Effects of eugenol on physicochemical properties of sturgeon skin collagen-chitosan composite membrane.

In this study, a series of collagen-chitosan-eugenol (CO-CS-Eu) flow-casting composite films were prepared using collagen from sturgeon skin, chitosan, and eugenol. The physicochemical properties, mechanical properties, microstructure, as well as antioxidant and antimicrobial activities of the composite membranes were investigated by various characterization techniques. The findings revealed that the inclusion of eugenol augmented the thickness of the film, darkened its color, reduced the transparency, and enhanced the ultraviolet light-blocking capabilities, with the physicochemical properties of the CO-CS-0.25%Eu film being notably favorable. Eugenol generates increasingly intricate matrices that disperse within the system, thereby modifying the optical properties of the material. Furthermore, the tensile strength of the film decreased from 70.97 to 20.32 MPa, indicating that eugenol enhances the fluidity and ductility of the film. Added eugenol also exhibited structural impact by loosening the film cross-section and decreasing its density. The Fourier transform infrared spectroscopy results revealed the occurrence of several intermolecular interactions among collagen, chitosan, and eugenol. Moreover, the incorporation of eugenol bolstered the antioxidant and antimicrobial capabilities of the composite film. This is primarily attributed to the abundant phenolic/hydroxyl groups present in eugenol, which can react with free radicals by forming phenoxy groups and neutralizing hydroxyl groups. Consequently, inclusion of eugenol substantially enhances the freshness retention performance of the composite film. PRACTICAL APPLICATION: ● The CO-CS-Eu film utilizes collagen from sturgeon skin, improving the use of sturgeon resources.● Different concentrations of eugenol altered its synergistic effect with chitosan.● The CO-CS-Eu film is composed of natural products with safe and edible properties.

Meningitis in neonate caused by Mycoplasma hominis: A case report.

Background: Mycoplasma hominis (M. hominis) commonly colonizes the genitourinary tract of adult women and may result in neonatal meningitis through vertical transmission. Although there are few case reports, if the treatment is not conducted timely, the disease progresses rapidly, which may lead to serious complications and a poor prognosis. Case presentation: In the present study, a 10-day-old full-term neonate who presented with fever as the initial symptom and was eventually diagnosed with meningitis caused by M. hominis was reported. In the present case, the pathogen was not detected during the initial routine investigations, and the therapeutic effects of empiric antibiotic therapy were poor. Metagenomic next-generation sequencing (mNGS) in the cerebrospinal fluid (CSF) was conducted with the detection of M. hominis, and the antibiotics were adjusted to moxifloxacin combined with doxycycline. The clinical symptoms of the pediatric patient disappeared with an improvement in related laboratory results. Conclusion: It was difficult to detect M. hominis by routine bacterial culture. Therefore, M. hominis infection should be checked for in children with meningitis who had a negative result in CSF culture and poor therapeutic effects of empirical medication. mNGS in CSF should be conducted as soon as possible, and sensitive antibiotics should be administered in time to reduce the incidence of complications and improve the prognosis.

Neuroligin-3-Mediated Synapse Formation Strengthens Interactions between Hippocampus and Barrel Cortex in Associative Memory.

Memory traces are believed to be broadly allocated in cerebral cortices and the hippocampus. Mutual synapse innervations among these brain areas are presumably formed in associative memory. In the present study, we have used neuronal tracing by pAAV-carried fluorescent proteins and neuroligin-3 mRNA knockdown by shRNAs to examine the role of neuroligin-3-mediated synapse formation in the interconnection between primary associative memory cells in the sensory cortices and secondary associative memory cells in the hippocampus during the acquisition and memory of associated signals. Our studies show that mutual synapse innervations between the barrel cortex and the hippocampal CA3 region emerge and are upregulated after the memories of associated whisker and odor signals come into view. These synapse interconnections are downregulated by a knockdown of neuroligin-3-mediated synapse linkages. New synapse interconnections and the strengthening of these interconnections appear to endorse the belief in an interaction between the hippocampus and sensory cortices for memory consolidation.

