm" rule on the selection criteria of the MP. In a four-arm study, blank bead (Callisphere, 100-300 µm), luminescent polystyrene microsphere (10, 100 µm), and sevelamer particle were transarterially administered to evaluate the threshold size of the MP size for intrahepatic or extrahepatic permeability. Another four-arm study was designed to clarify the safety and efficiency of preclinical transarterial sevelamer embolizationTASE tests over other techniques. Sham (saline), TASE, C-TACE, and D-TACE ( n = 6) were compared in terms of serum chemistry, histopathology, and tumor necrosis ratio. In the first trials, the "40 µm" rule was detectable on the VX2 cancer model, but the regulation has no application to the new embolic agent as sevelamer ultrafine particles have not been found to leak out from the VX2 lesions, only found in the embolized vessels. Pathology proves that less viable tumor residue was found 2 weeks after the procedure, evidencing a better therapeutic outcome. No adverse events were found except for a short stress response. These results indicate that sevelamer is a safe and efficient embolic as an alternative to the current MP-based embolization therapy techniques., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Xie, Li, Deng, Lv, Bi, Tang, Luo and Tang.)

It is a decade-long controversy that transarterial chemoembolization (TACE) has definite priority over transarterial embolization (TAE) in treating patients with hepatocellular carcinoma (HCC), since HCC cells are regularly resistant to chemotherapy by enhanced expression of proteins that confer drug resistance, and ABC transporters pump the intracellular drug out of the cell. We addressed this issue by modulating the chemo-environment. In an animal model, sevelamer, a polymeric phosphate binder, was introduced as an embolic agent to induce intratumoral inorganic phosphate (Pi) starvation, and trans-arterially co-delivered with doxorubicin (DOX). The new type of TACE was named as DOX-TASE. This Pi-starved environment enhanced DOX tumoral accumulation and retention, and DOX-TASE thereby induced more severe tumor necrosis than that induced by conventional TACE (C-TACE) and drug-eluting bead TACE (D-TACE) at the same dose. In vitro tests showed that Pi starvation increased the cellular accumulation of DOX in an irreversible manner and enhanced cytotoxicity and cell apoptosis by suppressing the expression of ABC transporters (P-glycoprotein (P-gp), BCRP, and MRP1) and the production of intracellular ATP. Our results are indicative of an alternative interventional therapy combining chemotherapy with embolization more effectively.

Arsenic trioxide (As 2 O 3 , ATO) has limited therapeutic benefit to treat solid tumors, whether used alone or in combination. Nanoscale drug delivery vehicles have great potential to overcome the limitation of the utility of ATO by rapid renal clearance and dose-limiting toxicity. Polymeric materials ranging from gelatin foam to synthetic polymers such as poly(vinyl alcohol) were developed for vascular embolic or chemoembolic applications. Recently, we have introduced sevelamer, an oral phosphate binder, as a new polymeric embolic for vascular interventional therapy. In this paper, sevelamer arsenite nanoparticle with a polygonal shape and a size of 50-300 nm, synthesized by anionic exchange from sevelamer chloride, was developed as a Pi-responsive bifunctional drug carrier and embolic agent for chemoembolization therapy. At the same arsenic dosage, sevelamer arsenite-induced severer tumor necrosis than ATO on the VX2 cancer model. In vitro tests evidenced that Pi deprivation by sevelamer could enhance ATO's anticancer effect. The results showed that ATO in Pi starvation reduced cell viability, induced more apoptosis, and diminished the mitochondrial membrane potential (Δψm) of cells since Pi starvation helps ATO to further down-regulate Bcl-2 expression, up-regulate Bax expression, enhance the activation of caspase-3 and increase the release of cytochrome c, and the production of excessive reactive oxygen species (ROS). Sevelamer arsenite not only plays a Pi-activated nano-drug delivery system but also integrated anticancer drug with embolic for interventional therapy. Therefore, our results presented a new administration route of ATO as well as an alternative chemoembolization therapy.

