Promoting osteogenesis and bone regeneration employing icariin-loaded nanoplatforms.

There is an increasing demand for innovative strategies that effectively promote osteogenesis and enhance bone regeneration. The critical process of bone regeneration involves the transformation of mesenchymal stromal cells into osteoblasts and the subsequent mineralization of the extracellular matrix, making up the complex mechanism of osteogenesis. Icariin's diverse pharmacological properties, such as anti-inflammatory, anti-oxidant, and osteogenic effects, have attracted considerable attention in biomedical research. Icariin, known for its ability to stimulate bone formation, has been found to encourage the transformation of mesenchymal stromal cells into osteoblasts and improve the subsequent process of mineralization. Several studies have demonstrated the osteogenic effects of icariin, which can be attributed to its hormone-like function. It has been found to induce the expression of BMP-2 and BMP-4 mRNAs in osteoblasts and significantly upregulate Osx at low doses. Additionally, icariin promotes bone formation by stimulating the expression of pre-osteoblastic genes like Osx, RUNX2, and collagen type I. However, icariin needs to be effectively delivered to bone to perform such promising functions.Encapsulating icariin within nanoplatforms holds significant promise for promoting osteogenesis and bone regeneration through a range of intricate biological effects. When encapsulated in nanofibers or nanoparticles, icariin exerts its effects directly at the cellular level. Recalling that inflammation is a critical factor influencing bone regeneration, icariin's anti-inflammatory effects can be harnessed and amplified when encapsulated in nanoplatforms. Also, while cell adhesion and cell migration are pivotal stages of tissue regeneration, icariin-loaded nanoplatforms contribute to these processes by providing a supportive matrix for cellular attachment and movement. This review comprehensively discusses icariin-loaded nanoplatforms used for bone regeneration and osteogenesis, further presenting where the field needs to go before icariin can be used clinically.

Maternal quercetin supplementation improved lipopolysaccharide-induced cognitive deficits and inflammatory response in a rat model of maternal immune activation.

BACKGROUND: There is strong evidence that prenatal infection during a specific period of brain development increases the risk of neurodevelopmental disorders, partly through immune-inflammatory pathways. This suggests that anti-inflammatory agents could prevent these disorders by targeting the maternal inflammatory response. In the present study, we used a rat model of maternal immune activation (MIA) to examine whether maternal quercetin (QE) supplementation can alleviate behavioral deficits and inflammatory mediators in the prefrontal cortex (PFC) and hippocampus of adult male offspring. METHODS: Pregnant rats were supplemented with QE (50 mg/kg) or vehicle throughout pregnancy and injected with either lipopolysaccharide (0.5 mg/kg) or saline on gestational days 15/16. At postnatal day 60, we evaluated the offspring's behavior, hippocampal and prefrontal cortex glial density, pro-inflammatory gene expression, and neuronal survival. RESULTS: Our data showed that maternal QE supplementation can prevent working and recognition memory impairments in adult MIA offspring. This behavioral improvement correlates with the decrease in MIA-induced expression of pro-inflammatory genes, microglia, and astrocyte densities, without affecting neuronal survival, in both PFC and CA1 hippocampus areas. CONCLUSION: Therefore, our study supports the potential preventive effect of QE on MIA-induced behavioral dysfunctions, at least in part, by suppressing the glial-mediated inflammatory response.

Conserved features of eye movement related eardrum oscillations (EMREOs) across humans and monkeys.

Auditory and visual information involve different coordinate systems, with auditory spatial cues anchored to the head and visual spatial cues anchored to the eyes. Information about eye movements is therefore critical for reconciling visual and auditory spatial signals. The recent discovery of eye movement-related eardrum oscillations (EMREOs) suggests that this process could begin as early as the auditory periphery. How this reconciliation might happen remains poorly understood. Because humans and monkeys both have mobile eyes and therefore both must perform this shift of reference frames, comparison of the EMREO across species can provide insights to shared and therefore important parameters of the signal. Here we show that rhesus monkeys, like humans, have a consistent, significant EMREO signal that carries parametric information about eye displacement as well as onset times of eye movements. The dependence of the EMREO on the horizontal displacement of the eye is its most consistent feature, and is shared across behavioural tasks, subjects and species. Differences chiefly involve the waveform frequency (higher in monkeys than in humans) and patterns of individual variation (more prominent in monkeys than in humans), and the waveform of the EMREO when factors due to horizontal and vertical eye displacements were controlled for. This article is part of the theme issue 'Decision and control processes in multisensory perception'.

