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As the largest internal organ of the human body, the liver has an extremely complex vascular network and multiple types of immune cells. It plays an important role in blood circulation, material metabolism, and immune response. Optical imaging is an effective tool for studying fine vascular structure and immunocyte distribution of the liver. Here, we provide an overview of the structure and composition of liver vessels, the three-dimensional (3D) imaging of the liver, and the spatial distribution and immune function of various cell components of the liver. Especially, we emphasize the 3D imaging methods for visualizing fine structure in the liver. Finally, we summarize and prospect the development of 3D imaging of liver vessels and immune cells.
Background: Renal ischemia-reperfusion injury (IRI) does not only affect kidneys, but also affects remote organs especially the liver. Stress may lead to further progression of renal and hepatic insults. This study was planned to explore the efficacy of olive oil (OO) on the assumed renal and hepatic changes of immobilization stress following renal IRI.
Methods: Seventy-seven adult male Wistar albino rats were divided into the following five groups; Sham-Operated Control group, Renal Ischemia-Reperfusion group, Stressed Renal Ischemia-Reperfusion group, OO-Supplemented Renal Ischemia-Reperfusion group) and OO-Supplemented Stressed Renal Ischemia-Reperfusion Group (OO+Stressed+IR). All animals were subjected to determination of renal and hepatic biochemical functions and histopathological examination.
Results: Renal IR significantly increased plasma creatinine and urea levels. This was associated with significant rise in serum levels of both ALT and AST, total bilirubin together with plasma level of TNF-α, whereas the plasma level of albumin (ALB) was significantly reduced. In addition, histological disruptions of kidneys and livers were observed. Chronic immobilization stress aggravated the effects of renal IR. Also, renal and hepatic morphological changes were more worsened. Whilst, OO supplementation resulted in significant amelioration of renal and hepatic functions. Also, the kidney and liver morphologic lesions were attenuated.
Conclusion: Renal IR not only affected the renal functional and structural integrity but also the remote organ, the liver. Chronic immobilization stress rendered the kidney and liver more prone to injury. OO improved renal and hepatic dysfunction and morphological damage mediated by renal IRI, in control rats and in those exposed to chronic stress which can be exerted partially via its antioxidant, anti- inflammatory and nitric oxide (NO) reducing activities.
Hepatic injury induced by blunt abdominal impact is a major cause of death in vehicle crashes. However, few works have been done effectively in cadaver experiments to clarify the liver’s specific dynamic behavior and mechanical characteristics. This paper described the dynamic behavior and mechanical characteristics of the liver under blunt impacts to the upper abdomen with the finite element model (FEM) of the Chinese human body — the 50 percentile-sized male (CHUBM-M50). The simulation matrix, three directions (frontal, oblique, lateral), and four speeds included in each group were designed with a 23.4kg, rigid cylindrical impactor aligning the T11 level. The liver deformation contours displayed compression against the spine and rotation in the horizontal plane, which were the two main features in liver motion. Pressure distribution in the liver capsule and parenchyma was discussed to elucidate the biomechanical characteristics related to impact direction. Generally, the stress distribution in the capsule was 10 times higher than that in the parenchyma. A discussion of the injury mechanism of the liver capsule and parenchyma observed in the simulations was given upon the pressure distribution. It demonstrated that the capsule could protect liver parenchyma at low-speed impacts and should not be neglected for understanding liver injury mechanisms.
Excessive consumption of analgesic drug acetaminophen (APAP) can cause severe oxidative stress-mediated liver injury. Here, we investigated the protective effect and mechanism of aged citrus peel (Chenpi, CP), a Chinese herb usually used in foods in Asia, against APAP-induced hepatotoxicity. CP water (CP-WE), ethanolic (CP-EE), and water extraction residue ethanolic (CP-WREE) extracts were prepared. We found that CP-WREE contained higher content of bioactive flavonoids, including narirutin, nobiletin, and tangeretin, and more effectively enhanced the Nrf2 pathway in ARE-luciferase reporter gene transfected human HepG2-C8 cells. In mouse AML-12 hepatocytes, CP-WREE minimized APAP-induced damage and lipid peroxidation and increased mRNA and protein expressions of Nrf2 and its downstream defense enzymes (HO-1, NQO1, and UGT1A). CP-WREE also downregulated HDACs and DNMTs, upregulated KDMs, and increased the unmethylated Nrf2 promoter level. Additionally, CP-WREE blocked in vitro DNA methyltransferase activity. Taken together, CP-WREE might attenuate oxidative stress-induced hepatotoxicity through epigenetically regulating Nrf2-mediated cellular defense system.
