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1.
Mol Cell Biochem ; 2024 May 25.
Article En | MEDLINE | ID: mdl-38795212

Radiotherapy is the conventional treatment for pelvic abdominal tumors. However, it can cause some damage to the small intestine and colorectal, which are very sensitive to radiation. Radiation-induced intestinal injury (RIII) affects the prognosis of radiotherapy, causing sequelae of loss of function and long-term damage to patients' quality of life. Swertiamarin is a glycoside that has been reported to prevent a variety of diseases including but not limited to diabetes, hypertension, atherosclerosis, arthritis, malaria, and abdominal ulcers. However, its therapeutic effect and mechanism of action on RIII have not been established. We investigated whether swertiamarin has a protective effect against RIII. In this article, we use irradiator to create cellular and mouse models of radiation damage. Preventive administration of swertiamarin could reduce ROS and superoxide anion levels to mitigate the cellular damage caused by radiation. Swertiamarin also attenuated RIII in mice, as evidenced by longer survival, less weight loss and more complete intestinal barrier. We also found an increase in the relative abundance of primary bile acids in irradiated mice, which was reduced by both FXR agonists and swertiamarin, and a reduction in downstream interferon and inflammatory factors via the cGAS-STING pathway to reduce radiation-induced damage.

2.
Microbiol Res ; 285: 127775, 2024 May 21.
Article En | MEDLINE | ID: mdl-38788350

Vibrio alginolyticus is one of the most common opportunistic pathogens in marine animals and humans. In this study, A transposon mutation library of the V. alginolyticus E110 was used to identify motility-related genes, and we found three flagellar and one capsular polysaccharide (CPS) synthesis-related genes were linked to swarming motility. Then, gene deletion and complementation further confirmed that CPS synthesis-related gene ugd is involved in the swarming motility of V. alginolyticus. Phenotype assays showed that the Δugd mutant reduced CPS production, decreased biofilm formation, impaired swimming ability, and increased cytotoxicity compared to the wild-type strain. Transcriptome analysis showed that 655 genes (15%) were upregulated and 914 genes (21%) were downregulated in the Δugd strain. KEGG pathway and heatmap analysis revealed that genes involved in two-component systems (TCSs), chemotaxis, and flagella assembly pathways were downregulated in the Δugd mutant. On the other hand, genes involved in pathways of human diseases, biosynthesis ABC transporters, and metabolism were upregulated in the Δugd mutant. The RT-qPCR further validated that ugd-regulated genes are associated with motility, biofilm formation, virulence, and TCSs. These findings imply that ugd may be an important player in the control of some physiological processes in V. alginolyticus, highlighting its potential as a target for future research and potential therapeutic interventions.

3.
Arch Virol ; 169(6): 127, 2024 May 24.
Article En | MEDLINE | ID: mdl-38789713

Herpesviruses adhere to a precise temporal expression model in which immediate-early (IE) genes play a crucial role in regulating the viral life cycle. However, there is a lack of functional research on the IE genes in Ictalurid herpesvirus 1 (IcHV-1). In this study, we identified the IcHV-1 ORF24 as an IE gene via a metabolic inhibition assay, and subcellular analysis indicated its predominant localisation in the nucleus. To investigate its function, we performed yeast reporter assays using an ORF24 fusion protein containing the Gal4-BD domain and found that BD-ORF24 was able to activate HIS3/lacZ reporter genes without the Gal4-AD domain. Our findings provide concrete evidence that ORF24 is indeed an IE gene that likely functions as a transcriptional regulator during IcHV-1 infection. This work contributes to our understanding of the molecular mechanisms underlying fish herpesvirus IE gene expression.


