Publications by authors named "Qin Lu"

415 Publications

Development of a sensitive indirect competitive enzyme-linked immunosorbent assay for high-throughput detection and risk assessment of aflatoxin B in animal-derived medicines.

Toxicon 2021 Apr 15. Epub 2021 Apr 15.

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. Electronic address:

Animal-derived medicine is an important part of traditional Chinese medicine (TCM). Studies have shown that many animal-derived medicinal products are susceptible to contaminate of aflatoxins, nevertheless, the rapid detection for animal-derived medicine is prone to be ignored. Here we developed a sensitive indirect competitive enzyme-linked immunosorbent assay (icELISA) for rapid screening of aflatoxin B (AFB) in ground beetle, cockroach, silkworm and earthworm. The sensitivity of the icELISA method was significantly enhanced. The IC for the four animal-derived medicinal samples ranged from 0.092 to 0.135 ng·mL; the limit of detection (LOD) was 0.008 - 0.020 ng·mL. To obtain high accuracy, the extraction solution and time were evaluated. By using this method, a total of 138 samples were investigated, and the detection rates of AFB in ground beetle and earthworm samples were 26.6% and 16.7%, respectively. The result was validated by liquid chromatography combined with tandem mass spectrometry, and an excellent correlation was observed between the two datasets, with a R value of 0.999. Our results indicate that the proposed method can be used for the rapid detection of AFB in animal-derived medicine. Furthermore, the quantitative risk assessment was conducted for ground beetle and earthworm based on the results, demonstrating that the intake of AFB in ground beetle had a slight threat to the risk of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxicon.2021.04.009DOI Listing
April 2021

Elucidating the Effect of Fine Lactose Ratio on the Rheological Properties and Aerodynamic Behavior of Dry Powder for Inhalation.

AAPS J 2021 Apr 15;23(3):55. Epub 2021 Apr 15.

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.

Dry powder inhaler (DPI) is recognized as the first choice for lung diseases' treatment. However, it lacks a universal way for DPI formulation development. Fine lactose is commonly added in DPIs to improve delivery performance; however, the fine ratio-dependent mechanism is unclear. Therefore, the objective of this study is to explore the influence of fine lactose ratio on DPI powder properties and aerodynamic behavior, and the fine lactose ratio-dependent mechanism involved during powder fluidization and lung deposition. Here salbutamol sulfate was used as a model drug, Lactohale® 206 as coarse carrier, and Lactohale® 300 as fine component; the mixtures were prepared at 1% drug content, with fine content up to 20%. It was shown that with the fine addition, flowability of the mixtures was improved, interaction among particles was increased, and the presence of fines could help to improve DPI's aerosolization performance. When the fines added were less than 3%, the "active site" hypothesis played a leading role. When the added fines were over 3% but less than 10%, fluidization enhancement mechanism was more important. After the added fines reaching 10%, aggregate mechanism started to dominate. However, FPF cannot be further increased once the fines reached 20%. Moreover, the correlations between FPF and dynamic powder parameters were verified in ternary mixtures, and cohesion had a greater impact on FPF than that of flowability. In conclusion, adding lactose fines is an effective way to improve lung deposition of DPI, with the concrete mechanism lactose fine ratio dependent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1208/s12248-021-00582-0DOI Listing
April 2021

A comparison of analgesic techniques for total knee arthroplasty: A network meta-analysis.

J Clin Anesth 2021 Apr 3;71:110257. Epub 2021 Apr 3.

Center for Applied Statistical Research and College of Mathematics, Jilin University, Changchun, China. Electronic address:

Study Objective: There is no established analgesic method for postoperative total knee arthroplasty. We comprehensively compared the analgesic methods for postoperative total knee arthroplasty.

Design: A network meta-analysis of randomised controlled trials was used to compare 18 interventions, which were ranked by six outcome indices, to select the best modality.

Setting: Postoperative recovery room and inpatient ward.

Patients: 98 randomised controlled trials involving 7452 patients (ASA I-III) were included in the final analysis.

Interventions: Studies that included the use of at least one of the following 12 nerve block(fascia iliaca compartment block (FIB), FNB, cFNB, single femoral nerve block (sFNB), adductor canal block (ACB), sciatic nerve block (SNB), obturator nerve block (ONB), continuous posterior lumbar plexus block (PSOAS), FNB + SNB, ACB + LIA, FNB + LIA, PCA + FNB).

Measurements: Pain intensity was compared using Visual Analogue Scale (VAS). Also, postoperative complications, function score, hospital length of stay, morphine consumption and patient satisfaction were measured.

Main Results: For visual analogue scale scores, continuous femoral nerve block (FNB) and FNB + sciatic nerve block (SNB) were the the most effective interventions. For reducing postoperative complications, fascia iliaca compartment block, FNB, SNB, and obturator nerve block showed the best results. For reducing postoperative morphine consumption, adductor canal block (ACB) + local infiltration analgesia (LIA) and FNB + SNB were preferred. For function scores (range of motion, Timed-Up-and-Go test), ACB and LIA were optimal choices. For reducing hospital length of stay and patient satisfaction, ACB + LIA and FNB + LIA were best, respectively.

Conclusions: Peripheral nerve block, especially FNB and ACB, is a better option than other analgesic methods, and its combination with other methods can be beneficial. Peripheral nerve block is a safe and effective postoperative analgesia method. However, our findings can only provide objective evidence. Clinicians should choose the treatment course based on the individual patient's condition and clinical situation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jclinane.2021.110257DOI Listing
April 2021

Design of biotin decorated enterocyte targeting muco-inert nanocomplexes for enhanced oral insulin delivery.

