Cortical thickness alterations are associated with astrocytes and excitatory neuron-specific transcriptome signatures in pediatric bipolar disorder.

Bipolar disorder (BD) is a heritable psychiatric disorder with a complex etiology that is often associated with cortical alterations. Morphometric studies in adults with BD are well established; however, few have examined cortical changes in pediatric BD (PBD). Additionally, the correlation between cortical thickness (CT) changes in PBD and gene expression remains elusive. Here, we performed an integrative analysis using neuroimaging data from 58 PBD individuals and the Allen human brain transcriptomic dataset. We applied partial least squares (PLS) regression analysis on structural MRI data and cortical gene expression, enrichment and specific cell type analysis to investigate the genetic correlates of CT alterations in PBD. We found the expression levels of PBD-related genes showed significant spatial correlations with CT differences. Further enrichment and specific cell type analysis revealed that transcriptome signatures associated with cortical thinning were enriched in synaptic signaling, ion channels, astrocytes, and excitatory neurons. Neurodevelopmental patterns of these genes showed significantly increased expression in the cerebellum, cortex, and subcortical regions during the adolescence period. These results highlight neurodevelopmental transcriptional changes could account for most of the observed correlations with CT differences in PBD, which offers a novel perspective to understand biological conceptualization mechanisms for the genetic correlates of CT alterations.

Immediate visual reproduction negatively correlates with brain entropy of parahippocampal gyrus and inferior occipital gyrus in bipolar II disorder adolescents.

BACKGROUND: Brain entropy reveals complexity and irregularity of brain, and it has been proven to reflect brain complexity alteration in disease states. Previous studies found that bipolar disorder adolescents showed cognitive impairment. The relationship between complexity of brain neural activity and cognition of bipolar II disorder (BD-II) adolescents remains unclear. METHODS: Nineteen BD-II patients (14.63 ±1.57 years old) and seventeen age-gender matched healthy controls (HCs) (14.18 ± 1.51 years old) were enlisted. Entropy values of all voxels of the brain in resting-state functional MRI data were calculated and differences of them between BD-II and HC groups were evaluated. After that, correlation analyses were performed between entropy values of brain regions showing significant entropy differences and clinical indices in BD-II adolescents. RESULTS: Significant differences were found in scores of immediate visual reproduction subtest (VR-I, p = 0.003) and Stroop color-word test (SCWT-1, p = 0.015; SCWT-2, p = 0.004; SCWT-3, p = 0.003) between the two groups. Compared with HCs, BD-II adolescents showed significant increased brain entropy in right parahippocampal gyrus and right inferior occipital gyrus. Besides, significant negative correlations between brain entropy values of right parahippocampal gyrus, right inferior occipital gyrus and immediate visual reproduction subtest scores were observed in BD-II adolescents. CONCLUSIONS: The findings of the present study suggested that the disrupted function of corticolimbic system is related with cognitive abnormality of BD-II adolescents. And from the perspective temporal dynamics of brain system, the current study, brain entropy may provide available evidences for understanding the underlying neural mechanism in BD-II adolescents.

Alterations of brainstem volume in patients with first-episode and recurrent major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a prevalent mental health condition characterized by recurrent episodes in a substantial proportion of patients. The number of previous episodes is one of the most crucial predictors of depression recurrence. However, the underlying neural mechanisms remain unclear. To date, there have been limited neuroimaging studies investigating morphological changes of the brainstem in patients with first-episode MDD (FMDD) and recurrent MDD (RMDD). This study aimed to examine volumetric changes of individual brainstem regions in relation to the number of previous episodes and disease duration. METHOD: A total of 111 individuals including 36 FMDD, 25 RMDD, and 50 healthy controls (HCs) underwent T1-weighted structural magnetic resonance imaging scans. A Bayesian segmentation algorithm was used to analyze the volume of each brainstem region, including the medulla oblongata, pons, midbrain, and superior cerebellar peduncle (SCP), as well as the whole brainstem volume. Analyses of variance (ANOVA) were performed to obtain brain regions with significant differences among three groups and then post hoc tests were calculated for inter-group comparisons. Partial correlation analyses were further conducted to identify associations between regional volumes and clinical features. RESULTS: The ANOVA revealed significant brainstem volumetric differences among three groups in the pons, midbrain, SCP, and the whole brainstem (F = 3.996 ~ 5.886, adjusted p = 0.015 ~ 0.028). As compared with HCs, both groups of MDD patients showed decreased volumes in the pons as well as the entire brainstem (p = 0.002 ~ 0.034), however, only the FMDD group demonstrated a significantly reduced volume in the midbrain (p = 0.003). Specifically, the RMDD group exhibited significantly decreased SCP volume when comparing to both FMDD (p = 0.021) group and HCs (p = 0.008). Correlation analyses revealed that the SCP volumes were negatively associated with the number of depressive episodes (r=-0.36, p < 0.01) and illness duration (r=-0.28, p = 0.035) in patients with MDD. CONCLUSION: The present findings provided evidence of decreased brainstem volume involving in the pathophysiology of MDD, particularly, volumetric reduction in the SCP might represent a neurobiological marker for RMDD. Further research is needed to confirm our observations and deepen our understanding of the neural mechanisms underlying depression recurrence.