Gene Expression Regulation, Viral , Genes, Immediate-Early , Animals , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Immediate-Early Proteins/genetics , Immediate-Early Proteins/metabolism , Viral Proteins/genetics , Viral Proteins/metabolism , Transcription, Genetic
4.
Chin Med ; 19(1): 73, 2024 May 22.
Article En | MEDLINE | ID: mdl-38778375

BACKGROUND: The restoration of cerebrovascular regulation and improvement of cerebral blood flow in ischaemic regions are crucial for improving the clinical prognosis after stroke. An-Gong-Niu-Huang-Wan (AGNHW) is a famous traditional compound Chinese medicine that has been used for over 220 years to treat acute ischaemic stroke; however, its role in the regulation of cerebral blood flow is still unclear. The aim of the present study was to investigate the regulatory effect of AGNHW on cerebral blood flow and microcirculation after ischaemic stroke and to elucidate the underlying mechanisms involved. METHODS: Male C57BL/6 mice were subjected to distal middle cerebral artery occlusion (dMCAO) and randomly assigned to the sham, MCAO, or AGNHW groups. AGNHW was administered intragastrically 1 h after dMCAO. The rotarod test was utilized to evaluate behavioural function; TTC was used to determine the infarct volume; and ischaemic injury was assessed by detecting brain levels of SOD, MDA and NO. Then, cortical perfusion and acetazolamide-induced cerebrovascular reactivity were assessed using laser speckle contrast imaging, and the velocity and flux of red blood cells in cortical capillaries were detected using two-photon laser scanning microscopy. In addition, we employed RNA-Seq to identify variations in gene expression profiles and assessed endothelium-dependent changes in microcirculatory dysfunction by measuring vasoactive mediator levels. RESULTS: AGNHW significantly increased cerebral blood flow, reduced the infarct volume, and promoted functional recovery after cerebral ischaemia. AGNHW increased the velocity and flux of red blood cells in capillaries and improved cerebrovascular reactivity in the ischaemic cortex. Furthermore, AGNHW regulated endothelium-dependent microcirculation, as evidenced by decreases in the expression of endothelins (Edn1, Edn3 and Ednrb) and the ratios of brain and serum TXB2/6-keto-PGF1α and ET-1/CGRP. CONCLUSIONS: AGNHW improved cerebral hypoperfusion, regulated cerebrovascular reactivity and attenuated microcirculatory dysfunction within the ischaemic cortex after stroke. This outstanding effect was achieved by modulating the expression of genes related to vascular endothelial cell function and regulating endothelium-dependent vasoactive mediators.

5.
Toxicology ; : 153836, 2024 May 18.
Article En | MEDLINE | ID: mdl-38768702

Caramel color is a widely used food pigment, and 2-Acetyl-4-tetrahydroxybutylimidazole (THI) is a by-products of Class III caramel color. Some studies have shown that THI can reduce the number of peripheral blood lymphocytes. However, the comprehensive mechanism of THI immunotoxicity requires further study. In this study, the effects of THI on lymphocyte count, humoral immunity, cellular immunity and nonspecific immunity were determined and the effect of the nutritional status of VB6 on THI immunotoxicity was evaluated. Female BALB/c mice were divided into 3 groups and fed chow containing different doses of VB6: VB6-normal (6mg/kg VB6), VB6-deprived (0.5mg/kg VB6) or VB6-enhanced (12mg/kg VB6) feed. Each group was further divided into 4 subgroups and treated with THI (0.5, 2.5 or 12.5mg/kg bw) or the solvent control by gavage for 30 days. The thymic cortical thickness was measured with ViewPoint; the proportions of major immune cells and T cells in peripheral blood and tissues were detected via flow cytometry; the transformation and proliferation abilities of T and B cells were detected via T and B lymphocyte proliferation assays; NK cell activity was assessed via lactate dehydrogenase assays; humoral immune function was assessed via plaque-forming cell assays; and the immune function of T lymphocytes was assessed via delayed type hypersensitivity assays. The results showed that compared with those in the corresponding control group, the white blood cell count and lymphocyte count decreased significantly in all the VB6-deprived groups, in the 2.5 and 12.5mg/kg VB6 groups, and in the 12.5mg/kg VB6-enhanced group. With increasing THI dose, the thymic cortical layer became thinner. In the thymus, THI increased the proportions of CD3+ T cells and mature CD8+ T cells and decreased the proportions of immature double-positive, double-negative T cells and CD69-expressing lymphocytes. The proportions of naïve T cells and Tcm (central memory T) cells related to homing decreased. The proportion of mature T cells in the spleen decreased significantly. The proliferation of T cells stimulated by ConA decreased after THI exposure. VB6-deficient mice were more sensitive to THI immunotoxicity, and supplementation with VB6 had a certain protective effect on these mice. The results of the PFC and NK cell activity assays indicated that THI exposure might not affect humoral immune or innate immune function.