Over the last decades, facing the blooming growth of technological progress, interest in digital devices such as computed tomography (CT) as well as magnetic resource imaging which emerged in the 1970s has continued to grow. Such medical data can be invested in numerous visual recognition applications. In this context, these data may be segmented to generate a precise 3D representation of an organ that may be visualized and manipulated to aid surgeons during surgical interventions. Notably, the segmentation process is performed manually through the use of image processing software. Within this framework, multiple outstanding approaches were elaborated. However, the latter proved to be inefficient and required human intervention to opt for the segmentation area appropriately. Over the last few years, automatic methods which are based on deep learning approaches have outperformed the state-of-the-art segmentation approaches due to the use of the relying on Convolutional Neural Networks. In this paper, a segmentation of preoperative patients CT scans based on deep learning architecture was carried out to determine the target organ’s shape. As a result, the segmented 2D CT images are used to generate the patient-specific biomechanical 3D model. To assess the efficiency and reliability of the proposed approach, the 3DIRCADb dataset was invested. The segmentation results were obtained through the implementation of a U-net architecture with good accuracy.
According to the principles of traditional Chinese medicine, channels and collaterals within the body provide pathways through which qi and blood travel, and each channel or collateral is linked with a specific organ. The Yinlingquan (spleen 9, SP9) and Ququan (liver 8, LR8) acupoints represent the sea points of the spleen and liver meridians, respectively, from which qi and blood flow into their specific visceral organs. The purpose of this study was to investigate the changes in blood flow/perfusion in the liver and spleen resulting from the application of 2 Hz electro-acupuncture (EA) to the Yinlingquan (SP9) or Ququan (LR8) acupoints. A total of 18 Spragrue-Dawley rats were randomly divided into three groups of six rats each as follows: sham group receiving sham EA; Yinlingquan (SP9) group receiving 2 Hz EA, applied at bilateral Yinlingquan (SP9) acupoints; and Ququan (LR8) groups receiving 2 Hz EA, applied at bilateral Ququan (LR8) acupoints. The mean blood flow/perfusion of the spleen and liver was recorded using a laser Doppler blood flow monitor prior to EA (representing the baseline), during EA, and post-EA. Each measurement period lasted ten minutes. Nitric oxide levels were also measured from the right femoral arterial blood, following the conclusion of each series of blood flow/perfusion recordings. The results indicate that the sham EA did not increase the mean blood flow/perfusion in the liver or spleen; 2 Hz EA at bilateral Yinlingquan (SP9) acupoints increased the mean blood flow/perfusion in the spleen, but not in the liver. In contrast, 2 Hz EA at bilateral Ququan (LR8) acupoints increased the mean blood flow/perfusion in the liver, but not in the spleen. Nitric oxide levels showed no significant difference between any of the groups at any stage of the measurements. According to the results, we conclude that EA at the Yinlingquan (SP9) and Ququan (LR8) acupoints can increase the blood flow in the spleen and liver, respectively.
Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)+iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100μg/mL) significantly inhibited AA+iron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly(ADP-ribose) polymerase. EKE attenuated hydrogen peroxide production, glutathione depletion, and mitochondrial membrane dysfunction. EKE also increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), transactivated anti-oxidant response element harboring luciferase activity, and induced the expression of anti-oxidant genes. Furthermore, the cytoprotective effect of EKE against AA+iron was blocked in Nrf2 knockout cells. Ultra-performance liquid chromatography analysis showed that EKE contained icariin, icaritin, and quercetin; icaritin and quercetin were both found to protect HepG2 cells from AA+iron via Nrf2 activation. In a CCl4-induced mouse model of liver injury, pretreatment with EKE (300mg/kg) for four consecutive days ameliorated CCl4-mediated increases in serum aspartate aminotransferase activity, histological activity index, hepatic parenchyma degeneration, and inflammatory cell infiltration. EKE also decreased the number of nitrotyrosine-, 4-hydroxynonenal-, cleaved caspase-3-, and cleaved poly(ADP-ribose) polymerase-positive cells in hepatic tissues. These results suggest EKE is a promising candidate for the prevention or treatment of oxidative stress-related liver diseases via Nrf2 activation.
