Preparation, multi-scale structures, and functionalities of acetylated starch: An updated review.

Acetylated starch has been widely used as food additives. However, there was limited information available regarding the impact of acetylation on starch structure and functionalities, as well as the advanced acetylation technologies. This review aimed to summarize current methods for starch acetylation and discuss the structure and functionalities of acetylated starch. Innovative techniques, such as milling, microwave, pulsed electric fields, ultrasonic, and extrusion, could be employed for environmental-friendly synthesis of acetylated starch. Acetylation led to the degradation of starch structures and weakening of the interactions between starch molecules, resulting in the disorganization of starch multi-scale ordered structure. The introduction of acetyl groups retarded the self-reassembly behavior of starch, leading to increased solubility, clarity, and softness of starch-based hydrogels. Moreover, the acetyl groups improved water/oil absorption capacity, emulsifiability, film-forming properties, and colonic fermentability of starch, while reduced the susceptibility of starch molecules to enzymes. Importantly, starch functionalities were largely influenced by the decoration of acetyl groups on starch molecules, while the impact of multi-scale ordered structures on starch physicochemical properties was relatively minor. These findings will aid in the design of structured acetylated starch with desirable functionalities.

Stellate ganglion block ameliorated central post-stroke pain with comorbid anxiety and depression through inhibiting HIF-1α/NLRP3 signaling following thalamic hemorrhagic stroke.

BACKGROUND: Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients' lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities. METHODS: Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow. RESULTS: Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. CONCLUSION: This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.

Spinal MCP-1 Contributes to Central Post-stroke Pain by Inducing Central Sensitization in Rats.

Central post-stroke pain (CPSP) is a highly refractory form of central neuropathic pain that has been poorly studied mechanistically. Recent observations have emphasized the critical role of the spinal dorsal horn in CPSP. However, the underlying mechanisms remain unclear. In this study, rats were subjected to thalamic hemorrhage to investigate the role of spinal monocyte chemoattractant protein-1 (MCP-1) and C-C motif chemokine receptor 2 (CCR2) in the development of CPSP. Immunohistochemical staining and ELISA were used to assess the expression changes of c-Fos, Iba-1, GFAP, MCP-1, and CCR2 in the dorsal horn of the lumbar spinal cord following thalamic hemorrhage, and the involvement of spinal MCP-1 in CPSP was examined by performing intrathecal anti-MCP-1 mAb injection to neutralize the spinal extracellular MCP-1. We demonstrated that intra-thalamic collagenase microinjection induced persistent bilateral mechanical pain hypersensitivity and facilitated the spontaneous pain behaviors evoked by intraplantar bee venom injection. Accompanying CPSP, the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn was significantly increased up to 28 days post-intra-thalamic collagenase microinjection. Intrathecal injection of minocycline and fluorocitrate dramatically reverses the bilateral mechanical pain hypersensitivity. Moreover, intra-thalamic collagenase microinjection dramatically induced the up-regulation of MCP-1 but had no effect on the expression of CCR2 in the bilateral lumbar spinal dorsal horn, and MCP-1 was primarily localized in the neuron. Intrathecal injection of anti-MCP-1 mAb was also able to reverse CPSP and reduce the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn. These findings indicated that spinal MCP-1 contributes to CPSP by mediating the activation of spinal neurons and glial cells following thalamic hemorrhage stroke, which may provide insights into pharmacologic treatment for CPSP.

Decomposing heritability and genetic covariance by direct and indirect effect paths.

Estimation of heritability and genetic covariance is crucial for quantifying and understanding complex trait genetic architecture and is employed in almost all recent genome-wide association studies (GWAS). However, many existing approaches for heritability estimation and almost all methods for estimating genetic correlation ignore the presence of indirect genetic effects, i.e., genotype-phenotype associations confounded by the parental genome and family environment, and may thus lead to incorrect interpretation especially for human sociobehavioral phenotypes. In this work, we introduce a statistical framework to decompose heritability and genetic covariance into multiple components representing direct and indirect effect paths. Applied to five traits in UK Biobank, we found substantial involvement of indirect genetic components in shared genetic architecture across traits. These results demonstrate the effectiveness of our approach and highlight the importance of accounting for indirect effects in variance component analysis of complex traits.