Carbohydr Polym 2021 Jun 27;261:117873. Epub 2021 Feb 27.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

The natural mucus cover has been a major obstacle to prevent enterocyte targeting particles from contact with the receptors. Thus, mucus penetration and intestinal targeting should be designed into one system. Based on the concept that biotin specifically recognizes epithelium receptors, enterocyte targeting muco-inert nanocomplexes were designed. Firstly, biotinylated chitosan (CS-Biotin) copolymers with different degree of substitution were synthesized and characterized. The nanocomplexes between CS-Biotin and insulin were prepared via self-assembly method. Thereafter, the nanocomplexes were fabricated by coating with various molecular weight hyaluronic acid (HA), which improved penetration efficiency in the mucus layer and small intestine in a HA molecular weight dependent manner. In vivo study indicated that hypoglycemic effect of the nanocomplexes was biotin modification degree and HA molecular weight dependent, with HA (200)-coated CS-Biotin21.8%/Insulin polyelectrolyte complex presenting the best performance. In conclusion, biotin decorated muco-inert nanocomplexes with HA coating are a promising platform for oral insulin delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carbpol.2021.117873DOI Listing
June 2021

Genome assembly and methylome analysis of the white wax scale insect provides insight into sexual differentiation of metamorphosis in hexapods.

Mol Ecol Resour 2021 Mar 11. Epub 2021 Mar 11.

Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.

Scale insects are hemimetabolous, showing "incomplete" metamorphosis and no true pupal stage. Ericerus pela, commonly known as the white wax scale insect (hereafter, WWS), is a wax-producing insect found in Asia and Europe. WWS displays dramatic sexual dimorphism, with notably different metamorphic fates in males and females. Males develop into winged adults, while females are neotenic and maintain a nymph-like appearance, which are flightless and remain stationary. Here, we report the de novo assembly of the WWS genome with a size of 638.30 Mbp (69.68 Mbp for scaffold N50) by PacBio sequencing and Hi-C. These data allowed us to perform a robust phylogenetic analysis comprising 24,923 gene orthogroups from 16 representative insect genomes. This analysis indicated that holometabola evolved from insects with incomplete metamorphosis in the Late Carboniferous, about 50 million years earlier than previously thought. To study the distinct developmental fates of males and females, we analysed the methylome landscape in either sex. Surprisingly, WWS displayed high methylation levels (4.42% for males) when compared to other insects. We observed differential methylation patterns in males and females for genes involved in steroid and sesquiterpenoid production as well as genes acting in fatty acid metabolism pathways. We measured titre profiles for ecdysone, the principal insect steroid hormone, and juvenile hormone (a sesquiterpenoid) in both males and females, which suggested that these hormones are the primary drivers of sexually dimorphic development. Our results provide a comprehensive genomic and epigenomic resource of scale insects that provide new insights into the evolution of metamorphosis and sexual dimorphism in insects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1755-0998.13376DOI Listing
March 2021

By inhibiting ADCY5, miR-18a-3p promotes osteoporosis and possibly contributes to spinal fracture.

Biochem Biophys Res Commun 2021 Apr 5;550:49-55. Epub 2021 Mar 5.

Department of Pain Management, The Affiliated Huai'an Hospital of Xuzhou Medical University and the Second People's Hospital of Huai'an, Huaian, 223001, Jiangsu, China. Electronic address:

To investigate the influence of miR-18a-3p and ADCY5 on OP and osteogenic differentiation of human Mesenchymal stem cell (hBMSCs) and its possible mechanism. Samples were collected from osteoporotic patients with or without vertebral compression fracture, and without OP volunteers. MiR-18a-3p and ADCY5 mRNA expression levels in the tissue samples and hBMSCs during osteogenic differentiation were detected。MiR-18a-3p mimic and OE-ADCY5 were introduced into hBMSCs to research the effects of miR-18a-3p and ADCY5 on osteogenesis differentiation of hBMSCs. Dual luciferase reporter system and RNA pull-down were applied to determine whether ADCY5 was a target gene of miR-18a-3p. Compared with the control group, ADCY5 expression level was down-regulated in patients with OP-no-Frx and OP-Frx, but that of miR-18a-3p was up-regulated. In addition, ADCY5 increased during osteogenesis differentiation of hBMSCs, whereas miR-18a-3p did not. OE-ADCY5 significantly facilitated calcium deposition, ALP activity, osteoblast protein expression (OSX, ALP and EUNX2), miR-18a-3p mimic inhibited osteogenic differentiation, and partially reversed the effect of OE-ADCY5 on osteogenic differentiation. In general, miR-18a-3p targets ADCY5 to promote OP and may be involved in spinal fracturs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2021.02.118DOI Listing
April 2021

Aloperine Inhibits Proliferation and Promotes Apoptosis in Colorectal Cancer Cells by Regulating the circNSUN2/miR-296-5p/STAT3 Pathway.

Drug Des Devel Ther 2021 25;15:857-870. Epub 2021 Feb 25.

Proctology Department, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.

Background: Aloperine can regulate miR-296-5p/Signal Transducer and Activator of Transcription 3 (STAT3) pathway to inhibit the malignant development of colorectal cancer (CRC), but the regulatory mechanism is unclear. This study explored the upstream mechanism of Aloperine in reducing CRC damage from the perspective of the circRNA-miRNA-mRNA regulatory network.

Methods: After treatment with gradient concentrations of Aloperine (0.1 mmol/L, 0.2 mmol/L, 0.4 mmol/L, 0.8 mmol/L and 1 mmol/L) for 24 hours, changes in CRC cell proliferation and apoptosis were detected by functional experiments. Data of the differential expression of miR-296-5p in CRC patients and healthy people were obtained from Starbase. The effects of Aloperine on 12 differentially expressed circRNAs were detected. The binding of miR-296-5p with NOP2/Sun RNA methyltransferase 2 (circNSUN2) and STAT3 was predicted by TargetScan and confirmed through dual-luciferase experiments. The expressions of circNSUN2, miR-296-5p and STAT3 as well as apoptosis-related genes in CRC cells were detected by qRT-PCR and Western blot as needed. Rescue experiments were conducted to test the regulatory effects of circNSUN2, miR-296-5p and STAT3 on CRC cells.

Results: Aloperine at a concentration gradient inhibited proliferation and promoted apoptosis in CRC cells. The abnormally low expression of miR-296-5p in CRC could be upregulated by Aloperine. Among the differentially expressed circRNAs in CRC, only circNSUN2 not only targets miR-296-5p, but also can be regulated by Aloperine. The up-regulation of circNSUN2 offset the inhibitory effect of Aloperine on cancer cells. The rescue experiments finally confirmed the regulation of circNSUN2/miR-296-5p/STAT3 axis in CRC cells.