Altered spatiotemporal consistency in pediatric bipolar disorder patients with and without psychotic symptoms.

OBJECTIVE: Psychotic symptoms are quite common in patients with pediatric bipolar disorder (PBD) and may affect the symptom severity and prognosis of PBD. However, the potential mechanisms are less well elucidated until now. Thus, the purpose of this study was to investigate the brain functional differences between PBD patients with and without psychotic symptoms. METHOD: A total of 71 individuals including: 27 psychotic PBD (P-PBD), 25 nonpsychotic PBD (NP-PBD), and 19 healthy controls were recruited in the present study. Each subject underwent 3.0 Tesla functional magnetic resonance imaging scan. Four-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was employed to detect the local brain activity changes. Analyses of variance (ANOVA) were used to reveal brain regions with significant differences among three groups groups of individuals, and inter-group comparisons were assessed using post hoc tests. RESULTS: The ANOVA obtained significant among-group FOCA differences in the left triangular inferior frontal gyrus, left supplementary motor area, left precentral gyrus, right postcentral gyrus, right superior occipital gyrus, and right superior frontal gyrus. Compared with the control group, the P-PBD group showed decreased FOCA in the left supplementary motor area and bilateral superior frontal gyrus and showed increased FOCA in the left triangular inferior frontal gyrus. In contrast, the NP-PBD group exhibited decreased FOCA in the right superior occipital gyrus and right postcentral gyrus and showed increased FOCA in the left orbital inferior frontal gyrus. Compared to the NP-PBD group, the P-PBD group showed decreased FOCA in the right superior frontal gyrus. CONCLUSION: The present findings demonstrated that the two groups of PBD patients exhibited segregated brain functional patterns, providing empirical evidence for the biological basis of different clinical outcomes between PBD patients with and without psychotic symptoms.

Altered Functional Integration in the Salience and Default Mode Networks in Euthymic Pediatric Bipolar Disorder.

Accumulating studies demonstrate emotional and cognitive dysregulation in the euthymic period of pediatric bipolar disorder (PBD). However, the relative contribution of functional integration in human brain to disturbed emotion and cognitive function in the euthymic PBD patients remains unclear. In this study, 16 euthymic PBD patients and 16 healthy controls underwent resting-state functional magnetic resonance imaging. A data-driven functional connectivity analysis was used to investigate functional connectivity changes of the euthymic PBD. Compared with healthy controls, the euthymic PBD exhibited greater global functional connectivity density in the left anterior insula and lower global functional connectivity density in the right temporoparietal junction, the left angular gyrus, and the bilateral occipital lobule. A distant functional connectivity analysis demonstrated altered integration within the salience and default mode networks in euthymic PBD. Correlation analysis found that altered functional connectivity of the salience network was related to the reduced performance in the backward digit span test, and altered functional connectivity of the default mode network was related to the Young Mania Rating Scale in euthymic PBD patients. Our findings indicated that disturbed functional integration in salience and default mode networks might shed light on the physiopathology associated with emotional and cognitive dysregulation in PBD.

Intrinsic brain abnormalities in young healthy adults with childhood trauma: A resting-state functional magnetic resonance imaging study of regional homogeneity and functional connectivity.