Multi-functional vesicles improve Helicobacter pylori eradication by a comprehensive strategy based on complex pathological microenvironment.

Helicobacter pylori (H. pylori), creating a global infection rate over 50%, presents great challenges in clinical therapies due to its complex pathological microenvironment in vivo. To improve the eradication efficacy, herein we fabricated a pharmaceutical vesicle RHL/Cl-Ch-cal where cholesterol-PEG, calcitriol and first-line antibiotic clarithromycin were co-loaded in the rhamnolipid-composed outer lipid layer. RHL/Cl-Ch-cal could quickly penetrate through gastric mucus layer to reach H. pylori infection sites, and then effectively destroyed the architecture of H. pylori biofilms, killed dispersed H. pylori and inhibited the re-adhesion of residual bacteria (called biofilms eradication tetralogy). Moreover, RHL/Cl-Ch-cal activated the host immune response to H. pylori by replenishing cholesterol to repair lipid raft on the cell membrane of host epithelial cells. Finally, RHL/Cl-Ch-cal killed the intracellular H. pylori through recovering the lysosomal acidification and assisting degradation. In experiments, RHL/Cl-Ch-cal demonstrated prominent anti-H. pylori efficacy in the classical H. pylori-infected mice model. Therefore, the study provides a "comprehensive attack" strategy for anti-H. pylori therapies including biofilms eradication tetralogy, immune activation and intracellular bacteria killing.

Antibiotics-free nanoparticles eradicate Helicobacter pylori biofilms and intracellular bacteria.

Biofilms and intracellular survival tremendously help Helicobacter pylori (H. pylori) escape from antibacterial agents attacking, therefore issuing extreme challenges to clinical therapies. Herein, we constructed fucoidan (FU)-coated nanoparticles (FU/ML-LA/EB NPs) via simple self-assembly of biguanide derivative (metformin-linoleic acid, ML) and linoleic acid (LA), encapsulating urease inhibitor ebselen (EB) instead of antibiotics to take antibacterial effect. Negatively charged FU/ML-LA/EB NPs easily penetrated through the gastric mucus layer to arrive at infection sites, then eradicated extracellular polymeric substances (EPS) to destroy H. pylori biofilms structure. After strengthening bacterial membrane permeability, the nanoparticles could enter H. pylori and kill bacteria by inhibiting the activity of urease. FU/ML-LA/EB NPs also entered H. pylori-infected host cells through receptor-mediated internalization, in which they activated AMPK to recover lysosomal acidification for killing intracellular H. pylori. Additionally, FU/ML-LA/EB NPs alleviated oxidative stress, hence reducing gastric mucosal damage and cutting off the pathways of carcinogenesis. Notably, H. pylori burden after FU/ML-LA/EB NPs treatment was reduced to a great extent in vivo, which was significantly lower than that after treatment with clinical therapy. Antibiotics-free FU/ML-LA/EB NPs improving bacterial eradication and alleviating oxidation stress made it a powerful approach against H. pylori.

Intervertebral foramen injection of plerixafor attenuates neuropathic pain after chronic compression of the dorsal root ganglion: Possible involvement of the down-regulation of Nav1.8 and Nav1.9.

Neuropathic pain is a common chronic pain condition with major impact on quality of life. However, its physiopathologic mechanism remains unknown and pain management is still a challenge. Accumulating evidence indicated that C-X-C chemokine receptor type 4 (CXCR4) played a critical role in the process of pain. Thus, the present study aimed to investigate whether intervertebral foramen injection of CXCR4 antagonist, plerixafor, was able to relieve neuropathic pain and explore the possible underlying mechanism. Chronic compression of the dorsal root ganglion (CCD) was established as a typical model of neuropathic pain. The results indicated that CCD induced multiple pain-related behaviors and the expression of CXCR4, Nav1.8 and Nav1.9 was significantly increased in compressed dorsal root ganglion (DRG) neurons. Knocking down CXCR4 expression could significantly reduce neuropathic pain and intervertebral foramen plerixafor injection (IVFP) dramatically decreased the up-regulation of Nav1.8 and Nav1.9 and attenuated neuropathic pain. The analgesic duration of IVFP was maintained at least for 24 h which was much longer than intervertebral foramen injection of Nav1.8 blocker and local anesthetics. Therefore, our study provided evidence that IVFP could reduce the expression of Nav1.8 and Nav1.9 in DRG neurons which might contribute to, at least in part, the analgesic effect of plerixafor on CCD-induced neuropathic pain. It is concluded that IVFP was an effective and applicable treatment approach for neuropathic pain.