6.
FASEB J ; 38(10): e23668, 2024 May 31.
Article En | MEDLINE | ID: mdl-38742811

Podocyte injury plays a critical role in the progression of diabetic kidney disease (DKD), but the underlying cellular and molecular mechanisms remain poorly understanding. MicroRNAs (miRNAs) can disrupt gene expression by inducing translation inhibition and mRNA degradation, and recent evidence has shown that miRNAs may play a key role in many kidney diseases. In this study, we identified miR-4645-3p by global transcriptome expression profiling as one of the major downregulated miRNAs in high glucose-cultured podocytes. Moreover, whether DKD patients or STZ-induced diabetic mice, expression of miR-4645-3p was also significantly decreased in kidney. In the podocytes cultured by normal glucose, inhibition of miR-4645-3p expression promoted mitochondrial damage and podocyte apoptosis. In the podocytes cultured by high glucose (30 mM glucose), overexpression of miR-4645-3p significantly attenuated mitochondrial dysfunction and podocyte apoptosis induced by high glucose. Furthermore, we found that miR-4645-3p exerted protective roles by targeting Cdk5 inhibition. In vitro, miR-4645-3p obviously antagonized podocyte injury by inhibiting overexpression of Cdk5. In vivo of diabetic mice, podocyte injury, proteinuria, and impaired renal function were all effectively ameliorated by treatment with exogenous miR-4645-3p. Collectively, these findings demonstrate that miR-4645-3p can attenuate podocyte injury and mitochondrial dysfunction in DKD by targeting Cdk5. Sustaining the expression of miR-4645-3p in podocytes may be a novel strategy to treat DKD.


Cyclin-Dependent Kinase 5 , Diabetes Mellitus, Experimental , Diabetic Nephropathies , Mice, Inbred C57BL , MicroRNAs , Mitochondria , Podocytes , Podocytes/metabolism , Podocytes/pathology , Animals , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Diabetic Nephropathies/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Mice , Mitochondria/metabolism , Male , Humans , Diabetes Mellitus, Experimental/metabolism , Cyclin-Dependent Kinase 5/metabolism , Cyclin-Dependent Kinase 5/genetics , Apoptosis , Glucose
7.
Article En | MEDLINE | ID: mdl-38711438

Poria sini decoction (PSD), a significant traditional Chinese herbal formula, is effective in liver cancer (LC) and chronic heart failure (CHF); however, little is known about its concurrent targeting mechanism. Methods. This study analyzed the potential molecular mechanism of PSD against the two distinct diseases using network pharmacology approaches, including multidatabase search, pharmacokinetic screening, network construction analysis, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and molecular docking to elaborate the active components, signaling pathways, and potential mechanisms of PSD in the treatment of both LC and CHF. Results. A total of 155 active components and 193 potential targets in PSD were identified. Bioinformatics analysis revealed that quercetin, isorhamnetin, and naringenin, etc. may be potential candidate agents. TNF, AKT1, and IL6, etc. could become potential therapeutic targets. TNF-α, NF-κB, PI3K-AKT, and TRP signaling pathways might play an important role in PSD against LC and CHF. Molecular docking results showed that most screened active compounds could embed itself into target proteins with a high binding affinity, and the hydrogen bonds number ≥3 indicated a more stable conformation of the compounds and target proteins. Overall, quercetin and isorhamnetin were the main active components, and TNF and AKT1 were the primary targets for PSD treatment of LC and CHF. Conclusions. This study illustrated that quercetin contained in PSD played an important role in the treatment of LC and CHF by acting on the key gene of TP53 and downregulating the PI3K-AKT signaling pathway.

