Injurious Agents Research Articles

A biomimetic multi-layer scaffold with collagen and zinc doped bioglass as a skin-regeneration agent in full-thickness injuries and its effects in vitro and in vivo

Due to the multilayer structure of skin tissue, the fabrication of a 3-layer scaffold could result in planned dermal regeneration. Herein, polyurethane (PU) and polycaprolactone (PCL), as a function of their mechanical stability and collagen due to its arginine-glycine-aspartic acid sequences, zinc ions because of overcoming the common problems of biological factors were employed. The scaffolds' physical, mechanical, and biological properties were examined by SEM, FTIR, contact angle, mechanical tensile, bacteriocidal efficacy, and hemolysis. Also, after L-929 fibroblast seeding, their biological activity was determined by SEM, DAPI, and MTT assays. Then, the cell-seeded scaffolds were implanted in full-thickness wounds of rats and evaluated by wound closure, histological, and molecular techniques. The in vivo studies showed better wound closure with the composite scaffold containing zinc ions. While its dermal re-organization was retarded in the presence of zinc ions compared to the composite scaffold containing non-doped bioglass. Despite this, the doped composite scaffold indicated better observations with the histological evaluations than the nontreated and bare scaffold groups. Real-time PCR confirmed the higher expression of FGF2 and FGFR genes in rats treated with the zinc-doped composite scaffold. In conclusion, PU/PCL-collagen/PCL-collagen containing the doped or non-doped nanoparticles showed better potential to heal dermal injuries.

Role of Txnrd3 in NiCl2-induced kidney cell apoptosis in mice: Potential therapeutic effect of melatonin

Nickel (Ni) exposure is a significant risk factor for kidney dysfunction and oxidative stress injury in humans. Thioredoxin reductase 3 (Txnrd3), an important enzyme in animals, plays a role in maintaining cellular homeostasis and regulating oxidative stress. However, its protective effect against kidney injury has been determined. Melatonin (Mel) has antioxidant and anti-apoptotic effects and therefore may be a preventive and therapeutic agent for kidney injury. Our study aimed to investigate the roles of Mel and Txnrd3 in the treatment of nickel-induced renal injury. We divided 80 wild-type mice and 80 Txnrd3 -/- mice (C57BL/6 N) into a control group treated with saline, Ni group treated with 10 mg/kg NiCl2, Mel group treated with 2 mg/kg Mel, and Ni + Mel group given NiCl2 and Mel for 21 days. Histopathological and ultrastructural observation of the kidney showed that nuclei were wrinkled and mitochondrial cristae were broken in the Ni group, and these changes were significantly attenuated by Mel treatment. Mitochondrial and nuclear damage improved significantly in the Ni + Mel and Txnrd3-/- Ni + Mel groups. Furthermore, NiCl2 exposure decreased T-AOC, SOD, and GSH activities in the kidney. The decreases in antioxidant enzyme activity were attenuated by Mel, and these improvements were abolished by Txnrd3 knockout. NiCl2-induced increases in the mRNA and protein levels of apoptosis factors (Bax, Cyt-c, caspase-3, and caspase-9) were attenuated by Mel treatment, and Txnrd3 knockout abolished the repressive effect of Mel on apoptosis genes. Overall, we concluded that Mel improves oxidative stress and apoptosis induced by NiCl2 by regulating Txnrd3 expression in the kidney. Our results provide evidence for the role of Mel in NiCl2-induced kidney injury and identify Txnrd3 as a potential therapeutic target for renal injury.

Chitosan-Based Nanogels Designed for Betanin-Rich Beetroot Extract Transport: Physicochemical and Biological Aspects.

Nanotechnology has emerged as a possible solution to improve phytochemicals' limitations. The objective of the present study was to encapsulate beetroot extract (BR Ext) within a chitosan (CS)-based nanogel (NG) designed via ionic crosslinking with tripolyphosphate (TPP) for betanin (Bet) delivery, mainly in the ophthalmic environment. BR Ext is rich in betanin (Bet) according to thin layer chromatography (TLC), UV-visible spectroscopy, and HPLC analysis. NG presented a monodisperse profile with a size of 166 ± 6 nm and low polydispersity (0.30 ± 0.03). ζ potential (ζ-Pot) of +28 ± 1 is indicative of a colloidally stable system. BR Ext encapsulation efficiency (EE) was 45 ± 3%. TEM, with the respective 3D-surface plots and AFM, showed spherical-elliptical-shaped NG. The BR Ext release profile was biphasic with a burst release followed by slow and sustained phase over 12 h. Mucoadhesion assay demonstrated interactions between NG with mucin. Moreover, NG provided photoprotection and pH stability to BR Ext. FRAP and ABTS assays confirmed that BR Ext maintained antioxidant activity into NG. Furthermore, in vitro assays using human retinal cells displayed absence of cytotoxicity as well as an efficient protection against injury agents (LPS and H2O2). NGs are a promising platform for BR Ext encapsulation, exerting controlled release for ophthalmological use.