The analgesic effects of ulinastatin either as a single agent or in combination with sufentanil: A novel therapeutic potential for postoperative pain.

Ulinastatin is a broad-spectrum protease inhibitor widely used for the treatment of various inflammation-related diseases owing to its recognized excellent anti-inflammatory and cytoprotective properties. However, whether ulinastatin can relieve postoperative pain remains unclear. In this study, we evaluated the analgesic effects of ulinastatin administered either as a single agent or in combination with sufentanil in a validated preclinical rat model of postoperative pain induced by plantar incision. We found that incisional surgery on the hind paw of these rats induced sustained ipsilateral mechanical pain hypersensitivity that lasted for at least 10 days. A single intraperitoneal (i.p.) injection of ulinastatin prevented the development and reversed the maintenance of incision-induced mechanical pain hypersensitivity in a dose-dependent manner. However, ulinastatin had no effect on the baseline nociceptive threshold. Moreover, repeated i.p. injections of ulinastatin persistently attenuated incision-induced mechanical pain hypersensitivity and promoted recovery from the surgery. The rats did not develop any analgesic tolerance over the course of repeated injections of ulinastatin. A single i.p. injection of ulinastatin was also sufficient to inhibit the initiation and maintenance of incision-induced hyperalgesic priming when the rats were subsequently challenged with an ipsilateral intraplantar prostaglandin E2 injection. Furthermore, the combined administration of ulinastatin and sufentanil significantly enhanced the analgesic effect of sufentanil on postoperative pain, which involved mechanisms other than a direct influence on opioid receptors. These findings demonstrated that ulinastatin had a significant analgesic effect on postoperative pain and might be a novel pharmacotherapeutic agent for managing postoperative pain either alone or as an adjuvant.

Ulinastatin Exhibits Antinociception in Rat Models of Acute Somatic and Visceral Pain Through Inhibiting the Local and Central Inflammation.

INTRODUCTION: Ulinastatin, a broad-spectrum serine protease inhibitor, has been widely used to treat various diseases clinically. However, so far, the antinociceptive effect of ulinastatin remains less studied experimentally and the underlying mechanisms of ulinastatin for pain relief remain unclear. This study aimed to find evidence of the analgesic effect of ulinastatin on acute somatic and visceral pain. METHODS: The analgesic effect of ulinastatin on acute somatic and visceral pain was evaluated by using formalin and acetic acid-induced writhing test. The analgesic mechanism of ulinastatin was verified by detecting the peripheral inflammatory cell infiltration and spinal glial activation with hematoxylin-eosin (H&E) and immunohistochemistry staining. RESULTS: We found that both of intraperitoneal (i.p.) pre-administration and post-administration of ulinastatin could reduce the total number of flinching and the licking duration following intraplantar formalin injection in a dose-related manner. However, the inhibitory effect of ulinastatin existed only in the second phase (Phase 2) of formalin-induced spontaneous pain response, with no effect in the first phase (Phase 1). The formalin-induced edema and ulcer were also improved by i.p. administration of ulinastatin. Moreover, i.p. administration of ulinastatin was also able to delay the occurrence of acetic acid-induced writhing and reduced the total number of writhes dose-dependently. We further demonstrated that ulinastatin significantly decreased the local inflammatory cell infiltration in injured paw and peritoneum tissue under formalin and acetic acid test separately. The microglial and astrocytic activation in the spinal dorsal horn induced by intraplantar formalin and i.p. acetic acid injection were also dramatically inhibited by i.p. administration of ulinastatin. CONCLUSION: Our results for the first time provided a new line of evidence showing that ulinastatin could attenuate acute somatic and visceral pain by inhibiting the peripheral and spinal inflammatory reaction.

Self-assembled nanomedicine combining a berberine derivative and doxorubicin for enhanced antitumor and antimetastatic efficacy via mitochondrial pathways.