OBJECTIVE: Childhood trauma confers great risk for the development of multiple psychiatric disorders; however, the neural basis for this association is still unknown. The present resting-state functional magnetic resonance imaging study aimed to detect the effects of childhood trauma on brain function in a group of young healthy adults. METHODS: In total, 24 healthy individuals with childhood trauma and 24 age- and sex-matched adults without childhood trauma were recruited. Each participant underwent resting-state functional magnetic resonance imaging scanning. Intra-regional brain activity was evaluated by regional homogeneity method and compared between groups. Areas with altered regional homogeneity were further selected as seeds in subsequent functional connectivity analysis. Statistical analyses were performed by setting current depression and anxiety as covariates. RESULTS: Adults with childhood trauma showed decreased regional homogeneity in bilateral superior temporal gyrus and insula, and the right inferior parietal lobule, as well as increased regional homogeneity in the right cerebellum and left middle temporal gyrus. Regional homogeneity values in the left middle temporal gyrus, right insula and right cerebellum were correlated with childhood trauma severity. In addition, individuals with childhood trauma also exhibited altered default mode network, cerebellum-default mode network and insula-default mode network connectivity when the left middle temporal gyrus, right cerebellum and right insula were selected as seed area, respectively. CONCLUSION: The present outcomes suggest that childhood trauma is associated with disturbed intrinsic brain function, especially the default mode network, in adults even without psychiatric diagnoses, which may mediate the relationship between childhood trauma and psychiatric disorders in later life.

Effect of Atomoxetine on the Cognitive Functions in Treatment of Attention Deficit Hyperactivity Disorder in Children with Congenital Hypothyroidism: A Pilot Study.

BACKGROUND: With early initiation of thyroxine supplementation, children with congenital hypothyroidism (CH) retain some subtle deficits, such as attention and inhibitory control problems. This study assessed the effects of atomoxetine on cognitive functions in treatment of attention deficit hyperactivity disorder (ADHD) symptoms in children with CH. METHODS: In a 6-month, open-labeled pilot study, 12 children were recruited and received atomoxetine. The measures of efficacy were scores on the Swanson, Nolan and Pelham Teacher and Parent Rating Scale, version IV (SNAP-IV) and Clinical Global Impression-Severity scale (CGI-S). The cognitive functions were evaluated with the Wechsler Intelligence Scale for Chinese Children, Digit Span, Wisconsin Card Sorting Test, and Stroop test. RESULTS: A statistically significant difference was found between the mean CGI-S and SNAP-IV scores before and after treatment (p < 0.01). All the indicators of cognitive functions at the endpoint were improved compared with those at baseline. No serious adverse events were reported. CONCLUSION: Atomoxetine appears to be useful in improving ADHD symptoms, as well as cognitive functions, in children with CH. Larger, randomized, double-blinded, clinical trials are required to replicate these results.

Alterations of regional homogeneity in pediatric bipolar depression: a resting-state fMRI study.

BACKGROUND: Pediatric bipolar disorder (PBD) has attracted increasing attentions due to its high prevalence and great influence on social functions of children and adolescents. However, the pathophysiology underlying PBD remains unclear. In the present study, the resting-state functional magnetic resonance imaging (fMRI) was used to detect abnormalities of baseline brain functions in depressed PBD youth. METHODS: Seventeen youth with PBD-depression aged 10 - 18 years old and 18 age- and sex-matched normal controls were recruited in this study. The fMRI data under resting state were obtained on a Siemens 3.0 Tesla scanner and were analyzed using the regional homogeneity (ReHo) method. Correlations between the ReHo values of each survived area and the severity of depression symptoms in patients were further analyzed. RESULTS: As compared with the control group, PBD-depression patients showed decreased ReHo in the medial frontal gyrus, bilateral middle frontal gyrus and middle temporal gyrus, and the right putamen. Significant negative correlations of the mood and feelings questionnaire scores with mean ReHo values in the medial frontal gyrus and the right middle frontal gyrus in PBD-depression patients were observed. CONCLUSION: Our results suggest that extensive regions with altered baseline brain activities are existed in PBD-depression and these brain regions mainly locate in the fronto-limbic circuit and associated striatal structures. Moreover, the present findings also add to our understanding that there could be unique neuropathophysiological mechanisms underlying PBD-depression.

