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1.
Drug Deliv ; 28(1): 700-708, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33818230

RESUMEN

Driven by the lifestyle habits of modern people, such as excessive smoking, drinking, and chewing betel nut and other cancer-causing foods, the incidence of oral cancer has increased sharply and has a trend of becoming younger. Given the current mainstream treatment means of surgical resection will cause serious damage to many oral organs, so that patients lose the ability to chew, speak, and so on, it is urgent to develop new oral cancer treatment methods. Based on the strong killing effect of photothermal therapy on exposed superficial tumors, we developed a pH-responsive charge reversal nanomedicine system for oral cancer which is a kind of classic superficial tumor. With excellent photothermal properties of polydopamine (PDA) modified black phosphorus nanosheets (BP NSs) as basal material, then used polyacrylamide hydrochloride-dimethylmaleic acid (PAH-DMMA) charge reversal system for further surface modification, which can be negatively charged at blood circulation, and become a positive surface charge in the tumor site weakly acidic conditions due to the breaking of dimethylmaleic amide. Therefore, the uptake of oral cancer cells was enhanced and the therapeutic effect was improved. It can be proved that this nanomedicine has excellent photothermal properties and tumor enrichment ability, as well as a good killing effect on oral cancer cells through in vitro cytotoxicity test and in vivo photothermal test, which may become a very promising new model of oral cancer treatment.

2.
J Econ Entomol ; 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33822096

RESUMEN

The honey bee is a significant crop pollinator and key model insect for understanding social behavior, disease transmission, and development. The ectoparasitic Varroa destructor mite put threats on the honey bee industry. A Varroa toxic protein (VTP) from the saliva of Varroa mites contributes to the toxicity toward Apis cerana and the deformed wing virus elevation in Apis mellifera. However, the immune response and hemolymph microbiota of honey bee species after the injection of recombinant VTP has not yet been reported. In this study, both A. cerana and A. mellifera worker larvae were injected with the recombinant VTP. Then the expressions of the honey bee immune genes abaecin, defensin, and domeless at three time points were determined by qRT-PCR, and hemolymph microbial community were analyzed by culture-dependent method, after recombinant VTP injection. The mortality rates of A. cerana larvae were much higher than those of A. mellifera larvae after VTP challenge. VTP injection induced the upregulation of defensin gene expression in A. mellifera larvae, and higher levels of abaecin and domeless mRNAs response in A. cerana larvae, compared with the control (without any injection). Phosphate buffer saline (PBS) injection also upregulated the expression levels of abaecin, defensin, and domeless in A. mellifera and A. cerana larvae. Three bacterial species (Enterococcus faecalis, Staphylococcus cohnii, and Bacillus cereus) were isolated from the hemolymph of A. cerana larvae after VTP injection and at 48 h after PBS injections. Two bacterial species (Stenotrophomonas maltophilia and Staphylococcus aureus) were isolated from A. mellifera larvae after VTP challenge. No bacterial colonies were detected from the larval hemolymph of both honey bee species treated by injection only and the control. The result indicates that abaecin, defensin, and domeless genes and hemolymph microbiota respond to the VTP challenge. VTP injection might induce the dramatic growth of different bacterial species in the hemolymph of the injected larvae of A. mellifera and A. cerana, which provide cues for further studying the interactions among the honey bee, VTP, and hemolymph bacteria.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 469-473, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812417