Mitochondria play a central role in cancer progression and tumor metastasis, and nanomedicines targeting mitochondria have emerged as a promising strategy for tumor therapy. However, mitochondria targeting strategies have not been widely explored in the inhibition of tumor metastasis, and they have disadvantages of complicated preparation, low drug loading, systemic toxicity of the carriers and poor accumulation at tumor sites. Here we firstly developed self-assembled nanodrugs with a high drug loading (∼68%) comprised of a berberine derivative (Ber) and doxorubicin (Dox) by a simple nano-precipitation method, which successfully altered the target location of Dox from the nucleus to mitochondria and therefore inhibited the proliferation, invasion and migration of MDA-MB-231 cells by triggering cell apoptosis. The surface of nanodrugs was modified with DSPE-PEG-folic acid (DSPE-PEG-FA) and hyaluronic acid (HA) for precise tumor recognition and enhanced accumulation (HA-FA-BD NDs). Upon arrival at the tumor site with the help of the enhanced permeability and retention (EPR) effect, the partial degradation of HA by hyaluronidase (HAase) at the tumor site allowed the partial exposure of the positively charged FA-BD NDs to the cells, then nanodrugs would accumulate and enter tumor cells by dual binding to both folic acid (FA) and CD-44 receptors. Once internalized into lysosomes, both the HA outer shell and DSPE-PEG-FA of nanodrugs were degraded or decomposed completely to expose positively charged BD NDs. Driven by delocalized lipophilic cations, nanodrugs could escape from lysosomes and reach mitochondria to induce a cascade reaction and finally cell apoptosis, as well as suppressing matrix metalloprotease (MMP)-2 and -9 activities and finally cell migration and invasion. In a xenograft mice model of MDA-MB-231 breast cancer cells, the nanodrugs repaired the defects in Mfn 1/Drp 1 mitochondrial proteins, suppressed the activity of MMP-2 and -9, and significantly inhibited tumor cell proliferation and pulmonary metastasis. Our study showed a promising strategy for the treatment of metastatic breast cancer by targeting mitochondria followed by enhanced apoptosis.

Antibacterial self-assembled nanodrugs composed of berberine derivatives and rhamnolipids against Helicobacter pylori.

The prevalence of infections with Helicobacter pylori (H. pylori) has progressively increased worldwide, which demonstrated to be closely correlated to its biofilm formation. H. pylori biofilms protect the bacteria by significantly decreasing their sensitivity to antibiotics. Moreover, H. pylori colonizes on the gastrointestinal tract epithelium which is covered by mucus layer, acting as another barrier to prevent antibacterial agents from reaching the colonization sites. Herein, we prepared four types of versatile self-assembled nanodrugs (BD/RHL NDs) containing lipophilic alkyl berberine derivatives (BDs) and rhamnolipids (RHL) to overcome the dual obstructions of both mucus layer and biofilms. Molecular dynamics simulations estimated that the driving forces for self-assembly of BD/RHL NDs were electrostatic and hydrophobic interactions. BD/RHL NDs, characterized by appropriate size, negative charge and enhanced hydrophilicity, successfully penetrated through mucus layer without interacting with mucins. In in vitro experiments, BD/RHL NDs exhibited substantial ability to eradicate H. pylori biofilms by destroying their extracellular polymeric substances (EPS) and killing planktonic H. pylori. Furthermore, BD/RHL NDs inhibited the adherence of H. pylori on both biotic and abiotic surfaces, therefore cut off the critical step of the biofilm re-formation which was associated with the recrudescence of infections. In an H. pylori-infected mice model, C10-BD/RHL NDs group showed 40 folds less remnant H. pylori and greater mucosal protection compared with the conventional clinical triple therapy. In conclusion, BD/RHL NDs could penetrate through mucus layer and effectively eradicate H. pylori biofilms in vitro and in vivo, providing a novel strategy for clinical treatment of biofilm-related infections.

Preparation and characterization of bear bile-loaded pH sensitive in-situ gel eye drops for ocular drug delivery.