8.
Nat Commun ; 15(1): 3782, 2024 May 06.
Article En | MEDLINE | ID: mdl-38710678

Thermoelectrics have great potential for use in waste heat recovery to improve energy utilization. Moreover, serving as a solid-state heat pump, they have found practical application in cooling electronic products. Nevertheless, the scarcity of commercial Bi2Te3 raw materials has impeded the sustainable and widespread application of thermoelectric technology. In this study, we developed a low-cost and earth-abundant PbS compound with impressive thermoelectric performance. The optimized n-type PbS material achieved a record-high room temperature ZT of 0.64 in this system. Additionally, the first thermoelectric cooling device based on n-type PbS was fabricated, which exhibits a remarkable cooling temperature difference of ~36.9 K at room temperature. Meanwhile, the power generation efficiency of a single-leg device employing our n-type PbS material reaches ~8%, showing significant potential in harvesting waste heat into valuable electrical power. This study demonstrates the feasibility of sustainable n-type PbS as a viable alternative to commercial Bi2Te3, thereby extending the application of thermoelectrics.

9.
Cell Metab ; 2024 May 02.
Article En | MEDLINE | ID: mdl-38718794

Although mechanical loading is essential for maintaining bone health and combating osteoporosis, its practical application is limited to a large extent by the high variability in bone mechanoresponsiveness. Here, we found that gut microbial depletion promoted a significant reduction in skeletal adaptation to mechanical loading. Among experimental mice, we observed differences between those with high and low responses to exercise with respect to the gut microbial composition, in which the differential abundance of Lachnospiraceae contributed to the differences in bone mechanoresponsiveness. Microbial production of L-citrulline and its conversion into L-arginine were identified as key regulators of bone mechanoadaptation, and administration of these metabolites enhanced bone mechanoresponsiveness in normal, aged, and ovariectomized mice. Mechanistically, L-arginine-mediated enhancement of bone mechanoadaptation was primarily attributable to the activation of a nitric-oxide-calcium positive feedback loop in osteocytes. This study identifies a promising anti-osteoporotic strategy for maximizing mechanical loading-induced skeletal benefits via the microbiota-metabolite axis.

10.
Curr Biol ; 34(9): 1918-1929.e5, 2024 05 06.
Article En | MEDLINE | ID: mdl-38636514

The insular cortex, or insula, is a large brain region involved in the detection of thirst and the regulation of water intake. However, our understanding of the topographical, circuit, and molecular mechanisms for controlling water intake within the insula remains parcellated. We found that type-1 cannabinoid (CB1) receptors in the insular cortex cells participate in the regulation of water intake and deconstructed the circuit mechanisms of this control. Topographically, we revealed that the activity of excitatory neurons in both the anterior insula (aIC) and posterior insula (pIC) increases in response to water intake, yet only the specific removal of CB1 receptors in the pIC decreases water intake. Interestingly, we found that CB1 receptors are highly expressed in insula projections to the basolateral amygdala (BLA), while undetectable in the neighboring central part of the amygdala. Thus, we recorded the neurons of the aIC or pIC targeting the BLA (aIC-BLA and pIC-BLA) and found that they decreased their activity upon water drinking. Additionally, chemogenetic activation of pIC-BLA projection neurons decreased water intake. Finally, we uncovered CB1-dependent short-term synaptic plasticity (depolarization-induced suppression of excitation [DSE]) selectively in pIC-BLA, compared with aIC-BLA synapses. Altogether, our results support a model where CB1 receptor signaling promotes water intake by inhibiting the pIC-BLA pathway, thereby contributing to the fine top-down control of thirst responses.


