Search

Objectives: This study aimed to elucidate the connection between osteoclastic forkhead transcription factor O1 (FoxO1) and periodontitis and explore the underlying mechanism by which FoxO1 knockdown regulates osteoclast formation. Materials and Methods: A conventional ligature‐induced periodontitis model was constructed to reveal the alterations in the proportion of osteoclastic FoxO1 in periodontitis via immunofluorescence staining. Additionally, RNA sequencing (RNA‐seq) was performed to explore the underlying mechanisms of FoxO1 knockdown‐mediated osteoclastogenesis, followed by western blotting, quantitative polymerase chain reaction, and enzyme‐linked immunosorbent assay. Results: FoxO1+ osteoclasts were enriched in the alveolar bone in experimental periodontitis. Moreover, FoxO1 knockdown led to impaired osteoclastogenesis with low expression of osteoclast differentiation‐related genes, accompanied by an insufficient osteoclast maturation phenotype. Mechanistically, RNA‐seq revealed that the nuclear factor kappa B (NF‐κB) and nucleotide‐binding oligomerization domain‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways were inhibited in FoxO1‐knockdown osteoclasts. Consistent with this, MCC950, an effective inhibitor of the NLRP3 inflammasome, substantially attenuated osteoclast formation. Conclusions: FoxO1 knockdown contributed to the inhibition of osteoclastogenesis by effectively suppressing NF‐κB signaling and NLRP3 inflammasome activation. This prospective study reveals the role of FoxO1 in mediating osteoclastogenesis and provides a viable therapeutic target for periodontitis treatment. [ABSTRACT FROM AUTHOR]

This document is a correction to a previously published paper titled "All-Natural Immunomodulatory Bioadhesive Hydrogel Promotes Angiogenesis and Diabetic Wound Healing by Regulating Macrophage Heterogeneity." The correction addresses mistakes in Figure 7A, which included the wrong image due to a computer lag during data processing. The incorrect images have been replaced, and errors in the annotations of other figures have also been corrected. The corrections do not impact the results and conclusions of the original article. [Extracted from the article]

Purpose: Accurately quantifying the amide proton transfer (APT) effect and the underlying exchange parameters is crucial for its applications, but previous studies have reported conflicting results. In these quantifications, the CEST effect from the fast exchange amine was always ignored because it was considered weak with low saturation powers. This paper aims to evaluate the influence of the fast exchange amine CEST on the quantification of APT at low saturation powers. Methods: A quantification method with low and high saturation powers was used to distinguish APT from the fast exchange amine CEST effect. Simulations were conducted to assess the method's capability to separate APT from the fast exchange amine CEST effect. Animal experiments were performed to assess the relative contributions from the fast exchange amine and amide to CEST signals at 3.5 ppm. Three APT quantification methods, each with varying degrees of contamination from the fast exchange amine, were employed to process the animal data to assess the influence of the amine on the quantification of APT effect and the exchange parameters. Results: The relative size of the fast exchange amine CEST effect to APT effect gradually increases with increasing saturation power. At 9.4 T, it increases from approximately 20% to 40% of APT effect with a saturation power increase from 0.25 to 1 μT. Conclusion: The fast exchange amine CEST effect leads overestimation of APT effect, fitted amide concentration, and amide–water exchange rate, potentially contributing to the conflicting results reported in previous studies. [ABSTRACT FROM AUTHOR]

Summary: Milk is an essential food, but a large part of adult's population is uncapable to digest lactose. Lactose intolerance can seriously affect the intestinal ecology and compromise the host's well‐being. In this scenario, the role of human gut microbiota is crucial, but little is known about that because few research studies were conducted, via either clinical trials or in vitro models. Also, due to the call to reduce animal testing in science, an in vitro model with the gut microbiota of lactose‐intolerant adults is necessary. This paper proposes an in vitro model coupling oro‐gastro‐duodenal digestion to colonic fermentation to evaluate lactose impact on colon microbiota of lactose‐intolerant adults. Microbiomics and metabolomics with respect to a baseline of fermentation were compared. Generally, when the insult was given, taxa specialised for dairy sugars were unaffected, but Bacteroidaceae and Lachnospiraceae were underrepresented. Lactose triggered raise of opportunistic Proteobacteria dominated by harmful Klebsiella. In addition, an important reduction of essential short‐chain fatty acids was observed, and in particular, that of butyrate. Although more observations need to be conducted, as well as a comparison with the healthy condition, the present work gives results for pre‐clinical application in the sight to reduce animal testing. [ABSTRACT FROM AUTHOR]

The International Society for Stem Cell Research (ISSCR) has recently released the 2021 update of its guidelines. The update includes detailed new recommendations on human-animal chimera research. This paper argues that the ISSCR recommendations fail to address the core ethical concerns raised by neurological chimeras-namely, concerns about moral status. In minimising moral status concerns, the ISSCR both breaks rank with other major reports on human-animal chimera research and rely on controversial claims about the grounds of moral status that many people will rightly reject. A more robust framework for regulating human-animal chimera research still needs to be developed., (© 2022 The Authors. Bioethics published by John Wiley & Sons Ltd.)

In this paper, wound dressing materials made of silk fibroin (SF) and transgenic SF with Arg-Gly-Asp motifs (TG-RGD SF) were developed. Initially, an animal evaluation experiment with mice to demonstrate the usefulness of SF film as a wound dressing was performed. The amorphous SF film was shown to promote the formation of granulation tissue and neovessels in the dermis, leading to skin regeneration. As a result, amorphous SF film is suitable for use as a wound dressing materials. Then, the SF- Human umbilical vein endothelial cells signaling pathway was determined by cell proliferation assay with pharmacological inhibitors. Subsequently, a mice evaluation experiment to assess the promotion of healing effects using TG-RGD SF was conducted and the results were compared with those obtained using SF. In the wound area evaluation and the quantitative evaluation of granulation tissue formation, the TG-RGD SF film promoted dermis regeneration more than the SF film. [ABSTRACT FROM AUTHOR]

Postoperative adhesions complicate the majority of surgical procedures, imposing an excess medical burden. The segregation of injured tissue from healthy tissue is considered the optimal therapeutic strategy. However, achieving hemostasis while preventing adhesions in the immediate postoperative setting continues to pose a significant challenge. This paper presents the in situ formation of an asymmetrically adhesive hydrogel barrier via a sprayable dry powder (SDP) that enables interfacial water‐induced, ultra‐rapid gelation. Owing to SDP hydrophilicity and the interstitial spaces between particles, it can rapidly and efficiently absorb interfacial water, thereby facilitating smooth cross‐linking between material functional groups and tissue functional groups. In addition, SDP becomes less adhesive after gelation as a layer of interfacial water forms on the surface of the SDP hydrogel, enhancing its anti‐adhesion properties. Animal experiment outcomes demonstrate that SDP exhibits significant asymmetric adhesive properties before and after gelation, successfully preventing postoperative adhesions. As a result, SDP heralds a novel approach to the development of adhesives that can simultaneously mitigate adhesions and promptly arrest bleeding. [ABSTRACT FROM AUTHOR]

Xin Li, Hao Xu, Jianfeng Yi, Chunlu Dong, Hui Zhang, Zhengfeng Wang, Long Miao, Wence Zhou. miR‐365 secreted from M2 Macrophage‐derived extracellular vesicles promotes pancreatic ductal adenocarcinoma progression through the BTG2/FAK/AKT axis. J Cell Mol Med. 2021; 25: 4671–4683. https://doi.org/10.1111/jcmm.16405. The above article, published online on 03 April 2021 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor‐in‐Chief, Stefan Constantinescu, The Foundation for Cellular and Molecular Medicine and John Wiley and Sons Ltd. The corresponding author asked to retract the article as they found that the animal experiments did not support all the conclusions of the paper. Subsequently, an investigation into concerns raised by a third party, revealed inappropriate duplications of images between this and other articles that were either previously published or published later in the same year. Thus, the editors consider the conclusions of this manuscript substantially compromised. Although the authors initially asked for the retraction, they did not agree to the retraction wording. [ABSTRACT FROM AUTHOR]