OBJECTIVES: In this study, a stable bear bile-loaded pH sensitive in-situ eye drop gel was prepared for sustain delivery and enhanced therapeutic application. MATERIALS AND METHODS: Bear bile-loaded in-situ ocular gels with different Carbopol/Hydroxypropyl methylcellulose (HPMC) ratios were prepared and their stability was tested in PBS at a series of pH at 40 °C. The morphology was observed by SEM examination and rheology was observed by Rheometer equipped with a 60-mm cone-plate at apex angle of 1°. Gel erosion and release kinetics of Tauroursodeoxycholic acid (TUDCA) was determined by HPLC. While, the in vivo dwelling time was obtained after administering the fluorescent-loaded gel in ocular disease-free New Zealand rabbits. Finally, biocompatibility and toxicity was observed by irritation test and H&E staining of eye-ball tissues, respectively. RESULTS: The bear bile-loaded in-situ ocular gel showed excellent stability at different pH (pH 5.0, 5.5, 6.0, 6.5, 7.0 and 8.0) up to 5 days, and bear bile extract significantly attenuated the gelling ability of the in-situ gel. The viscosity of in-situ gels formulation was decreased with increase in shear rate (0.01 to 100 s-1), and morphological examination of freeze-dried preparation showed three-dimensional reticular structure at physiological pH. The in-situ ocular gel exhibited promising sustained drug release up to 160 min in vitro, and showed prolonged retention time up to 3-folds in vivo. Finally, the biocompability data confirmed that the formulation did not induce any toxic effects and was completely compatible with eye tissues. CONCLUSION: pH sensitive in-situ ocular gel provides new research opportunities to efficiently treat eye diseases.

Activity of Sodium Lauryl Sulfate, Rhamnolipids, and N-Acetylcysteine Against Biofilms of Five Common Pathogens.

Bacteria in biofilms are more resistant to antibacterial agents than bacteria in planktonic form. Hence, antibacterial agents should be able to eradicate biofilms to ensure the best outcomes. Little is known about how well many antibacterial agents can disrupt biofilms. In this study, we compared sodium lauryl sulfate (SDS), rhamnolipids (RHL), and N-acetylcysteine (NAC) for their ability to eradicate mature biofilms and inhibit new biofilm formation against Helicobacter pylori, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus mutans. SDS and RHL effectively inhibited formation of five bacterial biofilms in a dose-dependent manner, even at concentrations below the minimal inhibitory concentrations (MICs), suggesting that their antibiofilm activities are unrelated to their antibacterial activities. In contrast, NAC at certain concentrations promoted biofilm formation by all bacteria except P. aeruginosa, whereas at supra-MIC concentrations, it inhibited biofilm formation against the four bacteria, suggesting that its antibiofilm activity depends on its antibacterial activity. NAC was ineffective at eradicating mature H. pylori biofilms, and it actually promoted their formation at concentrations >10 mg/mL. Our results suggest that RHL is superior at eradicating biofilms of H. pylori, E. coli, and S. mutans; SDS is more effective against S. aureus biofilms; and NAC is more effective against P. aeruginosa biofilms. Our results may help determine which antibiofilm agents are effective against certain bacterial strains and develop agents effective against specific bacterial threats.

Rhamnolipid-involved antibiotics combinations improve the eradication of Helicobacter pylori biofilm in vitro: A comparison with conventional triple therapy.

Antibiotics resistance of H. pylori has been increasing constantly accompanied with decreasing clearance rate clinically, which is demonstrated to be closely related to biofilms with higher resistance than planktonic bacteria for the dense extracellular polymeric substances. Rhamnolipid (RHL) is proved to not only damage the structure of biofilm, but also potentially inhibit bacterial adhesion. To investigate if RHL could promote eradicating rate of the conventional triple therapy to H. pylori biofilm and hence attenuate the resistance and relapse of H. pylori, first-line antibiotics clarithromycin (CLR), amoxicillin (AMX) or/and proton pump inhibitor (PPI) involved single, dual or triple therapies were compared with RHL-containing drug combinations on eradicating H. pylori biofilm. The residual biofilm biomass, the survival of bacteria inside the remaining biofilm and the planktonic bacteria dispersed from the biofilm after treatment were tested. Combination with RHL significantly improved the ability of antibiotics to eradicate H. pylori biofilm, especially RHL combined with AMX and PPI could eradicate more than 95% of biofilm showing much more effective ability than the conventional triple therapy CLR + AMX + PPI. Additionally, the combination of RHL and antibiotics could effectively inhibit the biofilm formation at lower concentration. Thus, RHL might be used as a potential antibiotic adjuvant on anti-H. pylori therapy to enhance eradicating ability of antibiotics to biofilms.

