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The yellow scorpion, Buthus boumalenii, has long been recognized as a potentially dangerous species endemic to Morocco. However, there is currently no data on the in vivo toxicity or effects of Buthus boumalenii venom, as it has not been studied to the best of our knowledge. In order to achieve the objective of this study, the LD50 of B. boumalenii venom will be initially calculated, followed by determining its impact on vital organs using histological, biochemical, and behavioral analyses. The investigation also explores potential neurobehavioral impairments in Swiss mice at intervals of 3 hours, 6 hours, and 12 hours post-envenomation. The LD50 for Buthus boumalenii scorpion venom in mice was determined to be 353 µg/kg based on body weight. The findings of the study highlight the potential lethality of B. boumalenii. Observations related to the poisoning provide indications of potential tissue damage in specific vital organs. To sum up, the venom from this scorpion has the potential to result in considerable medical complications, including fatalities, particularly in individuals at risk. Consequently, healthcare practitioners should be knowledgeable about the diverse scorpion species in their regions and adhere to contemporary medical protocols when addressing scorpion envenomation. [ABSTRACT FROM AUTHOR]

Background/Objectives: Stimulated capsaicin-sensitive peptidergic sensory nerves release somatostatin (SST), which has systemic anti-inflammatory and analgesic effects, correlating with the severity of tissue injury. Previous studies suggest that SST release into the systemic circulation is likely to serve as a protective mechanism during thoracic and orthopedic surgeries, scoliosis operations, and septic conditions, all involving significant tissue damage, pain, and inflammation. In a severe systemic inflammation rat model, SST released from sensory nerves into the bloodstream enhanced innate defense, reducing mortality. Inflammation is the key pathophysiological process responsible for the formation, progression, instability, and healing of atherosclerotic plaques. Methods: We measured SST-like immunoreactivity (SST-LI) in the plasma of healthy volunteers in different age groups and also that of stable angina patients with coronary heart disease (CHD) using ELISA and tracked changes during invasive coronary interventions (coronarography) with and without stent implantation. Samples were collected at (1) pre-intervention, (2) after coronarography, (3) 2 h after coronarography initiation and coronary stent placement, and (4) the next morning. Results: There was a strong negative correlation between SST-LI concentrations and age; the plasma SST-LI of older healthy volunteers (47–73 years) was significantly lower than in young ones (24–27 years). Baseline SST-LI in CHD patients who needed stents was significantly reduced compared to those not requiring stents. Plasma SST-LI significantly increased two hours post stent insertion and the next morning compared to pre-intervention levels. Conclusions: Age-related SST decrease might be a consequence of lower gene expression within specific hypo-thalamic nuclei as has been previously demonstrated in rodent animals. Reperfusion of ischemic myocardium post-stent implantation may trigger SST release, potentially offering protective benefits in coronary heart disease. Investigating this SST-mediated mechanism could offer valuable insights for future therapies. [ABSTRACT FROM AUTHOR]

An excessive inflammatory response plays an important role in pathological tissue damage associated with pathogen infection and tumorigenesis. Blood POZ-containing gene type 2 (BPOZ-2), an adaptor protein for the E3 ubiquitin ligase scaffold protein CUL3, is a negative regulator of the inflammatory response. In this study, we investigated the pathophysiological functions of BPOZ-2 in dextran sodium sulfate (DSS)-induced colon injury and diethylnitrosamine (DEN)-induced liver damage. Our results indicated that BPOZ-2 deficiency increased IL-1β induction after DSS and DEN treatment. In addition, BPOZ-2-deficient mice were more susceptible to DSS-induced colitis. Notably, BPOZ-2 deficiency aggravated DEN-induced acute liver injury. These results revealed that BPOZ-2 protected against pathological tissue damage with a dysregulated inflammatory response. • BPOZ-2-deficient mice are more susceptible to DSS-induced colitis and aggravates DEN-induced acute liver injury. • BPOZ-2 deficiency increases the inflammatory response in response to DSS and DEN treatment. • BPOZ-2 is a negative regulator of the inflammatory response. [ABSTRACT FROM AUTHOR]

Extravasation is a common and potentially severe complication of intravenous drug administration. The COVID-19 pandemic has resulted in a rapid upsurge in the use of remdesivir. Data about complications experienced during use of the drug are limited. The authors describe here the first case report of a patient with remdesivir extravasation in the UK, and a systematic review of all known cases worldwide, as well as their management and long term sequelae. Oedema was reported in all cases, erythema in five cases and pain in four cases. The one case with persistent sequelae had delayed diagnosis which may have caused potential for more severe injury. The two cases which had the fastest resolution of symptoms were those where the extravasation was noticed part-way through the infusion, hinting at a dose-dependent relationship. The acidic pH of remdesivir and high infiltration volumes are the factors which most likely explain the mechanism of tissue injury and should be the targets on which to base a treatment strategy. The clearest recommendation from our review is the importance of awareness to recognise injury early and prevent the most severe sequelae. The authors propose a recommendation for aspiration and hyaluronidase injection to "disperse and dilute" remdesivir. [ABSTRACT FROM AUTHOR]

Background and Objectives: Radiofrequency catheter ablation (RFCA) is a highly successful intervention. By comparing the lesion changes in prostate parenchymal and striated muscle tissues after RFCA with and without cooling, it was possible to assess the correlation between the shape regularity, area, and perimeter of the thermal lesion, and to predict the geometric shape changes of the lesions. Materials and Methods: A standard prostate and striated muscle RFCA procedure was performed on 13 non-purebred dogs in two sessions: no cooling and cooling with 0.1% NaCl solution. Microtome-cut 2–3 µm sections of tissue samples were stained with haematoxylin and eosin and further examined. The quotient formula was employed to evaluate the geometric shape of the damage zones at the ablation site. Results: The extent of injury following RFCA in striated muscle tissue was comparable to that in prostate parenchymal tissue. Regression analysis indicated a strong and positive relationship between area and perimeter in all experimental groups. In the experimental groups of parenchymal tissues with and without cooling, an increase in the area or perimeter of the damage zone corresponded to an increase in the quotient value. A similar tendency was observed in the striated muscle group with cooling. However, in the striated muscle group without cooling, an increase in lesion area or perimeter lowered the quotient value. Standardised regression coefficients demonstrated that in the striated muscle with cooling, the damage zone shape was more determined by area than perimeter. However, in the parenchymal tissue, the perimeter had a more substantial impact on the damage zone shape than the area. Conclusions: The damage area and perimeter have predictive power on the overall shape regularity of damage zone geometry in both striated muscles and parenchymal tissue. This approach is employed to achieve a balance between the need for tumour eradication and the minimisation of ablation-induced complications to healthy tissue. [ABSTRACT FROM AUTHOR]