α-Lipoic acid improves mitochondrial biogenesis and dynamics by enhancing antioxidant and inhibiting Wnt/Ca2+ pathway to relieve fluoride-induced hepatotoxic injury

Fluoride (F), widely present in water and food, poses a serious threat to liver health, and oxidative damage and mitochondrial damage are its main causes. As a natural mitochondrial protector and antioxidant, α-lipoic acid (ALA)'s alleviating effect on fluorosis liver injury and its underlying mechanism are still unclear. Therefore, this study established a fluorosis ALA intervention mice model to explore the mechanism of mitochondrial biogenesis, mitochondrial dynamics, and Wnt/Ca2+ pathway in ALA attenuating fluorosis liver injury. The results showed that ALA mitigated F-induced weight loss, hepatic structural and functional damage, hepatocytes mitochondrial damage, and decreased antioxidant levels. However, ALA did not reduce F accumulation in the femur. Further mRNA and protein detection results showed that F increased the expression levels of key genes in the mitochondrial fission (Drp1, Mff, and Fis1), mitophagy (Parkin, Pink1, and Prdx3), Wnt/Ca2+ pathway (Wnt5a and CaMK2), and rised the number and intensity of fluorescent spots of Drp1, but decreased the expression levels of key genes in the mitochondrial biogenesis (Sirt1, Sirt3, and PGC-1α) and fusion (OPA1, Mfn2, and Mfn1), and reduced the number and intensity of fluorescent spots of PGC-1α in the liver. However, the intervention of ALA relieved the F-induced changes in the expressions of the above genes. In conclusion, ALA mitigated F-induced hepatic injury through enhancing antioxidant capacity and inhibiting Wnt/Ca2+ pathway to improve mitochondrial biogenesis and dynamics disturbance. This study further reveals the hepatotoxic mechanism of F and the protective mechanism of ALA, and provides a theoretical basis for ALA as a potential preventive and palliative agent for F-induced hepatotoxic injury.

Local Use of Colistimethate Sodium as Antimicrobial Dressing Agent in Multidrug-resistant Gram-negative Bacteria-colonised Pressure Injuries in Spinal Cord Injury Patients: A Case Series

Abstract Despite advancements in dressing materials and techniques, the management of pressure injuries (PIs) remains a challenging problem for clinicians across the world. The failure to heal in PIs is multifactorial such as nutritional status of patients, bacterial load, site of ulcer, risk of contamination and presence of comorbidities. Multidrug-resistant (MDR) Gram-negative bacterial (GNB) infections are frequent occurrence in hospitalised patients with PI. The limited chemotherapeutic options available for treating MDR strains of GNB have forced the reintroduction of the cationic cyclic peptide, polymyxin E (colistin). We report a case series of seven patients of traumatic spinal cord injury with PIs and poor healing due to MDR GNB sensitive only to colistin. In view of the worsening condition of the PIs and financial constraints, it was decided to start colistin therapy locally by colistimethate sodium. All patients responded well to the treatment and got clinically better. In our study, we used the Pressure Ulcer Scale for Healing score, Functional Independence Measure and World Health Organization Quality of Life Brief Version score to measure the outcome. We found this novel dressing a very promising and cost-effective treatment option in achieving infection-free healing, especially against MDR strains of bacteria.