Objective: The objective of this review was to assess the accuracy of available means of determining the BBT (buccal bone thickness) and/or BBL (buccal bone level). This was translated into the following research question: What is the accuracy of the available means of visualizing the BBP (buccal bone plate) to establish the BBT and/or the BBL, when compared to control measurements? As control measurements histomorphometric measurements, direct measurements and cone‐beam computed tomography (CBCT) measurements in the absence of metal are accepted. Background Data: Methods The literary search was performed by searching the databases of MEDLINE, Embase, and Web of Science, up to July 13, 2021. Types of studies included were clinical, in vitro and animal trials, specifically looking into the bone level and/or bone thickness of the buccal bone plate at oral implants. Reference lists were hand searched for relevant articles. Two reviewers performed the data extraction and analysis. Only studies using reliable control measurements to evaluate the accuracy of the tested means of visualizing BBT and/or BBL were included for analysis. The QUADAS‐2 tool was used to perform bias analysis on the relevant studies. Extracted data was tabulated to show the differences between test and control measurements for BBT and BBL. For in vitro studies on CBCT measurements of BBT meta‐analysis could be performed. Results: A total of 1176 papers were identified in the search. Twenty‐two articles were used for data extraction and qualitative analysis. Of these studies nine were animal studies, 9 were in vitro studies and four were human studies. Six animal studies and three human studies provided data on probing. CBCT and sonography as techniques for visualizing the buccal bone plate. Probing at implant sites seems to provide data that correlates with a consistent distance from the BBP. Meta‐analysis for probing studies could not be performed due to heterogeneity in the setups of these studies. Eleven studies on CBCT were eligible for inclusion. Of these three were animal studies, the remaining 8 studies were all in vitro studies. Meta‐analysis was performed on the accuracy of CBCT for in vitro studies, finding a significant underestimation of the BBT when compared to control measurements by a mean difference of −0.15 mm with 95%CI [−0.26,−0.03]. Three studies were identified on measurement of BBT and/or BBL by sonography. This included one human study and two in vitro studies. The identified studies show a low error when determining the buccal bone level or thickness using sonography. All included studies possess a high risk of bias according to risk of bias analysis, mostly due to selection of the patient. Conclusion: A strong limitation of this systematic review is the inclusion of different studies with heterogeneous designs. Within the limits of this analysis it cannot be concluded that probing is an accurate way of visualizing the BBP. CBCT cannot yet be recommended as a standard diagnostic tool for follow‐up of the BBP at oral implants. The application of sonography as a diagnostic tool to visualize the BBP needs further scientific validation. [ABSTRACT FROM AUTHOR]

The use of laboratory animals in biomedical research is a matter of intense public debate. Recent statistics indicates that about half of the western population, sensitive to this discussion, would be in favor of animal testing while the other half would oppose it. Here, outlining scientific, historical, ethical, and philosophical aspects, we provide an integrated view explaining the reasons why biomedical research can hardly abandon laboratory animal testing. In this paper, we retrace the historical moments that mark the relationship between humans and other animal species. Then starting from Darwin's position on animal experimentation, we outline the steps that over time allowed the introduction of laws and rules that regulate animals' use in biomedical research. In our analysis, we present the perspectives of various authors, with the aim of delineating a theoretical framework within which to insert the ethical debate on laboratory animals research. Through the analysis of fundamental philosophical concepts and some practical examples, we propose a view according to which laboratory animals experimentation become ethically acceptable as far as it is guided by the goal of improving humans and other animal species (i.e., pets) life. Among the elements analyzed, there is the concept of responsibility that only active moral subjects (humans) have towards themselves and towards passive moral subjects (other animal species). We delineate the principle of cruelty that is useful to understand why research in laboratory animals should not be assimilated to a cruel act. Moreover, we touch upon the concepts of necessity and "good cause" to underline that, if biomedical research would have the possibility to avoid using animals, it would surely do that. To provide an example of the negative consequences occurring from not allowing laboratory animal research, we analyze the recent experience of Covid-19 epidemic. Finally, recalling the principle of "heuristics and biases" by Kahneman, we discuss why scientists should reconsider the way they are conveying information about their research to the general public., (© 2020 Society for the Study of Addiction.)

Save imaging techniques like MRI and PET scanning are of great advantage here and these techniques also play an important role in refining animal experiments.20 Nevertheless, it is extremely difficult to eliminate all animal models from physiological research. Recent 3D tissue models of human colonic epithelium have been developed which will improve the mechanistic understanding of human intestinal function.11 The possibility of obtaining the information required through ethical research on human subjects or human tissue should be considered. Factors that confound the prediction of renal medullary oxygenation and risk of acute kidney injury from measurement of bladder urine oxygen tension. In recent years, most of the manuscripts published as a regular paper in ACTA Physiologica are based on animal experiments. [Extracted from the article]

In this paper, we generated a short hairpin RNA growth differentiation factor‐11 (sh‐GDF11) and evaluated the effects of sh‐GDF11 on the pathogenesis of acute liver failure (ALF) in vitro and in vivo. Through bioinformatics study, the key gene related to ALF was assayed. Lipopolysaccharide (LPS) and D‐galactoamine (D‐GalN) were applied to establish the mouse model of LPS/D‐GalN‐induced liver injury, and TNF‐α and D‐Gal were used to construct an in vitro cell model, followed by treatment of sh‐GDF11 for analysis of liver cell proliferation. Bioinformatics analysis showed that the protective effect of sh‐GDF11 on ALF may be mediated by phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. The results of in vitro study found that sh‐GDF11 could promote cell proliferation and inhibit death by blocking the PI3K/Akt/mTOR signaling pathway. In vivo animal experiments further confirmed that sh‐GDF11 could suppress hepatocyte apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway. sh‐GDF11 relieved LPS/D‐GalN‐induced ALF by blocking the PI3K/Akt/mTOR signaling pathway, emphasizing its critical role in LPS/D‐GalN‐induced ALF treatment. [ABSTRACT FROM AUTHOR]

Aims: Aging is a critical contributing factor for cardiovascular diseases. The d‐galactose‐induced accelerated aging model is comparable to physiological aging from the cellular to the physiological level. The d‐galactose treatment induces mitochondrial dysfunction, increased reactive oxygen species (ROS) production, and upregulation of senescence‐related genes. Cordycepin, a functional element in Chinese traditional medicine, has multiple beneficial effects as an antioxidant and ROS scavenger, and has been reported to be effective in a number of ischemia models. This paper aims to investigate the cardioprotective effects of cordycepin in the d‐galactose accelerated aging model. Methods: In the current study, we employed the d‐galactose accelerated aging model to study the cardioprotective effect of cordycepin. Eight‐week‐old Sprague–Dawley rats, randomly divided into five groups, were given vehicle, d‐galactose (150 mg/kg/day), and cordycepin at 5, 10, and 20 mg/kg per day. At the end of the 8‐week treatment, rat cardiac structure and function were assessed with echocardiographic imaging and hemodynamic parameter analysis. Results: Cordycepin upregulated the expression of Klotho in serum and heart tissues. The expressions of senescence markers β‐galactosidase, p21, and oxidative stress marker malondialdehyde (MDA) were downregulated by cordycepin treatment. Reduction of levels and activity of the antioxidant factors superoxide dismutase (SOD) and catalase (CAT) induced by by d‐galactose treatment was ameliorated by cordycepin. Furthermore, cordycepin activated AMPK signaling in d‐galactose‐treated rats. After 8 weeks of treatment, we found that cordycepin improved myocardia contractility and hypertension caused by d‐galactose treatment. Mechanistically, reduced expression of the Klotho protein SOD1 caused by d‐galactose was recovered in rats co‐treated with cordycepin. Conclusion: Cordycepin could protect against cardiac dysfunction in a d‐galactose‐induced aging rat model, suggesting the therapeutic cardioprotective potential of cordycepin in aging. Geriatr Gerontol Int 2022; 22: 433–440. [ABSTRACT FROM AUTHOR]

Background: We recently showed that alcohol and cannabis can interact prenatally, and in a recent review paper, we identified parvalbumin‐positive (PV) interneurons in the hippocampus as a potential point of convergence for these teratogens. Methods: A 2 (Ethanol [EtOH], Air) × 2 (tetrahydrocannabinol [THC], Vehicle) design was used to expose pregnant Sprague‐Dawley rats to either EtOH or air, in addition to either THC or the inhalant vehicle solution, during gestational days 5–20. Immunohistochemistry was performed to detect PV interneurons in 1 male and 1 female pup from each litter at postnatal day 70. Results: Significant between‐group and subregion‐specific effects were found in the dorsal cornu ammonis 1 (CA1) subfield and the ventral dentate gyrus (DG). In the dorsal CA1 subfield, there was an increase in the number of PV interneurons in both the EtOH and EtOH +THC groups, but a decrease with THC alone. There were fewer changes in interneuron numbers overall in the DG, though there was a sex difference, with a decrease in the number of PV interneurons in the THC‐exposed group in males. There was also a greater cell layer volume in the DG in the EtOH +THC group than the control group, and in the CA1 region in the EtOH group compared to the control and THC groups. Conclusions: Prenatal exposure to alcohol and THC differentially affects parvalbumin‐positive interneuron numbers in the hippocampus, indicating that both individual and combined exposure can impact the balance of excitation and inhibition in a structure critically involved in learning and memory processes. [ABSTRACT FROM AUTHOR]

In recent years, negative pressure wound dressings have garnered widespread attentions. However, it is challenging to drain the accumulated fluid under negative pressures for hydrogel dressings. To address this issue, this study prepared a chemical/physical duel‐network PEG‐CMCS/AG/MXene hydrogel composed by chemical disulfide crosslinked network of four‐arm polyethylene glycol/carboxymethyl chitosan (4‐Arm‐PEG‐SH/CMCS), and the physical network of hydrogen bond of agar (AG). Under near‐infrared light (NIR) irradiation, the PEG‐CMCS/AG/MXene hydrogel undergoes photothermal heating due to integrate of MXene, which destructs the hydrogen bond network and allows the removal of exudate through a mechanism mimicking the sweat gland‐like effect of skin pores. The photothermal heating effect also enables the antimicrobial activity to prevent wound infections. The excellent electrical conductivity of PEG‐CMCS/AG/MXene can promote cell proliferation under the external electrical stimulation (ES) in vitro. The animal experiments of full‐thickness skin defect model further demonstrate its ability to accelerate wound healing. The conversion between thioester and thiol achieved with L‐cysteine methyl ester hydrochloride (L‐CME) can provides the on‐demand dissolution of the dressing in situ. This study holds promises to provide a novel solution to the issue of fluid accumulations under hydrogel dressings and offers new approaches to alleviating or avoiding the significant secondary injuries caused by frequent dressing changes. [ABSTRACT FROM AUTHOR]