This study aimed to compare the tissue damage caused by barbed sutures and conventional sutures using scanning electron microscopy (SEM). porcine myocardium was incised and sutured using different thread types: barbed suture, (STRATAFIX® Spiral PDS PLUS) and conventional sutures, (VICRYL® and PDS Plus®). Needle hole shapes were examined at magnifications of 30x-100x. VICRYL® suture damaged the tissue and created large gaps around the needle holes. The tissue around the needle holes was smoother and less damaged in the single suture ligations with PDS®; however, a large gap had formed. In the continuous suture with STRATAFIX®, the tissue around the needle holes was significantly smoother and minimally damaged, with no noticeable gaps around the needle holes. Barbed sutures reduced the load on needle holes and minimised tissue damage owing to the dispersion of traction forces by the barbs compared with conventional sutures. [ABSTRACT FROM AUTHOR]

BACKGROUND: Trauma, inflammation, tumors, and other factors commonly result in tissue defects, including damage to bones, joints, skeletal muscles, and associated blood vessels and nerves. Clinically, it is often challenging to repair all the functional injuries involving these tissues, posing great challenges for OBJECTIVE: To elucidate the application of 3D-printed hydrogel biomimetic structures in motor system tissue injuries. METHODS: Relevant literature published from 2003 to 2023 was retrieved from the CNKI, Wanfang Data, and PubMed databases. The Chinese and English search terms were “3D printing, hydrogel, bone, cartilage, muscle, nerve, vasculature, tissue engineering, biomimetics”. After screening, induction and summary, 63 relevant articles were finally included for review. RESULTS AND CONCLUSION: (1) 3D-printed hydrogels can be achieved in several different ways, such as direct 3D printing, hybrid mode 3D printing, or manufacturing 3D bio-inspired structures in hydrogels by printing intermediate molds. Among these manufacturing processes, extrusion-based printing is currently the most widely used for 3D printing hydrogels with bio-inspired structures. (2) Bioprinting hydrogels enables the production of biovascular structures with complex perfusion patterns, and it can induce the formation of biologically relevant, highly organized, and intact blood vessels. (3) By utilizing bioprinting technology, it is possible to mimic the hierarchical structure and function of natural bone, combining hydrogels with different types of cells and growth factors to create tissue engineering scaffolds that closely resemble the composition and structure of natural bone, thereby facilitating better bone regeneration. (4) Neural fiber structure can be bio-inspired by incorporating different fiber materials into the 3D-printed hydrogel conduit structure. (5) Utilizing specific hydrogel formulations, it is possible to simulate muscle bundle structures or engineer muscle tissues integrating blood vessels and nerves, which can enhance the repair of volumetric muscle injuries in vivo. (6) Based on current related research, methacrylated gelatin, which closely resembles the characteristics of the extracellular matrix, is often considered as a raw material for 3D printing various tissue bio-inspired structures. Researchers also incorporate different growth factors or cells into the hydrogels for bioprinting to achieve the desired tissue repair outcomes. (7) Although there is a lack of clinical trial reports on 3D-printed hydrogel bio-inspired structures, this indicates that the clinical translation of such materials still requires a long-term process. Further improvements are needed in terms of clinical applications, as well as comprehensive in vivo safety assessments. [ABSTRACT FROM AUTHOR]

Soft tissue is an important operation object in robot-assisted surgery and its mechanical response is of great significance to the precision of surgical operation. Accurate prediction of soft tissue mechanical properties can effectively avoid the potential damage of biological tissue caused by excessive operating force. In this paper, three typical mechanical responses of soft tissue were obtained by no-slip compression experiments of liver tissue. Second, the prediction model of soft tissue mechanical response based on gray prediction was established, and the influence of key parameters of the model on the precision of mechanical response prediction was analyzed. The results show that the gray prediction model can accurately predict the mechanical response of soft tissue, and the prediction accuracy is the highest when the number of historical data is 7. The prediction method of soft tissue mechanical response proposed in this paper will provide important data reference for accurate operation of surgery. [ABSTRACT FROM AUTHOR]

Medical needle innovations have utilized rotating motion to enhance tissue-cutting capabilities, reducing cutting force and improving clinical outcomes. This study analyzes the effects of six essential factors on insertion and extraction forces during bone marrow biopsy (BMB) procedures. The study uses Taguchi's L32 orthogonal array and numerically simulates the BMB process using the Lagrangian surface-based method on a three-dimensional (3D) heterogeneous Finite Element (FE) model of the human iliac crest. The study evaluates cutting forces in needle insertion and extraction using uni-directional (360° rotation) and bidirectional (180° clock and anti-clock rotation) bioinspired BMB needles. This work aims to create an AI tool that assists researchers and clinicians in selecting the most suitable and safe design parameters for a bio-inspired barbed biopsy needle. An efficient Graphical User Interface (GUI) has been developed for easy use and seamless interaction with the AI tool. With a remarkable accuracy rate exceeding 98%, the tool's predictions hold significant value in facilitating the development of environmentally conscious biopsy needles. The tool demonstrates significantly higher efficiency compared to Abaqus, rendering it a valuable asset for researchers and clinicians engaged in bio-inspired biopsy needle development. [ABSTRACT FROM AUTHOR]

Differential host responses in coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) remain poorly characterized. Here, we use next-generation sequencing to longitudinally analyze blood samples from pediatric patients with COVID-19 or MIS-C across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures of cell injury and death between COVID-19 and MIS-C, with increased multiorgan involvement in MIS-C encompassing diverse cell types, including endothelial and neuronal cells, and an enrichment of pyroptosis-related genes. Whole-blood RNA profiling reveals upregulation of similar pro-inflammatory pathways in COVID-19 and MIS-C but also MIS-C-specific downregulation of T cell-associated pathways. Profiling of plasma cell-free RNA and whole-blood RNA in paired samples yields different but complementary signatures for each disease state. Our work provides a systems-level view of immune responses and tissue damage in COVID-19 and MIS-C and informs future development of new disease biomarkers.

The present study proposes an advanced multi-field modeling approach to optimize in silico subcutaneous insulin release. We introduce a generalized fluid-pharmacokinetics framework, integrating syringe injection and subcutaneous permeability, thus advancing a first-of-its-kind computational model of insulin delivery port. The proposed theoretical framework comprises three main elements: (1) a realistic geometry model of a commercial port device and the surrounding subcutaneous tissues; (2) a staggered fluid dynamics model of syringe injection coupled with a multi-compartmental model of insulin absorption within a porous medium; (3) a computational-based device optimization to minimize the onset of lipodystrophies due to multiple injection procedures. A novel tissue lesion model is advanced, linking local subcutaneous pressure levels to altered permeability that comprise accumulation effects due to repeated injections. The computational framework was fine-tuned according to state-of-the-art experimental evidence, and extensive numerical analyses predicted unexplored insulin port devices behaviors thus allowing comparison of computed haematic insulin profiles with those obtained clinically. Accordingly, a vast parametric analysis was performed to identify the optimal conditions that minimize tissue lesions and support prolonged device usage.