Protective role of thymoquinone in hyperlipidemia-induced liver injury in LDL-R−/−mice

BackgroundHyperlipidemia, a heterogeneous group of disorders characterized by elevated plasma lipids in the blood, causes severe health problems, leading to fatty liver disease and nonalcoholic fatty liver disease. Thymoquinone, the major active chemical component of Nigella sativa, reportedly exerts a vast array of biological effects. Various studies have reported that Thymoquinone protects against liver injury.AimsThe aim of this study was to investigate the possible protective effects of Thymoquinone against liver injury in hyperlipidemia-induced LDL-R−/− mice.MethodsEight-week-old male LDL-R−/− mice were randomly divided into three groups: a control group fed a normal diet and two groups fed a high-cholesterol diet or high-cholesterol diet mixed with Thymoquinone. All groups were fed different diets for 8 weeks. Blood samples were obtained from the inferior vena cava and collected in serum tubes. The samples were then stored at − 80 °C until used. Longitudinal sections of liver tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the liver tissues were snap-frozen in liquid nitrogen for reverse transcription-polymerase chain reaction or western blotting.ResultsOur results demonstrated that Thymoquinone administration significantly reduced liver histological alterations by hyperlipidemia. Thymoquinone mitigated hyperlipidemia-induced liver injury as indicated by the suppression of metabolic characteristics, liver biochemical parameters, pyroptosis indicators, a macrophage marker, and the phosphatidylinositide 3-kinase signaling pathway.ConclusionsThymoquinone is a potential therapeutic agent for hyperlipidemia-induced liver injury.

Kinsenoside mitigates myocardial ischemia/reperfusion-induced ferroptosis via activation of the Akt/Nrf2/HO-1 pathway

Ischemia-induced myocardial infarction is regarded as one of the major killers of humans worldwide. Kinsenoside (KD), a primary active ingredient derived from Anoectochilus roxburghii, shows antioxidant and vascular protective properties. Myocardial ischemia/reperfusion (I/R) injury is associated with oxidative damage and could be regulated by KD. However, its targets and the exact mechanism by which it operates remains unclear. The aim of this study was to investigate the role of KD in myocardial I/R injury and to define the mechanism by which it works. We established both myocardial I/R model in vivo and hypoxia/reoxygenation (H/R) cardiomyocyte model in vitro in this study. KD can attenuate I/R-induced myocardial injury in vivo and inhibit H/R-induced injury in vitro in a dose-dependent manner. KD increased mitochondrial membrane potential, SOD activity, and GSH activity in cardiomyocytes, whereas MDA accumulation, iron accumulation, and Mito-ROS production were decreased. We intersected differentially expressed genes (DEGs) from RNA-seq results with ferroptosis-related genes, and found KD significantly downregulated COX2 expression and upregulated GPX4 expression. These findings were further confirmed by Western blot analysis. Additionally, KD increased AKT phosphorylation and Nrf2 translocation into the nucleus, as well as HO-1 expression. When Akt or Nrf2 were inhibited in the KD group, the anti-ferroptosis properties of KD were nullified. Thus, Kinsenoside may exert anti-ferroptosis effect in myocardial I/R injury by decreasing mitochondrial dysfunction and increasing anti-oxidation through the Akt/Nrf2/HO-1 signaling pathway, suggesting it could be used as a potential therapeutic agent for myocardial reperfusion injury.

A Comprehensive Overview of Organ Inflammatory Responses: Genesis, Possible Mechanisms, and Mediators of Inflammation

An immune system response known as inflammation can be carried on by a variety of things, such as infections, damaged cells, and noxious substances. These factors may cause acute or chronic inflammatory responses in the heart, pancreas, liver, kidney, lungs, brain, colon, and reproductive system, which may cause disease or tissue damage. Inflammatory cells and signaling pathways are activated by both pathogenic and non-pathogenic agents, cell injury, and infectious agents. The most ubiquitous types of these include tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), High mobility group box 1 protein (HMGB1), mitogen-activated protein kinase (MAPK), monocyte chemoattractant protein (MCP1), interleukin 1 beta (IL1β), and Janus kinase-signal transducer and activator of transcription (JAK-STAT). Severe inflammation has the potential to cause systemic inflammatory response syndrome. The most severe forms of this condition are characterized by hyperinflammation and can cause organ damage, shock, and even death. We concentrate on the origin of inflammation, all conceivable inflammatory mechanisms, and organ-specific inflammatory responses in this study on inflammatory reactions inside organs.

Synergistic Effects of Vitis vinifera L. and Centella asiatica against CCl4-Induced Liver Injury in Mice.