CASL: Capturing Activity Semantics through Location Information for Enhanced Activity Recognition.

Using portable tools to monitor and identify daily activities has increasingly become a focus of digital healthcare, especially for elderly care. One of the difficulties in this area is the excessive reliance on labeled activity data for corresponding recognition modeling. Labeled activity data is expensive to collect. To address this challenge, we propose an effective and robust semi-supervised active learning method, called CASL, which combines the mainstream semi-supervised learning method with a mechanism of expert collaboration. CASL takes a user's trajectory as the only input. In addition, CASL uses expert collaboration to judge the valuable samples of a model to further enhance its performance. CASL relies on very few semantic activities, outperforms all baseline activity recognition methods, and is close to the performance of supervised learning methods. On the adlnormal dataset with 200 semantic activities data, CASL achieved an accuracy of 89.07%, supervised learning has 91.77%. Our ablation study validated the components in our CASL using a query strategy and a data fusion approach.

A Phytomolecule Icariin Protects from Sarcopenia Partially by Suppressing Myosin Heavy Chain Degradation in Orchiectomized Rats.

Treatments are lacking for sarcopenia, which is an age-related disease characterized by loss of skeletal muscle mass, strength, and/or physical performance. Icariin is a phytomolecule from herbal Epimedium, a traditional Chinese medicine widely used to treat musculoskeletal disorders for thousands of years. Here the effects of icariin against sarcopenia are investigated and the underlying mechanism is elucidated. A classic rat model of bilaterally orchiectomized (ORX) is used to induce sarcopenia. After administration for 8 weeks, compared to the control group, the forelimb grip strength, the specific tetanic forces of the soleus (SOL) and extensor digitorum longus muscle (EDL) are higher, and the fiber cross-sectional areas (CSAs) of the gastrocnemius and tibialis anterior muscle are larger in the icariin group. In addition, icariin promotes mRNA and protein expressions of myosin heavy chain (MyHC) both in SOL and EDL. Mechanistically, icariin significantly suppresses the mRNA and protein expressions of FOXO3a, atrogin-1, and MuRF-1, which are related to the degradation of myosin heavy chain. Collectively, icariin protects from sarcopenia in ORX rats characterized by enhancing grip strength and skeletal muscle contraction, as well as increasing skeletal muscle CSA by inhibiting the ubiquitination degradation of the MyHC in skeletal muscle fibers.

Meta-analysis of the association between new hypoglycemic agents and digestive diseases.

BACKGROUND: New hypoglycemic agents include sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide 1 receptor agonists (GLP1RAs), and dipeptidyl peptidase-4 inhibitors (DPP4is). The association between each class of these new hypoglycemic drugs and the risks of various digestive system diseases is unknown. We aimed to explore this relationship by performing a meta-analysis. METHODS: We included large randomized trials of SGLT2is, GLP1RAs, and DPP4is. Outcomes of interest were 91 kinds of digestive diseases including 75 kinds of gastrointestinal disorders and 16 kinds of hepatobiliary disorders. Meta-analysis was done to generate pooled risk ratio (RR) and 95% confidence interval (CI). Subgroup analysis was conducted according to 3 different drug classes. RESULTS: We included 21 large trials in this meta-analysis. Compared with placebo, GLP1RAs were associated with the higher risks of gastric ulcer hemorrhage (RR 2.68, 95% CI 1.07-6.68; Pdrug = .035; I2 = 0), pancreatitis (RR 1.48, 95% CI 1.02-2.15; Pdrug = .041; I2 = 0), cholangitis acute (RR 5.96, 95% CI 1.04-34.08; Pdrug = .045; I2 = 0), and cholecystitis acute (RR 1.52, 95% CI 1.08-2.15; Pdrug = .017; I2 = 1.5%), but were not significantly associated with the occurrences of the other 87 kinds of digestive diseases (Pdrug ranged from .064 to .999). SGLT2is versus placebo were not significantly associated with the occurrences of 91 kinds of digestive diseases (Pdrug ranged from .077 to .995). DPP4is versus placebo were not significantly associated with the occurrences of 91 kinds of digestive diseases (Pdrug ranged from .085 to .999). CONCLUSIONS: Neither SGLT2is nor DPP4is are associated with the occurrences of various kinds of digestive diseases, whereas GLP1RAs are associated with the higher risks of 4 kinds of digestive diseases, namely, gastric ulcer hemorrhage, pancreatitis, cholangitis acute, and cholecystitis acute. These findings seem to suggest that GLP1RAs are not applicable for patients at high risk of 4 specific digestive diseases, whereas SGLT2is and DPP4is are safe for patients susceptible to digestive diseases. However, our findings require to be further verified by future studies with sufficient statistical power.