Chromium (Cr) is one of the most prevalent and potentially hazardous heavy metal found in the environment that can cause carcinogenic, genotoxic, and organ-specific irreversible complications. The most severe adverse outcome of Cr on humans involves oxidative stress. Melatonin was evidenced to alleviate such stress with various mechanisms including antioxidative potential and metal chelation. Male Wistar rats were divided into 4 groups and treated for 14 days. The first group (control) was treated with vehicle; the second group was orally administered with melatonin (20 mg/kg b.w./day); the third group was injected with sodium dichromate dihydrate (5 mg/kg bw, s.c. every alternate day); and the fourth group was administered with melatonin, 30 min before Cr administration. The treatment of rats with Cr (VI) was found to affect the metabolic pathways by altering the activities of enzymes possibly through uncompetitively binding with them. The current study also demonstrated that melatonin efficiently preserved the glucose levels and blood lipid profile. Moreover, melatonin was further found to protect the activities of glycolytic, Krebs’ cycle, and ETC enzymes. Further, melatonin pre-treatment reduced the production of O2.− anion free radical and Ca2+ overload to protect the mitochondria at the ultrastructural level and reduced DNA damage to some extent. Therefore, this research strongly recommends melatonin as a therapeutic molecule against Cr-induced oxidative stress-mediated liver, heart, and kidney disorders.

Coronaviruses can cause serious respiratory tract infections and may also impact other end organs such as the central nervous system, the lung and the heart. The coronavirus disease 2019 (COVID-19) has had a devastating impact on humanity. Understanding the mechanisms that contribute to the pathogenesis of coronavirus infections, will set the foundation for development of new treatments to attenuate the impact of infections with coronaviruses on host cells and tissues. During infection of host cells, coronaviruses trigger an imbalance between increased production of reactive oxygen species (ROS) and reduced antioxidant host responses that leads to increased redox stress. Subsequently, increased redox stress contributes to reduced antiviral host responses and increased virus-induced inflammation and apoptosis that ultimately drive cell and tissue damage and end organ disease. However, there is limited understanding how different coronaviruses including SARS-CoV-2, manipulate cellular machinery that drives redox responses. This review aims to elucidate the redox mechanisms involved in the replication of coronaviruses and associated inflammation, apoptotic pathways, autoimmunity, vascular dysfunction and tissue damage that collectively contribute to multiorgan damage.

Abstract Background Deteriorations in eggshell and bone quality are major challenges in aged laying hens. This study compared the differences of eggshell quality, bone parameters and their correlations as well as uterine physiological characteristics and the bone remodeling processes of hens laying eggs of different eggshell breaking strength to explore the mechanism of eggshell and bone quality reduction and their interaction. A total of 240 74-week-old Hy-line Brown laying hens were selected and allocated to a high (HBS, 44.83 ± 1.31 N) or low (LBS, 24.43 ± 0.57 N) eggshell breaking strength group. Results A decreased thickness, weight and weight ratio of eggshells were observed in the LBS, accompanied with ultrastructural deterioration and total Ca reduction. Bone quality was negatively correlated with eggshell quality, marked with enhanced structures and increased components in the LBS. In the LBS, the mammillary knobs and effective layer grew slowly. At the initiation stage of eggshell calcification, a total of 130 differentially expressed genes (DEGs, 122 upregulated and 8 downregulated) were identified in the uterus of hens in the LBS relative to those in the HBS. These DEGs were relevant to apoptosis due to the cellular Ca overload. Higher values of p62 protein level, caspase-8 activity, Bax protein expression and lower values of Bcl protein expression and Bcl/Bax ratio were seen in the LBS. TUNEL assay and hematoxylin-eosin staining showed a significant increase in TUNEL-positive cells and tissue damages in the uterus of the LBS. Although few DEGs were identified at the growth stage, similar uterine tissue damages were also observed in the LBS. The expressions of runt-related transcription factor 2 and osteocalcin were upregulated in humeri of the LBS. Enlarged diameter and more structural damages of endocortical bones and decreased ash were observed in femurs of the HBS. Conclusion The lower eggshell breaking strength may be attributed to a declined Ca transport due to uterine tissue damages, which could affect eggshell calcification and lead to a weak ultrastructure. Impaired uterine Ca transport may result in reduced femoral bone resorption and increased humeral bone formation to maintain a higher mineral and bone quality in the LBS. Graphical Abstract

Abstract Background Dental implants can cause complications, including the loosening of the abutment screw or fracture. However, there is no standardized technique for removing broken abutment screws. This necessitates further research. Objective This study aimed to measure heat generation during screw removal to better understand its implications for dental implant procedures. Material and methods The experimental setup involved using synthetic bone blocks and titanium implants. An ultrasonically operated instrument tip was utilized for screw removal. Infrared thermometry was employed for accurate temperature measurement, considering factors such as emissivity and distance. Statistical analysis using linear regression and ANOVA was conducted. Results The findings revealed an initial rapid temperature increase during the removal process, followed by a gradual decrease. The regression model demonstrated a strong correlation between time and temperature, indicating the heat generation pattern. Conclusion Heat generation during screw removal poses risks such as tissue damage and integration issues. Clinicians should minimize heat risks through an intermittent approach. The lack of a standardized technique requires further research and caution. Understanding the generated heat optimizes implant procedures.

Kai Guo,1,* Yong Wang,1,* Zi-Xuan Feng,1 Xiao-Ying Lin,1 Zhang-Rui Wu,1 Xin-Cao Zhong,1 Ze-Ming Zhuang,1 Tao Zhang,1 Jian Chen,2 Wei-Qiang Tan1 1Department of Plastic Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Ultrasonography, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Chen, Department of Ultrasonography, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang Province, People’s Republic of China, Email chenjianzuj4h@zju.edu.cn Wei-Qiang Tan, Department of Plastic Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China, Email tanweixxxx@zju.edu.cnAbstract: The various tissue damages are a severe problem to human health. The limited human tissue regenerate ability requires suitable biomaterials to help damage tissue repair and regeneration. Therefore, many researchers devoted themselves to exploring biomaterials suitable for tissue repair and regeneration. Polydopamine (PDA) as a natural and multifunctional material which is inspired by mussel has been widely applied in different biomaterials. The excellent properties of PDA, such as strong adhesion, photothermal and high drug-loaded capacity, seem to be born for tissue repair and regeneration. Furthermore, PDA combined with different materials can exert unexpected effects. Thus, to inspire researchers, this review summarizes the recent and representative development of PDA biomaterials in tissue repair and regeneration. This article focuses on why apply PDA in these biomaterials and what PDA can do in different tissue injuries. Keywords: polydopamine, biomaterial, tissue damage, tissue regeneration

Background: In the emergency department, many cases present with a bullet injury. Bullet injury accidents are highly sensitive cases due to the medico-legal aspect and political issues. Gunshot injuries have increased in the past few years because of the easy availability of guns and firearms. Young male adults are more involved in criminal activity and suicides. Gunshot injuries are high-energy injuries that lead to extensive soft tissue damage and bone fractures. Materials and Methods: This retrospective descriptive study was performed on eight patients with gunshot injuries between January 2021 and December 31, 2021. After initial first aid, patients underwent an X-ray and computed tomography for further assessment of soft tissue damage, surgical planning, and forensics. SPSS software was used to analyze the collected data and generate descriptive statistics, and the data were plotted in tabular format. Results: In this article, we discussed the imaging investigation modalities primarily used for firearm injury elaborated on the tissue damage due to firearms and secondary complications. Of eight patients, 87% had single bullet injuries, while 13% had shotgun injuries. In addition, 62% had head and neck injuries, whereas 38% had chest and abdomen injuries. Conclusion: There are many cases presented in the emergency department with firearm injuries. Radiological investigations are always essential for management or surgical planning to rule out the visceral damage and medico-legal aspects. For an accurate diagnosis, a radiologist must know about the essentials of firearm injuries.