Drinking , Insular Cortex , Receptor, Cannabinoid, CB1 , Animals , Receptor, Cannabinoid, CB1/metabolism , Male , Mice , Drinking/physiology , Insular Cortex/physiology , Cannabinoids/metabolism , Cannabinoids/pharmacology , Neurons/physiology , Neurons/metabolism , Mice, Inbred C57BL , Neuronal Plasticity/physiology , Basolateral Nuclear Complex/physiology , Basolateral Nuclear Complex/metabolism
11.
Sci Prog ; 107(2): 368504241232537, 2024.
Article En | MEDLINE | ID: mdl-38567422

Nasopharyngeal carcinoma is a malignant tumor that occurs in the epithelium and mucosal glands of the nasopharynx, and its pathological type is mostly poorly differentiated squamous cell carcinoma. Since the nasopharynx is located deep in the head and neck, early diagnosis and timely treatment are critical to patient survival. However, nasopharyngeal carcinoma tumors are small in size and vary widely in shape, and it is also a challenge for experienced doctors to delineate tumor contours. In addition, due to the special location of nasopharyngeal carcinoma, complex treatments such as radiotherapy or surgical resection are often required, so accurate pathological diagnosis is also very important for the selection of treatment options. However, the current deep learning segmentation model faces the problems of inaccurate segmentation and unstable segmentation process, which are mainly limited by the accuracy of data sets, fuzzy boundaries, and complex lines. In order to solve these two challenges, this article proposes a hybrid model WET-UNet based on the UNet network as a powerful alternative for nasopharyngeal cancer image segmentation. On the one hand, wavelet transform is integrated into UNet to enhance the lesion boundary information by using low-frequency components to adjust the encoder at low frequencies and optimize the subsequent computational process of the Transformer to improve the accuracy and robustness of image segmentation. On the other hand, the attention mechanism retains the most valuable pixels in the image for us, captures the remote dependencies, and enables the network to learn more representative features to improve the recognition ability of the model. Comparative experiments show that our network structure outperforms other models for nasopharyngeal cancer image segmentation, and we demonstrate the effectiveness of adding two modules to help tumor segmentation. The total data set of this article is 5000, and the ratio of training and verification is 8:2. In the experiment, accuracy = 85.2% and precision = 84.9% can show that our proposed model has good performance in nasopharyngeal cancer image segmentation.


Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Carcinoma/diagnostic imaging , Epithelium , Neck
12.
Comput Biol Med ; 174: 108453, 2024 May.
Article En | MEDLINE | ID: mdl-38636327

PURPOSE: Biopsies play a crucial role in determining the classification and staging of tumors. Ultrasound is frequently used in this procedure to provide real-time anatomical information. Using augmented reality (AR), surgeons can visualize ultrasound data and spatial navigation information seamlessly integrated with real tissues. This innovation facilitates faster and more precise biopsy operations. METHODS: We have developed an augmented reality biopsy navigation system characterized by low display latency and high accuracy. Ultrasound data is initially read by an image capture card and streamed to Unity via net communication. In Unity, navigation information is rendered and transmitted to the HoloLens 2 device using holographic remoting. Concurrently, a retro-reflective tool tracking method is implemented on the HoloLens 2, enabling the simultaneous tracking of the ultrasound probe and biopsy needle. Distinct navigation information is provided during in-plane and out-of-plane punctuation. To evaluate the effectiveness of our system, we conducted a study involving ten participants, assessing puncture accuracy and biopsy time in comparison to traditional methods. RESULTS: Ultrasound image was streamed from the ultrasound device to augmented reality headset with 122.49±11.61ms latency, while only 16.22±11.25ms was taken after data acquisition from image capture card. Navigation accuracy reached 1.23±0.68mm in the image plane and 0.95±0.70mm outside the image plane, within a depth range of 200 millimeters. Remarkably, the utilization of our system led to 98% and 95% success rate in out-of-plane and in-plane biopsy, among ten participants with little ultrasound experience. CONCLUSION: To sum up, this paper introduces an AR-based ultrasound biopsy navigation system characterized by high navigation accuracy and minimal latency. The system provides distinct visualization contents during in-plane and out-of-plane operations according to their different characteristics. Use case study in this paper proved that our system can help young surgeons perform biopsy faster and more accurately.