In surgery, the surgical smoke generated during tissue dissection and hemostasis can degrade the image quality, affecting tissue visibility and interfering with the further image processing. Developing reliable and interpretable computational imaging methods for restoring smoke‐affected surgical images is crucial, as typical image restoration methods relying on color‐texture information are insufficient. Here a computational polarization imaging method through surgical smoke is demonstrated, including a refined polarization difference estimation based on the discrete electric field direction, and a corresponding prior‐based estimation method, for better parameter estimation and image restoration performance. Results and analyses for ex vivo, the first in vivo animal experiments, and human oral cavity tests show that the proposed method achieves visibility restoration and color recovery of higher quality, and exhibits good generalization across diverse imaging scenarios with interpretability. The method is expected to enhance the precision, safety, and efficiency of advanced image‐guided and robotic surgery. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) play critical roles in the tumorigenesis and radiosensitivity of multiple cancers. Nevertheless, the biological functions of circRNA periostin (circ‐POSTN) in esophageal cancer (EC) progression and radiosensitivity have not been well elucidated. Methods: The expression of circ‐POSTN, microRNA‐876‐5p (miR‐876‐5p), and proto‐oncogene tyrosine‐protein kinase (FYN) was analyzed by quantitative reverse transcription PCR (RT‐qPCR). Cell proliferation was assessed by MTT, colony formation, and 5‐ethynyl‐2′‐deoxyuridine (EDU) assays. All protein levels were detected by western blot assay. Cell apoptosis and invasion were assessed by flow cytometry analysis and transwell assay, respectively. Dual‐luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction between miR‐876‐5p and circ‐POSTN or FYN. The role of circ‐POSTN in vivo was explored by establishing mice xenograft model. Results: Circ‐POSTN was overexpressed in EC tissues and cells. Knockdown of circ‐POSTN inhibited cell proliferation and invasion and elevated apoptosis and radiosensitivity in EC cells. MiR‐876‐5p was a direct target of circ‐POSTN, and its knockdown reversed the role of sh‐circ‐POSTN in EC cells. FYN was a direct target of miR‐876‐5p, and FYN elevation weakened the effects of miR‐876‐5p overexpression on the progression and radiosensitivity of EC cells. Moreover, circ‐POSTN acted as a miR‐876‐5p sponge to regulate FYN expression. Circ‐POSTN interference also suppressed tumor growth and enhanced radiosensitivity in vivo. Conclusion: Circ‐POSTN knockdown inhibited proliferation and invasion, but increased apoptosis and enhanced radiosensitivity in EC cells via modulating miR‐876‐5p/FYN axis, which might be a potential diagnostic and therapeutic target for EC. [ABSTRACT FROM AUTHOR]

Background: There is no evidence‐based guidance on the use of fractional CO2 laser in the excision of scars. Aim: To explore the effectiveness and safety of fractional CO2 laser in the treatment of keloids. Methods: In this meta‐analysis, we searched the PubMed, Embase, and Cochrane databases from inception to April 2023. We only included studies reporting fractional CO2 laser treatment of keloids. We excluded duplicate published studies, incomplete studies, those with incomplete data, animal experiments, literature reviews, and systematic studies. Results: The pooled results showed that the Vancouver Scar Scale (VSS) parameters of height weighted mean difference (WMD) = −1.10, 95% confidence interval (CI): −1.46 to −0.74), pigmentation (WMD = −0.61, 95% CI: −1.00 to −0.21), and pliability (WMD = −0.90, 95% CI: −1.17 to −0.63) were significantly improved after fractional CO2 laser treatment of keloids. However, vascularity did not significantly change. Additionally, the total VSS was significantly improved after treatment (WMD = −4.01, 95% CI: −6.22 to −1.79). The Patient Scars Assessment Scale was significantly improved after treatment (WMD = −15.31, 95% CI: −18.31 to −12.31). Regarding safety, the incidences of hyperpigmentation, hypopigmentation, pain, telangiectasia, and atrophy were 5%, 0%, 11%, 2% (95% CI: 0%–6%), and 0% (95% CI: 0%–4%), respectively. Conclusions: Fractional CO2 laser is effective in the treatment of keloids and can effectively improve the height, pigmentation, and pliability of scars, and patients are satisfied with this treatment. Further studies should explore the role of combination therapy. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic wounds are difficult to heal, but the pathogenesis is unknown. MicroRNAs (miRNAs) are thought to play important roles in wound healing. The effect of miR‐488‐3p in wound healing was studied in this article. Materials and Methods: The gene methylation was measured by methylation specific PCR (MSP) assay. A dual‐luciferase reporter assay was adopted to analyze the interaction between miR‐488‐3p and MeCP2. Results: Cytochrome P450 1B1 (CYP1B1) is a monooxygenase belonging to the cytochrome P450 family that aids in wound healing. Our findings showed that the miR‐488‐3p and CYP1B1 expression levels were much lower in wound tissues of diabetics with skin defects, but the methyl‐CpG‐binding protein 2 (MeCP2) level was significantly higher than that in control skin tissues. MiR‐488‐3p overexpression increased cell proliferation and migration, as well as HUVEC angiogenesis, while inhibiting apoptosis, according to function experiments. In vitro, MeCP2 inhibited wound healing by acting as a target of miR‐488‐3p. We later discovered that MeCP2 inhibited CYP1B1 expression by enhancing its methylation state. In addition, CYP1B1 knockdown inhibited wound healing. Furthermore, MeCP2 overexpression abolished the promoting effect of miR‐488‐3p on wound healing. It also turned out that CYP1B1 promoted wound healing by activating the Wnt4/β‐catenin pathway. Animal experiments also showed that miR‐488‐3p overexpression could accelerate wound healing in diabetic male SD rats. Conclusions: MiR‐488‐3p is a potential therapeutic target for diabetic wound healing since it improved wound healing by activating the CYP1B1‐mediated Wnt4/‐catenin signaling cascade via MeCP2. [ABSTRACT FROM AUTHOR]

Aimed to clarify the effect of quercetin and its derivatives on wound healing in animal experiments. PubMed, Embase, Science Direct, Web of Science, SinoMed, Vip Journal Integration Platform, China National Knowledge Infrastructure and WanFang databases were searched for animal experiments investigating the effect of quercetin and its derivatives on wound healing to April 2023. The Review Manager 5.4 software was used to conduct meta‐analysis. Eighteen studies were enrolled in this article. According to the SYRCLE's RoB tool assessment, these studies exposed relatively low methodological quality. It was shown that animals with cutaneous wound receiving quercetin had faster wound healing in wound closure (%) than the control group. Moreover, the difference in efficacy gradually emerged after third day (WMD = 7.13 [5.52, 8.74]), with a peak reached on the tenth day after wounding (WMD = 19.78 [17.82, 21.74]). Subgroup analysis revealed that quercetin for wound closure (%) was independent of the types of rats and mice, wound area and with or without diabetes. Clear conclusion was also shown regarding the external application of quercetin for wound healing (WMD = 17.77 [11.11, 24.43]). A significant reduction in the distribution of inflammatory cells occurred in the quercetin group. Quercetin could increase blood vessel density (WMD = 1.85 [0.68, −3.02]), fibroblast distribution and collagen fraction. Biochemical indicators, including IL‐1β, IL‐10, TNF‐α, TGF‐β, vascular endothelial growth factor (VEGF), hydroxyproline and alpha‐smooth muscle actin (α‐SMA), had the consistent results. Quercetin and its derivatives could promote the recovery of cutaneous wound in animals, through inhibiting inflammatory response and accelerating angiogenesis, proliferation of fibroblast and collagen deposition. [ABSTRACT FROM AUTHOR]

To date, the predictive role of laboratory indicators for the phenomenon of no flow is unclear. Hence, our objective was to conduct a meta‐analysis to investigate the association between laboratory parameters and the risk of the no‐reflow phenomenon in patients with ST‐elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (PCI). This, in turn, aims to offer valuable insights for early clinical prediction of no‐reflow. We searched Pubmed, Embase, and Cochrane Library from the establishment of the database to October 2023. We included case‐control or cohort study that patients with STEMI following primary PCI. We excluded repeated publication, research without full text, incomplete information or inability to conduct data extraction and animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data. The pooled results indicated that elevated white blood cell (WBC) count (odds ratio [OR] = 1.061, 95% confidence interval [CI]: 1.013–1.112), neutrophil count (OR = 1.324, 95% CI: 1.128–1.553), platelet (PLT) (OR = 1.002, 95% CI: 1.000–1.005), blood glucose (OR = 1.005, 95% CI: 1.002–1.009), creatinine (OR = 1.290, 95% CI: 1.070–1.555), total cholesterol (TC) (OR = 1.022, 95% CI: 1.012–1.032), d‐dimer (OR = 1.002, 95% CI: 1.001–1.004), and fibrinogen (OR = 1.010, 95% CI: 1.005–1.015) were significantly associated with increased risk of no‐reflow. However, elevated hemoglobin was significantly associated with decreased risk of no‐reflow. In conclusion, our comprehensive analysis highlights the predictive potential of various parameters in assessing the risk of no‐reflow among STEMI patients undergoing PCI. Specifically, WBC count, neutrophil count, PLT, blood glucose, hemoglobin, creatinine, TC, d‐dimer, and fibrinogen emerged as significant predictors. This refined risk prediction may guide clinical decision‐making, allowing for more targeted and effective preventive measures to mitigate the occurrence of no‐reflow in this patient population. [ABSTRACT FROM AUTHOR]