Conclusion: By regulating the circNSUN2/miR-296-5p/STAT3 pathway, Aloperine prevents the malignant development of CRC cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S288473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924259PMC
February 2021

Management of ETV6-ABL1-positive childhood acute lymphoblastic leukaemia: report of two cases, a literature review and a call for action.

Br J Haematol 2021 Apr 3;193(1):197-200. Epub 2021 Mar 3.

Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, People's Republic of China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.17271DOI Listing
April 2021

Synthesis and anticancer activity of paclitaxel-coumarin conjugate.

Curr Org Synth 2021 Mar 2. Epub 2021 Mar 2.

Anhui University of Chinese Medicine,Hefei, 230038. China.

Background: Paclitaxel, a natural diterpenoid compound, has anti-tumor effect by acting on tubulin; coumarin, another kind of natural product, has anti-tumor, antibacterial effects and so on. Moreover coumarin has fluorescence.

Objective: Multi target to combat tumor is an effective strategy in drug design. Therefore, combination of paclitaxel with other acticive moleculer to explore the novel lead with multi-functons is in demand.

Materials And Methods: To synthsize paclitaxel-coumarin conjugate via click chemistry and to investigate anticancer activity by MTT assay and the scratch test.

Results And Discussion: The results of MTT assay showed that compared with paclitaxel, the anti-tumor activity of the conjugate was significantly improved. The results of flow cytometry showed that the conjugate had stronger ability to induce apoptosis. The scratch test results showed that the conjugate had better anti- metastasis ability than paclitaxel.

Conclusion: These findings indicated that paclitaxel and coumarin had synergistic effect, which provided a new idea for the development of paclitaxel monitored by fluorescence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1570179418666210303113406DOI Listing
March 2021

A CRISPR-Cas autocatalysis-driven feedback amplification network for supersensitive DNA diagnostics.

Sci Adv 2021 Jan 27;7(5). Epub 2021 Jan 27.

State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha 410082, P. R. China.

Artificial nucleic acid circuits with precisely controllable dynamic and function have shown great promise in biosensing, but their utility in molecular diagnostics is still restrained by the inability to process genomic DNA directly and moderate sensitivity. To address this limitation, we present a CRISPR-Cas-powered catalytic nucleic acid circuit, namely, CRISPR-Cas-only amplification network (CONAN), for isothermally amplified detection of genomic DNA. By integrating the stringent target recognition, helicase activity, and trans-cleavage activity of Cas12a, a Cas12a autocatalysis-driven artificial reaction network is programmed to construct a positive feedback circuit with exponential dynamic in CONAN. Consequently, CONAN achieves one-enzyme, one-step, real-time detection of genomic DNA with attomolar sensitivity. Moreover, CONAN increases the intrinsic single-base specificity of Cas12a, and enables the effective detection of hepatitis B virus infection and human bladder cancer-associated single-nucleotide mutation in clinical samples, highlighting its potential as a powerful tool for disease diagnostics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abc7802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840123PMC
January 2021

Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation.

Ann Intensive Care 2021 Feb 11;11(1):33. Epub 2021 Feb 11.

Sorbonne Université, INSERM, Médecine Intensive Réanimation, Institut de Cardiologie, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France.

Background: The effect of cytomegalovirus (CMV) reactivation on the length of mechanical ventilation and mortality in immunocompetent ICU patients requiring invasive mechanical ventilation remains controversial. The main objective of this study was to determine whether preemptive intravenous ganciclovir increases the number of ventilator-free days in patients with CMV blood reactivation.

Methods: This double-blind, placebo-controlled, randomized clinical trial involved 19 ICUs in France. Seventy-six adults ≥ 18 years old who had been mechanically ventilated for at least 96 h, expected to remain on mechanical ventilation for ≥ 48 h, and exhibited reactivation of CMV in blood were enrolled between February 5th, 2014, and January 23rd, 2019. Participants were randomized to receive ganciclovir 5 mg/kg bid for 14 days (n = 39) or a matching placebo (n = 37).

Results: The primary endpoint was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included day 60 mortality. The trial was stopped for futility based on the results of an interim analysis by the DSMB. The subdistribution hazard ratio for being alive and weaned from mechanical ventilation at day 60 for patients receiving ganciclovir (N = 39) compared with control patients (N = 37) was 1.14 (95% CI from 0.63 to 2.06; P = 0.66). The median [IQR] numbers of ventilator-free days for ganciclovir-treated patients and controls were 10 [0-51] and 0 [0-43] days, respectively (P = 0.46). Mortality at day 60 was 41% in patients in the ganciclovir group and 43% in the placebo group (P = .845). Creatinine levels and blood cells counts did not differ significantly between the two groups.

Conclusions: In patients mechanically ventilated for ≥ 96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13613-020-00793-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876264PMC
February 2021

Clinical features in patients with Xq23 microdeletion: A case report and literature review (Xq23 microdeletions).

J Clin Res Pediatr Endocrinol 2021 Feb 4. Epub 2021 Feb 4.

Department of Pediatrics, Shangyu Pepole's Hospital.

Xq22.3-q23 microdeletion is a rare genomic disorder. The purpose of this study is to emphasize the correlation between clinical phenotype and genotype of proximal deletion on chromosome Xq22.3-q23. A 5 years old boy had a 671Kb microdeletion on Xq23 by chromosomal microarray analysis (CMA), including AMMECR1 and CHRDL1 genes. He presented microsomia, midface hypoplasia, right kidney dysplasia and mildly motor retardation, which have never been reported before to be related with Xq23 deletion. To our knowledge, this is the first case with Xq23 microdeletion. A total of 9 cases with microdeletion at Xq22.3-q23 covered AMMECR1 gene and 2 cases with CHRDL1 mutation were reviewed. These data indicated that Xq23 microdeletion with microsomia, midface hypoplasia, kidney dysplasia, mildly motor retardation was rare. The previous literature showed two novel point mutation in AMMECR1 and CHRDL1 with some phenotype different from the patient. Xq23 microdeletion should be considered for patients with microsomia, midface hypoplasia, kidney dysplasia and growth retardation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/jcrpe.galenos.2020.2020.0100DOI Listing
February 2021

Host innate immune responses of geese infected with goose origin nephrotic astrovirus.