The Factors Influencing the Renal Glucose Threshold in Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

OBJECTIVE: This study aims to explore the factors influencing the renal glucose threshold (RTG) in patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was conducted on 1009 hospitalized patients with T2DM using stratified random sampling. Blood glucose was monitored using a dynamic blood glucose monitor to obtain the mean blood glucose (MBG), which is used to calculate the RTG. The factors influencing the RTG were then analyzed. RESULTS: The mean RTG in patients with newly diagnosed T2DM was 203.58 ± 55.22 mg/dl. The correlation between the RTG and the various variables was analyzed, and the results demonstrated that the RTG was correlated with the patient's age (r = -0.14539, P = 0.0001); MBG (r = -0.35009, P = 0.0001); renal long neck (r = 0.16762, P = 0.0001); homeostatic model assessment for insulin resistance (r = -0.38322, P = 0.0001); homeostatic model assessment for beta-cell function (r = -0.22770, P = 0.0001); and the levels of glycated hemoglobin (HbA1c; r = 0.98994, P = 0.0001), blood urea nitrogen (r = -0.11093, P = 0.0004), creatinine (r = -0.26414, P = 0.0001), uric acid (r = -0.20149, P = 0.0001), total cholesterol (r = 0.13192, P = 0.0001), low-density lipoprotein (r = 0.12466, P = 0.0001), thyroid-stimulating hormone (r = -0.06346, P = 0.0460), beta-2 microglobulin (r = -0.08884, P = 0.0056), and 24-hour urine glucose (r = 0.32115, P = 0.0001). Multiple linear stepwise regression analysis revealed that the HbA1c, 24-hour urine glucose, estimated glomerular filtration rate (eGFR), D-dimer, and body mass index (BMI) should be included in the final model, and HbA1c had the greatest impact on the RTG followed in descending order by the 24-hour urine glucose, eGFR, D-dimer, and BMI (P < 0.05). CONCLUSION: The RTG increases in most patients with newly diagnosed diabetes. The risk factors for the RTG are HbA1c, 24-hour urine glucose, eGFR, D-dimer, and BMI.

PLGA/ß-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis.