RESUMEN

OBJECTIVE: To investigate the efficacy, safety and prognosis of auto-HSCT between classical and modified conditioning regimen in patients with B-cell non-Hodgkin lymphoma. METHODS: 36 patients diagnosed as B-cell non-Hodgkin lymphoma treated with autologous hematopoietic stem cell transplantation from January 2015 to June 2018 in Tianjin Cancer Hospital were retrospectively analyzed. The patients were divided into two groups: Idarubicin group and non-Idarubicin group. The overall survival (OS), progression-free survival (PFS), adverse reactions and hematopoietic reconstitution time between the two groups were compared. Survival analysis was performed by using the Kaplan-Meier method. Log-rank test was used for comparison between groups, and Cox regression was used for multivariate analysis. RESULTS: The median follow-up time was 29 months. Among these 36 patients with B-cell non-Hodgkin lymphoma before transplantation, 21 patients achieved CR and 15 patients achieved PR. The reconstitution time of neutrophil (P>0.05) and platelet (P>0.05) was not significantly different between Idarubicin and non-Idarubicin group. Also, the adverse reactions were not significantly different between two groups. The addition of idarubicin showed not aggravate the adverse reactions of patients. The OS and PFS of patients with idarubicin was longer than that of patients without idarubicin. The multivariate analysis showed that, the modified conditioning regimen and the remission state before transplantation were closely associated with prognosis. CONCLUSION: The above-mentioned results indicated that the combination of modified conditioning regimen with idarubicin can lengthen the OS and PFS of the patients significantly, and show not aggravate of bone marrow inhibition, moreover, the hematopoietic reconsititution time show not lengthen, which means that it can be a safe and effective choice for autologous HSCT in the patients with B cell non-Hodgkin lymphoma.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica , Linfocitos B , Supervivencia sin Enfermedad , Humanos , Linfoma no Hodgkin/terapia , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Trasplante Autólogo , Resultado del Tratamiento
4.
ACS Biomater Sci Eng ; 7(4): 1515-1525, 2021 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-33793187

RESUMEN

Immunotherapy is regarded as a potential strategy to combat cancer, especially when immunotherapy is combined with appropriate chemotherapy. However, the immunosuppressive tumor microenvironment (TME) and serious side effects extremely limit the application of immunotherapy. Herein, a self-stabilized hyaluronic acid nanoparticle is synthesized for tumor-targeted delivery of doxorubicin (DOX), cisplatin (CDDP), and resiquimod (R848) in osteosarcoma immunochemotherapy, which is referred to as CDDPNPDOX&R848. CDDPNPDOX&R848 exhibits sufficient stability, great pH responsibility, and brilliant tumor-targeting accumulation in vivo, which make it suitable for further in vivo applications. After intravenous injection, CDDPNPDOX&R848 can release the loaded cargoes under the acidic TME continuously. DOX can induce tumor cell apoptosis in combination with CDDP and trigger immunogenic cell death. More importantly, the immune-activated TME created by R848 can facilitate tumor-associated antigen presentation and antitumor immunity elicitation. Benefiting from the synergistic effect of chemotherapy and immunotherapy, the growth of tumors and lung metastasis was greatly inhibited by CDDPNPDOX&R848 in the K7M2 orthotopic osteosarcoma mouse model. Thus, this intelligent codelivery platform might be a competitive candidate for osteosarcoma immunochemotherapy.

5.
Int J Mol Sci ; 22(7)2021 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-33801703

RESUMEN

Salt stress is a major increasing threat to global agriculture. Pongamia (Millettia pinnata), a semi-mangrove, is a good model to study the molecular mechanism of plant adaptation to the saline environment. Calcium signaling pathways play critical roles in the model plants such as Arabidopsis in responding to salt stress, but little is known about their function in Pongamia. Here, we have isolated and characterized a salt-responsive MpCML40, a calmodulin-like (CML) gene from Pongamia. MpCML40 protein has 140 amino acids and is homologous with Arabidopsis AtCML40. MpCML40 contains four EF-hand motifs and a bipartite NLS (Nuclear Localization Signal) and localizes both at the plasma membrane and in the nucleus. MpCML40 was highly induced after salt treatment, especially in Pongamia roots. Heterologous expression of MpCML40 in yeast cells improved their salt tolerance. The 35S::MpCML40 transgenic Arabidopsis highly enhanced seed germination rate and root length under salt and osmotic stresses. The transgenic plants had a higher level of proline and a lower level of MDA (malondialdehyde) under normal and stress conditions, which suggested that heterologous expression of MpCML40 contributed to proline accumulation to improve salt tolerance and protect plants from the ROS (reactive oxygen species) destructive effects. Furthermore, we did not observe any measurable discrepancies in the development and growth between the transgenic plants and wild-type plants under normal growth conditions. Our results suggest that MpCML40 is an important positive regulator in response to salt stress and of potential application in producing salt-tolerant crops.