Korean red ginseng (KRG) is a traditional herbal medicine used to prevent several geriatric diseases due to its therapeutic effects on metabolic disorder, including type 2 diabetes and fatty liver disease. In this study, we investigated the effects of KRG on the progression of nonalcoholic steatohepatitis (NASH) in mice. NASH was induced by feeding a methionine- and choline-deficient high-fat or high-fat/high-sucrose diet for 6 or 13 weeks, respectively. Each diet group was also orally administered saline (group G0) or KRG extract (100, 200, or 400 mg/kg/day; groups G1, G2, and G4, respectively). KRG showed anti-inflammatory and antifibrogenic effects in the diet-induced NASH models. Furthermore, the expression levels of lipid metabolism-related genes were markedly decreased with KRG treatment in both diet-induced NASH groups. We next confirmed the expression levels of FABP4 in the liver and its ability to regulate inflammation and/or oxidative stress. We observed decreased levels of FABP4 mRNA and protein in the KRG-treated groups indicating that KRG affects the pathogenesis of NASH-related inflammatory responses by modulating FABP4 expression. Results of in vitro experiments showed similar patterns in cells treated with KRG, indicating that KRG treatment regulates the expression of FABP4 and subsequently reduces NASH related inflammation. Our findings suggest a novel role of KRG in NASH-related inflammatory responses via modulation of FABP4 expression in the liver. KRG may be a safe alternative therapy to prevent NASH progression.
This study presents a novel liver disease classification method by applying pattern recognition technique to automatically segmented liver from the images of computed tomographic (CT) scans. The methodology comprises of disease classification by the extraction of textural features from focal liver region bearing tumors. Two types of liver textures are investigated in this study for classification accuracy judgement. First, original liver texture is considered for feature extraction. Second, liver is used for feature extraction. The CT image dataset comprises 308 liver samples with 193 samples of malignant tumor and 115 samples of benign tumor. The entire liver tissue bearing tumor is segmented from the CT image automatically in the pre-processing stage using fuzzy transformation function and morphological processing. Four sets of textural feature matrices are applied to the liver for feature extraction. Gray level co-occurrence matrix (GLCM), standard deviation gray level co-occurrence matrix (SDGLCM), seven-moment matrix (7MM) and seven-moment gray level co-occurrence matrix (7MGLCM) are the combinational feature matrices applied to classify the liver as malignant or benign using support vector machines (SVMs). The best classification accuracy is achieved for original liver texture by 7MGLCM, which is 97% with AUC = 0.99 for training dataset and 97.8% with AUC = 1 for test dataset.
The present study evaluated the effects of heat-processed Scutellariae Radix (Scutellaria baicalensis) on lipopolysaccharide (LPS)-induced liver injury in mice. Scutellariae Radix heat-processed at 160∘C or 180∘C was orally administered at a dose of 100 mg/kg body weight for three days before the intraperitoneal injection of LPS, and the effects were compared with those of vehicle-treated LPS administered to control mice. The administration of Scutellariae Radix decreased the elevated serum monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), reactive oxygen species (ROS), nitrite/nitrate, peroxynitrite, and hepatic functional parameters, and reduced the increased ROS in the liver. The augmented expressions of hepatic oxidative stress and inflammation-related proteins, phospho-p38, phosphorylated extracellular signal-regulated kinase, phosphorylated c-Jun N-terminal kinase, nuclear factor-κ B p65, activator protein-1, cyclooxygenase-2, inducible nitric oxide synthase, MCP-1, intercellular adhesion molecule-1, tumor necrosis factor-α, and IL-6, were downregulated by the heat-processed Scutellariae Radix. Hematoxylin-eosin staining showed that the increased hepatocellular damage in the liver of LPS-treated mice improved with the administration of heat-processed Scutellariae Radix. Overall, the ameliorative effects of Scutellariae Radix were superior to those when heat-processed at 180∘C. Our results indicate that heat-processed Scutellariae Radix acts as an anti-inflammatory agent by ameliorating oxidative stress in the liver of mice with LPS-induced liver injury.