How living cells are affected during the cold atmospheric pressure plasma treatment.

When the electric discharge process is limited by high voltage electrodes shielding, the ionization measure would be controlled to less than one percent and the temperature to less than 37 °C even at atmospheric pressure, so-called cold atmospheric pressure plasma (CAP). CAP has been found to have profound medical applications in association with its reactive oxygen and nitrogen species (ROS/RNS). In this way that during plasma exposure, the subjected medium (e.g. cell cytoplasmic membrane in plasma therapy) interacts with ROS/RNS. Accordingly, a precise study of the mentioned interactions and their consequences on the cells' behavior changes, is necessary. The results lead to the reduction of possible risks and provide the opportunity of optimizing the efficacy of CAP before the development of CAP applications in the field of plasma medicine. In this report molecular dynamic (MD) simulation is used to investigate the mentioned interactions and a proper and compatible comparison with the experimental results is presented. Based on this, the effects of H2O2, NO and O2 on the living cell's membrane are investigated in biological conditions. Our results show that: i) The hydration of phospholipid polar heads would be enhanced associated with the H2O2 presence. ii) A new definition of the surface area assigned to each phospholipid (APL), more reliable and compatible with the physical expectations, is introduced. iii) The long-term behavior of NO and O2 is their penetration into the lipid bilayer and sometimes passing through the membrane into the cell. The latter would be an indication of internal cells' pathways activation leading to modification of cells' function.

Electrophysiological correlates of attentional capture in joint action.

In joint action, agents are assumed to represent their partner's task to optimize joint performance. However, the neurophysiological processes underlying the processing of the partner's task have not been widely investigated. Pairs of participants were asked to perform a joint version of a visual search task in either a cooperative or a competitive social context. During the task, one agent's neural activity was recorded using electroencephalography (EEG). The alpha-lateralization index was calculated as [(contralateral - ipsilateral)/(contralateral + ipsilateral)] × 100 to examine attentional selection or suppression of the laterally presented stimulus. A negative alpha-lateralization indicates lower alpha-band power over the contralateral sites compared with the ipsilateral sites and was related to attentional selection. A positive alpha-lateralization indicates higher alpha-band power over the contralateral sites compared with the ipsilateral sites and was related to attentional suppression. Behavioural results showed impeded search performance when the partner target was present. Furthermore, EEG time-frequency results showed that the partner target induced a negative parieto-occipital alpha-lateralization, indicating that it captured attention, when the agent target was absent. When the agent target was present, the parieto-occipital alpha-lateralization index was negative for laterally presented partner target in the cooperative and positive in the competitive social context, indicative of attentional capture in the cooperative condition and suppression of the partner target in the competitive condition. In sum, our study showed that humans tune their attentional processing towards a partner target in a joint action task. This attentional tuning was shown to be affected by social context and the presence of the agent's own target.

Conserved features of eye movement related eardrum oscillations (EMREOs) across humans and monkeys.

Auditory and visual information involve different coordinate systems, with auditory spatial cues anchored to the head and visual spatial cues anchored to the eyes. Information about eye movements is therefore critical for reconciling visual and auditory spatial signals. The recent discovery of eye movement-related eardrum oscillations (EMREOs) suggests that this process could begin as early as the auditory periphery. How this reconciliation might happen remains poorly understood. Because humans and monkeys both have mobile eyes and therefore both must perform this shift of reference frames, comparison of the EMREO across species can provide insights to shared and therefore important parameters of the signal. Here we show that rhesus monkeys, like humans, have a consistent, significant EMREO signal that carries parametric information about eye displacement as well as onset times of eye movements. The dependence of the EMREO on the horizontal displacement of the eye is its most consistent feature, and is shared across behavioral tasks, subjects, and species. Differences chiefly involve the waveform frequency (higher in monkeys than in humans) and patterns of individual variation (more prominent in monkeys than humans), and the waveform of the EMREO when factors due to horizontal and vertical eye displacements were controlled for.

Selection history and task predictability determine the precision expectations in attentional control.