To investigate whether human umbilical cord mesenchymal stem cell‐derived exosomes combined with gelatin methacryloyl (GelMA) hydrogel are beneficial in promoting healing of laser‐injured skin wounds in mice. Supernatants of cultured human umbilical cord mesenchymal stem cells (HUC‐MSCs) were collected to obtain human umbilical cord MSC‐derived exosomes (HUC‐MSCs‐Exos), which were combined with GelMA hydrogel complex to treat a mouse fractional laser injury model. The study was divided into PBS group, EX (HUC‐MSCs‐Exos) group, GEL (GelMA hydrogel) group and EX+GEL (HUC‐MSCs‐Exos combined with GelMA hydrogel) group. The healing of laser‐injured skin in each group was observed by gross view and dermatoscopy, and changes in skin structure, angiogenesis and proliferation‐related indexes were observed during the healing process of laser‐injured skin in each group. The results of the animal experiments showed that the EX and GEL groups alone and the EL+EX group exhibited less inflammatory response compared to the PBS group. The EX and GEL groups showed marked tissue proliferation and favourable angiogenesis, which promoted the wound healing well. The GEL+EX group had the most significant promotion of wound healing compared to the PBS group. qPCR results showed that the expression levels of proliferation‐related factors, including KI67 and VEGF and angiogenesis‐related factor CD31, were significantly higher in the GEL+EX group than in the other groups, with a time‐dependent effect. The combination of HUC‐MSCs‐Exos and GelMA hydrogel is beneficial in reducing the early inflammatory response of laser‐injured skin in mice and promoting its proliferation and angiogenesis, which in turn promotes wound healing. [ABSTRACT FROM AUTHOR]

A meta‐analysis was performed to assess the effects of different regenerative technologies and materials on wound healing after surgical endodontic therapy and provide a reference for surgical endodontic treatment. We searched for studies on the use of regenerative technologies and materials in surgical endodontic therapy via PubMed, MEDLINE, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data from the time of database creation to December 2022. Two researchers independently screened the literature, extracted information based on the inclusion and exclusion criteria, and evaluated the quality of the included studies. A meta‐analysis was performed using Review Manager 5.4. The results showed that the use of regenerative technologies and materials significantly reduced wound healing failures (risk ratio [RR]: 0.30, 95% confidence intervals [CI]: 0.22–0.40, p < 0.001). Moreover, autologous platelet concentrations (APCs) (RR: 0.28, 95% CI: 0.15–0.53, p < 0.001) and collagen membrane plus bovine‐derived hydroxyapatite (RR: 0.27, 95% CI. 0.12–0.61, p = 0.002) were more effective in improving wound healing failure rates than collagen membrane alone (RR: 0.51, 95% CI: 0.20–1.25, p = 0.140). Our findings showed that APCs, as well as collagen membrane plus bovine‐derived hydroxyapatite, significantly improved wound healing after surgical endodontic therapy. In contrast, collagen membrane alone did not significantly improve wound healing outcomes. However, currently available studies vary significantly in sample size and methodologies. Hence, high‐quality randomised controlled studies with large sample sizes are necessary to validate our findings. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between icariin and the osteoblastic differentiation of vascular smooth muscle cells (VSMCs) and the signal pathway involved. Methods: We applied a universally accepted calcification model of VSMCs induced by β glycerophosphate. Then the VSMCs calcification was observed by treatment with icariin and/or inhibitors of estrogen receptors (ERs) and p38‐mitogen‐activated protein kinase (MAPK) signaling. Results: Icariin inhibited osteoblastic differentiation and mineralization of VSMCs due to decreased ALP activity and Runx2 expression. Further study demonstrated that icariin exerted this suppression effect through activating p38‐MAPK but not extracellular‐regulated kinase, JNK or Akt. An inhibitor of p38‐MAPK partially reversed the inhibitory effects of icariin on osteoblastic differentiation. Interestingly, treatment of VSMCs with an ER antagonist ICI182780 and a selective ERα receptor antagonist PPT attenuated icariin‐mediated inhibition effect of VSMCs calcification, associated with suppression of p38‐MAPK phosphorylation. Conclusions: Icariin inhibited the osteoblastic differentiation of VSMCs, and that the inhibitory effects were mediated by p38‐MAPK pathways through ERα. [ABSTRACT FROM AUTHOR]

Detecting pathogens in the live animal trade is critical for tracking and preventing their movement, introduction and spillover into susceptible fauna. However, the scale of the live animal trade makes individually testing animals infeasible for all but the most economically important taxa. For instance, while the fungal pathogen, Batrachochytrium salamandrivorans (Bsal), threatens amphibian, particularly caudate diversity, in Europe and the Americas, screening even a fraction of the millions of live amphibians imported into the United States, alone, is impractically laborious and expensive. A promising alternative to individual‐level sampling (e.g. swabbing the skin of salamanders) is to instead collect DNA from the animals' environment (e.g. housing container or water) which allows us to screen a whole group of animals at a time.We used a series of experiments with Bsal‐spiked water and substrates and experimentally infected rough‐skinned newts (Taricha granulosa) to determine which methods yield the most Bsal environmental DNA (eDNA) and evaluate the capacity of these methods to detect Bsal‐infected animals in conditions found in captive settings and trade.We found that filtering water housing infected animals for even an hour can consistently recover detectable levels of Bsal eDNA, that there is little evidence of Bsal eDNA being clumped in housing containers or swamped or inhibited by dirty housing containers, and that eDNA‐based methods achieves an equivalent or higher chance of detecting Bsal infections in a (virtual) population of co‐housed newts with fewer samples than individual swabs.By sampling the genetic materials accumulated from a whole group of animals, eDNA‐based methods are a powerful means of detecting pathogens, such as Bsal, in shipments and captive populations. These methods bring routine pathogen surveillance into reach in many more contexts and can thus be an important tool in conservation and disease control. [ABSTRACT FROM AUTHOR]

Random skin flaps have limited clinical application as a broad surgical reconstruction treatment because of distal necrosis. The prolyl hydroxylase domain‐containing protein inhibitor roxadustat (RXD) enhances angiogenesis and reduces oxidative stress and inflammation. This study explored the function of RXD in the survival of random skin flaps. Thirty‐six male Sprague–Dawley rats were randomly divided into low‐dose RXD group (L‐RXD group, 10 mg/kg/2 day), high‐dose RXD group (H‐RXD group, 25 mg/kg/2 day), and control group (1 mL of solvent, 1:9 DMSO:corn oil). The proportion of surviving flaps was determined on day 7 after surgery. Angiogenesis was assessed by lead oxide/gelatin angiography, and microcirculation blood perfusion was evaluated by laser Doppler flow imaging. Specimens in zone II were obtained, and the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured as indicators of oxidative stress. Histopathological status was evaluated with haematoxylin and eosin staining. The levels of hypoxia‐inducible factor‐1α (HIF‐1α), vascular endothelial growth factor (VEGF), and the inflammatory factors interleukin (IL)‐1β, IL‐6, and tumour necrosis factor‐α (TNF‐α) were detected by immunohistochemistry. RXD promoted flap survival and microcirculatory blood perfusion. Angiogenesis was detected distinctly in the experimental group. SOD activity increased and the MDA level decreased in the experimental group. Immunohistochemistry indicated that the expression levels of HIF‐1α and VEGF were increased while the levels of IL‐6, IL‐1β, and TNF‐α were decreased after RXD injection. RXD promoted random flap survival by reinforcing vascular hyperplasia and decreasing inflammation and ischaemia‐reperfusion injury. [ABSTRACT FROM AUTHOR]

There is growing recognition that animal methods bias, a preference for animal‐based methods where they are not necessary or where nonanimal‐based methods may already be suitable, can impact the likelihood or timeliness of a manuscript being accepted for publication. Following April 2022 workshop about animal methods bias in scientific publishing, a coalition of scientists and advocates formed a Coalition to Illuminate and Address Animal Methods Bias (COLAAB). The COLAAB has developed this guide to be used by authors who use nonanimal methods to avoid and respond to animal methods bias from manuscript reviewers. It contains information that researchers may use during 1) study design, including how to find and select appropriate nonanimal methods and preregister a research plan, 2) manuscript preparation and submission, including tips for discussing methods and choosing journals and reviewers that may be more receptive to nonanimal methods, and 3) the peer review process, providing suggested language and literature to aid authors in responding to biased reviews. The author's guide for addressing animal methods bias in publishing is a living resource also available online at animalmethodsbias.org, which aims to help ensure fair dissemination of research that uses nonanimal methods and prevent unnecessary experiments on animals. [ABSTRACT FROM AUTHOR]