This study was initiated to determine the possible antidiabetic effects of total flavonoids of Litsea Coreana leve (TFLC), an alcohol extract from the dried leaves of Litsea Coreana leve, on type 2 diabetic rats. Male Sprague-Dawley rats (n = 40, 160–180 g) were divided into two groups and fed with normal chow diet (Normal Control group) or high-fat diet (HFD) for a period of 4 weeks. After 4 weeks of dietary manipulation, the HFD-fed rats were injected with 30 mg/kg streptozocin (STZ) to induce diabetes 72 hours after STZ injection. These diabetic rats were randomly divided into 3 groups (n = 10): Diabetic Control group, Diabetic + TFLC group and Diabetic + PIO group. Diabetic + TFLC group and Diabetic + PIO group were orally administered with 400 mg/kg TFLC or 10 mg/kg pioglitazone (all suspended in 0.5% CMC-Na) respectively for 6 weeks. All rats were examined for body weight, serum and hepatic biochemical indices, content of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and pathological changes in liver and pancreas, as well as protein tyrosine phosphatase 1B (PTP1B) expression in liver. The diabetic rats became obese, insulin resistant, hyperglycemic and hyperlipidemic. Treatment with TFLC showed a significant increase in insulin sensitivity, serum HDL-C level and SOD activities, meanwhile marked decrease in body weight, serum FFA, TC, TG, LDL-C, CRP, MDA content. TFLC also attenuated pathologic alterations in liver and pancreatic islet. Furthermore, TFLC was found to decrease the expression of PTP1B in diabetic rat liver. These results suggested that TFLC could ameliorate hyperglycemia, hyperlipoidemia, inflammation and oxidation stress, as well as insulin resistance of type 2 diabetic rats.
Endoplasmic reticulum stress (ERS) plays a crucial role in the development of insulin resistance and diabetes mellitus. Although antidiabetic use of mulberry leaves (MLs) has been popular due to their many anti-oxidative flavonoid compounds and free radical scavenging effects, ML’s effects on ERS in experimental diabetic hepatocyte injury remain unknown. To investigate how ML affect ERS in diabetic liver, Sprague–Dawley (SD) rats were assigned to induce diabetes by a single intraperitoneal injection of streptozocin (STZ; 55 mg/kg) and fed with either normal chow or a diet containing 25% mulberry leaf powder diet (MLD) and examined for 56 days. We observed that MLD improved the rats’ morphological and histopathological changes. Levels of ERS markers such as phosphorylated double-stranded RNA-dependent protein kinase-like endoplasmic reticulum kinase (PERK) and X-box binding protein 1 (XBP1) and the protein expression of glucose regulated protein 78 (GRP78) were significantly higher in the diabetic liver compared to normal liver. MLD for 8 weeks significantly reduced all of these markers. MLD also significantly decreased hepatocyte apoptosis, hepatic macrophage recruitment, cellular infiltration, and CCAAT/enhancer–binding protein homologous protein (CHOP), tumor necrosis factor receptor associated factor 2 (TRAF2), interleukin 1β (IL-1β) and sterol regulatory element binding protein isoform 1c (SREBP 1c) levels in diabetic liver. These results may suggest that MLs can preserve hepatic function in experimental diabetes by modulating ERS mediated apoptosis and liver damage.