Finite Element Analysis of Different Carbon Fiber Reinforced Polyetheretherketone Dental Implants in Implant-supported Fixed Denture.

OBJECTIVES: The purpose of this study is to determine the feasibility of polyetheretherketone-based dental implants, and analyze the stress and strain around different kinds of dental implants by finite element analysis. METHODS: The radiographic data was disposed to models in Mimics 19.0. 3D models of implants, crowns and jawbones were established and combined in SolidWorks 2018. Appling axial and oblique loads of 100 N, cloud pictures were exported in Ansys Workbench 18.0 to calculate and analyze the stress and strain in and around different implants. RESULTS: Oblique load tended to deliver more stress to bone tissue than axial load. The uniformity of stress distribution was the best for 30% short carbon fiber reinforced polyetheretherketone implants at axial and buccolingual directions. Stress shielding phenomenon occurred at the neck of 60% continuous carbon fiber reinforced polyetheretherketone and titanium implants. Stress concentration appeared in PEEK implants and the load of bone tissue would aggravate. CONCLUSIONS: 30% short carbon fiber reinforced polyetheretherketone implants demonstrate a more uniform stress distribution in bone-implant contact and surrounding bone than titanium. Stress shielding and stress concentration may be avoided in bone-implant interface and bone tissue. Bone disuse-atrophy may be inhibited in PEEK-based implants.

Structural and functional disruption of subcortical limbic structures related with executive function in pediatric bipolar disorder.

BACKGROUND: Impaired cognition has been demonstrated in pediatric bipolar disorder (PBD). The subcortical limbic structures play a key role in PBD. However, alternations of anatomical and functional characteristics of subcortical limbic structures and their relationship with neurocognition of PBD remain unclear. METHODS: Thirty-six PBD type I (PBD-I) (15.36 ± 0.32 years old), twenty PBD type II (PBD-II) (14.80 ± 0.32 years old) and nineteen age-gender matched healthy controls (HCs) (14.16 ± 0.36 years old) were enlisted. Primarily, the volumes of the subcortical limbic structures were obtained and differences in the volumes were evaluated. Then, these structures served as seeds of regions of interest to calculate the voxel-wised functional connectivity (FC). After that, correlation analysis was completed between volumes and FC of brain regions showing significant differences and neuropsychological tests. RESULTS: Compared to HCs, both PBD-I and PBD-II patients showed a decrease in the Stroop color word test (SCWT) and digit span backward test scores. Compared with HCs, PBD-II patients exhibited a significantly increased volume of right septal nuclei, and PBD-I patients presented increased FC of right nucleus accumbens and bilateral pallidum, of right basal forebrain with right putamen and left pallidum. Both the significantly altered volumes and FC were negatively correlated with SCWT scores. SIGNIFICANCE: The study revealed the role of subcortical limbic structural and functional abnormalities on cognitive impairments in PBD patients. These may have far-reaching significance for the etiology of PBD and provide neuroimaging clues for the differential diagnosis of PBD subtypes. CONCLUSIONS: Distinctive features of neural structure and function in PBD subtypes may contribute to better comprehending the potential mechanisms of PBD.

Curcumin-loaded mesoporous polydopamine nanoparticles modified by quaternized chitosan against bacterial infection through synergistic effect.

Clinically, open wounds caused by accidental trauma and surgical lesion resection are easily infected by external bacteria, hindering wound healing. Antibacterial photodynamic therapy has become a promising treatment strategy for wound infection. In this study, a novel antibacterial nanocomposite material (QMC NPs) was synthesized by curcumin, quaternized chitosan and mesoporous polydopamine nanoparticles. The results showed that 150 µg/mL QMC NPs had good biocompatibility and exerted excellent antibacterial activity against Staphylococcus aureus and Escherichia coli after blue laser irradiation (450 nm, 1 W/cm2). In vivo, QMC NPs effectively treated bacterial infection and accelerated the healing of infected wounds in mice.

Elevated specific peripheral cytokines found in major depressive disorder patients with childhood trauma exposure: a cytokine antibody array analysis.