A meta‐analysis investigation to measure the usefulness of platelet‐rich plasma (PRP) to manage skin wounds (SWs). A comprehensive literature inspection till February 2023 was applied and 1349 interrelated investigations were reviewed. The 22 chosen investigations enclosed animals' SWs were in the chosen investigations' starting point, 3348 of them were treated with PRP, and 2259 were control. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the usefulness of PRP to manage SWs by the dichotomous and continuous approaches and a fixed or random model. PRP significantly higher percent of decreases in open wound area (OWA) (MD, 10.07; 95% CI, 6.55‐13.59, P < 0.001), and lower healing time (HT) (MD, −6.31; 95% CI, −10.69 to −1.93, P = 0.005) compared to control in animals' SWs. PRP had a significantly higher percent of decreases in OWA and lower HT compared to control in animals' SWs. However, caused of the small sample sizes of several chosen investigations for this meta‐analysis, care must be exercised when dealing with its values. [ABSTRACT FROM AUTHOR]

Objectives: Current methods for periodontal regeneration do not promote collagen fiber insertions into new bone and cementum. We used a pig wound model to screen different functionalized collagen membranes in promoting periodontal reattachment to root surfaces. Methods: Treatment groups included (1) control with no membranes, (2) collagen‐coated membranes, (3) membranes with insulin‐like growth factor‐1 (IGF‐1), (4) membranes with amelotin, or (5) membranes attached with calcium phosphate cement (CPC), or with CPC combined with IGF‐1. Flap procedures were performed on mandibular and maxillary premolars of each pig. Results: Histomorphometric, micro‐CT, and clinical measurements obtained at 4 and 12 weeks after surgery showed cementum formation on denuded roots and reformation of alveolar bone, indicating that the pig model can model healing responses in periodontal regeneration. Calcium phosphate cement simplified procedures by eliminating the need for sutures and improved regeneration of alveolar bone (p < 0.05) compared with other treatments. There was a reduction (p < 0.05) of PD only for the IGF group. Large observed variances between treatment groups indicated that a priori power analyses should be conducted to optimize statistical analysis. Conclusions: Pigs can model discrete elements of periodontal healing using collagen‐based, functionalized membranes. Screening indicates that membrane anchorage with calcium phosphate cements improve regeneration of alveolar bone. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of activated charcoal‐based (AC) products on color alteration, remineralizing potential and surface roughness of dental enamel. Materials and Methods: Bovine incisors were cut into 6 × 6 × 2 mm fragments. Initial color (EasyShade, Vita) and surface roughness (Surfcorder SE1700, Kosakalab) readings were performed. Fragments were separated into five groups (n = 17) according to the treatment: Control: Fluoride toothpaste (Colgate Total 12, Colgate); Charcoal + NaF: AC toothpaste (ACT) with sodium fluoride (Colgate Natural Extracts, Colgate); Charcoal + MFP + n‐HA: ACT with sodium monofluorophosphate and nanohydroxyapatite (Black is White, Curaprox); Charcoal: Fluoride‐free ACT (ProActive, Hinode); and Charcoal powder: AC powder. Simulated toothbrushing was performed and final color and surface roughness readings were obtained. Fragments were then polished, and initial microhardness (HMV‐2, Shimatzu) readings were done. Samples were artificially demineralized and brushed again. Final microhardness readings were taken. Data were statistically analyzed. Results: Fluoride‐free charcoal presented the lowest surface roughness alteration (p < 0.05). Charcoal powder had the lowest color change (p < 0.05) and negative values for whiteness index for dentistry alteration. All the groups presented values below whiteness acceptability threshold and negative relative microhardness values. Control showed the highest remineralizing potential (p < 0.05). Conclusions: ACPs did not produce color alteration different from the fluoride toothpaste, except for Charcoal powder that caused less color change. ACPs caused surface roughness alteration similar to the fluoride toothpaste. ACT with fluoride and AC powder did not have remineralizing potential. Clinical Significance: Activated charcoal‐based products (ACP) promise effective tooth whitening and quick results, without teeth damage. In addition, some ACPs contain fluoride in toothpaste composition and promise rehardening potential. However, ACPs are not as effective as other whitening agents and can alter the surface roughness of the enamel. Even if the ACPs contain fluoride or other remineralizing agents, they might be ineffective. [ABSTRACT FROM AUTHOR]

Background: Periodontal disease is an inflammatory disease of periodontal tissues that is closely connected with systemic diseases. During periodontitis, the inappropriate recruitment and activation of monocytes–macrophages causes an increase in osteoclast activity and disrupts bone homeostasis. Therefore, it is a promising therapeutic strategy to treat periodontitis by regulating the functions of monocytes–macrophages. Litcubanine A (LA) is an isoquinoline alkaloid extracted from the traditional Chinese medicine Litsea cubeba, which was proven to have reproducible anti‐inflammatory effects, but its regulatory role on bone homeostasis in periodontitis is still not clear. Methods: In this study, zebrafish experiments and a mouse ligature‐induced periodontitis model were performed, and histological analysis was used to investigate the effect of LA on macrophage chemotaxis under the inflammatory environment. Real‐time PCR was used to detect the regulatory effect of LA (100 nM ~ 100 μM) on the chemotaxis function of macrophages induced by LPS. Apoptosis assay and flow cytometry were used to elucidate the influence of LA on macrophage apoptosis and proliferation. To further clarify the regulatory role of LA on macrophage osteoclast differentiation, real‐time PCR, histological analysis, western blot, and micro‐computed tomography (micro‐CT) were performed in vivo and in vitro to verify the impact of LA on bone homeostasis. Results: Compared with the control group, the chemotaxis function of macrophage was significantly attenuated by LA in vivo. LA could significantly inhibit the expression of genes encoding the chemokine receptors Ccr1 and Cxcr4, and its ligand chemokine Cxcl12 in macrophages, and suppresses the differentiation of osteoclastic precursors to osteoclasts through the MAPK signaling pathway. There were significantly lower osteoclast differentiation and bone loss in the LA group compared with the control in the ligature‐induced periodontitis model. Conclusion: LA is a promising candidate for the treatment of periodontitis through its reproducible functions of inhibiting monocyte–macrophage chemotaxis and osteoclast differentiation. Litcubanine A can significantly prevent periodontitis by inhibiting macrophage chemotaxis and osteoclast differentiation via the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: Paeoniflorin (Pae) is a monoterpene glycoside with immune‐regulatory effects. Several studies have already demonstrated the impact of Pae on periodontitis, but its effect on diabetic periodontitis is unclear. In this study, our aim was to test the hypothesis that Pae had a strong anti‐inflammatory effect that prevented bone loss in diabetic periodontitis. Methods: Thirty male Wistar albino rats were randomly divided into control (healthy, n = 10), periodontitis (PD) + diabetes (DM; n = 10), and PD + DM + Pae (n = 10) groups. Ligature‐induced periodontitis was created by placing 4–0 silk ligatures around the lower first molars on both sides of the mandibulae. Experimental DM was created via an injection of 50 mg/kg and streptozotocin (STZ). Hyperglycemia was confirmed by the blood glucose levels of rats (>300 mg/dL). The bone mineral density (BMD), trabecular number, trabecular thickness, and bone loss were measured by micro‐CT. The expression levels of IL‐1β, IL‐6, and TNF‐α were measured in tissue homogenates by ELISA. Results: The PD + DM + Pae group had significantly less alveolar crest resorption when compared to the PD + DM group. There was also a significant difference between the PD + DM + Pae group compared to PD + DM group in trabecular thickness, BMD, and the number of trabeculae. Pae application led to a statistically significant decrease in IL‐1β, IL‐6, and TNF‐α levels in diabetic periodontitis. Conclusion: Systemic application of Pae suppressed inflammation caused by PD and DM, leading to reduced bone loss and enhanced bone quality. [ABSTRACT FROM AUTHOR]

Background: Candida albicans is linked to persistent endodontic lesions. However, the recognition receptor that identifies it is not explored previously. Objectives: The aim of this study was to (1) establish a zymosan‐induced model of apical periodontitis in mouse, (2) observe the expression of Dectin‐1 and its possible relationship with toll‐like receptor (TLR) 2 and (3) observe relationship between Osteopontin (OPN) and inflammatory cytokines. Methods: A total of 138 Naval Medical Research Institute (NMRI) mice were randomly divided into; Experimental Group n = 69 and Zymosan Group n = 69. Periapical periodontitis was developed in right maxillary molar. The animals were sacrificed at 7, 21 and 42 days. Bone blocks containing the mesial root (n = 15 for qRT‐PCR, n = 45 for enzyme‐linked immune sorbent assay (ELISA)) were collected for mRNA expression and ELISA. While whole maxilla (n = 3 from each time interval) were used for histology and immunohistochemical analysis. One way analysis of variance (ANOVA) and Tuckey's posthoc was used for statistical analysis at p ≤.05. Results: TLR‐2, Dectin‐1 and TLR4‐positive cells was detected at all time intervals in both groups. A strong positive correlation was observed between TLR‐2 and Dectin‐1 in both lesions (regular r =.680, p =.015, zymosan (r =.861, p <.001)). A significant correlation was found between OPN and tumour necrosis factor‐alpha (TNF‐α) in zymosan lesion (r =.827, p =.001). Conclusions: Immune cells of inflamed periapical tissue expressed Dectin‐1 receptor in response to the microbial challenge from infected root canals and showed positive correlation with TLR‐2 and OPN suggesting a possible receptor collaboration mediated by OPN. The expression of OPN and TNF‐α showed positive correlation in response to fungal antigen, indicating a possible relationship. [ABSTRACT FROM AUTHOR]