Liver injury can be acute or chronic, resulting from a variety of factors, including viral hepatitis, drug overdose, idiosyncratic drug reaction, or toxins, while the progression of pathogenesis in the liver rises due to the involvement of numerous cytokines and growth factor mediators. Thus, the identification of more effective biomarker-based active phytochemicals isolated from medicinal plants is a promising strategy to protect against CCl4-induced liver injury. Vitis vinifera L. (VE) and Centella asiatica (CE) are well-known medicinal plants that possess anti-inflammatory and antioxidant properties. However, synergism between the two has not previously been studied. Here, we investigated the synergistic effects of a V. vinifera L. (VE) leaf, C. asiatica (CE) extract combination (VCEC) against CCl4-induced liver injury. Acute liver injury was induced by a single intraperitoneal administration of CCl4 (1 mL/kg). VCEC was administered orally for three consecutive days at various concentrations (100 and 200 mg/kg) prior to CCl4 injection. The extent of liver injury and the protective effects of VCEC were evaluated by biochemical analysis and histopathological studies. Oxidative stress was evaluated by measuring malondialdehyde (MDA) and glutathione (GSH) levels and Western blotting. VCEC treatment significantly reduced serum transaminase levels (AST and ALT), tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS). CCl4- induced apoptosis was inhibited by VCEC treatment by reducing cleaved caspase-3 and Bcl2-associated X protein (Bax). VCEC-treated mice significantly restored cytochrome P450 2E1, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) expression in CCl4-treated mice. In addition, VCEC downregulated overexpression of proinflammatory cytokines and hepatic nuclear factor kappa B (NF-κB) and inhibited CCl4-mediated apoptosis. Collectively, VCEC exhibited synergistic protective effects against liver injury through its antioxidant, anti-inflammatory, and antiapoptotic ability against oxidative stress, inflammation, and apoptosis. Therefore, VCEC appears promising as a potential therapeutic agent for CCl4-induced acute liver injury in mice.

Extracellular Succinate: A Physiological Messenger and a Pathological Trigger.

When tissues are under physiological stresses, such as vigorous exercise and cold exposure, skeletal muscle cells secrete succinate into the extracellular space for adaptation and survival. By contrast, environmental toxins and injurious agents induce cellular secretion of succinate to damage tissues, trigger inflammation, and induce tissue fibrosis. Extracellular succinate induces cellular changes and tissue adaptation or damage by ligating cell surface succinate receptor-1 (SUCNR-1) and activating downstream signaling pathways and transcriptional programs. Since SUCNR-1 mediates not only pathological processes but also physiological functions, targeting it for drug development is hampered by incomplete knowledge about the characteristics of its physiological vs. pathological actions. This review summarizes the current status of extracellular succinate in health and disease and discusses the underlying mechanisms and therapeutic implications.

A novel colchicine-myricetin heterozygous molecule: design, synthesis, and effective evaluations on the pathological models of acute lung injury in vitro and in vivo.

Acute lung injury (ALI) is an inflammatory condition and there are no effective treatments. A novel new compound----colchicine-myricetin hybrid (CMyrH) was herein designed and synthesized. To evaluate the activity of CMyrH in ALI, we used a bleomycin (BLM) induced BEAS-2B injury model in vitro and established a well-recognized rat model of BLM-induced lung injury in vivo. The results demonstrated that colchicine-myricetin hybrid protected BEAS-2B cells against BLM-induced cell injury in an increased dose manner, and reduced wet/dry weight ratio, histological scoring, and inflammation cytokines IL-1β, IL-6, IL-18, and TNF-α levels of lung tissue of the rats. Furthermore, we found colchicine-myricetin hybrid inhibited caspase-1, ASC, GSDMD, and NLRP-3 expression in vivo. Meanwhile, we used molecular docking to analyze the binding mode of colchicine-myricetin hybrid and human neutrophil elastase (HNE), it revealed that colchicine-myricetin hybrid showed strong binding affinity toward human neutrophil elastase when compared to its parent molecules. In conclusion, It is suggested that colchicine-myricetin hybrid antagonized acute lung injury by focusing on multi-targets via multi-mechanisms, and might be served as a potential therapeutic agent for acute lung injury.

Case Study: Deep Breath Intervention to Reduce Pain in Mild-head Injury Patients

Objective: To present upbringing with deep breath intervention to reduce pain in patients with mild head injuries. Methods: The method used is descriptive with a case study approach using nursing care that refers to the SDKI and SIKI books. The subjects in this study were 1 patient with a nursing diagnosis of acute pain in a patient with a minor head injury at the orchid room of the Banjar City Hospital. With data collection techniques include interviews, observations, physical examinations and documentation studies. Results: From nursing care in patients with chronic renal failure, the symptom that appears at the time of the assessment is pain. The nursing problem that arises is that acute pain is related to physical injury agents referring to the SDKI book. The intervention carried out to reduce pain is by deep breath relaxation techniques. During the intervention process, the action went smoothly until the evaluation. There are changes in pain. Conclusion: After deep breath intervention there was a change in pain from a scale of 5 to 2 (0-10), while the results of anamnesis obtained subjective data, the client said the pain was reduced.