In Turkish traditional medicine, the leaves, fruit and seeds of Prunus laurocerasus L., commonly called Cherry laurel, are used to treat various diseases such as cancer, diabetes, influenza, tonsillitis and scalp dandruff. The medicinal value of this plant can be attributed to its rich phenolic content and high antioxidant capacity. In this study, we investigated the efficacy of P. laurocerasus (PL) fruit extract in reducing the hepatorenal side effects of doxorubicin (DOX). Sprague- Dawley rats were divided into 4 groups as Control, DOX, PL500+DOX and PL1000+DOX (n=8). PL-extracts were given perorally for two weeks (500 or 1000 mg.kg-1.day-1). After 48--h of DOX injection (15 mg/kg, i.p.), the animals were sacrificed. Compared to control, in DOX group, we observed lower levels of serum albumin, higher alanine transaminase (ALT), aspartate transaminase (AST) and creatinine levels (P <0.001 for each one); decreased Glomerular filtration rate (GFR) (P <0.01); increased urinary neutrophil gelatinase-associated lipocalin (P <0.01); and kidney injury molecule-1 (P <0.001) levels. DOX-induced hepatorenal oxidative stress was approved by increased malondialdehyde (MDA) and decreased glutathione (GSH) levels and decreased superoxide dismutase (SOD) and catalase (CAT) (P <0.001 for each one) activities. Although PL-treatment did not change serum and urinary parameters, it significantly returned hepatic MDA and GSH levels, SOD and CAT activities (P <0.001 for each one) as well as renal MDA (P <0.001) and GSH (P <0.05) levels and CAT activity (P <0.001) to control levels. While high dose PL provided a more significant (P <0.05) reduction in renal lipid peroxidation, it did not significantly affect other parameters. With these observations, it can be suggested that rather than increasing the dose, a longer duration of PL treatment after DOX induction may be more effective in preventing tissue damage and oxidative stress. [ABSTRACT FROM AUTHOR]

Background: Dental implants can cause complications, including the loosening of the abutment screw or fracture. However, there is no standardized technique for removing broken abutment screws. This necessitates further research. Objective: This study aimed to measure heat generation during screw removal to better understand its implications for dental implant procedures. Material and methods: The experimental setup involved using synthetic bone blocks and titanium implants. An ultrasonically operated instrument tip was utilized for screw removal. Infrared thermometry was employed for accurate temperature measurement, considering factors such as emissivity and distance. Statistical analysis using linear regression and ANOVA was conducted. Results: The findings revealed an initial rapid temperature increase during the removal process, followed by a gradual decrease. The regression model demonstrated a strong correlation between time and temperature, indicating the heat generation pattern. Conclusion: Heat generation during screw removal poses risks such as tissue damage and integration issues. Clinicians should minimize heat risks through an intermittent approach. The lack of a standardized technique requires further research and caution. Understanding the generated heat optimizes implant procedures. [ABSTRACT FROM AUTHOR]

Gastrointestinal surgery using a stapler is usually associated with tissue damage, anastomosis leakage, bleeding, and other complications, which is one of the effective methods for treating digestive tract cancer. The cutting properties of staples and the tissue damage occurring in the process of stapling porcine esophageal and gastric tissues have been evaluated and a new type of stapler has been designed. Since different structural and mechanical properties esophageal and gastric tissues layers, the puncturing force exhibits a fluctuating trend. Compressive stress caused by the bending of the staple legs can lead to the destruction of the vascular network inside the tissue, tissue deforms and tears. Finally, a staple with an internal incision arc (IIA) tip is designed, which meeting the performance requirements. [ABSTRACT FROM AUTHOR]

An important unanswered question in regenerative biology is to what extent regeneration is accomplished by the reactivation of gene regulatory networks used during development versus the activation of regeneration-specific transcriptional programs. Following damage, Drosophila imaginal discs, the larval precursors of adult structures, can regenerate missing portions by localized proliferation of damage-adjacent tissue. Using single-cell transcriptomics in regenerating wing discs, we have obtained a comprehensive view of the transcriptome of regenerating discs and identified two regeneration-specific cell populations within the blastema, Blastema1 and Blastema2. Collectively, these cells upregulate multiple genes encoding secreted proteins that promote regeneration including Pvf1, upd3, asperous, Mmp1, and the maturation delaying factor Ilp8. Expression of the transcription factor Ets21C is restricted to this regenerative secretory zone; it is not expressed in undamaged discs. Ets21C expression is activated by the JNK/AP-1 pathway, and it can function in a type 1 coherent feedforward loop with AP-1 to sustain expression of downstream genes. Without Ets21C function, the blastema cells fail to maintain the expression of a number of genes, which leads to premature differentiation and severely compromised regeneration. As Ets21C is dispensable for normal development, these observations indicate that Ets21C orchestrates a regeneration-specific gene regulatory network. We have also identified cells resembling both Blastema1 and Blastema2 in scribble tumorous discs. They express the Ets21C-dependent gene regulatory network, and eliminating Ets21C function reduces tumorous growth. Thus, mechanisms that function during regeneration can be co-opted by tumors to promote aberrant growth.

A 37-year-old male, with a 5-year history of liposarcoma of the right thigh, was incidentally diagnosed with two huge thoracic metastases following a fall. One of these masses, measuring 22 cm, was located in the right chest apex, adjacent to a second 20 cm mass situated in the anterior mediastinum, partially invading the left chest. The patient underwent surgical intervention for mass resection that commenced with a hemi-clamshell incision, but was then extended by completing the lower median sternotomy in order to create a T shaped incision. This type of incision provides ample access for large mediastinal tumors that extensively extend into one side of the thoracic cavity, encompass the anterior mediastinum, and partially reach into the opposite cavity. It enhances visualization, facilitates access to vital organs, allows for precise surgical maneuvers, minimizes the risk of inadvertent tissue damage, and enables thorough oncological resection. [ABSTRACT FROM AUTHOR]

