[Diagnostic Values and Reliability of Cardiac Magnetic Resonance Tissue Tracking 2D and 3D Strain Assessments for Experimental Autoimmune Myocarditis in Rats].

OBJECTIVE: To determinethe diagnostic valuesand reliabilityof cardiac magnetic resonance tissue tracking (CMR-TT) derived two-dimensional(2D) and three-dimensional(3D) strains in assessing experimental autoimmunity myocarditis (EAM) in rats. METHODS: 20 Lewis rats were randomly divided into model and control groups. The animal model of autoimmune myocarditis was induced by injecting porcine cardiac myosin into the footpads of the rats.On day 35, all of the rats were examined using the 7.0T CMR cine scan. The cardiac function and global strain of the left ventricular of the rats were analyzed with specific cardiac post-processing. The rats were then sacrificed and myocardial samples were taken and stained with HE and Masson. The diagnostic values of the strain parameters were assessed by receiver operating characteristic (ROC) curves with the pathological results as diagnostic criteria.The reliability of the strain parameters were tested using interclass correlation coefficient (ICC), coefficients of variation (CV) and Bland-Altman. RESULTS: No abnormal pathological changes in myocardial cells were found in the control group. Myocarditis was successfully induced in all of the rats in the model group, showing myocardial fiber arrangement disorder, degeneration, necrosis, inflammatory cell infiltration and interstitial fibrosis. The ROC showed that 2D global strain parameters possessed higher diagnostic values than 3D strain parameters. The 2D had an area under the curve (AUC) of 0.96 in global circumferential strain (GCS), 0.95 in global radial strain (GRS), and 0.90 in global longitudinal strain (GLS), compared with 0.87 GCS, 0.85 GRS, and 0.77 GLS in the 3D, respectively.The reliability of the 2D strain parameters was high, except for inter-observer 2D GRS(ICC=0.893). The 3D strain parameters had lower reliability (ICCs:0.421-0.79) than the 2D strain parameters (ICCs:0.893-0.986). CONCLUSION: The diagnostic values of 2D strain parameters are higher than 3D strain parameters in diagnosing myocarditis.

Irisin attenuates vascular remodeling in hypertensive mice induced by Ang II by suppressing Ca2+-dependent endoplasmic reticulum stress in VSMCs.

Vascular remodeling plays a vital role in hypertensive diseases and is an important target for hypertension treatment. Irisin, a newly discovered myokine and adipokine, has been found to have beneficial effects on various cardiovascular diseases. However, the pharmacological effect of irisin in antagonizing hypertension-induced vascular remodeling is not well understood. In the present study, we investigated the protection and mechanisms of irisin against hypertension and vascular remodeling induced by angiotensin II (Ang II). Adult male mice of wild-type, FNDC5 (irisin-precursor) knockout, and FNDC5 overexpression were used to develop hypertension by challenging them with Ang II subcutaneously in the back using a microosmotic pump for 4 weeks. Similar to the attenuation of irisin on Ang II-induced VSMCs remodeling, endogenous FNDC5 ablation exacerbated, and exogenous FNDC5 overexpression alleviated Ang II-induced hypertension and vascular remodeling. Aortic RNA sequencing showed that irisin deficiency exacerbated intracellular calcium imbalance and increased vasoconstriction, which was parallel to the deterioration in both ER calcium dysmetabolism and ER stress. FNDC5 overexpression/exogenous irisin supplementation protected VSMCs from Ang II-induced remodeling by improving endoplasmic reticulum (ER) homeostasis. This improvement includes inhibiting Ca2+ release from the ER and promoting the re-absorption of Ca2+ into the ER, thus relieving Ca2+-dependent ER stress. Furthermore, irisin was confirmed to bind to its receptors, αV/ß5 integrins, to further activate the AMPK pathway and inhibit the p38 pathway, leading to vasoprotection in Ang II-insulted VSMCs. These results indicate that irisin protects against hypertension and vascular remodeling in Ang II-challenged mice by restoring calcium homeostasis and attenuating ER stress in VSMCs via activating AMPK and suppressing p38 signaling.

Bioactive ECM-Loaded SIS Generated by the Optimized Decellularization Process Exhibits Skin Wound Healing Ability in Type I Diabetic Rats.