Taking into consideration the previous evidence of revealing the relationship of early life adversity, major depressive disorder (MDD), and stress-linked immunological changes, we recruited 22 MDD patients with childhood trauma exposures (CTE), 21 MDD patients without CTE, and 22 healthy controls without CTE, and then utilized a novel cytokine antibody array methodology to detect potential biomarkers underlying MDD in 120 peripheral cytokines and to evaluate the effect of CTE on cytokine changes in MDD patients. Although 13 cytokines were identified with highly significant differences in expressions between MDD patients and normal controls, this relationship was significantly attenuated and no longer significant after consideration of the effect of CTE in MDD patients. Depressed individuals with CTE (TD patients) were more likely to have higher peripheral levels of those cytokines. Severity of depression was associated with plasma levels of certain increased cytokines; meanwhile, the increased cytokines led to a proper separation of TD patients from normal controls during clustering analyses. Our research outcomes add great strength to the relationship between depression and cytokine changes and suggest that childhood trauma may play a vital role in the co-appearance of cytokine changes and depression.

White matter integrity alterations in young healthy adults reporting childhood trauma: A diffusion tensor imaging study.

OBJECTIVE: To date, insufficient studies have focused on the relationship between childhood trauma and white matter integrity changes in healthy subjects. The aim of the present study was to explore the potential effects of childhood trauma on white matter microstructural changes by using voxel-based diffusion tensor imaging (DTI) to examine alterations in fractional anisotropy (FA) values in a group of young healthy adults. METHODS: A total of 21 healthy adults with a history of childhood trauma exposures and 21 age- and sex-matched individuals without childhood trauma were recruited in the present study. The Childhood Trauma Questionnaire was used to assess five aspects of childhood trauma exposures. DTI data were obtained on a Philips 3.0-Tesla scanner. Voxel-based analysis was conducted to compare white matter FA values between groups. RESULTS: Adults with self-reported childhood trauma experiences showed decreased white matter FA values in the genu and body of the corpus callosum and the left occipital fusiform gyrus (p < 0.001 uncorrected, voxel > 100). There was no significant difference in FA values between individuals with single and multiple childhood trauma exposures at the defined threshold. CONCLUSION: Our findings suggest that childhood trauma is associated with reduced microstructural integrity of the white matter in adulthood. These effects are still evident even in the absence of current psychiatric or medical symptoms, which may represent the vulnerability for developing mental disorders after childhood trauma experiences.

[Association between MAOA-u VNTR polymorphism and its interaction with stressful life events and major depressive disorder in adolescents].

OBJECTIVE: To investigate whether the genetic polymorphism, upstream variable number of tandem repeats (uVNTR), in the monoamine oxidase A (MAOA) gene, is associated with major depressive disorder (MDD) in adolescents and to test whether there is gene-environment interaction between MAOA-uVNTR polymorphism and stressful life events (SLEs). METHODS: A total of 394 Chinese Han subjects, including 187 adolescent patients with MDD and 207 normal students as a control group, were included in the study. Genotyping was performed by SNaP-shot assay. SLEs in the previous 12 months were evaluated. The groups were compared in terms of the frequency distributions of MAOA-uVNTR genotypes and alleles using statistical software. The binary logistic regression model of gene-environment interaction was established to analyze the association of the gene-environment interaction between MAOA-u VNTR genotypes and SLEs with adolescent MDD. RESULTS: The distribution profiles of MAOA-u VNTR genotypes and alleles were not related to the onset of MDD, severity of depression, comorbid anxiety and suicidal ideation/behavior/attempt in adolescents. The gene-environment interaction between MAOA-u VNTR genotypes and SLEs was not associated with MDD in male or female adolescents. CONCLUSIONS: It is not proven that MAOA-u VNTR polymorphism is associated with adolescent MDD. There is also no gene-environment interaction between MAOA-u VNTR polymorphism and SLEs that is associated with adolescent MDD.

Experimental study of dexamethasone-loaded hollow hydroxyapatite microspheres applied to direct pulp capping of rat molars.