Although many studies on mental health have been conducted among various populations during the COVID-19 pandemic, few studies have focused on post-traumatic growth (PTG) in the general population. The current study aimed to explore whether perceived social support, personality, and coping strategies are associated with PTG in the COVID-19 pandemic period. The study also investigated whether coping strategies mediate the relations between perceived social support, personality, and PTG. A total of 181 participants ( M age = 24) completed the self-report questionnaire online, which was distributed via various online channels, mainly in China and Sweden. The relations between the study variables were examined with correlation analyses and a multiple mediation analysis. Results showed that more than half of the participants (60.8%) reported experiences of PTG during the pandemic. Additionally, perceived social support, personality traits (extraversion, emotional stability, agreeableness, and conscientiousness) and coping strategies (problem-focused coping, emotion-focused coping, and social support coping) were positively correlated with PTG. In addition, coping strategies (problem-focused coping, emotion-focused coping, and avoidance coping) mediated the relations between perceived social support, personality traits and PTG. Theoretical and practical implications of this study are discussed, concluding that the findings of this study have the potential to guide intervention efforts to promote positive change during the pandemic.

Objective: Diabetic neuropathic pain (DNP) is one of the common complications in type 2 Diabetes Mellitus (DM) patients. However, molecular mechanisms in underlying diabetic neuropathic pain are still poorly understood. Kalirin-7, a multifunctional Rho GDP/GTP exchange factor, located at the excitatory synapses, was reported to modulate the neuronal cytoskeleton. Therefore, in this study, we explored the effects of Kalirin-7 on type 2 diabetic neuropathic pain and the mechanisms in spinal cord in rats., Methods: The type 2 diabetic neuropathic pain model was established in rats by feeding them with a high-sugar and high-fat diet for 8 weeks, and then fasting them for 12 hours, followed by a single intraperitoneal injection of STZ. Kalirin-7 was knocked down in the spinal cord by an intrathecal administration of Kalirin-7 siRNA., Results: The levels of Kalirin-7, p-NR2B and PSD-95 as well as the PSD-95-NR2B coupling were significantly increased in the spinal cord of type 2 DM rats. The knockdown of Kalirin-7 expression in the spinal cord by the intrathecal administration of Kalirin-7 siRNA not only reduced the levels of p-NR2B and the PSD-95-NR2B coupling in the spinal cord, but also relieved mechanical allodynia and thermal hyperalgesia in type 2 DM rats., Conclusions: Our findings suggest that spinally expressed Kalirin-7 likely contributes to type 2 diabetic neuropathic pain through regulating the PSD-95/NR2B interaction-dependent NR2B phosphorylation in the spinal cord., Competing Interests: None., (AJTR Copyright © 2020.)

The mechanisms underlying type-2 diabetic neuropathic pain (DNP) are unclear. This study investigates the coupling of postsynaptic density-95 (PSD-95) to N-methyl-D-aspartate receptor subunit 2B (GluN2B), and the subsequent phosphorylation of GluN2B (Tyr1472-GluN2B) in the spinal cord in a rat model of type-2 DNP. Expression levels of PSD-95, Tyr1472-GluN2B, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and its phosphorylated counterpart (Thr286-CaMKII), and α-amino-3-hydroxy-5-methyl-4-soxazole propionic acid receptor subtype 1 (GluR1) and its phosphorylated counterpart (Ser831-GluR1) were significantly increased versus controls in the spinal cord of type-2 DNP rats whereas the expression of total spinal GluN2B did not change. The intrathecal injection of Ro25-6981 (a specific antagonist of GluN2B) or Tat-NR2B9c (a mimetic peptide disrupting the interaction between PSD-95 and GluN2B) induced an antihyperalgesic effect and blocked the increased expression of Tyr1472-GluN2B, CaMKII, GluR1, Thr286-CaMKII, and Ser831-GluR1 in the spinal cords; the increase in spinal cord PSD-95 was not affected. These findings indicate that the PSD-95-GluN2B interaction may increase phosphorylation of GluN2B, and subsequently induce the expression of phosphorylation of CaMKII and GluR1 in the spinal cord of type-2 DNP rats. Targeting the interaction of PSD-95 with GluN2B may provide a new therapeutic strategy for type-2 DNP., (© 2020 American Association of Neuropathologists, Inc. All rights reserved.)