Microb Pathog 2021 Mar 28;152:104753. Epub 2021 Jan 28.

Institute of Animal Husbandry and Veterinary Sciences, Hubei Academy of Agricultural Sciences, Special One, Nanhuyaoyuan, Hongshan District, Wuhan, 430064, China; Key Laboratory of Prevention and Control Agents for Animal Bacteriosis, Special 1, Nanhuyaoyuan, Hongshan District, Wuhan, 430064, China. Electronic address:

A novel goose astrovirus (GoAstV) outbreak in goslings, characterized by severe articular and visceral gout with high mortality, occurred in China. Although the pathogenesis of GoAstV-infected goslings has been explored in several studies, the host-immune response remains unclear. In this study, a goose astrovirus was isolated from goslings in Xiaogan, and designated as the HBXG strain. The full-length genome of HBXG was 7170 nt. A sequence analysis and phylogenetic trees revealed HBXG belonged to the novel GoAstV. We evaluated the viral distribution systematically and estimated immune related gene expression in HBXG-infected goslings. Results showed that GoAstV replicated quickly in many tissues and the highest titer was observed in the kidney, which reached 10 copies. TLR3, RIG-I and MDA5 were involved in the host-immune response to GoAstV, and the expression of IFN types I (IFN-α, IFN-β), inflammatory cytokines (IL-8, IL-10, TNF-α), antiviral proteins (Mx, OASL, PKR) and MHC-I were also upregulated during the infection. In contrast, the expression of proinflammatory cytokines (IL-1β, IL-6) and MHC-II were inhibited at 3 dpi. This study suggests that GoAstV is highly pathogenic to goslings, causing multiple systemic infections in tissues and the host-immune response is activated early in infection. However, rapid viral replication, suppression of inflammatory cytokines (IL-1β, IL-6) and MHC-II expressions were the possible reasons why the host-immune response cannot provide enough protection against GoAstV infection. This study is the first report to illuminate the immune response in goslings infected with GoAstV and offers insight into the pathogenesis of GoAstV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.micpath.2021.104753DOI Listing
March 2021

Ethnoracial patterns of violence in Guatemala: An empirical examination of the relationship between Mayan-majority municipalities and homicide rates in Guatemala.

J Community Psychol 2021 Jan 19. Epub 2021 Jan 19.

Mennonite Central Committee, Guatemala, El Salvador.

The current study empirically tests the relationship between homicide rates and the population of indigenous Mayans at the municipal level in Guatemala. Using data from the most recent Guatemalan Census (2018) and independently aggregated national police data on homicides, we also propose models of possible pathways for the relationship between the ethnoracial composition of municipal population and homicide rates. Due to consistent non-normal distribution of demographic data in Guatemala, we used a maximum likelihood estimation of linear regression models and nonparametric bootstrapping method to test the theoretical relationships. The results showed a strong negative relationship between Mayan majority municipalities and homicide rates, mediated by living in municipality of birth. Findings suggest that attachment to place in Mayan majority municipalities in Guatemala is a strong protective factor for exposure to homicide, even in areas of high out-migration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcop.22506DOI Listing
January 2021

(p)ppGpp synthetases are required for the pathogenicity of Salmonella Pullorum in chickens.

Microbiol Res 2021 Apr 5;245:126685. Epub 2021 Jan 5.

Key Laboratory of Prevention and Control Agents for Animal Bacteriosis, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, 430064, China; Hubei provincial key laboratory of animal pathogenic microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, 430064, China. Electronic address:

Salmonella Pullorum is a pathogen specific to birds that can cause Pullorum disease in young chickens and lead to considerable economic losses in the poultry industry. During transmission and infection, S. Pullorum will encounter various environmental stresses and host defenses. The stringent response is an important adaptation response induced by (p)ppGpp, and in Salmonella, (p)ppGpp is synthesized by two (p)ppGpp synthetases, RelA and SpoT. To investigate the role of (p)ppGpp synthetases in the adaptation and pathogenicity of S. Pullorum, a (p)ppGpp synthetases mutant (ΔrelAΔspoT) was constructed, and its physiological phenotypes and pathogenicity, as well as transcription profiling, were compared with the parent strain. The ΔrelAΔspoT mutant showed decreased ability to form biofilms, and reduced resistance to acidic, alkaline, high osmolarity and HO conditions. The internalization of the ΔrelAΔspoT mutant into host cells in vitro and its lethality and colonization abilities within young chickens were also significantly reduced. RNA sequencing showed that the (p)ppGpp synthetases did not only affect the classic stringent response, such as inhibition of DNA replication and protein synthesis, but also controlled the expression of many virulence factors, in particular, the Salmonella pathogenicity island 1 (SPI-1) and SPI-2 type III secretion systems (T3SSs), and adhesion factors. These results suggest that the (p)ppGpp synthetases are required for the pathogenicity of S. Pullorum by affecting its stress response and the expression of the virulence factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.micres.2020.126685DOI Listing
April 2021

Impact of mandibular advancement device therapy on cerebrovascular reactivity in patients with carotid atherosclerosis combined with OSAHS.

Sleep Breath 2021 Jan 7. Epub 2021 Jan 7.

Department of Dentistry, Xuanwu Hospital Capital Medical University, #45 Xicheng District, Beijing, 100053, China.

Purpose: Obstructive sleep apnea-hypopnea syndrome (OSAHS) may affect cerebrovascular reactivity (CVR), representing cerebrovascular endothelial function, through complex cerebral functional changes. This study aimed to evaluate the change of CVR after 1-month and 6-month mandibular advancement device (MAD) treatment of patients with carotid atherosclerosis (CAS) combined with OSAHS.

Methods: Patients with carotid atherosclerosis combined with OSAHS who voluntarily accepted Silensor-IL MAD therapy were prospectively enrolled. All patients underwent polysomnographic (PSG) examinations and CVR evaluation by breath-holding test using transcranial Doppler ultrasound at baseline (T0), 1 month (T1), and 6 months (T2) of MAD treatment.