The study investigated the ability of bioactive materials used to restore enamel and dentine specimens to prevent caries. Enamel (n = 50) and dentine (n = 50) specimens were obtained from bovine incisors, prepared, and randomly allocated to one of five groups according to the restorative treatment: alkasite without adhesive system; alkasite with adhesive system; high viscosity glass ionomer cement; resin composite; no restoration; negative control group. Specimens were restored, exposed to a thermal cycling aging protocol, sterilized, and exposed to a cariogenic challenge induced by Streptococcus mutans and then submitted to surface and subsurface microhardness tests and polarized light microscopy to verify the caries lesion development in enamel or dentine surrounding the restorative materials. Data were analyzed using one‐way ANOVA. In enamel and dentine, glass ionomer cement, alkasite without and with adhesive system presented a lower percentage surface microhardness loss than resin composite and negative control. Enamel subsurface microhardness presented no statistically significant differences between glass ionomer cement, alkasite without and with adhesive system. Glass ionomer cement also did not present statistically significant differences from resin composite and the negative control. In dentine, glass ionomer cement showed the highest subsurface microhardness values. In conclusion, bioactive restorative materials provide greater protection to enamel and dentine against surface caries development than resin composite. [ABSTRACT FROM AUTHOR]

Engineered grafts constitute an alternative to autologous transplant for repairing severe peripheral nerve injuries. However, current clinically available solutions have substantial limitations and are not suited for the repair of long nerve defects. A novel design of nerve conduit is presented here, which consists of a chitosan porous matrix embedding a 3D‐printed poly‐ε‐caprolactone mesh. These materials are selected due to their high biocompatibility, safe degradability, and ability to support the nerve regeneration process. The proposed design allows high control over geometrical features, pores morphology, compression resistance, and bending stiffness, yielding tunable and easy‐to‐manipulate grafts. The conduits are tested in chronic animal experiments, aiming to repair a 15‐mm long gap in the sciatic nerve of rats, and the results are compared with an autograft. Electrophysiological and nociception tests performed monthly during a 4‐month follow‐up show that these conduits allow a good degree of muscle functional recovery. Histological analyses show abundant cellularization in the wall and in the lumen of the conduits and regenerated axons within all rats treated with these grafts. It is suggested that the proposed conduits have the potential to repair nerves over the limiting gap length and can be proposed as strategy to overcome the limitations of autograft. [ABSTRACT FROM AUTHOR]

Background: Since there is currently no conclusion on the efficacy and adverse effects of oxymetazoline, this meta‐analysis attempts to explore its efficacy and adverse events, so as to provide guidance for clinical medication. Methods: We searched PubMed, Embase, and Cochrane Library from the establishment of the database to May 2021. We included studies that patients were randomly assigned to receive oxymetazoline or vehicle, and we excluded duplicate publications, research without full text, incomplete information or inability to conduct data extraction, animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data. Results: The pooled results show that the 3 (RR = 1.76, 95% CI: 1.53–2.03), 6 (RR = 1.71, 95% CI: 1.47–2.00), 9 (RR = 1.63, 95% CI: 1.40–1.90), 12 (RR = 1.41, 95% CI: 1.18–1.67) ‐hours CEA success rate and the 3 (RR = 1.65, 95% CI: 1.34–2.03), 6 (RR = 1.75, 95% CI: 1.43–2.14), 9 (RR = 1.63, 95% CI: 1.33–2.00), 12 (RR = 1.78, 95% CI: 1.45–2.18) ‐hours SSA success rate after oxymetazoline treatment for rosacea is significantly higher than that of vehicle. Additionally, the pooled results show that the incidence of TEAEs after treatment with oxymetazoline is significantly higher than that of vehicle (RR = 1.34, 95% CI: 1.10–1.2). However, our analysis of specific adverse events found that the oxymetazoline group was only significantly higher than the vehicle group in the incidence of application‐site dermatitis (RR = 8.91, 95% CI: 1.76–45.23), and there was no statistical significance in the difference in the incidence of other adverse events. Conclusion: Oxymetazoline is effective and can be selected for the treatment of persistent facial erythema of rosacea. Additionally, application‐site dermatitis was the most important one. [ABSTRACT FROM AUTHOR]

Background: Characterizations based on anatomically realistic phantoms are highly effective to perform accurate technical validation of imaging systems. Specifically for photoacoustic imaging (PAI), although a variety of phantom models with simplified geometries are reported, an unmet need still exists to establish morphologically realistic heterogeneous pre‐clinical phantoms. So the development of a mouse‐mimicking phantom can reduce the use of animals for the validation and standardization studies of pre‐clinical PAI systems and thus eventually translate the PAI technology to clinical research. Purpose: Here we designed, developed, and fabricated a stable phantom that mimics the detailed morphology of a mouse, to be used as a realistic tool for PAI. Methods: The mouse phantom, has been designed by using a combination of image modeling and 3D‐printing techniques. As a tissue‐mimicking material, we have used copolymer‐in‐oil‐based material that was recently proposed by the International Photoacoustic Standardization Consortium (IPASC). In particular, the anatomically realistic phantom has been modeled by using the real atlas of a mouse as a reference. The mouse phantom includes a 3D‐printed skeleton and the main abdominal organs such as the liver, spleen, and kidneys obtained by using doped copolymer‐in‐oil material with 3D‐printed molds. In addition, the acoustic and optical properties of the tissue‐mimicking material and the long‐term stability have been broadly characterized. Results: Furthermore, our studies showed that the phantom is durable and stable for more than 200 days, under normal storage and repeated use. Fabrication protocol is easy to reproduce. As a result, the proposed morphologically realistic mouse phantom offers durability, material compatibility, and an unprecedented realistic resemblance to the actual rodents' anatomy in PAI. Conclusion: This durable morphologically realistic mouse phantom would minimize the animal experiments in compliance with the 3R principle of Replacement, Reduction, and Refinement. To our knowledge, this is the first time an anatomically realistic heterogeneous mouse phantom has been proposed for PAI in pre‐clinical animal imaging and tested its durability over 200 days. [ABSTRACT FROM AUTHOR]

Objective: Fibrotic tissues are characterized by excessive crosslinking between extracellular matrix (ECM) proteins, rendering them more resistant to degradation. Although increased crosslinking of ECM is thought to play an important role for progression of tissue fibrosis, enhanced ECM crosslinking has not yet been targeted therapeutically in systemic sclerosis (SSc). Here, we investigated the role of transglutaminase 2 (TG2), a central crosslinking enzyme, in the activation of SSc fibroblasts. Methods: We assessed TG2 expression and activity using TG2 staining, Western blotting, and TG2 activity assays. We inhibited TG2 in fibroblasts cultured under standard 2‐dimensional conditions and in a 3‐dimensional full‐thickness equivalent skin model using monoclonal inhibitory anti‐TG2 antibodies. Results: TG2 expression was increased in the skin of patients with SSc compared with healthy controls, with levels particularly high in patients with SSc‐associated interstitial lung disease. TG2 expression and TG2 activity were also increased in SSc dermal fibroblasts. Moreover, the levels of circulating TG2 in the plasma samples from SSc patients were increased versus samples from healthy controls. Anti‐TG2 antibodies did not show consistent antifibrotic effects across different fibroblast cell lines under 2‐dimensional culture conditions; however, anti‐TG2 antibodies effectively reduced transforming growth factor β–induced dermal thickening, myofibroblast differentiation, and collagen accumulation in the 3‐dimensional full‐thickness model of human skin. Conclusion: We provide the first evidence, to our knowledge, that inhibition of TG2 might be a potential antifibrotic approach in SSc. Our findings have translational potential as anti‐TG2 antibodies are currently evaluated in a phase II clinical trial in chronic allograft injury and would thus be available for clinical studies in SSc (ClinicalTrials.gov identifier: NCT04335578). [ABSTRACT FROM AUTHOR]