Background/Objectives: Stimulated capsaicin-sensitive peptidergic sensory nerves release somatostatin (SST), which has systemic anti-inflammatory and analgesic effects, correlating with the severity of tissue injury. Previous studies suggest that SST release into the systemic circulation is likely to serve as a protective mechanism during thoracic and orthopedic surgeries, scoliosis operations, and septic conditions, all involving significant tissue damage, pain, and inflammation. In a severe systemic inflammation rat model, SST released from sensory nerves into the bloodstream enhanced innate defense, reducing mortality. Inflammation is the key pathophysiological process responsible for the formation, progression, instability, and healing of atherosclerotic plaques. Methods: We measured SST-like immunoreactivity (SST-LI) in the plasma of healthy volunteers in different age groups and also that of stable angina patients with coronary heart disease (CHD) using ELISA and tracked changes during invasive coronary interventions (coronarography) with and without stent implantation. Samples were collected at (1) pre-intervention, (2) after coronarography, (3) 2 h after coronarography initiation and coronary stent placement, and (4) the next morning. Results: There was a strong negative correlation between SST-LI concentrations and age; the plasma SST-LI of older healthy volunteers (47–73 years) was significantly lower than in young ones (24–27 years). Baseline SST-LI in CHD patients who needed stents was significantly reduced compared to those not requiring stents. Plasma SST-LI significantly increased two hours post stent insertion and the next morning compared to pre-intervention levels. Conclusions: Age-related SST decrease might be a consequence of lower gene expression within specific hypo-thalamic nuclei as has been previously demonstrated in rodent animals. Reperfusion of ischemic myocardium post-stent implantation may trigger SST release, potentially offering protective benefits in coronary heart disease. Investigating this SST-mediated mechanism could offer valuable insights for future therapies.

Background and Objectives: Radiofrequency catheter ablation (RFCA) is a highly successful intervention. By comparing the lesion changes in prostate parenchymal and striated muscle tissues after RFCA with and without cooling, it was possible to assess the correlation between the shape regularity, area, and perimeter of the thermal lesion, and to predict the geometric shape changes of the lesions. Materials and Methods: A standard prostate and striated muscle RFCA procedure was performed on 13 non-purebred dogs in two sessions: no cooling and cooling with 0.1% NaCl solution. Microtome-cut 2–3 µm sections of tissue samples were stained with haematoxylin and eosin and further examined. The quotient formula was employed to evaluate the geometric shape of the damage zones at the ablation site. Results: The extent of injury following RFCA in striated muscle tissue was comparable to that in prostate parenchymal tissue. Regression analysis indicated a strong and positive relationship between area and perimeter in all experimental groups. In the experimental groups of parenchymal tissues with and without cooling, an increase in the area or perimeter of the damage zone corresponded to an increase in the quotient value. A similar tendency was observed in the striated muscle group with cooling. However, in the striated muscle group without cooling, an increase in lesion area or perimeter lowered the quotient value. Standardised regression coefficients demonstrated that in the striated muscle with cooling, the damage zone shape was more determined by area than perimeter. However, in the parenchymal tissue, the perimeter had a more substantial impact on the damage zone shape than the area. Conclusions: The damage area and perimeter have predictive power on the overall shape regularity of damage zone geometry in both striated muscles and parenchymal tissue. This approach is employed to achieve a balance between the need for tumour eradication and the minimisation of ablation-induced complications to healthy tissue.

Swelling in the vocal folds is caused by the local accumulation of fluid, and has been implicated as a phase in the development of phonotraumatic vocal hyperfunction and related structural pathologies, such as vocal fold nodules. It has been posited that small degrees of swelling may be protective, but large amounts may lead to a vicious cycle wherein the engorged folds lead to conditions that promote further swelling, leading to pathologies. As a first effort to explore the mechanics of vocal fold swelling and its potential role in the etiology of voice disorders, this study employs a finite-element model with swelling confined to the superficial lamina propria, which changes the volume, mass, and stiffness of the cover layer. The impacts of swelling on a number of vocal fold kinematic and damage measures, including von Mises stress, internal viscous dissipation, and collision pressure, are presented. Swelling has small but consistent effects on voice outputs, including a reduction in fundamental frequency with increasing swelling (10 Hz at 30 % swelling). Average von Mises stress decreases slightly for small degrees of swelling but increases at large magnitudes, consistent with expectations for a vicious cycle. Both viscous dissipation and collision pressure consistently increase with the magnitude of swelling. This first effort at modeling the impact of swelling on vocal fold kinematics, kinetics, and damage measures highlights the complexity with which phonotrauma can influence performance metrics. Further identification and exploration of salient candidate measures of damage and refined studies coupling swelling with local phonotrauma are expected to shed further light on the etiological pathways of phonotraumatic vocal hyperfunction. [ABSTRACT FROM AUTHOR]

Aim: This study investigates the protective effects of Dinoprost against Ischemia/ Reperfusion (I/R) damage in the rat ovary, focusing on the expression of cyclooxygenase-2 (COX-2), Interleukin-1β (IL1β), and Tumor Necrosis Factor-α (TNF-α). Additionally, the impact of Dinoprost on reducing hemorrhage in the ovarian tissue is evaluated. Materials and Methods: A total of 24 rats were randomly divided into four groups: Control, Ischemia (Isch), I/R, and Dino+I/R. Ischemia was induced by clamping the ovarian blood supply, followed by reperfusion. Dinoprost was administered before reperfusion in the Dino+I/R group. COX-2, IL1β, and TNF-α expression levels were assessed through histochemical and immunochemical analyses. Hemorrhage in the ovarian tissue was also examined. Results: The Dino+I/R group exhibited a significant decrease in COX-2 expression compared to the Isch and I/R groups (p<0.05). However, there were no significant changes in the expression levels of IL1β and TNF-α among the groups. Notably, the Dino+I/R group showed significantly reduced hemorrhage compared to the Isch and I/R groups (p<0.05). Conclusion: Dinoprost demonstrated a protective effect against I/R damage in the rat ovary, primarily by attenuating COX-2 expression and reducing hemorrhage. These findings suggest the potential therapeutic utility of Dinoprost in mitigating ovarian I/R injury, emphasizing its role in preserving ovarian function and fertility. [ABSTRACT FROM AUTHOR]

Severe infections induce immune defense mechanisms and initial tissue damage, which produce an inflammatory neutrophil response. Upon dysregulation of these responses, inflammation, further tissue damage, and systemic spread of the pathogen may occur. Subsequent vascular inflammation and activation of coagulation processes may cause microvascular obstruction at sites distal to the primary site of infection. Low immunoglobulin (Ig) M and IgG levels have been detected in patients with severe infections like sCAP and sepsis, associated with increased severity and mortality. Based on Ig's modes of action, supplementation with polyvalent intravenous Ig preparations (standard IVIg or IgM/IgA-enriched Ig preparations) has long been discussed as a treatment option for severe infections. A prerequisite seems to be the timely administration of Ig preparations before excessive tissue damage has occurred and coagulopathy has developed. This review focuses on nonclinical and clinical studies that evaluated tissue-protective activities resulting from interactions of Igs with neutrophils, complement, and the coagulation system. The data indicate that coagulopathy, organ failure, and even death of patients can possibly be prevented by the timely combined interactions of (natural) IgM, IgA, and IgG with neutrophils and complement. [ABSTRACT FROM AUTHOR]