Augmented Reality , Humans , Ultrasonography/methods , Ultrasonography/instrumentation , Image-Guided Biopsy/instrumentation , Image-Guided Biopsy/methods
13.
bioRxiv ; 2024 Mar 12.
Article En | MEDLINE | ID: mdl-38558985

Ingestive behavior is driven by negative internal hunger and thirst states, as well as by positive expected rewards. Although the neural substrates underlying feeding and drinking behaviors have been widely investigated, they have primarily been studied in isolation, even though eating can also trigger thirst, and vice versa. Thus, it is still unclear how the brain encodes body states, recalls the memory of food and water reward outcomes, generates feeding/drinking motivation, and triggers ingestive behavior. Here, we developed an INstrument for Gauging Eating and Thirst (INGEsT), a custom-made behavioral chamber which allows for precise measurement of both feeding and drinking by combining a FED3 food dispenser, lickometers for dispensing liquid, a camera for behavioral tracking, LED light for optogenetics, and calcium imaging miniscope. In addition, in vivo calcium imaging, optogenetics, and video recordings are well synchronized with animal behaviors, e.g., nose pokes, pellet retrieval, and water licking, by using a Bpod microprocessor and timestamping behavioral and imaging data. The INGEsT behavioral chamber enables many types of experiments, including free feeding/drinking, operant behavior to obtain food or water, and food/water choice behavior. Here, we tracked activity of insular cortex and mPFC Htr3a neurons using miniscopes and demonstrate that these neurons encode many aspects of ingestive behavior during operant learning and food/water choice and that their activity can be tuned by internal state. Overall, we have built a platform, consisting of both hardware and software, to precisely monitor innate ingestive, and learned operant, behaviors and to investigate the neural correlates of self-motivated and learned feeding/drinking behaviors.

14.
ACS Omega ; 9(16): 18119-18126, 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38680373

The wedge-shaped sample cell, by offering a comprehensive representation of scattering information in turbid media, significantly enhances the informational content conveyed by spectral images compared to flat sample cells. To further refine the accuracy of turbid medium component detection utilizing wedge-shaped sample cells, this work undertakes modeling and analysis of the influence of different wedge angles on detection precision. In this study, employing a 5° gradient in the incident angle of light, we investigate the impact of incident angles ranging from 10 to 45° on the turbid medium component analysis. Validation experiments are performed by utilizing solutions of Indian ink and fat emulsion at varying ratios. Experimental findings demonstrate that under identical experimental conditions, the wedge-shaped sample cell model at an incident angle of 35° yields optimal analysis results. Utilizing partial least-squares regression (PLSR) for the corresponding optical parameters, the highest value of Rp reached 0.980, with an RMSEP of 0.002. When compared to the model with a 30° incident angle, Rp increased by 0.033, and RMSEP decreased by 0.008. In comparison to the flat sample cell model, Rp increased by 0.041, and RMSEP decreased by 0.004. This study, through continuous variation of wedge angles and PLSR modeling and prediction, further enhances the accuracy of turbid medium component detection, laying an experimental foundation for subsequent analysis of turbid medium components based on wedge-shaped sample cells.

15.
Sci Bull (Beijing) ; 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38688741

Thermoelectric materials have a wide range of application because they can be directly used in refrigeration and power generation. And the Bi2Te3 stand out because of its excellent thermoelectric performance and are used in commercial thermoelectric devices. However, n-type Bi2Te3 has seriously hindered the development of Bi2Te3-based thermoelectric devices due to its weak mechanical properties and inferior thermoelectric performance. Therefore, it is urgent to develop a high-performance n-type Bi2Te3 polycrystalline. In this work, we employed interstitial Cu and the hot deformation process to optimize the thermoelectric properties of Bi2Te2.7Se0.3, and a high-performance thermoelectric module was fabricated based on this material. Our combined theoretical and experimental effort indicates that the interstitial Cu reduce the defect density in the matrix and suppresses the donor-like effect, leading to a lattice plainification effect in the material. In addition, the two-step hot deformation process significantly improves the preferred orientation of the material and boosts the mobility. As a result, a maximum ZT of 1.27 at 373 K and a remarkable high ZTave of 1.22 across the temperature range of 300-425 K are obtained. The thermoelectric generator (TEG, 7-pair) and thermoelectric cooling (TEC, 127-pair) modules were fabricated with our n-type textured Cu0.01Bi2Te2.7Se0.3 coupled with commercial p-type Bi2Te3. The TEC module demonstrates superior cooling efficiency compared with the commercial Bi2Te3 device, achieving a ΔT of 65 and 83.4 K when the hot end temperature at 300 and 350 K, respectively. In addition, the TEG module attains an impressive conversion efficiency of 6.5% at a ΔT of 225 K, which is almost the highest value among the reported Bi2Te3-based TEG modules.