6.
Artículo en Inglés | MEDLINE | ID: mdl-33833508

RESUMEN

Background: Penehyclidine hydrochloride is a selective antagonist of M1 and M3 receptors. Clinical studies suggest that it is a potential drug for the treatment of chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate the effect of penehyclidine hydrochloride on the inflammatory response of lung tissue during mechanical ventilation in rats with COPD and explore the role of the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) signaling pathway. Methods: Eight-week-old male Sprague Dawley rats were exposed to cigarette smoke for 30 minutes every day for two months, and on the first and thirtieth days, 200 ug of lipopolysaccharide was injected into the trachea. Two months later, the rats were randomly divided into the control group (C), model group (M), model + normal saline group (N), and penehyclidine hydrochloride group (H) to undergo anesthesia and mechanical ventilation. In group H, 1 mg/kg of penehyclidine hydrochloride was injected intravenously. Results: The results showed that: ① Compared with group C, the other groups all showed typical chronic obstructive pathological changes in the lung tissue; their wet/dry weight ratio (W/D), TNF-α, JNK, and p-JNK levels increased (P < 0.05), and their interleukin (IL)-10 levels decreased (P < 0.05). ② Compared with group M, there was no significant change in the lung tissue indexes in group N (P > 0.05). ③ Compared with group N, the W/D, TNF-α, JNK, and p-JNK levels in group H decreased (P < 0.05), while the levels of IL-10 increased (P < 0.05). Conclusion: Penehyclidine hydrochloride can alleviate the pulmonary inflammatory response in rats with COPD undergoing mechanical ventilation. The JNK/SAPK signaling pathway may be involved in this process.

7.
J Org Chem ; 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33835809

RESUMEN

A convenient one-pot, three-component reaction has been developed for the synthesis of 3-aroylimidazo[1,2-a]-N-heterocycles from aryl ketones and 2-amino-N-heterocycles using dimethyl sulfoxide as a methylene donor. The reaction proceeds smoothly catalyzed by I2 in the presence of K2S2O8 and affords the desired products in moderate to good yields. This protocol offers significant superiority in accessing biologically active 3-aroylimidazo[1,2-a]-N-heterocycles with various substitution patterns.

8.
Diabetol Metab Syndr ; 13(1): 39, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33836817

RESUMEN

OBJECTIVE: To investigate the effects of intermittently scanned continuous glucose monitoring (isCGM) on blood glucose control, clinical value of blood glucose monitoring and production of urinary ketone bodies in pregestational diabetes mellitus. METHOD: A total of 124 patients with pregestational diabetes mellitus at 12-14 weeks of gestation admitted to the gestational diabetes clinic of our hospital from December 2016 to December 2018 were selected and randomly divided into two groups. Sixty patients adopted self-monitoring of blood glucose (SMBG) were taken as the control group, and the other 64 patients adopted isCGM system by wearing the device for 14 days. Blood sugar control, glycosylated albumin level, ketone production in urine, the maximum and minimum of blood sugar value measured by different monitoring methods and their occurrence time were observed in the two groups. RESULT: (1) No statistically significant differences were found between the groups in terms of maternal age, gestational age at first visit, family history, duration of diabetes, education level, total insulin dose, chronic hypertension, abortion history, nulliparity, assisted reproductive technology, history of macrosomia childbirth, pre-pregnancy BMI, and overweight (%) at the first visit and hypoglycemia, (2) the value of Glycated Albumin was lower in the CGM group compared to the control group at 2ed weeks (14.6 ± 2.2 vs. 16.8 ± 2.7, p < 0.001). The women in the CGM group spent increased time in the recommended glucose control target range of 3.5-7.8 mmol/L (69 ± 10% vs. 62 ± 11%, p < 0.001) and reduced time above target compared with those in the control group at 2 weeks (25 ± 7% vs. 31 ± 8%, p < 0.001). In the second week of the study, the positive rate of urinary ketone body in isCGM group was lower than that in the control group (42 ± 5 vs. 54 ± 5, p < 0.001), and (3) the minimum blood glucose of 31.2% (20/64) cases in isCGM group appeared during 0:00-2:59 at night, and 26.6% (17/64) cases appeared during 3:00-5:59 at night. The minimum values of 40.0% (24/60) cases in the control group appeared within the 30 min before lunch, 23.3% (14/60) within the 30 min before breakfast, and 11.7% (7/60) within the 30 min before dinner. The cases of minimum of blood sugar before meals accounted for 75% of all the minimum values, and the cases of minimum at night only accounted for 8.3%. CONCLUSION: Intermittently scanned continuous glucose monitoring can reduce hyperglycemia exposure and ketone body formation in pregestational diabetes mellitus. In addition, isCGM is better than SMBG in detecting nocturnal hypoglycemia.