The inhibitory effect of quercetin-3-glucuronide on pulmonary injury in vitro and in vivo.

Pulmonary injury is defined as a progressive inflammation. Extensive pro-inflammatory cytokines are secreted from alveolus, associated with the production of reactive oxygen species (ROS) and apoptosis. The model of endotoxin lipopolysaccharide (LPS)-stimulated lung cells has been applied to mimic the pulmonary injury. Some antioxidants and anti-inflammatory compounds can be used as chemopreventive agents of pulmonary injury. Quercetin-3-glucuronide (Q3G) has been showed to exert antioxidant, anti-inflammatory, anti-cancer, anti-aging and anti-hypertension effects. The aim of the study is to examine the inhibitory potential of Q3G on pulmonary injury and inflammation in vitro and in vivo. Firstly, human lung fibroblasts MRC-5 cells pre-treated with LPS were demonstrated to cause survival loss and ROS generation, were recovered by Q3G. Q3G also exhibited the anti-inflammatory effects on the LPS-treated cells with a reduction in the activation of NLRP3 [nucleotide-binding and oligomerization domain (NOD)-like receptor protein 3] inflammasome, leading to pyroptosis. Also, Q3G showed the anti-apoptotic effect in the cells might be mediated via inhibition of mitochondrial apoptosis pathway. To further explore in vivo pulmonary-protective effect of Q3G, C57BL/6 mice were intranasally exposed to a combination of LPS and elastase (LPS/E) to perform the pulmonary injury model. The results revealed that Q3G ameliorated pulmonary function parameters and lung edema in the LPS/E-induced mice. Q3G also suppressed the LPS/E-stimulated inflammation, pyroptosis and apoptosis in the lungs. Taken together, this study suggested the lung-protective potential of Q3G via downregulation of inflammation, pyroptotic and apoptotic cell death, contributing to its chemopreventive activity of pulmonary injury.

THE IMPORTANCE OF HYDROTHERAPY IN THE REHABILITATION OF SEQUELS IN NEUROLOGICAL PATIENTS

Introduction: The neurological sequelae are result from the brain damages occasioned by pathologies that affect the central nervous system and/or peripheral nervous system resulting in malfunction, limitations and physical and/or cognitive incapacities. Among the resulting sequels from the brain damages are found the muscle weakness, hypertonia, hypotonia, limited range of motion, difficulty transferring and walking, sensory loss, incoordination and postural instability. The hydrotherapy is a specialty of aquatic physiotherapy that uses water in all its states, as a treating agent of injuries and physical conditions. It will act in the rehabilitation of these patients promoting a greater evolution of themselves due to the facilitations given by the aquatic environment during the exercises which will entail in respiratory, cardiovascular, musculoskeletal and psychological benefits. Objective: To analyze hydrotherapy in the rehabilitation of sequelae in neurological patients. Method: It was performed a file search in the Scielo (Scientific Eletronic Library On-line), Google Scholar and PubMed database in the English and Portuguese languages. Bibliographic research bases were also used. Conclusion: Based on the surveys investigated, it was found that the use of hydrotherapy in the rehabilitation of neurological sequelae was extremely favorable in the recovery of patients, providing a significant improvement and a superior evolution to the traditional treatments performed on the ground.

Osmotherapy and the management of traumatic brain injury: still a dilemma.

Despite extensive study and use, selecting an osmotherapy agent for traumatic brain injury remains a dilemma. This article explores the challenges in managing patients with traumatic brain injury and the ongoing debate surrounding the efficacy of different hyperosmolar agents as treatment options.