Objective: The present study determines whether Cav-1 modulates the initiation, development and maintenance of type-2 DNP via the Rac1/NOX2-NR2B signaling pathway., Methods: After regular feeding for three days, these rats were randomly divided into two groups: control group with normal-diet (maintenance feed) ( n =8); type-2 DM group ( n =8). In the type-2 DM group, the rats were fed with a high-fat and high-sugar diet, and received a single intraperitoneal streptozotocin (STZ) injection (35 mg/kg). At two weeks after STZ injection, these diabetic neuropathic pain (DNP) rats were treated with daidzein (0.4 mg/kg/day) and N-tert-Butyl-α-phenylnitrone (PBN, 100 mg/kg/day) for 14 days. After the type-2 DNP model was successfully established, the rats were assigned into four groups: DNP group, DNP+Da group (DNP rats with Cav-1 specific inhibitor daidzein), DNP+PBN group (DNP rats treated with ROS scavenger PBN), and SC group (solvent control group). Then, the mechanical and thermal hyperalgesia were assayed to evaluate the function of the caveolin 1-Recombinant Human Ras-Related C1/nicotinamide adenosine diphosphate oxidase 2-NR2B gene (Cav-1-Rac1/NOX2-NR2B) signaling pathway. In the mechanism study, the protein expression levels of p-Caveolin-1, Rac1, NOX2, p-NR2B and t-NR2B, the production of ROS, and the distribution of Cav-1 and NOX2 in the spinal cord were observed., Results: The present study revealed that p-Cav-1 was persistently upregulated and activated in the spinal cord microglia in type-2 DNP rats. The use of the pharmacological inhibitor of Cav-1 and a ROS scavenger resulted to a significantly relieved mechanical allodynia and thermal hyperalgesia. In addition, it was demonstrated that Cav-1 promoted ROS generation via the activation of Rac1-dependent NADPH oxidase (NOX)., Conclusion: The present data suggests that Cav-1 in the spinal cord modulates type-2 DNP via regulating the Rac1/NOX2-NR2B pathway., Competing Interests: None., (AJTR Copyright © 2020.)

This study aims to determine whether caveolin-1 (Cav-1) participates in the process of diabetic neuropathic pain by directly regulating the expression of toll-like receptor 4 (TLR4) and the subsequent phosphorylation of N-methyl-D-aspartate receptor 2B subunit (NR2B) in the spinal cord. Male Sprague-Dawley rats (120-150 g) were continuously fed with high-fat and high-sugar diet for 8 weeks, and received a single low-dose of intraperitoneal streptozocin injection in preparation for the type-II diabetes model. Then, these rats were divided into five groups according to the level of blood glucose, and the mechanical withdrawal threshold and thermal withdrawal latency values. The pain thresholds were measured at 3, 7, and 14 days after animal grouping. Then, eight rats were randomly chosen from each group and killed. Lumbar segments 4-6 of the spinal cord were removed for western blot analysis and immunofluorescence assay. Cav-1 was persistently upregulated in the spinal cord after diabetic neuropathic pain in rats. The downregulation of Cav-1 through the subcutaneous injection of Cav-1 inhibitor daidzein ameliorated the pain hypersensitivity and TLR4 expression in the spinal cord in diabetic neuropathic pain (DNP) rats. Furthermore, it was found that Cav-1 directly bound with TLR4, and the subsequent phosphorylation of NR2B in the spinal cord contributed to the modulation of DNP. These findings suggest that Cav-1 plays a vital role in DNP processing at least in part by directly regulating the expression of TLR4, and through the subsequent phosphorylation of NR2B in the spinal cord., (© 2019 Wiley Periodicals, Inc.)

Compound xueshuantong capsule (CXC) is an oral traditional Chinese herbal formula (CHF) comprised of Panax notoginseng (PN), Radix astragali (RA), Salvia miltiorrhizae (SM), and Radix scrophulariaceae (RS). The present investigation was designed to explore the core bioactive components promoting blood circulation in CXC using high-performance liquid chromatography (HPLC) and animal studies. CXC samples were prepared with different proportions of the 4 herbs according to a four-factor, nine-level uniform design. CXC samples were assessed with HPLC, which identified 21 components. For the animal experiments, rats were soaked in ice water during the time interval between two adrenaline hydrochloride injections to reduce blood circulation. We assessed whole-blood viscosity (WBV), erythrocyte aggregation and red corpuscle electrophoresis indices (EAI and RCEI, respectively), plasma viscosity (PV), maximum platelet aggregation rate (MPAR), activated partial thromboplastin time (APTT), and prothrombin time (PT). Based on the hypothesis that CXC sample effects varied with differences in components, we performed grey relational analysis (GRA), principal component analysis (PCA), ridge regression (RR), and radial basis function (RBF) to evaluate the contribution of each identified component. Our results indicate that panaxytriol, ginsenoside Rb1, angoroside C, protocatechualdehyde, ginsenoside Rd, and calycosin-7-O-β-D-glucoside are the core bioactive components, and that they might play different roles in the alleviation of circulation dysfunction. Panaxytriol and ginsenoside Rb1 had close relevance to red blood cell (RBC) aggregation, angoroside C was related to platelet aggregation, protocatechualdehyde was involved in intrinsic clotting activity, ginsenoside Rd affected RBC deformability and plasma proteins, and calycosin-7-O-β-D-glucoside influenced extrinsic clotting activity. This study indicates that angoroside C, calycosin-7-O-β-D-glucoside, panaxytriol, and protocatechualdehyde may have novel therapeutic uses.