Objective: Acute pain is the most common type of pain. The aim of the present work was carried out to study the antinociceptive effect and pharmacological mechanisms of thiocyanoacetamide (Thm) in rats exposed to thermal pain stimulus. Materials and Methods: The anti‐nociceptive effect of the newly synthesized compound, Thm was studied in comparison to that of paracetamol (Para), dexamethasone (Dex), and morphine (Morph) at different doses using a hot plate test at a constant temperature of 48.0 ± 0.5°C. During this test, the latency time (LT) was measured when rats express pain behavior. Then, the pharmacological mechanisms were determined using receptor‐antagonist drugs. Results: Firstly, the obtained result showed pain modulation of the pretreated rats with Thm at 10 mg/kg dose proved by the delay of latency time during the thermal test. This significant antinociceptive activity of the thiocyanoacetamide was more effective than that of paracetamol or dexamethasone and less than that of morphine. Second, the pretreatment with acebutolol or risperidone antagonist drugs of, respectively, adrenergic and serotonin receptors demonstrated the elimination of pain modulation with Thm 10 mg/kg dose proved by a short latency time of rat's response in hot plate test. In this case, the pharmacological mechanism of Thm was characterized by the involvement of adrenergic and serotoninergic systems. Conclusions: It may be concluded that Thm constitutes a promising antinociceptive drug including beta‐adrenergic and serotoninergic targets. The present study warrants further investigation to determine the side effects of this compound. [ABSTRACT FROM AUTHOR]

Aim: Necroptosis participates in the pathogenesis of many inflammatory diseases, including periodontitis. Here, we aimed to investigate the role and mechanism of necroptosis inhibitors in attenuating periodontitis. Materials and Methods: The Gene Expression Omnibus (GEO) dataset GSE164241 was re‐analysed to identify the role of necroptosis in periodontitis. Gingival specimens from healthy subjects or periodontitis patients were collected to evaluate the expression level of necroptosis‐associated proteins. The therapeutic effect of necroptosis inhibitors on periodontitis was assessed in vivo and in vitro. Moreover, Transwell assays and Western blotting and siRNA transfection were used to identify the effects of necroptotic human gingival fibroblasts (hGFs) on THP‐1 macrophages. Results: Re‐analysis revealed that gingival fibroblasts (GFs) in periodontitis gingiva showed the highest area under the curve score of necroptosis. Elevated levels of necroptosis‐associated proteins were identified in GFs in periodontitis gingiva collected from patients and mice. In ligature‐induced periodontitis mice, local administration of receptor interacting protein kinase 3(RIPK3) inhibitor GSK′872 or sh‐mixed‐lineage kinase domain‐like pseudokinase (Mlkl) markedly abrogated necroptosis and rescued periodontitis. Analogously, necroptosis inhibitors alleviated the inflammatory response and release of damage‐associated molecular patterns in lipopolysaccharide‐ or LAZ (LPS + AZD'5582 + z‐VAD‐fmk, necroptosis inducer)‐induced GFs and then reduced THP‐1 cell migration and M1 polarization. Conclusions: Necroptosis in GFs aggravated gingival inflammation and alveolar bone loss. Necroptosis inhibitors attenuate this process by modulating THP‐1 macrophage migration and polarization. This study offers novel insights into the pathogenesis and potential therapeutic targets of periodontitis. [ABSTRACT FROM AUTHOR]

The electrospun polylactide (PLA) anti‐adhesion fiber‐type film coated with carboxymethylcellulose (CMC) was manufactured and evaluated for its usability through animal experiments. The PLA anti‐adhesion film developed in this study is an adhesion preventive film of a double composite structure with both hydrophobicity and hydrophilicity. This film has the anti‐adhesion effect due to hydrophobic PLA that do not melt easily in the body and at the same time is easily attached to the surgical site by hydrophilic CMC that reacts easily to body fluids and changes quickly to mucus. In this study, the diameter and the pore diameter of the PLA fiber and thickness of PLA film made by electrospinning was 0.2–0.4, 1–10, and 30–50 μm, respectively. Through observation of surface structure (×5000 magnification), the most suitable concentration of CMC to maintain pores on the PLA film as much as possible is 0.5% wt/vol. The CMC content in the PLA film coated with 0.5% wt/vol of CMC was measured to be 5.41% wt/wt and its tensile strength was about 2.92 times higher than that of the noncoated PLA film with CMC. The porosity of CMC‐coated PLA film (5.41% wt/wt) was found to be 76.4%. In the animal experiment, 20 white mice (10 as a control group and 10 as an experimental group) were used to determine the degree of adhesion prevention. As a result of observing adhesion and anti‐adhesion between the cecum and the peritoneum by performing U‐shaped laparotomy on white mice at the third week after surgery, the incidence of adhesion in the control group was 90%, whereas the experimental group was 20%. [ABSTRACT FROM AUTHOR]

Background: Optimal functional recovery following peripheral nerve injuries (PNIs) is dependent upon early recognition and prompt referral to specialist centres for appropriate surgical intervention. Technologies which facilitate the early detection of PNI would allow faster referral rates and encourage improvements in patient outcomes. Serum Neurofilament light chain (NfL) measurements are cheaper to perform, easier to access and interpret than many conventional methods used for nerve injury diagnosis, such as electromyography and/or magnetic resonance imaging assessments, but changes in serum NfL levels following traumatic PNI have not been investigated. This pre‐clinical study aimed to determine whether serum NfL levels can: (1) detect the presence of a nerve trauma and (2) delineate between different severities of nerve trauma. Methods: A rat sciatic nerve crush and common peroneal nerve crush were implemented as controlled animal models of nerve injury. At 1‐, 3‐, 7‐ and 21‐days post‐injury, serum samples were retrieved for analysis using the SIMOA® NfL analyser kit. Nerve samples were also retrieved for histological analysis. Static sciatic index (SSI) was measured at regular time intervals following injury. Results: Significant 45‐fold and 20‐fold increases in NfL serum levels were seen 1‐day post‐injury following sciatic and common peroneal nerve injury, respectively. This corresponded with an eightfold higher volume of axons injured in the sciatic compared to the common peroneal nerve (p <.001). SSI measurements post‐injury revealed greater reduction in function in the sciatic crush group compared with the common peroneal crush group. Conclusions: NfL serum measurements represent a promising method for detecting traumatic PNI and stratifying their severity. Clinical translation of these findings could provide a powerful tool to improve the surgical management of nerve‐injured patients. [ABSTRACT FROM AUTHOR]

Background: Clinical use of botulinum neurotoxins (BoNTs) in masticatory muscles is usually bilateral, but most studies on the functional consequences of BoNT treatment have used unilaterally treated animals. Objectives: To test the hypothesis that bilateral BoNT treatment of the rabbit masseter hampers mastication and to assess its effects on bone density of the mandibular condyles. Methods: Ten 5‐month‐old female rabbits received injections of BoNT into both masseter muscles and nine sham animals received saline. Body weight, incisor bite force during masseter tetany, and surface and fine‐wire electromyography (EMG) of the masseter and medial pterygoid muscles were assessed at regular intervals. Half the sample was terminated after 4 weeks and the remainder after 12 weeks. Muscles were weighed and mandibular condyles were scanned with microCT to analyse bone density. Results: BoNT rabbits lost weight and required a soft‐food diet. Incisor occlusal force plummeted after BoNT injection and remained lower than the shams. The duration of masticatory cycles was increased in the BoNT rabbits for 5 weeks, with most of the increase due to the adductor burst. Masseteric EMG amplitude began to improve at Week 5, but remained low on the working side throughout the experiment. At the 12‐week endpoint, masseter muscles were smaller in the BoNT rabbits. Medial pterygoid muscles did not compensate. Condylar bone density was reduced. Conclusion: Bilateral treatment of the rabbit masseter by BoNT severely affected chewing performance. Even after a 3‐month recovery period, deficits remained in bite force, muscle size and condylar bone density. [ABSTRACT FROM AUTHOR]

Repair of bone defects, especially critical‐sized bone defects, remains a major clinical problem, and bone nonunion is the biggest challenge. Herein, melt‐extrusion 3D printing is applied to prepare biodegradable composite scaffolds containing bioactive glass (BAG), calcium sulfate hemihydrate (CSH), and polylactic acid (PLA). The compressive strength of scaffolds is similar to that of human bone tissue. In vitro and in vivo experiments show that the scaffolds have good biocompatibility. The scaffold can maintain the biomechanical stability of the bone defect area during the follow‐up period of 20 weeks and has no damage to liver and kidney in animal experiments. Scaffold degradation is accompanied by trabecular bone and vessel neogenesis. While the PLA group and control group cannot carry out effective bone defect repair, the bone defect repair effect of the PLA‐CSH‐BAG group is satisfactory. In conclusion, the biodegradable porous scaffold has been proposed as a safe and effective approach for the repair of bone defects. [ABSTRACT FROM AUTHOR]