Results: Of 46 patients (mean age 54.4 ± 12.4 years, mean body mass index [BMI] 27.5 ± 4.5 kg/m), 41 patients (responsive group) responded to the 1-month and 6-month treatment of MAD, an effective treatment rate of 89%. The remaining 5 patients (non-responsive group) were younger (47.4 ± 13.5 years) and had a higher BMI (35.8 ± 1.8 kg/m). The responsive group had an improvement of apnea-hypopnea index (AHI) (events/h) from 33.0 ± 25.0 (T0) to 12.4 ± 10.4 (T1) and 8.7 ± 8.8 (T2), P < 0.001; minimum arterial oxygen saturation (minSpO) (%) increased from 79.8 ± 9.1 (T0) to 81.8 ± 9.4 (T1) and 85.2 ± 5.4 (T2), P < 0.01; longest apnea (LA) (s) decreased from 46.5 ± 23.1 (T0) to 33.3 ± 22.7 (T1) and 29.4 ± 18.5 (T2), P < 0.001; T90 (%) decreased from 10.3 ± 14.9 (T0) to 6.1 ± 11.8 (T1) and 3.3 ± 7.5 (T2), P < 0.05. Sleep architecture of these patients also improved significantly. The responsive group had a significant increase in left, right, and mean breath-holding index (BHI): left BHI(/s) from 0.52 ± 0.42 (T0) to 0.94 ± 0.56 (T1) and 1.04 ± 0.64 (T2), P < 0.01; right BHI(/s) from 0.60 ± 0.38 (T0) to 1.01 ± 0.58 (T1) and 1.11 ± 0.60 (T2), P < 0.01; mean BHI(/s) from 0.56 ± 0.38 (T0) to 0.97 ± 0.55 (T1) and 1.07 ± 0.59 (T2), P < 0.01), suggesting improved CVR.

Conclusion: Effective MAD therapy is beneficial for restoring cerebrovascular endothelial function in patients with CAS and OSAHS in a short period (1 month and 6 months).

Trial Registration: Clinical trial registration number: NCT03665818. September 11, 2018.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11325-020-02230-xDOI Listing
January 2021

Sympathetic Nerve Control of Blood Pressure Response during Exercise in Peripheral Artery Disease and Current Application of Experimental Disease Models.

Authors:
Lu Qin Jianhua Li

Am J Biomed Sci Res 2020 25;9(3):204-209. Epub 2020 Jun 25.

Heart & Vascular Institute, The Penn State University College of Medicine, US.

In patients with peripheral artery disease (PAD), the blood supply directed to the lower limbs is reduced. This results in severe limb ischemia and thereby intermittent claudicating which is characterized by pain in lower limbs that occurs with walking and is relieved by rest. Of note, PAD can extremely affect the quality of living of patients and increase high risk of coronary and cerebral vascular accidents. However, effective treatments of PAD are still challenging in clinics. A number of reports have demonstrated the beneficial effects of supervised exercise on symptoms of PAD patients. This review will summarize results obtained from recent human and animal studies, which include the abnormalities in sympathetic control of blood pressure response during exercise in PAD, and rationality of animal models used for study human PAD. Nonetheless, additional in-depth studies are necessary to better explore the underlying mechanisms of the exaggerated responses of sympathetic nerve and blood pressure in PAD at molecular and cellular levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.34297/AJBSR.2020.09.001387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774331PMC
June 2020

Clopidogrel-Induced Gastric Injury in Rats is Attenuated by Stable Gastric Pentadecapeptide BPC 157.

Drug Des Devel Ther 2020 21;14:5599-5610. Epub 2020 Dec 21.

Department of Gastroenterology, Zhongda Hospital Affiliated to Southeast University, Nanjing 210009, People's Republic of China.

Aim: Although Clopidogrel is safe in healthy volunteers, it can induce recurrence of gastric ulcers in high-risk patients. Here, we investigated the protective effect of the natural product, stable gastric pentadecapeptide 157 (BPC 157) on Clopidogrel-induced gastric injury.

Methods: We used acetic acid to induce gastric ulcer in Sprague Dawley rats. Clopidogrel alone or in combination with BPC 157 or L-NAME (nitric oxide system blockade) were administered after healing of acetic acid-induced ulcer. One percent methylcellulose solution was used as control. Ulcer recurrence rate and the ulcer index were compared between these groups. Gastric mucosal apoptosis rate, microscopic inflammation activity and angiogenesis markers vascular endothelial growth factor A () and were examined by TUNEL, histological evaluations (HE) and immunohistochemistry (IHC). Pathways involved, expressions of endoplasmic reticulum (ER) stress apoptosis marker , angiogenic markers and its receptor , and endothelial NO synthase () were all analyzed by Western blot.

Results: This study indicated that Clopidogrel significantly induced the gastric ulcers recurrence, severe inflammation and ER stress related apoptosis of the gastric mucosa, suppressed the synthesis of angiogenic markers and . Furthermore, Clopidrogel intervention resulted in the activation of protein kinase B () and p38 mitogen-activated protein kinase (). BPC 157 attenuated the gastric mucosal damage caused by Clopidogrel and reversed these molecular effects. However, NO blockade L-NAME weakened the protective effect and thus the molecular effects of BPC 157 on gastric mucosa.

Conclusion: In conclusion, these results suggest that BPC 157 inhibited Clopidogrel-induced gastric mucosa injury partially by inhibition of gastric mucosa cell ER stress-mediated apoptosis and inflammation, and promoting gastric mucosa angiogenesis via mediated- signaling pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S284163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763470PMC
December 2020

A novel motif in the 5'-UTR of an orphan gene 'Big Root Biomass' modulates root biomass in sesame.

Plant Biotechnol J 2020 Dec 28. Epub 2020 Dec 28.

Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture and Rural Affairs, Wuhan, China.