16.
ACS Appl Mater Interfaces ; 16(12): 14548-14560, 2024 Mar 27.
Article En | MEDLINE | ID: mdl-38501200

The triply periodic minimal surface (TPMS) is a highly useful structure for bone tissue engineering owing to its nearly nonexistent average surface curvature, high surface area-to-volume ratio, and exceptional mechanical energy absorption properties. However, limited literature is available regarding bionic zirconia implants using the TPMS structure for bone regeneration. Herein, we employed the digital light processing (DLP) technology to fabricate four types of zirconia-based TPMS structures: P-cell, S14, IWP, and Gyroid. For cell proliferation, the four porous TPMS structures outperformed the solid zirconia group (P-cell > S14 > Gyroid > IWP > ZrO2). In vitro assessments on the biological responses and osteogenic properties of the distinct porous surfaces identified the IWP and Gyroid structures as promising candidates for future clinical applications of porous zirconia implants because of their superior osteogenic capabilities (IWP > Gyroid > S14 > P-cell > ZrO2) and mechanical properties (ZrO2 > IWP > Gyroid > S14 > P-cell). Furthermore, the physical properties of the IWP/Gyroid surface had more substantial effects on bone immune regulation by reducing macrophage M1 phenotype polarization while increasing M2 phenotype polarization compared with the solid zirconia surface. Additionally, the IWP and Gyroid groups exhibited enhanced immune osteogenesis and angiogenesis abilities. Collectively, these findings highlight the substantial impact of topology on bone/angiogenesis and immune regulation in promoting bone integration.


Angiogenesis , Osseointegration , Zirconium , Porosity , Biocompatible Materials/pharmacology , Printing, Three-Dimensional
17.
Front Pharmacol ; 15: 1355774, 2024.
Article En | MEDLINE | ID: mdl-38515844

Minocycline is a tetracycline commonly used for several dermatological diseases. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but severe adverse event which can be caused by minocycline. An 18-year-old male patient developed fever, acute rash, pharyngeal pain, lymphadenopathy, hematologic abnormalities, increased creatinine level, elevated liver enzyme levels, and splenomegaly 4 weeks after the oral treatment of minocycline, 100 mg daily, for acne. Once diagnosed with DRESS syndrome, intravenous methylprednisolone was applied and his clinical manifestations and laboratory results remarkably improved. Then, a total of 13 DRESS syndrome cases induced by minocycline were reviewed and their clinical characteristics were summarized. In these cases, only two patient (15.4%) was present with pharynx involved. In conclusion, we reported a rare minocycline-induced DRESS syndrome who developed fever, eosinophilia, acute rash, pharyngitis, lymphadenopathy, acute kidney injury, hepatitis, and splenomegaly. Our report provides detailed clinical features of minocycline-induced DRESS syndrome, which helps us further understand this severe adverse event.