Patients with diabetes have 15-25% chance for developing diabetic ulcers as a severe complication and formidable challenge for clinicians. Conventional treatment for diabetic ulcers is to surgically remove the necrotic skin, clean the wound, and cover it with skin flaps. However, skin flap often has a limited efficacy, and its acquisition requires a second surgery, which may bring additional risk for the patient. Skin tissue engineering has brought a new solution for diabetic ulcers. Herein, we have developed a bioactive patch through a compound culture and the optimized decellularization strategy. The patch was prepared from porcine small intestinal submucosa (SIS) and modified by an extracellular matrix (ECM) derived from urine-derived stem cells (USCs), which have low immunogenicity while retaining cytokines for angiogenesis and tissue regeneration. The protocol included the optimization of the decellularization time and the establishment of the methods. Furthermore, the in vitro mechanism of wound healing ability of the patch was investigated, and its feasibility for skin wound healing was assessed through an antishrinkage full-thickness skin defect model in type I diabetic rats. As shown, the patch displayed comparable effectiveness to the USCs-loaded SIS. Our findings suggested that this optimized decellularization protocol may provide a strategy for cell-loaded scaffolds that require the removal of cellular material while retaining sufficient bioactive components in the ECM for further applications.

Effects of Yue-Bi-Tang on water metabolism in severe acute pancreatitis rats with acute lung-kidney injury.

BACKGROUND: The complications acute lung injury and acute kidney injury caused by severe inflammation are the main reasons of high mortality of severe acute pancreatitis (SAP). These two complications can both lead to water metabolism and acid-base balance disorders, which could act as additional critical factors affecting the disease trend. Aquaporins (AQPs), which can regulate the transmembrane water transport, have been proved to participate in the pathophysiological process of SAP and the associated complications, such as acute lung injury and acute kidney injury. Thus, exploring herbs that can effectively regulate the expression of AQP in SAP could benefit the prognosis of this disease. AIM: To determine whether Yue-Bi-Tang (YBT) can regulate the water metabolism in rats with severe acute pancreatitis via regulating the expression of aquaporins. METHODS: Sprague-Dawley rats were randomly divided into three groups, sham operation group (SOG), model group (MG), and treatment group (TG). SAP was induced with 3.5% sodium taurocholate in the MG and TG. Rats in the TG were administered with YBT while SOG and MG rats were given the same volume of saline. Blood and tissue samples were harvested to detect serum inflammatory cytokines, histopathological changes, malondialdehyde and superoxide dismutase in the lung, and protein and mRNA expression of kidney injury molecule-1, α-smooth muscle actin, and vimentin in the kidney, and AQP1 and 4 in the lung, pancreas, and kidney. RESULTS: The serum interleukin-10, tumor necrosis factor α, and creatinine levels were higher in the MG than in the SOG. Tumor necrosis factor α level in the TG was lower than that in the MG. Malondialdehyde level in lung tissues was higher than in the SOG. The pathological scores and edema scores of the pancreas, lung, and kidney tissues in the MG were all higher than those in the SOG and TG. The protein expression of AQP4 in lung tissues and AQP1 in kidney tissues in the MG were higher than those in the SOG and TG. The expression of vimentin was significantly higher in the MG than in the SOG. The expression of AQP1 mRNA in the lung and kidney, and AQP4 mRNA in the kidney was up-regulated in the MG compared to the SOG. CONCLUSION: YBT might regulate water metabolism to reduce lung and kidney edema of SAP rats via decreasing AQP expression, and alleviate the tissue inflammatory injury.