Predictive processing frameworks have demonstrated the central role that prediction plays in a range of cognitive processes including bottom-up and top-down mechanisms of attention control. However, relatively little is understood about how predictive processes interact with the third main determinant of attentional priority - selection history. In this experiment, participants developed a history of either color or shape selection while we observed the impact of these histories in an additional singleton search task using behavioral measures and ERP measures of attentional control. Throughout the experiment, participants were encouraged to predict the upcoming display, but prediction errors were either high or low depending on session. Persistent group differences in our results showed that selection history contributes to the precision weighting of a stimulus, and that this is mediated by overall prediction error. Color-singleton distractors captured attention and required greater suppression when participants had a history of color selection; however, these participants gained large benefits when the upcoming stimuli were highly predictable. We suggest that selection history modulates the precision expectations for a feature in a persistent and implicit way, producing an attentional bias that predictability can help to counteract, but cannot prevent or eliminate entirely.

Gene Expression Programming Model for Tribological Behavior of Novel SiC-ZrO2-Al Hybrid Composites.

In order to improve product format quality and material flexibility, variety of application, and cost-effectiveness, SiC, ZrO2, and Al hybrid composites were manufactured in the research utilizing the powder metallurgy (PM) technique. A model was created to predict the tribological behavior of SiC-ZrO2-Al hybrid composites using statistical data analysis and gene expression programming (GEP) based on artificial intelligence. For the purpose of examining the impact of zirconia concentration, sliding distance, and applied stress on the wear behavior of hybrid composites, a comprehensive factor design of experiments was used. The developed GEP model was sufficiently robust to achieve extremely high accuracy in the prediction of the determine coefficient (R2), the root mean square error (RMSE), and the root relative square error (RRSE). The maximum state of the RMSE was 0.4357 for the GEP-1 (w1) model and the lowest state was 0.7591 for the GEP-4 (w1) model, while the maximum state of the RRSE was 0.4357 for the GEP-1 (w1) model and the minimum state was 0.3115 for the GEP-3 model (w1).

Applying extrusion-based 3D printing technique accelerates fabricating complex biphasic calcium phosphate-based scaffolds for bone tissue regeneration.

BACKGROUND: Tissue engineering (TE) is the main approach for stimulating the body's mechanisms to regenerate damaged or diseased organs. Bone and cartilage tissues due to high susceptibility to trauma, tumors, and age-related disease exposures are often need for reconstruction. Investigation on the development and applications of the novel biomaterials and methods in bone tissue engineering (BTE) is of great importance to meet emerging today's life requirements. AIM OF REVIEW: Biphasic calcium phosphates (BCPs) offer a chemically similar biomaterial to the natural bone, which can significantly promote cell proliferation and differentiation and accelerate bone formation and reconstruction. Recent advancements in the bone scaffold fabrication have led to employing additive manufacturing (AM) methods. Extrusion-based 3D printing, known also as robocasting method, is one of the extensively used AM techniques in BTE applications. This review discusses materials and methods utilized for BCP robocasting. KEY SCIENTIFIC CONCEPTS OF REVIEW: Recent advancements and existing challenges in the use of additives for bioink preparation are critically discussed. Commercialization and marketing approach, post-processing steps, clinical applications, in-vitro and in-vivo evaluations beside the biological responses are also reviewed. Finally, possible strategies and opportunities for the use of BCP toward injured bone regeneration are discussed.

The Analysis of SNPs' Function in miR-21 and miR146a/b in Multiple Sclerosis and Active Lesions: An In Silico Study.

Multiple sclerosis (MS) is a central nervous disorder caused by several factors. Studies have recently shown that non-coding RNA such as miRNA could participate in MS initiation, progression, and active lesion. This study aims to theoretically analyze the potential impact of single-nucleotide polymorphisms (SNPs) on mir-21 and mir-146a/b, which has been previously demonstrated as MS microRNA signature. To fulfill this purpose, the SNPs were investigated for functionality through several online tools, including miRNA-SNP, SNP2-TFBS, RBP-Var, and RNAfold. Furthermore, SNPs of miR-21 and miR-146a/b that exist in pre-miRNA, mature miRNA, and promoter area were extracted; moreover, miRNA and RNA-binding protein interactions were analyzed. This article presented a list of validated SNPs that could affect the expression or function of miR-21 and miR-146a/b for the future practical study of MS and active lesions.

Combined influences of strategy and selection history on attentional control.