Hypoxia-inducible factor-1 (HIF-1) is an α∕β dimeric transcription factor. Because HIF-1α is instable with oxygen, HIF-1 is scarce in normal mammalian cells. However, HIF-1α is expressed in pathological conditions such as cancer and obesity. Inhibiting HIF-1α may be of therapeutic value for these pathologies. Here, we investigated whether emodin, derived from the herb of Rheum palmatum L, which is also known as Chinese rhubarb, and is native to China, regulates HIF-1α expression. Male C57BL/6 mice without or with diet-induced obesity were treated with emodin for two weeks, while control mice were treated with vehicle. HIF-1α expression was determined by Western blot. We found that emodin inhibited obesity-induced HIF-1α expression in liver and skeletal muscle but did not regulate HIF-1α expression in the kidneys or in intra-abdominal fat. In vitro, emodin inhibited HIF-1α expression in human HepG2 hepatic cells and Y1 adrenocortical cells. Further, we investigated the mechanisms of HIF-1α expression in emodin-treated HepG2 cells. First, we found that HIF-1α had normal stability in the presence of emodin. Thus, emodin did not decrease HIF-1α by stimulating its degradation. Importantly, emodin decreased the activity of the signaling pathways that led to HIF-1α biosynthesis. Interestingly, emodin increased HIF-1α mRNA in HepG2 cells. This may be a result of feedback in response to the emodin-induced decrease in the protein of HIF-1α. In conclusion, emodin decreases hepatic HIF-1α by inhibiting its biosynthesis.
Hepatocellular carcinoma is an important health problem in Asia. A blend of herbal extracts containing radix bupleuri (KY88) was tested for its effects on liver cancer cells. A hepatocellular carcinoma cell line (HB8064) was cultured with methanol extract of KY88. We were able to produce a dose-dependent inhibition of cancer cell proliferation. At IC50 and IC100, KY88 induces a DNA ladder pattern, indicating the presence of apoptosis. We also checked the changes of the levels of interleukin (IL)-2, -4 and -6, interferon (INF)-γ and tumor necrosis factor (TNF)-α by ELISA kits. After 24 hours of culture, there was activation of IL-2 and -4 and TNF-α. However, significant changes were observed only for IL-4 and TNF-α. Therefore, we concluded that KY88 is able to induce apoptosis, which may be regulated through changes in IL-4 and TNF-α.
This study was designed to determine whether FPS-1, the water-soluble polysaccharide isolated from fuzi, protected against hepatic damage in hepatic ischemia-reperfusion injury in rats, and its mechanism. SD rats were subjected to 60 min of hepatic ischemia, followed by 120 min reperfusion. FPS-1 (160 mg/kg/day) was administered orally for 5 days before ischemia-reperfusion injury in treatment group. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and albumin (ALB) were assayed to evaluate liver functions. Liver samples were taken for histological examination and determination of malondialdehyde (MDA), superoxide dismutase (SOD), that catalase (CAT) in liver. Na+-K+-ATPase and Ca2+-ATPase in mitochondria were measured with colorimetry method. Morphological changes were also investigated by using both light microscopy and electron microscopy (EM). In addition, apoptosis and oncosis were detected by Annexin V-FITC/PI immunofluorescent flow cytometry analysis. Serum AST and ALT levels were elevated in groups exposed to ischemia-reperfusion (p < 0.05). Ischemia-reperfusion caused a marked increase in MDA level, and significant decreases in hepatic SOD and CAT (p < 0.05). Na+-K+-ATPase and Ca2+-ATPase were reduced in ischemia-reperfusion groups compared to the sham group (p < 0.05). Oncosis and apoptosis were also observed in ischemia-reperfusion groups. Pretreatment with FPS-1 reversed all these biochemical parameters as well as histological alterations, evidently by increased SOD, CAT, reduced MDA and histological scores compared to the model group (p < 0.05). FPS-1 could attenuate the necrotic states by the detection of immunofluorescent flow cytometry analysis. Pretreatment with FPS-1 reduced hepatic ischemia-reperfusion injury through its potent antioxidative effects and attenuation of necrotic states.
This piece of work investigates the application of histogram equalization method to clinical images for noise removal and efficient image enhancement without any information loss. Computed tomographic (CT) images of the abdomen bearing liver tumour are kept under study. Liver exhibits heterogeneous combination of intensities which makes it a challenging task to enhance the liver tumour embedded in the image. Distortion occurs due to the presence of quantum noise in the CT scans and important information of the image is suppressed. The methodology adopted in this paper comprises of two stages. Initially pixel based intensity transformation is adopted for de-noising the background of the image by the selection of appropriate threshold levels. The resultant image gives a noise free background and the foreground features are enhanced. In the next stage histogram equalization filters are applied to the transformed image. The equalization method which gives uniform image enhancement with lesser mean square error (MSE) and increased peak signal to noise ratio (PSNR) is supposed to be an effective method for efficient enhancement of the images. This study deals with the application of histogram equalization methods to CT images which can aid the radiologists for better visualization and diagnosis of the disease.