Background: Mechanical ischemic preconditioning (MIPC) is defined as applying brief periods of ischemia before tissue reperfusion. This mechanism protects tissues against injury from sustained ischemia followed by reperfusion. We aimed to analyze the effects of MIPC on the tolerance of muscle flap tissue depending on the type and duration of ex vivo cold ischemia storage. Methods: We studied the effects of MIPC on interstitial edema, inflammation, and muscle necrosis. Thirty-two porcine latissimus dorsi flaps were equally divided over four groups. Groups were divided based on the application of MIPC (every 15 min for a total of 1 h) or not, and the submersion into heparin or IGL-1®. Iterative biopsies were performed before harvesting the flap and one, two and 3 h after cold ischemia storage. Results: Preconditioning free flaps before cold storage in heparin significantly decreased muscle necrosis, interstitial edema, and muscle cell size. Respectively, a decrease of 67%, 37% and 28% was seen in this group (p < 0.05). Preconditioning free flaps before cold storage in IGL-1® reduced necrosis by 26%, interstitial edema by 37% and muscle cell size by 33% (p < 0.05). Conclusions: We found that MIPC significantly reduces interstitial edema, inflammation and necrosis and may increase the rate of successful revascularizations. However, studies assessing those tissular damage parameters after reperfusion of the flap need to be performed to assess more correctly inflammation and post-operative infections and to confirm the potential benefits of ICP. Level of evidence: Not gradable [ABSTRACT FROM AUTHOR]

Collagen, the most abundant protein in our bodies, plays a crucial role in maintaining the structural integrity of various tissues and organs. Beyond its involvement in skin elasticity and joint health, emerging research suggests that collagen may significantly impact the treatment of complex diseases, particularly those associated with tissue damage and inflammation. The versatile functions of collagen, including skin regeneration, improving joint health, and increasing bone strength, make it potentially useful in treating different diseases. To the best of my knowledge, the strategy of using collagen to treat comorbid diseases has not been widely studied. This paper aims to explore the potential of collagen in treating comorbid diseases, including rheumatoid arthritis, osteoarthritis, osteoporosis, psoriatic arthritis, sarcopenia, gastroesophageal reflux, periodontitis, skin aging, and diabetes mellitus. Collagen-based therapies have shown promise in managing comorbidities due to their versatile properties. The multifaceted nature of collagen positions it as a promising candidate for treating complex diseases and addressing comorbid conditions. Its roles in wound healing, musculoskeletal disorders, cardiovascular health, and gastrointestinal conditions highlight the diverse therapeutic applications of collagen in the context of comorbidity management. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder, and numerous aberrations of T cell responses have been reported and were implicated in its pathophysiology. Recently, CD4-positive T cells with cytotoxic potential were shown to be involved in autoimmune disease progression and tissue damage. However, the effector functions of this cell type and their potential molecular mechanisms in SLE patients remain to be elucidated. In this study, we find that cytotoxic CD4+CD28− T cells are expanded in SLE patients with flow cytometry analysis, and the percentage of CD4+CD28− T cells positively correlates with the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI). Furthermore, our study suggests that interleukin-15 (IL-15) promotes the expansion, proliferation, and cytotoxic function of CD4+CD28− T cells in SLE patients through activation of the Janus kinase3-STAT5 pathway. Further study indicates that IL-15 not only mediates the upregulation of NKG2D, but also cooperates with the NKG2D pathway to regulate the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. Together, our study demonstrated that proinflammatory and cytolytic CD4+CD28− T cells expand in SLE patients. The pathogenic potential of these CD4+CD28− T cells is driven by the coupling of the IL-15/IL-15R signaling pathway and the NKG2D/DAP10 signaling pathway, which may open new avenues for therapeutic intervention to prevent SLE progression. [ABSTRACT FROM AUTHOR]

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Background: A potentially fatal complication of sepsis is septic acute kidney injury. Stem cell therapy is a potential new method of treating sepsis and has been applied to treat some human diseases. Objectives: This study investigated the effects of secretome-MSCs on NGAL, CRP, NF-κB, and MMP-9 proteins, and histopathology in mice with septic AKI. Methods: A post-test-only group design was conducted in 30 Balb/C male mice, which were randomly assigned to five groups: the control group was intraperitoneally injected with 0.5 ml of 0.9 % NaCl, the septic AKI, and the treatment groups (T1, T2, and T3) were intraperitoneally injected with 0.5 ml of 0.9 % NaCl and 0.3 mg/kg BW LPS single dose for three days. Three-day treatments of 150, 300, and 600 µl secretome-MSCs were administered intraperitoneally into the treatment groups. Furthermore, kidney and blood samples were collected for biochemical and histopathological analyses. Results: The T1, T2, and T3 groups had lower expression of NF-κB and MMP-9 and significantly lower CRP and NGAL levels than that of septic AKI group. T1 (1.21 ± 0.19), T2 (0.75 ± 0.22), and T3 (0.38 ± 0.14) groups demonstrated lower average scores for inflammation, necrosis, hemorrhage, and degeneration compared to septic AKI group (2.17 ± 0.13). Conclusions: Administration of 600 µl/20 g BW secretome-MSCs suppresses NF-κB and MMP-9 expression and reduces CRP and NGAL levels. Meanwhile, the 150 and 300 µl/20 g BW doses also indicated a greater improvement in renal tissue damage of mice with septic AKI.

Bisphenol A (BPA) is one of the environmental endocrine disruptors, due to its chemical stability it exists in abundant concentrations in water and soil consequently accumulating in the food chain and causing many endocrine-related health problems. So far, studies on the effects of BPA on marine invertebrates have focused on acute toxicity, endocrine regulation, reproduction, and development. However, fewer studies have been conducted on marine benthos. The current study aimed to detect the accumulation of BPA and its impact on tissue structure, antioxidant capacity, and immune indexes in marine worm, Urechis unicinctus. U. unicinctus, as a common marine benthic animal, were exposed to different concentrations of BPA. Blood cells and intestinal tract were taken for tissue structure inspection, and supernatant of the coelomic fluid was collected for oxidative and antioxidant biomarkers. Results showed that the accumulation of BPA in muscles of U. unicinctus tended to increase with exposure time. BPA induced a rise in H2O2 and MDA content, and altered the activities of CAT, T-SOD, GST, LSZ and ACP, weaken the immune system functions. Moreover, pathological observation showed that BPA caused severe histopathology in the respiratory intestine, stomach, and midgut. These results will be helpful to understand the response mechanism of U. unicinctus under BPA exposure and provide a reference for controlling the aquaculture conditions and marine water quality of U. unicinctus.