Visual attention is guided by top-down mechanisms and pre-stimulus task preparation, but also by selection history (i.e., the bias to prioritize previously attended items). Here we examine how these influences combine. Two groups of participants completed two intermingled tasks. One task involved categorization of a unique target; one group categorized the target based on color, and the other based on shape. The other task involved searching for a target defined by unique shape while ignoring a distractor defined by unique color. Our expectation was that the search task would be difficult for the color-categorization group because their categorization task required attentional resolution of color, but the search task required that they ignore color. In some experimental blocks, trials from the two tasks appeared predictably, giving the color-categorization group an opportunity to strategically prepare by switching between color-prioritizing and shape-prioritizing attentional templates. We looked to pre-stimulus oscillatory activity as a direct index of this preparation, and to reaction times and post-stimulus ERPs for markers of resultant change in attentional deployment. Results showed that preparation in the color-categorization group optimized attentional templates, such that these participants became less sensitive to the color distractor in the search task. But preparation was not sufficient to entirely negate the influence of selection history, and participants in the color-categorization group continued to show a propensity to attend to the color distractor. These results indicate that preparatory effort can be scaled to the anticipated attentional requirements, but attention is nevertheless considerably biased by selection history.

Improvement of clinical outcome, laboratory findings and inflammatory cytokines levels using plasmapheresis therapy in severe COVID-19 cases.

INTRODUCTION: Cytokine storm is one of the consequences of the severe forms of COVID-19 due to excessive immune response. In this study, we investigated the therapeutic effect of plasmapheresis and its role on the inflammatory cytokines levels in patients suffering from severe COVID-19. METHODS: In plasmapheresis group, 22 severe cases of COVID-19 receiving three cycles of plasmapheresis with time interval of 24-36 h and 22 COVID-19 patients as the control group were enrolled. Clinical history and laboratory parameters as well as IL-1, IL-6, IFN-γ and IL-17 cytokines serum levels in the time points of before and after plasmapheresis were studied. RESULTS: In severe COVID-19 patients, plasmapheresis significantly improved clinical and laboratory parameters such as cough, weakness, fever, blood oxygen saturation and CRP levels. Serum levels of IL-1, IL-6, IFN-γ and IL-17 in the group of patients receiving plasmapheresis, had a significant decrease following plasmapheresis courses. Although only IL-6 level in the control group had a significant decrease between the days 1-14 of disease. Also, at both time points of before and after plasmapheresis, serum levels of IL-1, IL-6, IFN-γ and IL-17 were inversely correlated to blood oxygen saturation. CONCLUSION: Based on the obtained results, plasmapheresis therapy in severe forms of COVID-19 can effectively improve the clinical symptoms of the disease and reduce inflammatory markers. Therefore, it is suggested that plasmapheresis can be evaluated in standard treatment protocols for severe forms of COVID-19.

In silico Analysis of Polymorphisms in microRNAs Deregulated in Alzheimer Disease.

BACKGROUND: Alzheimer's disease (AD) is a degenerative condition characterized by progressive cognitive impairment and dementia. Findings have revolutionized current knowledge of miRNA in the neurological conditions. Two regulatory mechanisms determine the level of mature miRNA expression; one is miRNA precursor processing, and the other is gene expression regulation by transcription factors. This study is allocated to the in-silico investigation of miRNA's SNPs and their effect on other cell mechanisms. METHODS: We used databases which annotate the functional effect of SNPs on mRNA-miRNA and miRNA-RBP interaction. Also, we investigated SNPs which are located on the promoter or UTR region. RESULTS: miRNA SNP3.0 database indicated several SNPs in miR-339 and miR-34a in the upstream and downstream of pre-miRNA and mature miRNAs. While, for some miRNAs miR-124, and miR-125, no polymorphism was observed, and also miR-101 with ΔG -3.1 and mir-328 with ΔG 5.8 had the highest and lowest potencies to produce mature microRNA. SNP2TFBS web-server presented several SNPs which altered the Transcription Factor Binding Sites (TFBS) or generated novel TFBS in the promoter regions of related miRNA. At last, RBP-Var database provided a list of SNPs which alter miRNA-RBP interaction pattern and can also influence other miRNAs' expression. DISCUSSION: The results indicated that SNPs microRNA affects both miRNA function and miRNA expression. Our study expands molecular insight into how SNPs in different parts of miRNA, including the regulatory (promoter), the precursor (pre-miRNA), functional regions (seed region of mature miRNA), and RBP-binding motifs, which theoretically may be correlated to the Alzheimer's disease.

Anesthetic efficacy of ketamine-diazepam, ketamine-xylazine, and ketamine-acepromazine in Caspian Pond turtles (Mauremys caspica).