OBJECTIVES: Vascularization is an essential step in successful bone tissue engineering. The induction of angiogenesis in bone tissue engineering can be enhanced through the delivery of therapeutic agents that stimulate vessel and bone formation. In this study, we show that cucurbitacin B (CuB), a tetracyclic terpene derived from Cucurbitaceae family plants, facilitates the induction of angiogenesis in vitro. METHODS: We incorporated CuB into a biodegradable poly (lactide-co-glycolide) (PLGA) and ß-tricalcium phosphate (ß-TCP) biomaterial scaffold (PT/CuB) Using 3D low-temperature rapid prototyping (LT-RP) technology. A rat skull defect model was used to verify whether the drug-incorporated scaffold has the effects of angiogenesis and osteogenesis in vivo for the regeneration of bone defect. Cytotoxicity assay was performed to determine the safe dose range of the CuB. Tube formation assay and western blot assay were used to analyze the angiogenesis effect of CuB. RESULTS: PT/CuB scaffold possessed well-designed bio-mimic structure and improved mechanical properties. CuB was linear release from the composite scaffold without affecting pH value. The results demonstrated that the PT/CuB scaffold significantly enhanced neovascularization and bone regeneration in a rat critical size calvarial defect model compared to the scaffold implants without CuB. Furthermore, CuB stimulated angiogenic signaling via up-regulating VEGFR2 and VEGFR-related signaling pathways. CONCLUSION: CuB can serve as promising candidate compound for promoting neovascularization and osteogenesis, especially in tissue engineering for repair of bone defects. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study highlights the potential use of CuB as a therapeutic agent and strongly support its adoption as a component of composite scaffolds for tissue-engineering of bone repair.

Perforalactones D and E, two new C-20 quassinoids with potential activity to induce lysosomal biogenesis from the twigs of Harrisonia perforata (Blanco) Merr.

Two new quassinoids (1 and 2) were isolated from the twigs of Harrisonia perforata (Blanco) Merr. Perforalactone E (2) possesses an uncommon hexacyclic 1α,12α:5α,13α-dicyclo-9ßH-picrasane skeleton. Its structure was determined based on spectroscopic data and X-ray crystallography. Compounds 1 and 2 could significantly induce lysosomal biogenesis through transcriptional activation of lysosomal genes.

Effectiveness and safety of traditional Chinese herbs in children with cough variant asthma: a systematic review and Meta-analysi.

OBJECTIVE: To systematically investigate the clinical effectiveness and safety of traditional Chinese herbs (TCHs) as an alternative to conventional medicine (CM) in children with cough variant asthma(CVA). METHODS: Randomized controlled trial (RCT) studies that were published from their inceptions to March 31, 2020, were identified from the electronic databases of China National Knowledge Infrastructure, Wangfang, PubMed, and Cochrane Central Library. The primary outcome of the review was the total effective rate (TER), and the secondary outcomes were immunoglobulin E (IgE), peak expiratory flow (PEF), adverse drug reactions, and relapse rates of interventions. RESULTS: For the Meta-analysis, 13 studies involving 992 children with CVA were included. In terms of TER and IgE, the experimental interventions of TCH, when compared with the control interventions of CM, on pediatric CVA were found to be significantly effective (P < 0.0001), whereas for spirometry, PEF was not significantly improved in the TCH group (P = 0.48). The incident rates of adverse drug reaction and relapse were found to be significantly lower in the TCH group than those in the CM group (P = 0.02 and P < 0.0001, respectively). CONCLUSION: Compared with CM therapy, the effects of TCH therapy on pediatric CVA were significantly beneficial in terms of TER and IgE, but not for PEF, and the methodological quality of included studies was poor. Therefore, the results should be interpreted with caution. More randomized controlled trials with rigorous experimental methodologies are required for objectivity in the future.

Stable directional emission in active optical waveguides shielding external environmental influences.

The skillful confinement of light brought by the composite waveguide structure has shown great possibilities in the development of photonic devices. It has greatly expanded the application range of an on-chip system in dark-field imaging and confined the laser when containing an active medium. Here we experimentally proved a stable directional emission in an active waveguide composed of metal and photonic crystal, which is almost completely unaffected by the external environment and different from the common local light field that is seriously affected by the structure. When the refractive index of samples on the surface layer changes, it can ensure the constant emission intensity of the internal mode, while still retaining the external environmental sensitivity of the surface mode. It can also be used for imaging and sensing as a functional slide. This research of chip-based directional emission is very promising for various applications including quantitative detection of biological imaging, coupled emission intensity sensing, portable imaging equipment, and tunable micro lasers.