The purpose of this study was to explore the protective effect of SeMet on renal injury induced by AFB1 in rabbits and its molecular mechanism. Forty rabbits of 35 days old were randomly divided into control group, AFB1 group (0.3 mg AFB1/kg b.w), 0.2 mg/kg Se + AFB1 group (0.3 mg AFB1/kg b.w + 0.2 mg SeMet/kg feed) and 0.4 mg/kg Se + AFB1 group (0.3 mg AFB1/kg b.w + 0.4 mg SeMet/kg feed). The SeMet treatment group was fed different doses of SeMet diets every day for 21 days. On the 17–21 day, the AFB1 treatment group, the 0.2 mg/kg Se + AFB1 group and the 0.4 mg/kg Se + AFB1 group were administered 0.3 mg AFB1 /kg b.w by gavage (dissolved in 0.5 ml olive oil) respectively. The results showed that AFB1 poisoning resulted in the changes of renal structure, the increase of renal coefficient and serum biochemical indexes, the ascent of ROS and MDA levels, the descent of antioxidant enzyme activity, and the significant down-regulation of Nrf2, HO-1 and NQO1. Besides, AFB1 poisoning increased the number of renal apoptotic cells, rised the levels of PTEN, Bax, Caspase-3 and Caspase-9, and decreased the levels of PI3K, AKT, p-AKT and Bcl-2. In summary, SeMet was added to alleviate the oxidative stress injury and apoptosis of kidney induced by AFB1, and the effect of 0.2 mg/kg Se + AFB1 is better than 0.4 mg/kg Se + AFB1.

Total body irradiation (TBI) is a commonly used conditioning regimen for hematopoietic stem cell transplant (HCT), but dose heterogeneity and long-term organ toxicity pose significant challenges. Total marrow irradiation (TMI), an evolving radiation conditioning regimen for HCT can overcome the limitations of TBI by delivering the prescribed dose targeted to the bone marrow (BM) while sparing organs at risk. Recently, our group demonstrated that TMI up to 20 Gy in relapsed/refractory AML patients was feasible and efficacious, significantly improving 2-year overall survival compared to the standard treatment. Whether such dose escalation is feasible in elderly patients, and how the organ toxicity profile changes when switching to TMI in patients of all ages are critical questions that need to be addressed. We used our recently developed 3D image-guided preclinical TMI model and evaluated the radiation damage and its repair in key dose-limiting organs in young (~8 weeks) and old (~90 weeks) mice undergoing congenic bone marrow transplant (BMT). Engraftment was similar in both TMI and TBI-treated young and old mice. Dose escalation using TMI (12 to 16 Gy in two fractions) was well tolerated in mice of both age groups (90% survival ~12 Weeks post-BMT). In contrast, TBI at the higher dose of 16 Gy was particularly lethal in younger mice (0% survival ~2 weeks post-BMT) while old mice showed much more tolerance (75% survival ~13 weeks post-BMT) suggesting higher radio-resistance in aged organs. Histopathology confirmed worse acute and chronic organ damage in mice treated with TBI than TMI. As the damage was alleviated, the repair processes were augmented in the TMI-treated mice over TBI as measured by average villus height and a reduced ratio of relative mRNA levels of amphiregulin/epidermal growth factor (areg/egf). These findings suggest that organ sparing using TMI does not limit donor engraftment but significantly reduces normal tissue damage and preserves repair capacity with the potential for dose escalation in elderly patients.

Contaminants in aquatic ecosystems cause tissue damage in fish. In some cases, the effects of pesticide degradation on non-target organisms (aquatic) are greater than on target organisms (pests), which in turn causes faster and more aquatic deaths. The use of safety stimuli seems to be essential. The aim of this study was to investigate the effect of different prebiotic levels of Pleurotus ostreatus on histological characteristics of tilapia (Oreochromis niloticus) exposed to chlorpyrifos. This research was conducted in the fall of 2019. For this purpose, 120 tilapia fry were divided into 4 treatments for 42 days. Then, 0.5 ppm concentration of chlorpyrifos was added to each group for 16 days. At the end of the period, the fish were anesthetized with clove anesthetic solution (220 mg / l) and their liver tissue and gills were isolated for histological studies .The results showed that the treatments exposed to 0.5 ppm chlorpyrifos (poisoned control without prebiotics) had the most destructive effect on liver and gill tissue. However, combined prebiotic treatments of Pleurotus ostreatus and chlorpyrifos improved tissue damage, indicating detoxification, and a concentration of 0.2 ppt Pleurotus ostreatus had the best performance against tissue damage to the liver and gills of tilapia, indicating improved resistance. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Health Science Yuksek Ihtisas University / Yüksek İhtisas Üniversitesi Sağlık Bilimleri Dergisi is the property of Journal of Health Science Yuksek Ihtisas University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Somatostatin (SST) released from capsaicin-sensitive sensory nerves in response to stimulation exerts systemic anti-inflammatory, analgesic actions. Its elevation correlates with the extent of tissue injury. We measured plasma SST alterations during spine operations (scoliosis and herniated disc) to determine whether its release might be a general protective mechanism during painful conditions. Sampling timepoints were baseline (1), after: soft tissue retraction (2), osteotomy (3), skin closure (4), the following morning (5). Plasma SST-like immunoreactivity (SST-LI) determined by radioimmunoassay was correlated with pain intensity and the correction angle (Cobb angle). In scoliosis surgery, postoperative pain intensity (VAS 2.) 1 day after surgery significantly increased (from 1.44 SEM ± 0.68 to 6.77 SEM ± 0.82, p = 0.0028) and positively correlated with the Cobb angle (p = 0.0235). The baseline Cobb degree negatively correlated (p = 0.0459) with the preoperative SST-LI. The plasma SST-LI significantly increased in fraction 3 compared to the baseline (p < 0.05), and significantly decreased thereafter (p < 0.001). In contrast, in herniated disc operations no SST-LI changes were observed in either group. The VAS decreased after surgery both in the traditional (mean 6.83 to 2.29, p = 0.0005) and microdiscectomy groups (mean 7.22 to 2.11, p = 0.0009). More extensive and destructive scoliosis surgery might cause greater tissue damage with greater pain (inflammation), which results in a significant SST release into the plasma from the sensory nerves. SST is suggested to be involved in an endogenous postoperative analgesic (anti-inflammatory) mechanism. [ABSTRACT FROM AUTHOR]

Simple Summary: Genotype VII Newcastle disease virus (NDV) is renowned for its high tropism to the immune organs of chickens, and macrophages are a critical component in the antiviral innate immune system. The objective of this study is to investigate the role of macrophages in the pathogenesis of genotype VII NDV in chickens. Genotype VII NDV has significantly higher infectivity in macrophages compared to genotype IV NDV. Macrophage depletion resulted in no changes in virulence and virus replication but a significant deterioration of tissue damage in the spleen. Therefore, macrophages play an important role in alleviating tissue lesions caused by genotype VII NDV infection. Long-term evolution of Newcastle disease virus (NDV) results in substantial alteration in viral pathogenesis. NDVs of genotype VII, a late genotype, show marked tropism to lymphoid tissues, especially to macrophages in chickens. However, the role of macrophages in the pathogenesis of genotype VII NDV is still unclear. Herein, NDV infectivity in macrophages and the role of macrophages in the pathogenesis of genotype VII NDV in chickens were investigated. We reported that NDV strains of genotype VII (JS5/05) and IV (Herts/33) can replicate in the adherent (predominantly macrophages) and non-adherent cells (predominantly lymphocytes) derived from chicken peripheral blood mononuclear cells (PBMCs), and significantly higher virus gene copy was detected in the adherent cells. In addition, JS5/05 had significantly higher infectivity in PBMC-derived adherent cells than Herts/33, correlating with its enhanced tropism to macrophages in the spleen of chickens. Interestingly, the depletion of 68% of macrophages exerted no significant impact on clinical signs, mortality and the systematic replication of JS5/05 in chickens, which may be associated with the contribution of non-depleted macrophages and other virus-supportive cells to virus replication. Macrophage depletion resulted in a marked exacerbation of tissue damage and apoptosis in the spleen caused by JS5/05. These findings indicated that macrophages play a critical role in alleviating tissue damage caused by genotype VII NDV in chickens. Our results unveiled new roles of macrophages in NDV pathogenesis in chickens. [ABSTRACT FROM AUTHOR]