Acute lung injury (ALI) is characterized by pulmonary edema, in which the epithelial sodium channel (ENaC) has a critical role in the clearance of edema fluid from the alveolar space. Lipopolysaccharide (LPS), frequently employed to induce ALI in experimental animal models, has been reported to regulate ENaC expression and alveolar fluid clearance. The role of LPS in regulating ENaC expression is currently controversial, with increases and decreases reported in ENaC expression in response to LPS treatment, as well as reports that ENaC expression is not affected by LPS induction. The present study aimed to systematically analyze the regulation of α‑ENaC expression in LPS models of ALI at different pathological stages in vitro and in vivo. ENaC expression was observed to increase ≤8 h after LPS treatment, and to decrease thereafter. This finding may explain the contradictory data regarding α‑ENaC expression in response to LPS in the lung. The results of the present study, in combination with those of previous studies, indicate that the modulation of α-ENaC expression may not be a direct genetic response to LPS exposure, but a general response of the lung to the pathological changes associated with inflammation, hypoxia and endothelial and epithelial damage involved in the development of ALI. The findings of this study may have potential clinical significance for understanding the pathogenesis of ALI and improving patient outcome.

NaoShuanTong capsule (NSTC), an oral traditional Chinese medicine formula, is composed of Pollen Typhae , Radix Paeoniae Rubra , Rhizoma Gastrodiae , Radix Rhapontici and Radix Curcumae . It has been widely used to treat ischemic stroke in clinic for many years in China. In addition to neuronal apoptosis, haemorheology and cerebral energy metabolism disorders also play an important role in the pathogenesis and development of ischemic stroke. The present study was designed to evaluate the in vivo protective effects of NSTC on haemorheology and cerebral energy metabolism disorders in rats with blood stasis. Sixty specific pathogen-free sprague-dawley rats, male only, were randomly divided into six groups (control group, model group, aspirin (100 mg/kg/d) group, NSTC low-dose (400 mg/kg/d) group, NSTC intermediate-dose (800 mg/kg/d) group, NSTC high-dose (1600 mg/kg/d) group) with 10 animals in each. The rats except those in the control group were placed in ice-cold water (0-4 °C) for 5 min during the time interval (4 h) of two adrenaline hydrochloride injections (0.8 mg/kg) to induce blood stasis. After treatment, whole blood viscosity at three shear rates, plasma viscosity and erythrocyte sedimentation rate significantly decreased in NSTC intermediate- and high-dose groups; erythrocyte aggregation index and red corpuscle electrophoresis index significantly decreased in all the three dose NSTC groups. Moreover, treatment with high-dose NSTC could significantly improve Na + -K + adenosine triphosphatase (ATPase) and Ca 2+ ATPase activity, as well as lower lactic acid level in brain tissues. These results demonstrated the protective effects of NSTC on haemorheology and cerebral energy metabolism disorders, which may provide scientific information for the further understanding of mechanism(s) of NSTC as a clinical treatment for ischemic stroke. Furthermore, the protective effects of activating blood circulation as observed in this study might create valuable insight for the utilisation of NSTC to be a feasible alternative therapeutic agent for patients with blood stasis.

In order to discuss the potential ecological risk of heavy metals of the typical dredged mud in Shanghai, the Hakanson potential ecological risks method was used to analyse and assess the potential ecological risks of heavy metals, including Hg, Cd, Cu, Pb, As,Cr and Zn in dredged mud from the following three areas-the dock apron of Huangpu River, the mouth of the Yangtze River and inland waterways. The results showed that the mean values of ecological risk index (Er(i)) of the seven heavy metals are 20.05, 17.49, 8.82, 5.71, 4.68, 1.74 and 1.13, respectively, all of which belonged to the low ecological risk; Cd (one location in inland waterways) and Hg (three locations in the mouth of the Yangtze River and one location in inland waterways) are the most hazardous elements, with the Er(i) > 40, which belonged to the medium ecological risk or the high ecological risk, and other elements belonged to the low ecological risk. From the results of ecological risk indices(ERI) of the heavy metals in Shanghai dredged mud, the risk of the heavy metals belonged to the low ecological risk. The ERI of inland waterways, the mouth of the Yangtze River and the dock apron of the Huangpu River were 81.4, 57.7 and 52.5, respectively, which all belong to the low ecological risk.