Astrocytic c-Jun N-terminal kinase-histone deacetylase-2 cascade contributes to glutamate transporter-1 decrease and mechanical allodynia following peripheral nerve injury in rats.

Decrease of glutamate transporter-1 (GLT-1) in the spinal dorsal horn after nerve injury induces enhanced excitatory transmission and causes persistent pain. Histone deacetylases (HDACs)-catalyzed deacetylation might contribute to the decrease of GLT-1, while the detailed mechanisms have yet to be fully elaborated. Spinal nerve ligation (SNL) induced significant increases of HDAC2 and decreases of GLT-1 in spinal astrocytes. Intrathecal infusion of the HDAC2 inhibitors attenuated the decrease of GLT-1 and enhanced phosphorylation of glutamate receptors. GLT-1 and phosphorylated c-Jun N-terminal kinase (JNK) were highly colocalized in the spinal cord, and a large number of pJNK positive cells were HDAC2 positive. Intrathecally infusion of the JNK inhibitor SP600125 significantly inhibited SNL-induced upregulation of HDAC2. SNL-induced HDAC2 up-regulation could be inhibited by the neutralizing anti-tumor necrosis factor-α (TNF-α) binding protein etanercept or the microglial inhibitor minocycline. In cultured astrocytes, TNF-α induced enhanced phosphorylation of JNK and a significant increase of HDAC2, as well as a remarkable decrease of GLT-1, which could be prevented by SP600125 or the HDAC2 specific inhibitor CAY10683. Our data suggest that astrocytic JNK-HDAC2 cascade contributes to GLT-1 decrease and mechanical allodynia following peripheral nerve injury. Neuroimmune activation after peripheral nerve injury could induce epigenetic modification changes in astrocytes and contribute to chronic pain maintenance.

New Secodaphnane-Type Alkaloids with Cytotoxic Activities from Daphniphyllum angustifolium Hutch.

One new Daphniphyllum alkaloid, daphnioldhanol A (1), together with three known ones, were isolated from the stem part of Daphniphyllum angustifolium Hutch. Their structures were elucidated by spectroscopic methods and comparing with the literature data. Compound 2 is a new natural product, but known by synthesis as a racemate. Compound 1 exhibited week cytotoxic activity against Hela cell line with IC50 of 31.9 µM.

[Preparation of Cangyi nanoemulsion in situ gel and drug release mechanism of nasal mucosa in vitro].

To prepare Cangyi nanoemulsion in situ gel and study its nasal mucosa release mechanism in vitro. After proper treatment of different drugs in the compound, the prescription of nanoemulsion was determined by pseudo-ternary phase diagram method. With the ratio of mixed emulsifier to oil phase [(S+COS)/O], the ratio of mixed emulsifier(K_m), the ratio of water phase to mixed emulsifier and oil phase[W/(S+COS+O)] as investigation factors and the normalized value(OD) as evaluation index, the prescription of Cangyi nanoemulsion was optimized by central composite design-response surface method. With the ratio of poloxamer 407(P407) and poloxamer 188(P188) as the investigation factors and the gelation temperature as the evaluation index, the in situ gel prescription of Cangyi nanoemulsion was optimized. The improved Franz diffusion cell was used to explore the nasal mucosa drug-release mechanism of Cangyi nanoemulsion in situ gel with oxymatrine, ferulic acid and salvianolic acid B content as indexes. The optimal prescription of Cangyi nanoemulsion in situ gel was as follows: 6.862% castor oil polyoxyl(EL), 4.262% absolute ethanol, 1.392% ethyl oleate, 7% P407 and 6% P188. The average pH was 5.55 and the average gelation temperature was 32.8 ℃. In vitro release studies showed that oxymatrine, ferulic acid and salvianolic acid B were released simultaneously and the drug release behavior was consistent with that in Higuchi model. The preparation process of Cangyi nanoemulsion in situ gel is stable, with suitable pH value, gelation temperature and viscosity. It has a certain slow-release effect, and can meet the needs of local nasal drug use.