Background: Chronic ethanol overconsumption promotes alcohol‐associated liver disease (ALD), characterized by hepatocyte injury, inflammation, hepatic stellate cell (HSC) activation, and fibrosis. Hyaluronan (HA) concentration is greater in livers and blood from advanced ALD patients than patients with advanced non‐ALD. In the liver, HSCs are the major HA producers. The relationship between ethanol, HA, and HSC activation is incompletely understood. Thus, here, we tested the hypothesis that ethanol enhances HSC activation in a HA‐dependent manner. Methods: Liver tissue microarrays (TMAs) containing steatotic livers from donors with or without a history of alcohol consumption were used to measure HA and collagen content. Mice were fed a moderate (2%, v/v) ethanol‐containing diet or pair‐fed control diet for 2 days, after which they were given a single carbon tetrachloride (CCl4) injection. To inhibit HA synthesis, we provided 4‐methylumbelliferone (4MU) daily. We used LX2 cells, a human HSC cell line, to determine the impact ethanol had on LPS responses, with or without concurrent 4MU exposure. Results: CCl4 induced liver injury, but it did not differ between ethanol or control diet fed mice with or without 4MU treatment. Ethanol feeding enhanced CCl4‐induced hepatic HA content, which was paralleled by HA synthase (Has)2 transcript abundance; 4MU treatment normalized both. Consistently, HSC activation, assessed by measuring αSMA mRNA and protein, was induced by CCl4 exposure, enhanced by ethanol feeding, and normalized by 4MU. Hepatic transcripts, but not protein, for Ccl2 were enhanced by ethanol feeding and normalized by 4MU exposure. Finally, ethanol‐exposed LX2 cells made more LPS‐stimulated CCL2 mRNA and protein than cells not exposed to ethanol; 4MU prevented this. Conclusion: These data show that ethanol augments HSC activation through HA synthesis and enhances hepatic profibrogenic features. Therefore, targeting HSC HA production could potentially attenuate liver disease in ALD patients. [ABSTRACT FROM AUTHOR]

Background: The basis for familial alcohol use disorder (AUD) remains an enigma due to various biological and societal confounds. The present study used three of the most adopted and documented rat models, combining the alcohol‐preferring/non‐alcohol‐preferring (P/NP) lines and high alcohol‐drinking/low alcohol‐drinking (HAD/LAD) replicated lines, of AUD as examined through the lens of whole genomic analyses. Methods: We used complete genome sequencing of the P/NP lines and previously published sequences of the HAD/LAD replicates to enhance the discovery of variants associated with AUD and to remove confounding with genetic background and random genetic drift. Specifically, we used high‐order statistical methods to search for genetic variants whose frequency changes in whole sets of gene ontologies corresponded with phenotypic changes in the direction of selection, that is, ethanol‐drinking preference. Results: Our first finding was that in addition to variants causing translational changes, the principal genetic changes associated with drinking predisposition were silent mutations and mutations in the 3′ untranslated regions (3′UTR) of genes. Neither of these types of mutations alters the amino acid sequence of the translated protein but they influence both the rate and conformation of gene transcription, including its stability and posttranslational events that alter gene efficacy. This finding argues for refocusing human genomic studies on changes in gene efficacy. Among the key ontologies identified were the central genes associated with the Na+ voltage–gated channels of neurons and glia (including the Scn1a, Scn2a, Scn2b, Scn3a, Scn7a, and Scn9a subtypes) and excitatory glutamatergic secretion (including Grm2 and Myo6), both of which are essential in neuroplasticity. In addition, we identified "Nociception or Sensory Perception of Pain," which contained variants in nociception (Arrb1, Ccl3, Ephb1) and enlist sodium (Scn1a, Scn2a, Scn2b, Scn3a, Scn7a), pain activation (Scn9a), and potassium channel (Kcna1) genes. Conclusion: The multi‐model analyses used herein reduced the confounding effects of random drift and the "founders" genetic background. The most differentiated bidirectionally selected genes across all three animal models were Scn9a, Scn1a, and Kcna, all of which are annotated in the nociception ontology. The complexity of neuroplasticity and nociception adds strength to the hypothesis that neuroplasticity and pain (physical or psychological) are prominent phenotypes genetically linked to the development of AUD. [ABSTRACT FROM AUTHOR]

Background: Minibeam radiation therapy (MBRT) is an innovative dose delivery method with the potential to spare normal tissue while achieving similar tumor control as conventional radiotherapy. However, it is difficult to use a single dose parameter, such as mean dose, to compare different patterns of MBRT due to the spatially fractionated radiation. Also, the mechanism leading to the biological effects is still unknown. Purpose: This study aims to demonstrate that the hydrogen peroxide (H2O2) distribution could serve as a surrogate of dose distribution when comparing different patterns of MBRT. Methods: A free diffusion model (FDM) for H2O2 developed with Fick's second law was compared with a previously published model based on Monte Carlo & convolution method. Since cells form separate compartments that can eliminate H2O2 radicals diffusing inside the cell, a term describing the elimination was introduced into the equation. The FDM and the diffusion model considering removal (DMCR) were compared by simulating various dose rate irradiation schemes and uniform irradiation. Finally, the DMCR was compared with previous microbeam and minibeam animal experiments. Results: Compared with a previous Monte Carlo & Convolution method, this analytical method provides more accurate results. Furthermore, the new model shows H2O2 concentration distribution instead of the time to achieve a certain H2O2 uniformity. The comparison between FDM and DMCR showed that H2O2 distribution from FDM varied with dose rate irradiation, while DMCR had consistent results. For uniform irradiation, FDM resulted in a Gaussian distribution, while the H2O2 distribution from DMCR was close to the dose distribution. The animal studies' evaluation showed a correlation between the H2O2 concentration in the valley region and treatment outcomes. Conclusion: DMCR is a more realistic model for H2O2 simulation than the FDM. In addition, the H2O2 distribution can be a good surrogate of dose distribution when the minibeam effect could be observed. [ABSTRACT FROM AUTHOR]

Excellent capability of exosome derived from human adipose‐derived stem cell (ADSC) manifested in improving the quality of wound healing with SMD (STD Mean Difference). However, it is still in the preclinical stage and its efficacy remains uncertain. Emphasised the need for a systematic review of preclinical studies to the validity of it in ameliorate wound healing quality which accelerate the clinical application translation. We performed a systematic literature review to identify all published controlled and intervention studies comparing exosome derived from human ADSC with placebo in animal models of wound closure during wound healing. PubMed, Embase and Cochrane were employed. Risk of bias assessed by the SYRCLE tool aimed at preclinical animal studies. Administration of exosome derived from human ADSC extremely improved wound closure compared with controls, which is primary outcome (SMD 1.423, 95% confidence interval (CI) 1.137–1.709 P <.001), the same effect as ADSC. The therapeutic effect is further enhanced by modified ADSC‐EV. Other outcomes: density and the number of blood vessels: (SMD 1.593 95% CI 1.007–2.179 P <.001)；Fibrosis‐related protein expression was highly expressed in the early term of wound healing, decreased in shaping period, which automatically regulates wound collagen deposition. Scar size, number of fibroblast and epithelial cell migration and proliferation expressed were ranked as follows: modified adipose stem cell exosomes > adipose stem cell exosomes > controls. Exosome derived from human ADSC, especially after enrichment for specific non‐coding RNA, is a promising approach to improve healing efficiency. [ABSTRACT FROM AUTHOR]

A new recombinant proteolytic enzyme, isolated from maggot saliva, with fibrinolytic action has been investigated through a series of non‐clinical toxicology and in‐vitro/in‐vivo pharmacology studies to explore its potential safety and efficacy as an enzymatic debridement agent for use in chronic wounds. Studies indicate that the enzyme has a good safety profile. When locally administered, it is not detrimental to wound healing, is non‐sensitising and is rapidly inactivated in the systemic circulation. Adverse effects are limited, at very high concentrations, to transient erythema at the site of application. In‐vitro testing indicates that the enzyme, whilst selective for fibrin, has additional proteolytic action against collagen and elastin, with enzymatic action for all three substrates being dose dependent. In‐vivo, we used an established MRSA biofilm model, in which microbiological counts were used as a surrogate for debridement efficacy. Here, we showed that higher concentrations of the enzyme in a formulated proprietary gel, significantly reduced MRSA counts over a period of 2 to 14 days, and significantly improved the vascularity of the wound at 14 days. Together, these data support the potential for this maggot‐derived proteolytic enzyme as a clinically effective debriding agent. [ABSTRACT FROM AUTHOR]

The current study was aimed at the assessment of the effect of chitosan‐ZnO/Selenium nanoparticles scaffold on infected wound healing and care of paediatric surgery treatment. The nanoparticle scaffolds were developed from sources such as chitosan (CS), different concentrations of zinc oxide (ZnO), and Selenium (SeNPs) nanoparticles by freeze‐drying method. The structural and chemical properties of nanoparticles were investigated by UV–Vis, fourier transform infrared spectroscopy (FTIR), and phase identification by x‐ray diffraction analysis. The surface morphology of CS, chitosan‐ZnO (CS‐ZnO) and chitosan‐ZnO/SeNPs was analysed using a scanning electron microscope. The incorporation of ZnO and SeNPs along with CS polymer induces antioxidant and antimicrobial functions. The bacterial susceptibility to nanoparticle scaffolds against Escherichia coli and Staphylococcus aureus showed the excellent antibacterial effects of ZnO and SeNPs. In‐vitro studies of fibroblast of NIH 3 T3 and HaCaT cell lines revealed the biocompatibility, cell adhesion, cell viability, and proliferation of scaffold in the wound site. Also, results of in‐vivo studies strongly enhanced collagen synthesis, re‐epithelialization, and rapid wound closure. Thus, the synthesised chitosan‐ZnO/SeNPs nanoparticle scaffold resulted in significant improvement in histopathological indices in the full thickness of wound healing after nursing care of paediatric fracture surgery. [ABSTRACT FROM AUTHOR]