OBJECTIVES: The objective of this study was to assess the efficacy of different anesthetic drug combinations on the Caspian Pond turtles (Mauremys caspica). SUBJECTS AND METHODS: Three groups of the Caspian Pond turtles (n = 6) were anesthetized with three different drug combinations. Initially, a pilot study was conducted to determine the best drug doses for the anesthetization of the turtles, and according to these results, ketamine-diazepam (120 mg/kg ketamine hydrochloride [5%] and 2 mg/kg diazepam [5%]), ketamine-acepromazine (120 mg/kg ketamine hydrochloride [5%] and 1 mg/kg acepromazine [1%]), and ketamine-xylazine (120 mg/kg ketamine hydrochloride [5%] and 1 mg/kg xylazine [2%]) were injected intramuscularly. The onset times of anesthetization and the recovery time were measured. Statistical analysis of the data was performed using one-way analysis of variance followed by t-tests, and P < 0.05 was considered statistically significant. RESULTS: There were statistically significant differences in the mean of the onset times of anesthesia and recovery time among the three drug combinations depending on the treatment used. The onset of anesthesia of the animals treated with the ketamine-diazepam combination was 60% and 42% shorter, for male and female turtles, respectively, compared to that obtained with the ketamine-acepromazine combination and 64% (male turtles) and 50% (female turtles) shorter than that obtained with the ketamine-xylazine combination. Further, the recovery time, in male turtles, was 17% shorter in animals treated with the first drug combination than those treated with the ketamine-acepromazine combination and 37% shorter than those treated with the ketamine-xylazine combination. The recovery time, in female turtles, did not seem to be significantly different among treatments. CONCLUSIONS: The study showed that the ketamine-diazepam drug combination is the anesthetic combination with the fastest onset time and shortest recovery time.

Effect of electric charging on the velocity of water flow in CNT.

The role of electrical charge in controlling the velocity of water molecules in a finite single-walled carbon nanotube (CNT) was studied in detail using molecular dynamics simulation. Different test cases were examined to determine the parameters affecting the control of water-flow velocity in CNT upon electrically charging the surface of a CNT. The results showed that charge magnitude and volume, as well as the charging scenario, are the parameters having greatest effect. The implementation of electric charge on the surface of a CNT was demonstrated to decrease the resistance of CNT to incoming water flow at the entrance, but to increase friction-type resistance to flow along the CNT. Therefore, through controlling the magnitude of electric charge, water flow through the CNT may be accelerated, or decelerated. The results show that the velocity of molecular flow in the CNT increases to a maximum value, and then decreases with electric charge regardless of its sign. In the case studied here, this maximum velocity occurs at electric charging of ±0.25e/atom. It was also shown that, to reach similar flow velocities in a CNT, it is not sufficient to merely implement equal volumes of electric charge, where the volume of electric charging is defined as charge magnitude × charging time. In fact , both magnitude of charging and volume of electric charging must be equal to each other. These findings, together with options to implement scenarios with alternative charging, provide the means to effectively adjust desired velocities in a CNT.

Investigation on the effect of different levels of dried sweet orange (Citrus sinensis) pulp on performance, carcass characteristics and physiological and biochemical parameters in broiler chicken.

Utilization of agricultural by-products in animal nutrition is a matter of great concern. Dried sweet orange (Citrus sinensis) pulp (DCSP) is a potential source of valuable nutrients and natural antioxidants for poultry feed. In the experiment, a feeding trial was conducted in order to investigate the effect of different levels of dried orange residues in diet on broiler growth performance, carcass characteristics, blood metabolites, humoral immunity, and cecum microbial population. A total of 200 one day experimental broiler chicks were distributed into a completely randomized design (CRD) which included 5 dietary treatments with 4 replicates per each treatment and 10 birds fed in each replicate. The experimental treatments consist of a control group (without additive), 0.5%, 1.0%, 1.5%, and 2% of DCSP (residue) in diet. Weight gain, feed intake and feed conversion ratio (FCR) were measured. Blood parameters and carcass traits were measured in the postnatal 35th day. The highest level of dried orange residues in treatment 5 (T5) had significantly increased the feed intake and body weight of broilers in groups and overall during the rearing period (P > 0.05). Different levels of dried orange residues had no significant effect on chicken FCR. Using of dried orange residues significantly decreased the liver and abdominal fat of broilers (P < 0.05). T5 has also significantly lower level of triglyceride than the control (T1) and treatment 2 (T2) (P < 0.05). In conclusion, the use of dried orange residues improved some performance (e.g. feed intake and body weight gain), decreased liver and abdominal fat and also serum triglyceride level in broiler chicken.