CD1d1 intrinsic signaling in macrophages controls NLRP3 inflammasome expression during inflammation.

Dysregulation of immune responses in the gut often associates with inflammatory bowel diseases (IBD). Mouse CD1d1, an ortholog of human CD1d mainly participating in lipid-antigen presentation to NKT cells, is able to generate intrinsic signals upon stimulation. Mice with macrophage-specific CD1d1 deficiency (LymCD1d1-/- ) acquire resistance to dextran sodium sulfate (DSS)-induced colitis, attributing to the transcriptional inhibition of NLRP3 inflammasome components. The hyperactivation of NLRP3 inflammasome accounts for gut epithelial proliferation and intestine-blood barrier integrity. Mechanistically, occupancy by the natural ligand glycosphingolipid iGb3, CD1d1 responds with intracellular Ser330 dephosphorylation thus to reduce the Peroxiredoxin 1 (PRDX1)-associated AKT-STAT1 phosphorylation and subsequent NF-κB activation, eventually causing transcriptional down-regulation of Nlrp3 and its immediate substrates Il1b and Il18 in macrophages. Therefore, the counterbalancing role of CD1d1 in macrophages appears to determine severity of DSS-mediated colitis in mice. These findings propose new intervention strategies for treating IBD and other inflammatory disorders.

miRNA-324/-133a essential for recruiting new synapse innervations and associative memory cells in coactivated sensory cortices.

After the integrative storage of associated signals, a signal induces the recollection of its associated signal, or the other way around. This associative memory is essential to associative thinking, logical reasoning, imagination and computation. In terms of cellular mechanisms underlying associative memory, new mutual synapse innervations are formed among those coactivated neurons, so that they are recruited to be associative memory cells or associative memory neurons. These associative memory cells receive new synapse innervations alongside innate synapse inputs and encode signals carried by these inputs. We proposed to examine microRNAs as initiative factors for recruiting new synapse innervations and associative memory cells. In a mouse model of associative memory characterized as the reciprocal retrieval of associated whisker and odor signals, barrel and piriform cortical neurons gain their ability to encode whisker and odorant signals based on the newly formed synapse innervations between these coactivated cortices besides innate synapse inputs. miRNA-324 and miRNA-133a are required for recruiting these new synapse innervations and associative memory cells as well as sufficient for facilitating their recruitments, but not for innate synapse inputs. Therefore, the coactivation of sensory cortices through microRNA as initiative factor to recruit new mutual synapse innervations and associative memory cells for associative memory.

microRNA-15b contributes to depression-like behavior in mice by affecting synaptic protein levels and function in the nucleus accumbens.

Major depression is a prevalent affective disorder characterized by recurrent low mood. It presumably results from stress-induced deteriorations of molecular networks and synaptic functions in brain reward circuits of genetically-susceptible individuals through epigenetic processes. Epigenetic regulator microRNA-15b inhibits neuronal progenitor proliferation and is up-regulated in the medial prefrontal cortex of mice that demonstrate depression-like behavior, indicating the contribution of microRNA-15 to major depression. Using a mouse model of major depression induced by chronic unpredictable mild stress (CUMS), here we examined the effects of microRNA-15b on synapses and synaptic proteins in the nucleus accumbens of these mice. The application of a microRNA-15b antagomir into the nucleus accumbens significantly reduced the incidence of CUMS-induced depression and reversed the attenuations of excitatory synapse and syntaxin-binding protein 3 (STXBP3A)/vesicle-associated protein 1 (VAMP1) expression. In contrast, the injection of a microRNA-15b analog into the nucleus accumbens induced depression-like behavior as well as attenuated excitatory synapses and STXBP3A/VAMP1 expression similar to the down-regulation of these processes induced by the CUMS. We conclude that microRNA-15b-5p may play a critical role in chronic stress-induced depression by decreasing synaptic proteins, innervations, and activities in the nucleus accumbens. We propose that the treatment of anti-microRNA-15b-5p may convert stress-induced depression into resilience.