Examining leopard attacks: spatio-temporal clustering of human injuries and deaths in Western Himalayas, India

Shared spaces in Africa and Asia accommodate both humans and big cats. This engenders rare but distinctive cases of human fatalities by lions, tigers, and leopards. Among big cats, leopards have the widest range and occur even among high densities of humans. This increased potential for encounters with humans results in attacks, exemplified most by India where 50% of the states report human injuries and deaths due to leopards. Himachal Pradesh (HP) state reported 30 lethal and 287 non-lethal leopard attacks on humans per year between 2004 – 2015 (N=317). Identifying patterns in big cat attacks on people facilitates targeted interventions for decreasing such fatalities. This study aims to detect if leopards are cluster-causing agents of human injuries and deaths. We identify the patterns of leopard attacks on humans in Himachal Pradesh by examining the following questions: (a) do leopard-attributed attacks on humans cluster in space and time? and among the leopard-attributed attacks (b) do unprovoked attacks on humans cluster spatio-temporally? and (c) what environmental factors are associated with the clustered leopard attacks on humans? We employed a space-time permutation scan statistic commonly used in epidemiology to test for spatio-temporal clustering of leopard attacks. Attacks were spread across 75% (~42,000 km sq.) of HP in 11 out of 12 districts. We found that 23% of attacks clustered into 12 significant spatio-temporal clusters. Nearly 14% of the leopard-attributed attacks (N=317) were unprovoked and attacks displaying “predatory” signs did not form significant clusters. Binomial regression models were run to test association of eight environmental factors with clustered attacks. We found that leopard-attributed attacks farther away from the protected area boundary and closer to the district boundary had higher probability of clustering. The framework developed in this study to identify the outbreak of unprovoked leopard attacks confirms the absence of dedicated “man-eaters” in the study region. This approach can be applied to adaptively manage human-wildlife conflict and it also demonstrates the utility of scan statistic in ecological research.

Ameliorating effects of berberine on sepsis-associated lung inflammation induced by lipopolysaccharide: molecular mechanisms and preclinical evidence.

As a life-threatening disorder, sepsis-associated lung injury is a dysregulated inflammatory response to microbial infection, characterized by the infiltration of inflammatory cells into lung tissues and excessive production of pro-inflammatory mediators. Therefore, immunomodulatory/anti-inflammatory agents are a potential treatment for sepsis-associated lung injury. Berberine, one of the well-studied medicinal plant-derived compounds, has shown promising anti-inflammatory potential in inflammatory conditions, through modulating excessive immune responses induced by various immune cells. A systematic literature search in electronic databases indicated several publications that studied the effect of berberine on lipopolysaccharide (LPS)-induced sepsis in preclinical investigations. The current review article aims to provide evidence on the effects of berberine against LPS-induced acute lung injury (ALI), together with underlying molecular mechanisms. The findings reveal that berberine through inhibiting the excessive production of multiple pro-inflammatory cytokines, suppressing the infiltration of immune cells into lung tissues, as well as preventing pulmonary edema and coagulation, can relieve pulmonary histopathological changes from LPS-mediated inflammation, thereby attenuating sepsis-associated lung injury and lethality in the experimental models. In conclusion, berberine shows great potential as a preventing and therapeutic agent for sepsis-associated lung injury, however, further proof-of-concept studies and clinical investigations are warranted for translating these preclinical findings into clinical practices.

Neutrophil membrane-camouflaged nanoparticles alleviate inflammation and promote angiogenesis in ischemic myocardial injury.

Acute myocardial infarction (AMI) induces a sterile inflammatory response, leading to cardiomyocyte damage and adverse cardiac remodeling. Interleukin-5 (IL-5) plays an essential role in developing eosinophils (EOS), which are beneficial for the resolution of inflammation. Furthermore, the proangiogenic properties of IL-5 also contribute to tissue healing following injury. Therefore, targeted delivery of IL-5 is an innovative therapeutic approach for treating AMI. It has been shown that conventional IL-5 delivery can result in undesirable adverse effects and potential drug overdose. In this study, we successfully synthesized a biomimetic IL-5 nanoparticle by camouflaging the IL-5 nanoparticle in a neutrophilic membrane. The administration of neutrophil membrane-camouflaged nanoparticles (NM-NPIL-5) in the in vivo model showed that these nanoparticles promoted EOS accumulation and angiogenesis in the infarcted myocardium, thereby limiting adverse cardiac remodeling after AMI. Our results also demonstrated that the NM-NPIL-5 could serve as neutrophil "decoys" to adsorb and neutralize the elevated neutrophil-related cytokines in the injured heart by inheriting multiple receptors from their "parent" neutrophils. Finally, the targeted delivery of NM-NPIL-5 protected the cardiomyocytes from excessive inflammatory-induced apoptosis and maintained cardiac function. Our findings provided a promising cardiac detoxification agent for acute cardiac injury.