Developing crops with improved root system is crucial in current global warming scenario. Underexploited crops are valuable reservoirs of unique genes that can be harnessed for the improvement of major crops. In this study, we performed genome-wide association studies on seven root traits in sesame (Sesamum indicum L.) and uncovered 409 significant signals, 19 quantitative trait loci containing 32 candidate genes. A peak SNP significantly associated with root number and root dry weight traits was located in the promoter of the gene named 'Big Root Biomass' (BRB), which was subsequently validated in a bi-parental population. BRB has no functional annotation and is restricted to the Lamiales order. We detected the presence of a novel motif 'AACACACAC' located in the 5'-UTR of BRB in single and duplicated copy in accessions with high and small root biomass, respectively. A strong expression level of BRB was negatively correlated with high root biomass, and this was attributed to the gene SiMYB181 which represses the activity of BRB by binding specifically to the single motif but not to the duplicated one. Curiously, the allele that enhanced BRB expression has been intensively selected by modern breeding. Overexpression of BRB in Arabidopsis modulates auxin pathway leading to reduced root biomass, improved yield parameters under normal growth conditions and increased drought stress sensitivity. Overall, BRB represents a solid gene model for improving the performance of sesame and other crops.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pbi.13531DOI Listing
December 2020

HIF-1α inhibition alleviates the exaggerated exercise pressor reflex in rats with peripheral artery disease induced by femoral artery occlusion.

Authors:
Lu Qin Jianhua Li

Physiol Rep 2021 Jan;8(24):e14676

Heart and Vascular Institute, The Pennsylvania State University College of Medicine, Hershey, PA, USA.

Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor mediating adaptive responses to hypoxia and ischemia. Our previous work showed that HIF-1α is increased in muscle sensory nerves of rats with peripheral artery disease (PAD) induced by femoral artery occlusion. The present study was further to examine the role played by HIF-1α in regulating the response of arterial blood pressure (BP) to the activation of muscle afferent nerve during static muscle contraction in rats with femoral artery occlusion. A rat model of femoral artery ligation was used to study PAD in this study. Western blot analysis was employed to examine the protein levels of HIF-1α in the dorsal root ganglion (DRG) tissues. BAY87, a synthesized compound with the characteristics of highly potent and specific suppressive effects on expression and activity of HIF-1α, was given into the arterial blood supply of the ischemic hindlimb muscles before the exercise pressor reflex was evoked by static muscle contraction. First, HIF-1α was increased in the DRG of occluded limbs (optical density: 0.89 ± 0.13 in control versus 1.5 ± 0.05 in occlusion; p < 0.05, n = 6 in each group). Arterial injection of BAY87 (0.2 mg/kg) then inhibited expression of HIF-1α in the DRG of occluded limbs 3 hr following its injection (optical density: 1.02 ± 0.09 in occluded limbs with BAY87 versus 1.06 ± 0.1 in control limbs; p > 0.05, n = 5 in each group). In addition, muscle contraction evoked a greater increase in BP in occluded rats. BAY87 attenuated the enhanced BP response in occluded rats to a greater degree than in control rats. Our data suggest that the inhibition of HIF-1α alleviates the exaggeration of the exercise pressor reflex in rats under ischemic circumstances of the hindlimbs in PAD induced by femoral artery occlusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14814/phy2.14676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757375PMC
January 2021

Molecular evolution and deorphanization of bitter taste receptors in a vampire bat.

Integr Zool 2020 Dec 2. Epub 2020 Dec 2.

Department of Ecology, Tibetan Centre for Ecology and Conservation at WHU-TU, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.

Bats represent the largest dietary radiation in a single mammalian order, and have become an emerging model group for studying dietary evolution. Taste receptor genes have proven to be molecular signatures of dietary diversification in bats. For example, all 3 extant species of vampire bats have lost many bitter taste receptor genes (Tas2rs) in association with their dietary shift from insectivory to sanguivory. Indeed, only 8 full-length Tas2rs were identified from the high-quality genome of the common vampire bat (Desmodus rotundus). However, it is presently unknown whether these bitter receptors are functional, since the sense of taste is less important in vampire bats, which have an extremely narrow diet and rely on other senses for acquiring food. Here, we applied a molecular evolutionary analysis of Tas2rs in the common vampire bat compared with non-vampire bats. Furthermore, we provided the first attempt to deorphanize all bitter receptors of the vampire bat using a cell-based assay. We found that all Tas2r genes in the vampire bat have a level of selective pressure similar to that in non-vampire bats, suggesting that this species must have retained some bitter taste functions. We demonstrated that 5 of the 8 bitter receptors in the vampire bat can be activated by some bitter compounds, and observed that the vampire bat generally can not detect naturally occurring bitter compounds examined in this study. Our study demonstrates functional retention of bitter taste in vampire bats as suggested by cell-based functional assays, calling for an in-depth study of extra-oral functions of bitter taste receptors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1749-4877.12509DOI Listing
December 2020

Role of aspartate ammonia-lyase in Pasteurella multocida.

BMC Microbiol 2020 12 3;20(1):369. Epub 2020 Dec 3.

Institute of Animal Husbandry and Veterinary Sciences, Hubei Academy of Agricultural Sciences, Special one, Nanhuyaoyuan, Hongshan District, Wuhan, 430064, China.

Background: Pasteurella multocida is responsible for a highly infectious and contagious disease in birds, leading to heavy economic losses in the chicken industry. However, the pathogenesis of this disease is poorly understood. We recently identified an aspartate ammonia-lyase (aspA) in P. multocida that was significantly upregulated under iron-restricted conditions, the protein of which could effectively protect chicken flocks against P. multocida. However, the functions of this gene remain unclear. In the present study, we constructed aspA mutant strain △aspA::kan and complementary strain C△aspA::kan to investigate the function of aspA in detail.

Result: Deletion of the aspA gene in P. multocida resulted in a significant reduction in bacterial growth in LB (Luria-Bertani) and MH (Mueller-Hinton) media, which was rescued by supplementation with 20 mM fumarate. The mutant strain △aspA::kan showed significantly growth defects in anaerobic conditions and acid medium, compared with the wild-type strain. Moreover, growth of △aspA::kan was more seriously impaired than that of the wild-type strain under iron-restricted conditions, and this growth recovered after supplementation with iron ions. AspA transcription was negatively regulated by iron conditions, as demonstrated by quantitative reverse transcription-polymerase chain reaction. Although competitive index assay showed the wild-type strain outcompetes the aspA mutant strain and △aspA::kan was significantly more efficient at producing biofilms than the wild-type strain, there was no significant difference in virulence between the mutant and the wild-type strains.