Mucus penetration enhanced lipid polymer nanoparticles improve the eradication rate of Helicobacter pylori biofilm.

The resistance of Helicobacter pylori (H. pylori) to conventional antibiotic treatments becomes prevalent recently. The biofilm formation was found to be highly correlated with the antibiotic resistance of H. pylori in the last decades. Moreover, H. pylori colonizes on the digestive tract epithelium located under the mucus layers, which further reduces therapeutic efficacy as mucus layers trap and remove exogenous substances including drugs. Herein, we reported a novel lipid polymer nanoparticles (LPNs) to overcome both biofilm and mucus layers obstruction. LPNs employed chitosan nanoparticle (CS NPs) as the core, mixed lipid layer containing rhamnolipids (RHL) as the shell and the surface of LPNs was further modified with DSPE-PEG2000 to improve hydrophilicity. Clarithromycin (CLR), a first-line drug for H. pylori infection, was encapsulated in LPNs. LPNs, especially the formulation utilizing 100% of RHL as the lipid shell, exhibited excellent eradicating ability to H. pylori biofilm, which was mainly reflected in the significant reduction of biofilm biomass and viability, destruction of biofilm architecture and elimination of extracellular polymeric substances (EPS). The anti-biofilm activities of LPNs are related to: 1) the disrupting effect of RHL on biofilm matrix; 2) antibacterial effects of CLR and CS NPs on biofilm bacteria and 3) inhibitory effects of CS NPs and RHL on bacteria adhesion and biofilm formation. Furthermore, PEGylated LPNs could rapidly penetrate through mucus without interacting with mucins and effectively eradicate H. pylori biofilm under mucus layer. In conclusion, a novel approach of drug-containing LPNs that could penetrate through mucus layers and effectively eradicate H. pylori biofilm provides new ways to treat persistent H. pylori infections.

Impact of inhalational anesthetics on postoperative cognitive function: Study protocol of a systematic review and meta-analysis.

BACKGROUND: Conflict findings of the impact of inhalational anesthetics on postoperative cognitive function are reported. No systematic review has been performed to solve the problem. The aim of the study was to assess the effect of different inhalational anesthetics on postoperative cognitive function in a network meta-analysis. METHODS: We will search MEDLINE, EMBASE, the Central Register of Controlled Trials in the Cochrane library, and CINAHL for randomized controlled trials or cohort studies assessing the short-term or long-term cognitive function of elderly patients (over 60 years) receiving major surgeries and inhalational anesthetics (desflurane, isoflurane, sevoflurane, halothane, and nitrous oxide) during surgery. Two reviewers will independently screen study eligibility, extract information from eligible studies, and appraise study quality. The impact of inhalational anesthetics will be assessed through: incidence of postoperative cognitive dysfunction at 1 week, 3 months, 1 year, and over 1 year after surgery; incidence of post-operative delirium; test of postoperative cognitive function. RESULTS: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. CONCLUSION: To our knowledge, this systematic review will be the first to evaluate existing research on the incidence of postoperative cognitive function after inhalational anesthetics. Our study will assess the effect of different inhalational anesthetics on postoperative cognitive function. ETHICS AND DISSEMINATION: The review will be finished in December 2017, and the result will be published in a peer-reviewed journal or disseminated through conference posters or abstracts. REVIEW REGISTRATION NUMBER: CRD42017056675 (www.crd.york.ac.uk/PROSPERO).

[Effects of salidroside-pretreatment on neuroethology of rats after global cerebral ischemia-reperfusion].