A novel type lavandulyl flavonoid from Sophora flavescens as potential anti-hepatic injury agent that inhibit TLR2/NF-κB signaling pathway.

Sophora flavescens Aiton, was a crucial source of Traditional Chinese Medicine (TCM) that has benefited human health for hundreds of years. Alkaloids and flavonoids were the major bioactive constituents from S. flavescens, which had been widely used for liver disease treatment in China. However, the liver-protective components of flavonoids from S. flavescens and their mechanism of action were not clear. This work aimed to evaluate the in vitro hepatoprotective activities of 35 flavonoids from S. flavescens and screen active compounds. Furthermore, it was conducted to demonstrate the hepatoprotective effects of a new active compound (kurarinol A, 1) was isolated by authors and the ethyl acetate (EtOAc) extract form S. flavescens against carbon tetrachloride (CCl4)-induced hepatic injury in Kunming (KM) mice, meanwhile revealed the potential mechanism. The 35 flavonoids from S. flavescens were co-incubated with HepG2 cells and treated with 0.35% CCl4 for 6h cell viability was measured by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. Then, in vivo animal experiments, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the serum were analyzed, the degree of hepatic injury was examined using hematoxylin-eosin (H&E) staining, the mRNA expression of Superoxide Dismutase 2 (SOD2), Nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α), interleukin-1β (IL-1β), and the protein levels of nuclear factor-kappa B p65/p-p65 (NF-κB p65/p-p65), toll-like receptor 2 (TLR2), IL-1β and cyclooxygenase-2 (COX2) in hepatic tissues were detected. The lavandulyl flavonoid (kurarinol A, 1) and the EtOAc extract from S. flavescens showed protective effects on CCl4-injured HepG2 cells, increasing cell viability from 24.5% to 61.3% and 91.8%, respectively. What's more, we found that treatment with kurarinol A (1) and the EtOAc extract lead to a significant reduction in hepatotoxicity in response to acute CCl4 exposure. Compared with the model group, experimental results exhibited kurarinol A (10mg/kg, i.p.) and the EtOAc extract (300mg/kg, i.p.) could decrease the levels of AST, ALT, ALP and tissue damage. Further mechanistic investigations revealed that up-regulated the mRNA expression of SOD2, Nrf2, OH-1 and down-regulated the IL-1β in liver tissues, respectively. Additionally, Western blot analyses elucidated that inhibition of IL-1β, TLR2, COX-2, NF-κB (p65/p-p65) via TLR2/NF-κB signaling pathway by kurarinol A and the EtOAc extract contribute to its hepatoprotective activity. These findings demonstrated that the novel compound (kurarinol A, 1) possessed notable hepatoprotective activity against CCl4. It was confirmed that kurarinol A had a certain effect on mice with liver damage induced by CCl4, and its mechanism could be include inhibiting inflammation and reducing of oxidative stress reaction by regulating expression of related genes and proteins. Thus, kurarinol A could as a novel active agent that contributes to the hepatoprotective activity of S. flavescens for the treatment of live injury.

Nursing Care in Post SC Patients with Intervention Application of Foot Massage Therapy: Case Study

Introduction: Sectio caeasar is labor by making an abdominal incision to remove the fetus. Sectio caesarea delivery is the process of removing the baby by dissecting the mother's abdomen by making an incision in the uterine wall. Sectio caesarea is the main medical action to save the life of the mother and also the baby. This study aims to describe nursing care in postpartum section caesarae mothers with the application of foot massage therapy to reduce pain.Methods: This research uses a case study design. Data collection ranging from assessment to nursing evaluation was carried out in the Anggrek room of RSUD dr. TC. Hillers Maumere in January 2023. The samples used were 2 patients who were hospitalized for at least 3 days. Data collection techniques use interviews, observations and documentation studies.Results: assessment of two respondents who were postpartum mothers through day SC to those who experienced pain during the treatment period. The diagnosis established is Acute Pain associated with Physical Injury Agents (sectio caesarea surgical procedure: disconnection of tissue incontuinity) Intervention is carried out is the application of foot massage therapy, observation of pain scales and vital signs and collaborative for further action. Evaluation after treatment pain reduced, no signs of infectionConclusion: After foot massage for 3 days for 15-20 minutes showed a decrease in search in postpartum Sectio caeasarea patientsKeywords: Foot massage, sectio caessarea, pospartum