9.
Front Cell Infect Microbiol ; 11: 638785, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33842388

RESUMEN

Background: Dengue fever is a mosquito-borne febrile illness. Southeast Asia experienced severe dengue outbreaks in 2019, and over 1000 cases had been reported in Jiangxi, a previously known low-epidemic region in China. However, the emergence of a dengue virus epidemic in a non-epidemic region remains unclear. Methods: We enrolled 154 dengue fever patients from four hospitals in Jiangxi, from April 2019 to September 2019. Real-time PCR, NS1 antigen rapid test, and IgM, IgG tests were performed, and 14 samples were outsourced to be sequenced metagenomically. Results: Among the 154 cases, 42 were identified as imported and most of them returned from Cambodia. A total of 113 blood samples were obtained and 106 were identified as DENV-1, two as DENV-2, and five were negative through RT-PCR. All DENV-1 strains sequenced in this study were all classified to one cluster and owned a high similarity with a Cambodia strain isolated in 2019. The evolutionary relationships of amino acid were consistent with that of nucleotide genome result. The sequence-based findings of Jiangxi strains were consistent with epidemiological investigation. Conclusion: Epidemiological analysis demonstrated that the emergence of dengue cases led to autochthonous transmission in several cities in Jiangxi, a low-epidemic region before. This study emphasized future prevention and control of dengue fever in both epidemic and non-epidemic regions.

10.
Mol Med Rep ; 23(6)2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33846780

RESUMEN

Spinal cord injury (SCI) is one of the most debilitating of all the traumatic conditions that afflict individuals. For a number of years, extensive studies have been conducted to clarify the molecular mechanisms of SCI. Experimental and clinical studies have indicated that two phases, primary damage and secondary damage, are involved in SCI. The initial mechanical damage is caused by local impairment of the spinal cord. In addition, the fundamental mechanisms are associated with hyperflexion, hyperextension, axial loading and rotation. By contrast, secondary injury mechanisms are led by systemic and cellular factors, which may also be initiated by the primary injury. Although significant advances in supportive care have improved clinical outcomes in recent years, a number of studies continue to explore specific pharmacological therapies to minimize SCI. The present review summarized some important pathophysiologic mechanisms that are involved in SCI and focused on several pharmacological and non­pharmacological therapies, which have either been previously investigated or have a potential in the management of this debilitating injury in the near future.