18.
Inflammation ; 2024 Mar 22.
Article En | MEDLINE | ID: mdl-38517649

Ankylosing spondylitis (AS) is a common chronic progressive inflammatory autoimmune disease. T helper 17 (Th17) cells are the major effector cells mediating AS inflammation. Histone 3 Lys 27 trimethylation (H3K27me3) is an inhibitory histone modification that silences gene transcription and plays an important role in Th17 differentiation. The objective of this study was to investigate the expression of H3K27me3 in patients with AS and to explore its epigenetic regulation mechanism of Th17 differentiation during AS inflammation. We collected serum samples from 45 patients with AS at various stages and 10 healthy controls to measure their Interleukin-17 (IL-17) levels using ELISA. A quantitative polymerase chain reaction was used to quantify the mRNA levels of RORc and the signaling molecules of the JAK2/STAT3 pathway, JMJD3, and EZH2. Additionally, Western blot analysis was performed to quantify the protein levels of H3K27me3, RORγt, JAK2, STAT3, JMJD3, and EZH2 in cell protein extracts. The results showed that H3K27me3 expression in peripheral blood mononuclear cells (PBMCs) was significantly lower in patients with active AS compared to both the normal control groups and those with stable AS. Moreover, a significant negative correlation was observed between H3K27me3 expression and the characteristic transcription factor of Th17 differentiation, RORγt. We also discovered that patients with active AS exhibited significantly higher levels of JMJD3, an inhibitor of H3K27 demethylase, compared to the normal control group and patients with stable AS, while the expression of H3K27 methyltransferase (EZH2) was significantly lower. These findings suggest that H3K27me3 may be a dynamic and important epigenetic modification in AS inflammation, and JMJD3/EZH2 regulates the methylation level of H3K27me3, which may be one of the key regulatory factors in the pathogenesis of AS. These findings contribute to our understanding of the role of epigenetics in AS and may have implications for the development of novel therapeutic strategies for AS.

19.
Article En | MEDLINE | ID: mdl-38498744

Cognitive impairment is one of the most common non-motor symptoms of Parkinson's disease (PD). Previous studies have demonstrated that low-intensity transcranial ultrasound stimulation can significantly suppress the motor symptoms of PD. However, whether ultrasound stimulation can improve cognitive ability in PD and the related neural oscillation mechanism remain unclear to date. To evaluate the effect of ultrasound stimulation on memory ability in PD and explore its neural oscillation mechanism. Ultrasonography was used for 7-day stimulation of the CA1 in transgenic mice with PD. The working memory ability of the PD mice was then tested using novel object discrimination, and the local field potential and spikes in the mice CA1 were recorded at the same time as in the behavioral test. We found that ultrasound stimulation of the PD mice CA1 for 4 days: 1) significantly increased their learning and memory ability, although the learning and memory ability on the 7th day after the stimulation stopped was not significantly different from that before stimulation (P>0.05); 2) significantly increased the relative power of theta, low gamma, and high gamma frequency bands of the local field potential, and the phase amplitude coupling strength between theta and low gamma and between theta and high gamma; and 3) modulated the phase-locking angle between the spike of interneuron and theta wave to a 180°-360° rise cycle. Transcranial ultrasound stimulation can improve the learning and memory abilities of PD mice, and evoking neural oscillations in the CA1 is the potential mechanism.


Memory, Short-Term , Parkinson Disease , Mice , Animals , Memory, Short-Term/physiology , Cognition , Ultrasonography
20.
J Adhes Dent ; 26(1): 79-86, 2024 Jan 15.
Article En | MEDLINE | ID: mdl-38465402

PURPOSE: This investigation aimed to assess the impact of additive manufacturing-generated surface textures on zirconia bond strength. MATERIALS AND METHODS: Zirconia samples (n = 144) fabricated using digital light-processing (DLP) technology were categorized into 6 groups according to the type of surface conditioning (group NN: no designs, no air abrasion; group NY: no designs, with air abrasion; group GN: groove designs, no air abrasion; group GY: groove designs with air abrasion; group HN: hexagon grid, no air abrasion; group HY: hexagon grid, with air abrasion). Composite resin cylinders were cemented to the treated zirconia surfaces with dual-curing, self-adhesive resin cement (Clearfil SA Luting). The shear bond strength (SBS) was tested after water storage for 3 days or 3 days with an additional 10,000 thermocycles. RESULTS: The zirconia samples fabricated using DLP technology have high accuracy. The SBS of the NY, GY, and HY groups did not significantly differ after 3 days, and neither did the SBS of the NN, GN, and HN groups. The NN, NY, and HY groups exhibited reduced SBS compared to their initial values following artificial aging, while the SBS of the remaining three groups were not diminished. The GY group obtained the highest SBS value after aging. CONCLUSION: Printing grooves with air abrasion can improve the bond strength.


Dental Bonding , Air Abrasion, Dental , Surface Properties , Resin Cements/chemistry , Composite Resins , Shear Strength , Zirconium/chemistry , Materials Testing , Dental Stress Analysis
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