Conclusion: These results demonstrate that aspA is required for bacterial growth in complex medium, and under anaerobic, acid, and iron-limited conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12866-020-02049-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713322PMC
December 2020

Pituitary Adenylate Cyclase-Activating Polypeptide: A Promising Neuroprotective Peptide in Stroke.

Aging Dis 2020 Dec 1;11(6):1496-1512. Epub 2020 Dec 1.

3Department of Neurosurgery, Loma Linda University, Loma Linda, CA, USA.

The search for viable, effective treatments for acute stroke continues to be a global priority due to the high mortality and morbidity. Current therapeutic treatments have limited effects, making the search for new treatments imperative. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a well-established cytoprotective neuropeptide that participates in diverse neural physiological and pathological activities, such as neuronal proliferation, differentiation, and migration, as well as neuroprotection. It is considered a promising treatment in numerous neurological diseases. Thus, PACAP bears potential as a new therapeutic strategy for stroke treatment. Herein, we provide an overview pertaining to the current knowledge of PACAP, its receptors, and its potential neuroprotective role in the setting of stroke, as well as various mechanisms of neuroprotection involving ionic homeostasis, excitotoxicity, cell edema, oxidative stress, inflammation, and cell death, as well as the route of PACAP administration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14336/AD.2020.0626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673855PMC
December 2020

Reclassification of the biocontrol agents BY-2 and Tu-100 as and insights into the genomic and specialized metabolite diversity of the species.

Microbiology (Reading) 2020 12;166(12):1121-1128

Microbiomes, Microbes and Informatics Group, Organisms and Environment Division, School of Biosciences, Cardiff University, Cardiff, CF10 3AX, Wales, UK.

The genomes of two historical species strains isolated from the roots of oilseed rape and used routinely in PR China as biocontrol agents to suppress disease were sequenced. Average nucleotide identity (ANI) and digital DNA-DNA hybridization analyses demonstrated that they were originally misclassified as and now belong to the bacterial species . A broader ANI analysis of available genomes identified 292 genomes that were then subjected to core gene analysis and phylogenomics. Prediction and dereplication of specialized metabolite biosynthetic gene clusters (BGCs) defined the prevalence of multiple antimicrobial-associated BGCs and highlighted the natural product potential of . By defining the core and accessory antimicrobial biosynthetic capacity of the species, we offer an in-depth understanding of natural product capacity to facilitate the selection and testing of strains for use as biological control agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1099/mic.0.000986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819358PMC
December 2020

Identification of novel CEBPA double mutations capable of promoting familial AML via the suppression of myeloid differentiation.

Am J Transl Res 2020 15;12(10):6965-6972. Epub 2020 Oct 15.

Department of Hematology, Children's Hospital of Soochow University Soochow 215025, Jiangsu, China.

CCAAT-enhancer-binding protein α (CEBPA) gene carrying two mutations (CEBPA double mutations) is known to promote familial acute myeloid leukemia (AML). However, the underlying mechanism by which CEBPA double mutations promote AML remains poorly understood. Here we report that a family with three generations suffering from familial AML carries novel double mutations of CEBPA. Seven bases of GCGCGGG were inserted into the N-terminal c.113-114 of CEBPA as germline mutations and three bases of AAG were inserted into the C-terminal c.939-940 as a somatic mutation. To test the functional impact of this double mutation, we constructed plasmid encoding the double mutants of CEBPA and transfected it into the myeloid precursor 32Dcl3 cells. Lentiviral induced overexpression of CEBPA with these double mutations inhibited myeloid differentiation of these 32Dcl3 cells, and led to approximately 4-fold fewer frequency of CD11b expression. Our results confirm that the double mutations of CEBPA at both N- and C-terminals are potentially to induce leukemogenesis of AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653564PMC
October 2020

Exploration of plasma interleukin-27 levels in asthma patients and the correlation with lung function.

Respir Med 2020 12 29;175:106208. Epub 2020 Oct 29.

Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Respiratory Diseases, National Ministry of Health of the People's Republic of China and National Clinical Research Center for Respiratory Disease, Wuhan, China. Electronic address:

Background: IL-27 attenuates allergic inflammation and improves lung function in mouse models of allergic asthma. However, plasma IL-27 levels of asthma patients and the association with clinical features remain poorly understood.

Methods: This study examined plasma IL-27 protein expression in untreated asthma patients and controls, analyzed its correlation with Th2 inflammation and lung function, and evaluated the effect of corticosteroids on IL-27 expression.

Results: Plasma IL-27 levels were lower in untreated asthma patients compared to controls. Plasma IL-27 levels were inversely correlated with sputum IL-5 mRNA expression in Th2 group. The Th2IL-27 subgroup suffered from the highest airway hyperresponsiveness (AHR) and the worst pulmonary function. The patients in Th2IL-27 subgroup were less likely to be atopic and had the worst improvement of symptoms after four weeks of standard treatment. In vitro, dexamethasone could decrease the expression of IL-27 in THP-1 cell line. The majority of asthma patients had further decreased IL-27 levels after standard treatment, whereas patients with sustained high levels of IL-27 post-treatment had more blood neutrophils at baseline compared with those without.

Conclusions: The results indicate that low levels of IL-27 in peripheral blood are closely related to Th2 inflammation and lung function of asthma patients. Low IL-27 levels in combination with high Th2 inflammation identify an asthma phenotype with high AHR and substantial response to corticosteroids. Understanding of this interaction could help to elucidate the inherent inflammation heterogeneity of asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rmed.2020.106208DOI Listing
December 2020

Exploring the influence of inhaled liposome membrane fluidity on its interaction with pulmonary physiological barriers.

Biomater Sci 2020 Dec 4;8(23):6786-6797. Epub 2020 Nov 4.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.