11.
Sci Transl Med ; 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33820835

RESUMEN

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies are a key class of therapeutics which may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555 (also known as bamlanivimab), a potent anti-spike neutralizing antibody from a hospitalized, convalescent patient with coronavirus disease 2019 (COVID-19). Biochemical, structural, and functional characterization of LY-CoV555 revealed high-affinity binding to the receptor-binding domain, angiotensin converting enzyme 2 binding inhibition, and potent neutralizing activity. A pharmacokinetic study of LY-CoV555 conducted in cynomolgus monkeys demonstrated a mean half-life of 13 days, and clearance of 0.22 mL/hr/kg, consistent with a typical human therapeutic antibody. In a rhesus macaque challenge model, prophylactic doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract in samples collected through study Day 6 following viral inoculation. This antibody has entered clinical testing and is being evaluated across a spectrum of COVID-19 indications, including prevention and treatment.

12.
Sensors (Basel) ; 21(5)2021 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-33806414

RESUMEN

Localization for estimating the position and orientation of a robot in an asymmetrical environment has been solved by using various 2D laser rangefinder simultaneous localization and mapping (SLAM) approaches. Laser-based SLAM generates an occupancy grid map, then the most popular Monte Carlo Localization (MCL) method spreads particles on the map and calculates the position of the robot by a probabilistic algorithm. However, this can be difficult, especially in symmetrical environments, because landmarks or features may not be sufficient to determine the robot's orientation. Sometimes the position is not unique if a robot does not stay at the geometric center. This paper presents a novel approach to solving the robot localization problem in a symmetrical environment using the visual features-assisted method. Laser range measurements are used to estimate the robot position, while visual features determine its orientation. Firstly, we convert laser range scans raw data into coordinate data and calculate the geometric center. Secondly, we calculate the new distance from the geometric center point to all end points and find the longest distances. Then, we compare those distances, fit lines, extract corner points, and calculate the distance between adjacent corner points to determine whether the environment is symmetrical. Finally, if the environment is symmetrical, visual features based on the ORB keypoint detector and descriptor will be added to the system to determine the orientation of the robot. The experimental results show that our approach can successfully determine the position of the robot in a symmetrical environment, while ordinary MCL and its extension localization method always fail.

13.
Tree Physiol ; 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33823048

RESUMEN

The scandent shrub plant form is a variant of liana that has upright and self-supporting stems when young but later becomes a climber. We aimed to explore the associations of stem and leaf traits among sympatric lianas, scandent shrubs and trees, and the effects of growth form and leaf habit on variation in stem or leaf traits. We measured 16 functional traits related to stem xylem anatomy, leaf morphology and nutrient stoichiometry in eight liana, eight scandent shrub and 21 tree species co-occurring in a subalpine cold temperate forest at an elevation of 2,600-3,200 m in Southwest China. Overall, lianas, scandent shrubs and trees were ordered along a fast-slow continuum of stem and leaf functional traits, with some traits overlapping. We found a consistent pattern of lianas > scandent shrubs > trees for hydraulically weighted vessel diameter, maximum vessel diameter and theoretical hydraulic conductivity. Vessel density and sapwood density showed a pattern of lianas = scandent shrubs < trees, and lianas < scandent shrubs = trees, respectively. Lianas had significantly higher specific leaf area and lower carbon concentration than co-occurring trees, with scandent shrubs showing intermediate values that overlapped with lianas and trees. The differentiation among lianas, scandent shrubs and trees was mainly explained by variation in stem traits. Additionally, deciduous lianas were positioned at the fast end of the trait spectrum, and evergreen trees at the slow end of the spectrum. Our results showed for the first time clear differentiation in stem and leaf traits among sympatric liana, scandent shrub and tree species in a subalpine cold temperate forest. This work will contribute to understanding the mechanisms responsible for variation in ecological strategies of different growth forms of woody plants.