Synthesis and biological evaluation of novel pyrazolo[3,4-b]pyridines as cis-restricted combretastatin A-4 analogues.

Twenty-six novel pyrazolo[3,4-b]pyridine-bridged analogues of combretastatin A-4 possessing 3,4,5-trimethoxylphenyl groups, were synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. Preliminary biological evaluation demonstrated that some of the target compounds displayed significant antiproliferative effectagainst four different cell lines including MCF-7, MDA-MB-231, HeLa and Kyse150. The most active analogue 6n was found to induce HeLa cells arrest in the G2/M phase in a dose-dependent manner. Molecular modeling studies indicated that derivative 6n most likely occupies the colchicine site of tubulin. The initial results suggest that the 3,4,5-trimethoxyphenyl substituted pyrazolo[3,4-b]pyridine could serve as a promising scaffold for development of potent tubulin inhibitors as anticancer agents.

Exendin-4 attenuates pain-induced cognitive impairment by alleviating hippocampal neuroinflammation in a rat model of spinal nerve ligation.

Glucagon-like peptide-1 receptor has anti-apoptotic, anti-inflammatory, and neuroprotective effects. It is now recognized that the occurrence and development of chronic pain are strongly associated with anti-inflammatory responses; however, it is not clear whether glucagon-like peptide-1 receptor regulates chronic pain via anti-inflammatory mechanisms. We explored the effects of glucagon-like peptide-1 receptor on nociception, cognition, and neuroinflammation in chronic pain. A rat model of chronic pain was established using left L5 spinal nerve ligation. The glucagon-like peptide-1 receptor agonist exendin-4 was intrathecally injected into rats from 10 to 21 days after spinal nerve ligation. Electrophysiological examinations showed that, after treatment with exendin-4, paw withdrawal frequency of the left limb was significantly reduced, and pain was relieved. In addition, in the Morris water maze test, escape latency increased and the time to reach the platform decreased following exendin-4 treatment. Immunohistochemical staining and western blot assays revealed an increase in the numbers of activated microglia and astrocytes in the dentate gyrus of rat hippocampus, as well as an increase in the expression of tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6. All of these effects could be reversed by exendin-4 treatment. These findings suggest that exendin-4 can alleviate pain-induced neuroinflammatory responses and promote the recovery of cognitive function via the glucagon-like peptide-1 receptor pathway. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Renmin Hospital of Wuhan University of China (approval No. WDRM 20171214) on September 22, 2017.

Involvement of human and canine MRP1 and MRP4 in benzylpenicillin transport.

The blood-brain barrier (BBB) is a dynamic and complex interface between blood and the central nervous system (CNS). It protects the brain by preventing toxic substances from entering the brain but also limits the entry of therapeutic agents. ATP-binding cassette (ABC) efflux transporters are critical for the functional barrier and present a formidable impediment to brain delivery of therapeutic agents including antibiotics. The aim of this study was to investigate the possible involvement of multidrug resistance-associated protein 1 and 4 (MRP1 and MRP4), two ABC transporters, in benzylpenicillin efflux transport using wild-type (WT) MDCKII cells and cells overexpressing those human transporters, as well as non-selective and selective inhibitors. We found that inhibiting MRP1 or MRP4 significantly increased [3H]benzylpenicillin uptake in MDCKII-WT, -MRP1 or -MRP4 cells. Similar results were also found in HepG2 cells, which highly express MRP1 and MRP4, and hCMEC/D3 cells which express MRP1. The results indicate that human and canine MRP1 and MRP4 are involved in benzylpenicillin efflux transport. They could be potential therapeutic targets for improving the efficacy of benzylpenicillin for treating CNS infections since both MRP1 and MRP4 express at human blood-brain barrier.