Background: Dexamethasone (DEX) exerts anti-inflammatory and osteogenic effects. Hydroxyapatite is commonly used in bone repair due to its osteoconductivity, osseointegration, and osteogenesis induction. Hollow hydroxyapatite (HHAM) is often used as a drug carrier. Objective: This study aimed to investigate the histological responses of exposed dental pulp when dexamethasone-loaded nanohydroxyapatite microspheres (DHHAM) were used as a direct capping agent. Methods: Cavities were created in the left maxillary first molar of Wistar rats and filled with Dycal, HHAM, and DHHAM. No drug was administered to the control group. The rats were sacrificed at 1, 2, and 4 weeks after the procedure. The molars were extracted for fixation, demineralization, dehydration, embedding, and sectioning. H&E staining was performed to detect the formation of reparative dentin. H&E and CD45 immunohistochemical staining were performed to detect pulp inflammation. Immunohistochemical staining was performed to assess the expressions of dentin matrix protein 1 (DMP-1), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1ß. Results: The results of H&E and CD45 immunohistochemical staining showed that the degree of inflammation in the DHHAM group was less than that in the Control and HHAM groups at 1, 2, and 4 weeks after capping of the rat molar teeth (p<0.01). The H&E staining showed that the percentage of reparative dentin formed in the DHHAM group was higher than that in the Control, HHAM (p<0.001), and Dycal groups (p<0.01) at 1 and 2 weeks, and was significantly higher than that in the Control group (p<0.001) and the HHAM group (p<0.01) at 4 weeks. The immunohistochemical staining showed a lower range and intensity of expression of IL-1ß, IL-6, and TNF-α and high expression levels of DMP-1 in the DHHAM group at 1, 2, and 4 weeks after pulp capping relative to the Control group. Conclusions: DHHAM significantly inhibited the progression of inflammation and promoted reparative dentin formation.

The Different Impact of Depressive or Manic First-episode on Pediatric Bipolar Disorder Patients: Evidence From Resting-state fMRI.

Bipolar disorder may begin as depression or mania, which can affect the treatment and prognosis of bipolar disorder. However, the physiological and pathological differences of pediatric bipolar disorder (PBD) patients with different onset symptoms are not clear. The purpose of this study was to investigate the differences of clinical, cognitive function and intrinsic brain networks in PBD patients with first-episode depression and first-episode mania. A total of 63 participants, including 43 patients and 20 healthy controls, underwent resting-state fMRI scans. PBD patients were classified as first-episode depressive and first-episode manic based on their first-episode symptoms. Cognitive tests were used to measure attention and memory of all participants. Independent component analysis (ICA) was used to extract the salience network (SN), default-mode network (DMN), central executive network (ECN) and limbic network (LN) for each participant. Spearman rank correlation analysis was performed between abnormal activation and clinical and cognitive measures. The results showed that there were differences in cognitive functions such as attention and visual memory between first-episode depression and mania, as well as differences activation in anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), precuneus, inferior parietal cortex and parahippocampus. And significant associations of brain activity with clinical assessments or cognition were found in different patients. In conclusion, we found differential impairments in cognitive and brain network activation in first-episode depressive and first-episode manic PBD patients, and correlations were found between these impairments. These evidences may shed light on the different developmental paths of bipolar disorder.

Osseointegration behavior of carbon fiber reinforced polyetheretherketone composites modified with amino groups: An in vivo study.

Polyetheretherketone (PEEK) has become increasingly popular in dentistry and orthopedics due to its excellent chemical stability, reliable biosafety, and low elastic modulus. However, PEEK's biomechanical strength and bioactivity are limited and need to be increased as an implant material. The previous study in vitro has shown that the amino-functionalized carbon fiber reinforced PEEK (A-30%-CPEEK) possessed enhanced mechanical property and bioactivity. This study aims to evaluate the effect of amino groups modification on the osseointegration behavior of carbon fiber reinforced PEEK (30%-CPEEK) in rabbits. Herein, 30%-CPEEK and A-30%-CPEEK implant discs were implanted in rabbit skulls for 5 weeks, with pure titanium implants serving as a control. The bone-forming ability and osseointegration in vivo were systematically investigated by micro-computed tomography analysis, scanning electron microscope observation, and histological evaluation. Our results showed that all detection parameters were significantly different between the A-30%-CPEEK and 30%-CPEEK groups, favoring those in the A-30%-CPEEK, whose appraisal parameters were equal to or better than pure titanium. Therefore, this study supported the importance of amino groups in facilitating the new bone formation and bone-implant integration, suggesting that A-30%-CPEEK with enhanced osseointegration will be a promising material for dental or orthopedic implants.