14.
Immunity ; 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33823129

RESUMEN

An effective vaccine for respiratory syncytial virus (RSV) is an unrealized public health goal. A single dose of the prefusion-stabilized fusion (F) glycoprotein subunit vaccine (DS-Cav1) substantially increases serum-neutralizing activity in healthy adults. We sought to determine whether DS-Cav1 vaccination induces a repertoire mirroring the pre-existing diversity from natural infection or whether antibody lineages targeting specific epitopes predominate. We evaluated RSV F-specific B cell responses before and after vaccination in six participants using complementary B cell sequencing methodologies and identified 555 clonal lineages. DS-Cav1-induced lineages recognized the prefusion conformation of F (pre-F) and were genetically diverse. Expressed antibodies recognized all six antigenic sites on the pre-F trimer. We identified 34 public clonotypes, and structural analysis of two antibodies from a predominant clonotype revealed a common mode of recognition. Thus, vaccination with DS-Cav1 generates a diverse polyclonal response targeting the antigenic sites on pre-F, supporting the development and advanced testing of pre-F-based vaccines against RSV.

15.
Proc Natl Acad Sci U S A ; 118(11)2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33836571

RESUMEN

Noeggerathiales are enigmatic plants that existed during Carboniferous and Permian times, ∼323 to 252 Mya. Although their morphology, diversity, and distribution are well known, their systematic affinity remained enigmatic because their anatomy was unknown. Here, we report from a 298-My-old volcanic ash deposit, an in situ, complete, anatomically preserved noeggerathialean. The plant resolves the group's affinity and places it in a key evolutionary position within the seed plant sister group. Paratingia wuhaia sp. nov. is a small tree producing gymnospermous wood with a crown of pinnate, compound megaphyllous leaves and fertile shoots each with Ω-shaped vascular bundles. The heterosporous (containing both microspores and megaspores), bisporangiate fertile shoots appear cylindrical and cone-like, but their bilateral vasculature demonstrates that they are complex, three-dimensional sporophylls, representing leaf homologs that are unique to Noeggerathiales. The combination of heterospory and gymnospermous wood confirms that Paratingia, and thus the Noeggerathiales, are progymnosperms. Progymnosperms constitute the seed plant stem group, and Paratingia extends their range 60 My, to the end of the Permian. Cladistic analysis resolves the position of the Noeggerathiales as the most derived members of a heterosporous progymnosperm clade that are the seed plant sister group, altering our understanding of the relationships within the seed plant stem lineage and the transition from pteridophytic spore-based reproduction to the seed. Permian Noeggerathiales show that the heterosporous progymnosperm sister group to seed plants diversified alongside the primary radiation of seed plants for ∼110 My, independently evolving sophisticated cone-like fertile organs from modified leaves.

16.
Colloids Surf B Biointerfaces ; 203: 111742, 2021 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-33838581

RESUMEN

Angiogenesis is critical for tissue repair and regeneration, including implant osseointegration. It is well known that macrophages exert immunomodulatory functions in angiogenesis. However, whether macrophage-derived exosomes participate in the process is still unclear. Cobalt (Co) ions are frequently used as implant additives to mimic hypoxic microenvironment, which can induce angiogenesis through stabilizing hypoxia inducible factor-1α (HIF-1α) of macrophages and endothelial cells (ECs). The present work attempts to investigate whether exosomes derived from macrophages upon Co ion stimulation can mediate angiogenesis and the possible mechanism. The results show that the exosomes promote endothelial migration and angiogenesis in vitro and in vivo, particularly when Co ion concentration is 200 µM. Further studies reveal that the exosomes upregulating nitric oxide (NO), vascular endothelial growth factor (VEGF), and integrin ß1 expression may be the underlying mechanism of the observations. Our findings provide new insights for Co ion mediated macrophage-EC communication and surface design of biomaterials from the perspective of pro-angiogenesis.