Objective: To estabolish a quantitative analysis method for pharmacokinetics and bioavailability of Puerarin self-microemulsion in Beagle dogs., Methods: A crossover design was use to detect the pharmacokinetic parameters of Puerarin self-microemulsion and suspension in Beagle dogs. The concentration of Puerarin in plasma was determined with HPLC, the pharmacokinetics parameters and bioavailability was calculated with DAS 2. 1. 1 programs., Results: T(max) of Puerarin self-microemulsion and suspension were 3.0 h and 2.0 h, C(max) were 2.14 mg/L and 1.061 mg/L, AUC(0-24) were 10.642 mg h/L and 3 mg x h/L, respectively. The bioavailability of Puerarin self-microemulsion relative to Puerarin suspension were 354.73%., Conclusion: Puerarin self-microemulsion can significantly improve the bioavailability in Beagle dogs.

Novel solid lipid nanoparticle (SLN) system is prepared with Compritol ATO 888 and tricaprylic glyceride. DSC, XRD, SAXS and NMR are employed to study the novel carrier property and microstructure. When the peak melting point decreased from 70.8 degrees C to 61.4 degrees C, the enthalpy sharply decreased. It could be concluded that the regular crystal lattices in the novel carriers are broken out for the oil joined in them. Melting behavior is occurred at -17.7 degrees C while novel SLN is composed of oil and solid lipid mixture from the DSC measurement. Most alpha phase and least beta' phase are in the nano carrier system whether drug loading or not from the XRD investigation. There is only 0.1 nm change of long space among the novel SLN made of mixture and the lipid matrix and traditional SLN; therefore, it is impossible of the oil molecular insert into the solid glyceride structure. Since the different melting behavior (DSC measurements) and molecular move state (NMR investigations), two lipid matrix are still in two state of liquid and solid lipid in the novel SLN carrier. Presume the microstructure of the novel SLN prepared by our experiment would be that liquid oil has formed superfine nano accommodation encapsulated with solid lipid, but the whole particle is still in nano size range.

Purpose: The study was conducted to investigate the antifertility effectiveness of copper/low-density polyethylene nanocomposite (nano-Cu/LDPE) and its influence on the endometrial environment in rats., Methods: One hundred and seventy sexually mature female Sprague-Dawley (SD) rats were randomly divided into five groups: sham-operated control group (SO group, n=10), bulk copper group (Cu group, n=40), LDPE group (n=40), and nano-Cu/LDPE groups I (n=40) and II (n=40). Twenty rats in each group except for the SO group were mated with male rats of proven fertility, from 30 days after insertion, and the antifertility rates (ATs) were observed at Day 11 of pregnancy. The concentrations of prostaglandin E(2) (PGE(2)) and tissue plasminogen activator (tPA) in the endometrium of the remaining rats in each group were measured by using ELISA at the 30th and 60th day after insertion, respectively., Results: ATs in the Cu group and nano-Cu/LDPE groups I and II (100%) were significantly higher than those in the LDPE group (p<.05). Compared with those in the SO group, the concentrations of PGE(2) and tPA in all experimental groups except for PGE(2) levels in the LDPE group were significantly increased at Day 30 after insertion, and these parameters in the nano-Cu/LDPE groups were significantly lower than in the Cu group (p<.05). At Day 60 after insertion, tPA levels were still higher in the Cu and nano-Cu/LDPE groups, but there was no difference in PGE(2) levels in all groups except for the Cu group., Conclusion: Nano-Cu/LDPE exhibits satisfactory contraceptive efficacy with less influence on the endometrium PGE(2) and tPA levels.