BACKGROUND: Platelet-derived extracellular vesicles are the most abundant vesicles in the circulation, rich in bioactive molecules, genetic material, proteins and other information molecules, involved in cellular communication and material exchange, not only has good procoagulant activity, but also has the promotion of tissue repair and regeneration, and has a wide range of applications in regenerative medicine. OBJECTIVE: To elaborate the secretion mechanism of platelet-derived extracellular vesicles, their application in regenerative medicine, and limiting factors for clinical transformation, and to provide some theoretical support for the clinical translation of platelet-derived extracellular vesicles. METHODS: A computerized search of the PubMed database from January 2005 to August 2023 was applied to articles relating to platelet-derived extracellular vesicles with the search terms “platelet-derived, platelet-rich plasma, extracellular vesicles, isolated, microvesicles exosomes, applications”. A total of 62 articles that met the subject criteria were finally included. RESULTS AND CONCLUSION: (1) Activated platelet-derived extracellular vesicles produce two types of vesicles, platelet-derived microparticles, whose secretion may be associated with the asymmetry of the actin cytoskeleton, and platelet-derived exosomes, which may be associated with the regulation of H+ -ATPase. (2) Platelet-derived extracellular vesicles are potential effectors of platelet concentrates and platelets themselves, and may intervene in tissue regeneration by promoting angiogenesis, influencing cellular behavior, promoting coagulation and hemostasis, and exerting inflammatory effects. (3) Platelet-derived extracellular vesicles have been reported preclinically in the field of regenerative medicine such as tissue injury, muscle regeneration, cartilage regeneration, and osteoarthritis, and clinical trial data are available as potential therapeutic approaches for wound healing. However, factors such as isolation methods, sample sources, and the types of activators limit the clinical translation of platelet-derived extracellular vesicles into the field of regenerative medicine. (4) In the future, platelet-derived extracellular vesicles may become a cell-free alternative to platelet-rich plasma in regenerative medicine, but the clinical translation of platelet-derived extracellular vesicles needs to actively search for specific markers to differentiate platelet-derived microparticles from plateletderived exosomes. The mechanism of activator-stimulated platelet-derived extracellular vesicle production, as well as the optimal method of platelet-derived extracellular vesicle collection, the optimal method of storage, the shelf life of the platelet-derived extracellular vesicles, the recommended dosage of plateletderived extracellular vesicles for clinical application, and the optimal clinical indications need to be further investigated. [ABSTRACT FROM AUTHOR]

Spilled petroleum pollution caused by seaborne oil transportation is a major marine environmental problem in the world. Petroleum pollutants contain significant amounts of low-molecular-weight alkanes and aromatics that induce toxic effects once taken up by marine organisms. Polycyclic aromatic hydrocarbons (PAHs) are a class of organic compounds with the most significant toxic environmental effects. As bivalves, which have a strong enrichment and tolerance capacity for PAHs in water, are widely distributed and easy to obtain, they are often used as model organisms for monitoring and evaluating offshore marine pollution. The blood clam (Tegillarca granosa), a bivalve with high economic value, is widely distributed in mudflats along the coast of Zhejiang Province. Blood clams have characteristics of benthic life, making them more likely to be exposed to petroleum pollutants. At present, there are few studies on the toxic effects of PAH exposure on blood clams. Herein, we chose benzo[a]pyrene (BaP), a typical PAH congener, as a contaminant, and investigated the toxic effects of acute BaP exposure on blood clams and their potential coping mechanisms.Blood clams required for the experiment were collected from Dongji Island and acclimated for a week in the laboratory. After acclimation, several healthy blood clams were randomly divided into the artificial sea water (ASW) (control group), dimethyl sulfoxide (DMSO) (solvent control group, 0.01% VDMSO/VASW), 10 μg/L BaP exposure group, and 100 μg/L BaP exposure groups based on the previous studies of our research group combined with the literature. Each group was set up with three replicates, each containing 40 individuals. The experiment lasted 96 h, and separate glass tanks were used to place all individuals in each replicate. One blood clam was randomly selected from each replicate of each concentration group at 0, 24, 48, and 96 h of exposure. After dissection on ice, the digestive gland was immediately separated using sterile forceps and scissors and stored at –80℃. The paraffin section was then used to observe the lesions of the digestive gland. A colorimetric assay was used to determine the activities of antioxidant enzymes and key enzymes involved in neurotransmission at different time points. The cell damage degree was also determined by measuring the levels of 8-hydroxy-2′- deoxyguanosine (8-OHdG) and malondialdehyde (MDA). In addition, enzyme-linked immunosorbent assays were used to determine DNA methylation levels. Finally, we measured the relative mRNA expression of antioxidant enzymes and performed a correlation analysis.Results showed prominent hemocyte infiltration and necrotic areas in the digestive gland of the blood clam after a total of 96 h of exposure to 10 and 100 μg/L BaP, indicating inflammation. The sloughing of digestive cells from the inner wall of the digestive tubule led to atrophy. Increased oxidative stress was indicated by elevated MDA and 8-OHdG content, leading to damage at the cellular level, such as lipid peroxidation and oxidative DNA damage. The activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione-S-transferase (GST), increased significantly 24 h post-exposure. This phenomenon further indicated that BaP exposure induced oxidative stress in the blood clam, with the antioxidant defense system actively regulating BaP-induced oxidative stress. The activities of two key neurotransmitter enzymes, acetylcholinesterase and acetylcholine transferase, were significantly reduced, indicating that the stress caused by BaP may induce neurotoxicity in the blood clam. In addition, we analyzed the changes in DNA methylation levels and gene expression of antioxidant enzymes in the blood clam under acute BaP exposure, finding that the DNA methylation levels were significantly decreased compared to pre-exposure, while the mRNA expression of SOD, CAT, and GST was significantly increased. Correlation analysis showed a negative correlation between DNA methylation and the gene expression of antioxidant enzymes, implying that blood clams may activate the antioxidant systems to fight against BaP toxicity by reducing DNA methylation levels. In conclusion, acute BaP exposure exerts a significant toxic effect on the blood clam, primarily characterized by histological damage, oxidative stress, and neurotoxicity. Moreover, changes in DNA methylation levels in the blood clam may be involved in the regulatory process of BaP toxic effects. This study is expected to provide new ideas for the in-depth exploration of the intrinsic regulatory mechanisms of bivalves in response to petroleum pollutant stress, and will be beneficial for resource conservation of the blood clam under the threat of petroleum pollution.