17.
J Cell Mol Med ; 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33837646

RESUMEN

Plexin D1 (PLXND1), which was previously thought to mediate semaphorin signalling, belongs to the Plexin family of transmembrane proteins. PLXND1 cooperates mostly with the coreceptor neuropilin and participates in many aspects of axonal guidance. PLXND1 can also act as both a tumour promoter and a tumour suppressor. Emerging evidence suggests that mutations in PLXND1 or Semaphorin 3E, the canonical ligand of PLXND1, can lead to serious cardiovascular diseases, such as congenital heart defects, CHARGE syndrome and systemic sclerosis. Upon ligand binding, PLXND1 can act as a GTPase-activating protein (GAP) and modulate integrin-mediated cell adhesion, cytoskeletal dynamics and cell migration. These effects may play regulatory roles in the development of the cardiovascular system and disease. The cardiovascular effects of PLXND1 signalling have gradually been elucidated. PLXND1 was recently shown to detect physical forces and translate them into intracellular biochemical signals in the context of atherosclerosis. Therefore, the role of PLXND1 in cardiovascular development and diseases is gaining research interest because of its potential as a biomarker and therapeutic target. In this review, we describe the cardiac effects, vascular effects and possible molecular mechanisms of PLXND1 signalling.

18.
Int J Biol Macromol ; 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33838188

RESUMEN

Composites materials comprised of biopolymeric aerogel matrices and inorganic nano-hydroxyapatite (n-HA) fillers have received considerable attention in bone engineering. Although with significant progress in aerogel-based biomaterials, the brittleness and low strengths limit the application. The improvements in toughness and mechanical strength of aerogel-based biomaterials are in great need. In this work, an alkali urea system was used to dissolve, regenerate and gelate cellulose and silk fibroin (SF) to prepare composite aerosol. A dual network structure was shaped in the composite aerosol materials interlaced by sheet-like SF and reticular cellulose wrapping n-HA on the surface. Through uniaxial compression, the density of the composite aerogel material was close to the one of natural bone, and mechanical strength and toughness were high. Our work indicates that the composite aerogel has the same mechanical strength range as cancellous bone when the ratio of cellulose, n-HA and SF being 8:1:1. In vitro cell culture showed HEK-293T cells cultured on composite aerogels had high ability of adhesion, proliferation and differentiation. Totally, the presented biodegradable composite aerogel has application potential in bone tissue engineering.

19.
Eur J Med Chem ; 218: 113383, 2021 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-33799069

RESUMEN

Histone deacetylase 6 (HDAC6) has become a promising therapeutic target for central nervous system diseases due to its more complex protein structure and biological functions. However, low brain penetration of reported HDAC6 inhibitors limits its clinical application in neurological disorders. Therefore, the benzazepine, a brain-penetrant rigid fragment, was utilized to design a series of selective HDAC6 inhibitors to improve brain bioavailability. Various synthetic strategies were applied to assemble the tetrahydro-benzazepine ring, and 22 compounds were synthesized. Among them, compound 5 showed low nanomolar potency and strong isozyme selectivity for the inhibition of HDAC6 (IC50 = 1.8 nM, 141-fold selectivity over HDAC1) with efficient binding patterns like coordination with the zinc ion and π-π stacking effect. Western blot results showed it could efficiently transport into SH-SY5Y cells and selectively enhance the acetylation level of α-tubulin with a moderate effect on Histone H3. Notably, pharmacokinetic studies demonstrated that compound 5 (brain/plasma ratio of 2.30) had an excellent ability to penetrate the blood-brain barrier of C57 mice. In male rats with transient middle cerebral artery occlusion (MCAO), compound 5 significantly reduced the cerebral infarction from 21.22% to 11.47% and alleviated neurobehavioral deficits in post-ischemic treatment, which provided a strong rationale for pursuing HDAC6-based therapies for ischemic stroke.

20.
Stem Cell Res ; 53: 102314, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33799282

RESUMEN

A healthy 31-year-old Chinese Han female donated peripheral blood mononuclear cells (PBMC). Her PBMCs were reprogrammed with human OKSM (OCT3/4, KLF4 SOX2, and c-MYC) transcription factors by the non-integrating episomal vector system. Immunocytochemistry for pluripotency markers confirmed the pluripotency of transgene-free iPSCs. Their ability to differentiate spontaneously three germ layers in vitro is also confirmed. The iPSC line displayed a normal karyotype. This model can be used as a control in pathological mechanism studies.

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