Antibacterial properties of antimicrobial peptide HHC36 modified polyetheretherketone.

Introduction: Polyetheretherketone (PEEK) is considered to be a new type of orthopedic implant material due to its mechanical properties and biocompatibility. It is becoming a replacement for titanium (Ti) due to its near-human-cortical transmission and modulus of elasticity. However, its clinical application is limited because of its biological inertia and susceptibility to bacterial infection during implantation. To solve this problem, there is an urgent need to improve the antibacterial properties of PEEK implants. Methods: In this work, we fixed antimicrobial peptide HHC36 on the 3D porous structure of sulfonated PEEK (SPEEK) by a simple solvent evaporation method (HSPEEK), and carried out characterization tests. We evaluated the antibacterial properties and cytocompatibility of the samples in vitro. In addition, we evaluated the anti-infection property and biocompatibility of the samples in vivo by establishing a rat subcutaneous infection model. Results: The characterization test results showed that HHC36 was successfully fixed on the surface of SPEEK and released slowly for 10 days. The results of antibacterial experiments in vitro showed that HSPEEK could reduce the survival rate of free bacteria, inhibit the growth of bacteria around the sample, and inhibit the formation of biofilm on the sample surface. The cytocompatibility test in vitro showed that the sample had no significant effect on the proliferation and viability of L929 cells and had no hemolytic activity on rabbit erythrocytes. In vivo experiments, HSPEEK can significantly reduce the bacterial survival rate on the sample surface and the inflammatory reaction in the soft tissue around the sample. Discussion: We successfully loaded HHC36 onto the surface of SPEEK through a simple solvent evaporation method. The sample has excellent antibacterial properties and good cell compatibility, which can significantly reduce the bacterial survival rate and inflammatory reaction in vivo. The above results indicated that we successfully improved the antibacterial property of PEEK by a simple modification strategy, making it a promising material for anti-infection orthopedic implants.

Protein-polysaccharide-based delivery systems for enhancing the bioavailability of curcumin: A review.

In recent years, a wide attention has been paid to curcumin in medicine due to its excellent physiological activities, including anti-inflammatory, antioxidant, antibacterial, and nerve damage repair. However, the low solubility, poor stability, and rapid metabolism of curcumin make its bioavailability low, which affects its development and application. As a unique biopolymer structure, protein-polysaccharide (PRO-POL)-based delivery system has the advantages of low toxicity, biocompatibility, biodegradability, and delayed release. Many scholars have investigated PRO-POL -based delivery systems to improve the bioavailability of curcumin. In this paper, we focus on the interactions between different proteins (e.g. casein, whey protein, soybean protein isolate, pea protein, zein, etc.) and polysaccharides (chitosan, sodium alginate, hyaluronic acid, pectin, etc.) and their effects on complexes diameter, surface charge, encapsulation drive, and release characteristics. The mechanism of the PRO-POL-based delivery system to enhance the bioavailability of curcumin is highlighted. In addition, the application of PRO-POL complexes loaded with curcumin is summarized, aiming to provide a reference for the construction and application of PRO-POL delivery systems.

Application of biomolecules modification strategies on PEEK and its composites for osteogenesis and antibacterial properties.

As orthopedic and dental implants, polyetheretherketone (PEEK) is expected to be a common substitute material of titanium (Ti) and its alloys due to its good biocompatibility, chemical stability, and elastic modulus close to that of bone tissue. It could avoid metal allergy and bone resorption caused by the stress shielding effect of Ti implants, widely studied in the medical field. However, the lack of biological activity is not conducive to the clinical application of PEEK implants. Therefore, the surface modification of PEEK has increasingly become one of the research hotspots. Researchers have explored various biomolecules modification methods to effectively enhance the osteogenic and antibacterial activities of PEEK and its composites. Therefore, this review mainly summarizes the recent research of PEEK modified by biomolecules and discusses the further research directions to promote the clinical transformation of PEEK implants.