Objective: To investigate a new strategy of polylactic acid (PLA) nanoparticles delivery system coating nuclear factor-kappaB (NF-kappaB) decoy oligonucleotides (ODNs) for inhibiting TF expression in cultured brain microvascular endothelial cells(BMECs)., Methods: PLA nanoparticles coating FITC-labeled NF-kappaB decoy ODNs were formulated by nano-deposition method and the characteristics of nanoparticles were detected. BMECs were isolated and cultured in vitro. The cellular uptake and intracellular localization of nanoparticles in BMECs was detected by flow cytometry and confocal microscopy. Changes in the expressions of TF and nuclear protein P65 were examined by RT-PCR and Western blot in NF-kappaB decoy ODNs transfected BMECs by LPS stimulation., Results: The decoy-nanoparticles obtained were uniform spherical particles with an effective diameter of 162.1 nm and a polydispersity index of 0.118. NF-kappaB decoy ODNs encapsulated in nanoparticles could be released in a controlled manner in phosphate-buffered saline for up to 28 days. It was observed that the cellular uptake of nanoparticles were increased with the time of incubation and the concentration of nanoparticles in the medium. Nanoparticles localized mainly in the BMECs cytoplasm. LPS-induced upregulation of TF transcription was inhibited by NF-kappaB decoy ODNs transfection but not by missense ODNs transfection. Furthermore, changes in the transcription level of TF were paralleled by a reduction of capacity of P65 in nuclear extract of NF-kappaB decoy ODNs transfected cells., Conclusions: These findings offer a potential therapeutic strategy in the control of TF expression in BMECs in vitro.

The blood-brain barrier (BBB) is a huge obstacle in therapy of brain diseases, for it hinders the delivery of water-soluble molecules and those with molecular weight above 500 from the circulation system to the brain. Polysorbate 80 (Tween 80, T-80)-coated polylactid acid(PLA) nanoparticles represent a tool to transport such drugs across the BBB. Transcytosis is put forward as one mechanism of drug-loaded nanoparticles across the blood-brain barrier (BBB). However little is known about it. Electron microscopy is an important method in the investigation on nanoparticles injected into the experimental mice. In this study it was found by fluorescence microscope that fluorescence existed along the capillary dissepiment. Some nanoparticles distributed in the brain capillary endothelial cells and brain tissue outside the microvaculum, which was observed by transmission electron microscopy. These particles were proved to be the Copper chlorophyll loaded nanoparticles which containing Cu detected by AEM. The in vivo experiments demonstrated directly that the PLA nanoparticles can pass the BBB indeed and transcytosis by microvascular endothelial cells may be the mechanism. The results provided an efficient way of drug-delivery targeting the brain. Copper chlorophyll could be used as a new symbol of nanoparticles in in vivo experiment.

With the development of IUDs, a number of copper-bearing devices are now commercially available, including the copper-T, the Multiload and the copper-T in various other forms, so-called "the second-generation" IUDs. In this article, we report on nano-Cu/low-density polyethylene composite as a potential copper carrier in IUD. Two issues for the new material are addressed: the effectiveness of polymers in reducing the initial burst in cupric ion release and the amount and pattern of continuing release. The aim of this study was to investigate copper ion release from this composite as a basis for considering its used in an IUD.

In this paper, we introduced a novel storage architecture "Unified Storage Network", which merges NAC(Network Attached Channel) and SAN(Storage Area Network), and provides the file I/O services as NAS devices and provides the block I/O services as SAN. To overcome the drawbacks from FC, we employ iSCSI to implement the USN(Unified Storage Network). To evaluate whether iSCSI is more suitable for implementing the USN, we analyze iSCSI protocol and compare it with FC protocol from several components of a network protocol which impact the performance of the network. From the analysis and comparison, we can conclude that the iSCSI is more suitable for implementing the storage network than the FC under condition of the wide-area network. At last, we designed two groups of experiments carefully.

Although Lyme disease is commonly seen in the southcentral United States, the epidemiology of the disease is poorly defined there. The purpose of this study was to document the presence of Borrelia burgdorferi in ticks collected in southeastern Missouri and around the city of St. Louis. Spirochetes were detected and identified as B. burgdorferi by immunofluorescent antibody (IFA) tests using the monoclonal antibody H5332 in 1.9% of Amblyomma americanum and 2.0% of Dermacentor variabilis ticks collected. The identity of IFA-positive organisms was verified by polymerase chain reactions (PCRs) with two different sets of B. burgdorferi-specific primers followed by Southern blotting. The DNA sequences of amplified 371-basepair PCR products from two positive Missouri ticks showed 97-98% identity with that obtained by the same method for the B31 strain of B. burgdorferi. These results confirm that B. burgdorferi is present in questing D. variabilis and A. americanum ticks in areas of Missouri where Lyme disease occurs. Additional studies are needed to determine the role of these ticks in the epidemiology of Lyme disease in Missouri and neighboring states.