Liposomes are promising vectors for pulmonary drug delivery, and have been used in marketed inhalation products. Membrane fluidity is an important property of liposomes. However, the influence of liposome membrane fluidity on its interaction with pulmonary physiological barriers is still unclear and needs elucidation. Here, a series of PEGylated DPPC (1,2-dihexadecanoyl-rac-glycero-3-phosphocholine) liposomes with different membrane fluidity were prepared, and their interaction with different pulmonary physiological barriers, including the mucus permeation capacity, macrophage uptake, trachea distribution and retention behavior, was investigated. The liposomes exhibited sizes of around 100 nm, near-neutral surface charge, and the membrane fluidity increased with increasing cholesterol ratio. In vitro studies showed that the liposomes with lower membrane fluidity presented optimal mucus permeation efficiency, while those with higher membrane fluidity displayed lower macrophage uptake. An in vivo trachea distribution study revealed that liposomes with low or medium membrane fluidity exhibited enhanced trachea permeation. No significant difference in lung retention was found among these liposomes. In conclusion, the mucus permeation and macrophage phagocytosis behavior of liposomes could be well tuned by changing their membrane fluidity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0bm01529fDOI Listing
December 2020

Stretchable Electrochemical Biosensing Platform Based on Ni-MOF Composite/Au Nanoparticle-Coated Carbon Nanotubes for Real-Time Monitoring of Dopamine Released from Living Cells.

ACS Appl Mater Interfaces 2020 Nov 25;12(44):49480-49488. Epub 2020 Oct 25.

School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, P. R. China.

Existing electrochemical biosensing platforms, using traditional rigid and unstretchable electrodes, cannot monitor the biological signaling molecules released by cells in a mechanically deformed state in real time. Here, a stretchable and flexible electrochemical sensor was developed based on nickel metal-organic framework composite/Au nanoparticle-coated carbon nanotubes (Ni-MOF composite/AuNPs/CNTs) for sensitive detection of dopamine (DA) released by C6 living cells in real time. A Ni-MOF composite was obtained by introducing Ni, NiO, and a carbon frame onto the surface of two-dimensional (2D) Ni-MOF nanosheets using an efficient one-step calcination method. The hybrid of Ni-MOF composite/AuNPs/CNTs that deposited on the poly(dimethylsiloxane) (PDMS) film endowed the sensor with excellent electrochemical performance with a wide linear range of 50 nM to 15 μM and a high sensitivity of 1250 mA/(cm M) and also provided the sensor with desirable stability against mechanical deformation. Furthermore, the stretchable electrode also displayed good cellular compatibility while C6 living cells can be cultured and proliferated on it with strong adhesion. Then, the DA released by C6 living cells with chemical induction in both natural and stretched states was monitored using our stretchable and flexible electrochemical sensor in real time. This indicates that our new design of flexible Ni-MOF composite/AuNPs/CNTs/PDMS (NACP) film electrodes provides more opportunities for the detection of chemical signals released from cells and soft living organisms even under mechanically deformed states.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c16060DOI Listing
November 2020

Sarpogrelate and rosuvastatin synergistically ameliorate aortic damage induced by hyperlipidemia in apolipoprotein E-deficient mice.

Exp Ther Med 2020 Dec 9;20(6):170. Epub 2020 Oct 9.

Department of Cardiology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.

The current study aimed to investigate whether sarpogrelate and rosuvastatin possess anti-arterial injury, and attempted to elucidate the mechanism of action underlying this activity. Sarpogrelate, a 5-hydroxytryptamine type 2A antagonist, is extensively used to prevent arterial thrombosis; however, its effects on atherosclerosis remain unknown. In the present study, sarpogrelate combined with rosuvastatin or rosuvastatin alone were administered to male ApoE mice fed a high-fat diet (HFD) for 8 weeks. Metabolic parameters in the blood samples were analyzed using an automatic analyzer. Aortic tissues were stained with hematoxylin and eosin for morphological analysis. The expression levels of oxidized-low density lipoprotein (LDL) specific scavenging receptors, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and cluster of differentiation 68 were detected via immunostaining. mRNA expression levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α were determined via reverse transcription-quantitative PCR analysis, while protein expression levels of LOX-1 and phosphor(p)-ERK were determined via western blot analysis. The results demonstrated that sarpogrelate combined with rosuvastatin treatment significantly decreased total cholesterol and LDL cholesterol levels in the serum, and alleviated intimal hyperplasia and lipid deposition, accompanied by decreased inflammatory cell infiltration and lower expression levels of inflammatory cytokines, compared with rosuvastatin monotherapy or HFD treatment. Furthermore, sarpogrelate combined with rosuvastatin treatment significantly decreased the expression levels of LOX-1 and p-ERK. Taken together, these results suggest that the positive effects of sarpogrelate combined with rosuvastatin treatment on aortic injury may be associated with the regulation of the LOX-1/p-ERK signaling pathway. Sarpogrelate and rosuvastatin synergistically decreased aortic damage in ApoE HFD mice, and thus provide a basis for the treatment of aortic injury caused by hyperlipidemia with sarpogrelate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2020.9300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571328PMC
December 2020

Nerve growth factor in muscle afferent neurons of peripheral artery disease and autonomic function.

Authors:
Lu Qin Jianhua Li

Neural Regen Res 2021 Apr;16(4):694-699

Heart & Vascular Institute, Penn State University College of Medicine, Hershey, PA, USA.

In peripheral artery disease patients, the blood supply directed to the lower limbs is reduced. This results in severe limb ischemia and thereby enhances pain sensitivity in lower limbs. The painful perception is induced and exaggerate during walking, and is relieved by rest. This symptom is termed by intermittent claudication. The limb ischemia also amplifies autonomic responses during exercise. In the process of pain and autonomic responses originating exercising muscle, a number of receptors in afferent nerves sense ischemic changes and send signals to the central nervous system leading to autonomic responses. This review integrates recent study results in terms of perspectives including how nerve growth factor affects muscle sensory nerve receptors in peripheral artery disease and thereby alters responses of sympathetic nerve activity and blood pressure to active muscle. For the sensory nerve receptors, we emphasize the role played by transient receptor potential vanilloid type 1, purinergic P2X purinoceptor 3 and acid sensing ion channel subtype 3 in amplified sympathetic nerve activity responses in peripheral artery disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/1673-5374.293132DOI Listing
April 2021