OBJECTIVE: To study the effects of salidroside-pretreatment on changes of neuroethology in rats with global cerebral ischemia-reperfusion injury so as to investigate its probable mechanism. METHODS: Sixty SD male rats were randomly divided into sham-operated group, untreated group and salidroside-pretreated group. The rats in salidroside-pretreated group were intraperitoneally administered with salidroside for seven days. The dose of salidroside was 12 mg/(kg.d). Thirty minutes after the last administration, the acute global cerebral ischemia-reperfusion in rats of the untreated group and the salidroside-pretreated group was induced by using the modified Pulsinelli's 4-vessel occlusion method. Five rats in each group were killed to obtain their brains 24 hours after reperfusion. The water content in the right brain was measured by calculating the ratio of dry weight to wet weight of the right brain. Activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in hippocampus of the rats were measured. Then neurological severity scores (NSSs) of the other 15 rats in each group were observed respectively before and 6, 12, 24, 48 and 96 h after reperfusion. At the fifth day after reperfusion, the test of Morris water maze was carried out to examine the memories and learning abilities of the rats. RESULTS: The content of MDA, the activity of SOD, the NSS, the mean incubation period and the ratio of time in the second quadrant in the untreated group were significant different from those in the sham-operated group (P<0.05). Compared with the untreated group, the brain water content, the content of MDA and the NSS degraded, and the mean incubation period shortened in salidroside-pretreated group. The activity of SOD and the ratio of residence time in the second quadrant increased in salidroside-pretreated group as compared with the untreated group (P<0.05). CONCLUSION: Salidroside can reduce the degree of cerebral edema of rats with global cerebral ischemia-reperfusion injury, relieve the metabolism abnormity of free radical and improve the function of cognition.

[Transcatheter pulmonary valve replacement in sheep: 6-month evaluation of self-expanding valved stents].

OBJECTIVE: The purpose of this study was to determine the feasibility of transcatheter pulmonary valve replacement in sheep up to 6 months post procedure. METHODS: Fresh sheep pericardium treated with a 0.6% glutaraldehyde solution for 36 hours was sutured to a valvular ring and then fixed onto a newly designed nitinol self-expandable stent. Thoracotomy was performed in sheep (23.5 +/- 3.1) kg under general anesthesia and the device was delivered into the native pulmonary valve of the sheep via the anterior wall of right ventricle by catheter and fooled for 6 months. RESULTS: One sheep died 4 months after the procedure due to in-stent thrombosis. Another 4 animals survived the 6-month observing period. Angiographic and hemodynamic measurements confirmed good positioning and function of the stents with a competent valve immediately post procedure and 6 months post the procedure in surviving animals. CONCLUSION: Implantation of the nitinol self-expandable stent in the pulmonary valve position by a transcatheter approach is feasible and good function of transcatheter implanted memory nitinol valved stents was shown after 6 months of implantation in sheep.

[Autologous sinoatrial node cells heterotopic transplantation for treating bradycardia: an experiment with dogs].

OBJECTIVE: To explore the feasibility of autografting sinoatrial nodal cells heterotopic transplantation to construct an ectopia pacemaker for treating bradycardia. METHODS: Sixteen healthy adult dogs were randomly divided into 2 equal groups: graft group and control group. The sinoatrial node (SAN) of the dogs in the graft group was harvested and digested into cell suspension in vitro, then injected to the autogenic right ventricular wall adjacent to heart apex. Commensurable culture medium was injected to the same position with the dogs in control group. Two week later, all dogs underwent transcatheter ablation of His bundle to create a complete heart block model and an electrophysiology study was carried out. In order to investigate the change of rhythm, isoproterenol and atropine was injected respectively to dogs of the graft group. Two weeks later the dogs were killed with their hearts taken out. Immunofluorescence histochemistry was used to investigate the survival of grafted cells and gap junction formed between grafted cells and ventricular myocytes. RESULTS The isolated cells from SAN retained active and beating. After ablation, the heart rate of the dogs of the graft group was (91 +/- 14) bpm, significantly higher than that of the control group, [(49 +/- 11) bpm, t = 6. 672, P < 0.01], and electrocardiography showed that these ventricular rhythms originated from the cell transplant sites. After the injection of isoproterenol the ventricular rate of the graft group was (118 +/- 15) bpm, significantly higher than that before the injection, (95 +/- 11) bpm, t = 3.491, P < 0.01), however, after the injection of atropine, the heart rate of the graft group was (101 +/- 17) bpm, not significantly different from that before the injection, [(95 +/- 11) bpm, t = 0.838, P > 0.05]. Immunofluorescence staining showed that the grafted autografting sinoatrial nodal cells all survived and that there was connexin-43 expression among the cells. CONCLUSION: Transplantation of autologous SAN cells into the right ventricular wall can boost the ventricular rhythm which is sensitive to isoproterenol but not to atropine. Grafted SAN cells can form gap junctions with adjacent myocytes.