High strain rate compression of soft tissues has recently gained attention due to its application in computational simulation of traumatic injuries. To understand high rate tissue behavior, a comparative study is needed to examine the biomechanical responses of multiple soft tissues. We hypothesized that the underlying mechanisms of soft tissue high rate compression is dependent upon water, microstructural organization, and extracellular matrix (ECM). Porcine brain, liver, and tendon, which have similar material density (brain: 1.05g/cm3, liver: 1.06g/cm3, and tendon: 1.12g/cm3) and water content (brain: ∼78%, liver: ∼71–75%, and tendon: ∼70%) but different cellularity and ECM properties, were subjected to polymeric split Hopkinson pressure bar (PSHPB) testing. Hydrated brain tissue, due to its high microstructural cavities (cavity area fraction=0.49±0.26) and low ECM content, had a high initial stress spike of 0.22±0.12MPa. Hydrated liver, with moderate microstructural cavities (cavity area fraction=0.30±0.07) and moderate ECM content, had a moderate stress spike of 0.10±0.04MPa. Hydrated tendon had low microstructural cavities (cavity area fraction=0.03±0.02) and high ECM content and had a minimal initial stress spike of 0.02±0.01MPa. Electron microscopy of the tissues’ microstructural cavities revealed a first-order estimation of water content that was not bound to ECM (e.g., intracellular water). Linear regression analysis showed that the initial spike was highly correlated (r2=0.9532) with intracellular water. To understand the role of water in each tissue’s response to high deformation, each soft tissue was completely dehydrated and subjected to the same PSHPB compression test. After removal of all the water, neither the brain, liver, nor tendon revealed an initial stress spike, implicating the essential nature of water in the initial responses of high-rate compression. These results suggest that cellular water and ECM content play a critical role in the biomechanical responses to high strain rate compression.
Huai-Shan-Yao (Chinese yam; Rhizome Dioscoreae) is a common food in china. In the present study, we evaluated the protective effects of the crude extract of Huai-Shan-Yao on acute kidney and liver injuries in rats induced by ethanol. Results of pharmacological, biochemical and pathologic observations all showed that rats treated with the extract of Huai-Shan-Yao had decreased damage in renal tubules as well as decreased inflammation in the central vein and necrosis in the liver tissue.
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Momordica charantia (MC) is a plant belonging to the family Cucurbitaceae. MC has antidiabetic, antibacterial, antioxidant, antimutagenic, antiulcerative, antiinflammatory and antilipidemic effects. However, information on the effect of MC on fracture union is lacking. This study aimed to examine the effect of MC on fracture union histopathologically and biomechanically. A total of 42 male Wistar-Albino rats were randomly divided into 3 groups, 14 in each group. A diaphyseal fracture was created on the right tibia of all rats. All fractures were fixed with a Kirschner (K) wire. The rats in Group I did not undergo any further procedures (Control group). Group II rats were treated with 0.9% saline oral gavage at a dose of 500μL/day for 28 days [Saline (S) group]. The rats in Group III were given 300mg/kg MC extract per day, dissolved in 500μL 0.9% saline by oral gavage for 28 days [MC (Extract) group]. After 28 days, all rats were sacrificed. Each group was randomly divided into two subgroups. The histopathological examination was performed on the right tibia of rats in the first subgroup and the biomechanical examination in the second subgroup. The kidneys and livers of all rats were evaluated histopathologically. Fracture union was significantly better in the Extract group compared with the Control and S groups histopathologically. The fracture inflammation values were lower in the Extract group than in the other groups. No statistically significant difference was found between the groups in terms of possible side effects to kidneys and livers. In terms of biomechanics, fracture union was significantly better in the Extract group compared with the Control and S groups except yield displacement values. MC had a positive effect on fracture union histopathologically and biomechanically.
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