Optimal dosing time of Dachengqi decoction for protection of extrapancreatic organs in rats with experimental acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction. Dachengqi decoction (DCQD) has a potential role in protecting the extrapancreatic organs, but the optimal oral administration time remains unclear. AIM: To screen the appropriate oral administration time of DCQD for the protection of extrapancreatic organs based on the pharmacokinetics and pharmacodynamics of AP rats. METHODS: This study consisted of two parts. In the first part, 24 rats were divided into a sham-operated group and three model groups. The four groups were intragastrically administered with DCQD (10 g/kg) at 4 h, 4 h, 12 h, and 24 h postoperatively, respectively. Tail vein blood was taken at nine time points after administration, and then the rats were euthanized and the extrapancreatic organ tissues were immediately collected. Finally, the concentrations of the major DCQD components in all samples were detected. In the second part, 84 rats were divided into a sham-operated group, as well as 4 h, 12 h, and 24 h treatment groups and corresponding control groups (4 h, 12 h, and 24 h control groups). Rats in the treatment groups were intragastrically administered with DCQD (10 g/kg) at 4 h, 12 h, and 24 h postoperatively, respectively, and rats in the control groups were administered with normal saline at the same time points. Then, six rats from each group were euthanized at 4 h and 24 h after administration. Serum amylase and inflammatory mediators, and pathological scores of extrapancreatic organ tissues were evaluated. RESULTS: For part one, the pharmacokinetic parameters (C max, T max, T 1/2, and AUC 0 → t) of the major DCQD components and the tissue distribution of most DCQD components were better when administering DCQD at the later (12 h and 24 h) time points. For part two, delayed administration of DCQD resulted in lower IL-6 and amylase levels and relatively higher IL-10 levels, and pathological injury of extrapancreatic organ tissues was slightly less at 4 h after administration, while the results were similar between the treatment and corresponding control groups at 24 h after administration. CONCLUSION: Delayed administration of DCQD might reduce pancreatic exocrine secretions and ameliorate pathological injury in the extrapancreatic organs of AP rats, demonstrating that the late time is the optimal dosing time.

Comparison of small intestinal submucosa and polypropylene mesh for abdominal wall defect repair.

Abdominal wall defects are a common medical problem, and inadequate repair methods can lead to serious complications. Abdominal wall reconstruction using autologous tissue, or non-biological, biological, or composite patches is often performed to repair defective areas. In particular, composite patches containing both polymeric and biological materials have gained increasing attention due to their good mechanical properties and biocompatibility. However, it is still unclear whether the quality of repairs using composite patches is superior to that of a biological patch. Based on the limitations of previous studies, we compared small intestinal submucosa (SIS) patches with SIS + polypropylene mesh (PPM) patches for repairing abdominal wall defects in adult beagle dogs. Forty-five female dogs were subjected to surgical resection to produce abdominal wall defects. SIS or SIS + PPM was used as patch for the defects. Morphology, biomechanics, and histological evaluations were performed to evaluate the efficacy and safety of such therapies. Our findings demonstrated that SIS had advantages over SIS + PPM considering biological activity and histocompatibility without increasing the risk of repair failure.

Association analysis of cytokine polymorphisms and plasma level in Northern Chinese Han patients with paroxysmal nocturnal hemoglobinuria.

BACKGROUND: While the incidence of paroxysmal nocturnal hemoglobinuria (PNH) is relatively high in Northern China, the exact mechanism of the disease remains unknown. Immunoregulatory cytokine polymorphisms can directly regulate the expression levels of cytokines, which play a crucial role in many diseases. The purpose of this study was to study cytokine gene single nucleotide polymorphisms (SNPs) and the correlated cytokine expression levels in relationship to the PNH pathogenesis. METHODS: Peripheral blood samples were collected from 30 PNH patients and 40 healthy donors; all of the samples were collected from the Han people of Northern China. Eight SNP loci in five cytokine genes, including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), transforming growth factor-beta (TGF-ß), interleukin-6 (IL-6), and IL-10, and aplastic anemia (AA) were assessed. TNF-a, TGF-b, IFN-g, IL-6, and IL-10 were analyzed by sequence-specific primer polymerase chain reaction (PCR-SSP). The plasma protein levels of TNF-a, TGF-b, and IFN-g were assessed by an ELISA. RESULTS: The PNH patients had a lower frequency of the TC/GG genotype of the TGF-b gene (P < 0.01) and a higher frequency of the C allele in the TGF-b gene (+10) compared to the controls (P < 0.05). The predominant genotype of the +874 locus of the IFN-g gene was TA in the PNH patients, while that in the predominant genotype was AA in the control group and was statistically significant (P < 0.001). The frequency of the T allele in the IFN-g gene was dramatically higher in the PNH patients than in the controls (P < 0.05). The PNH patients had a reduced frequency of the GC and CC genotypes, as well as the C allele at locus -174 of the IL-6 gene compared to the controls (P < 0.01). In addition, the plasma concentrations of TNF-a, TGF-b, and IFN-g were significantly higher in the PNH group compared to the control group (P < 0.01). CONCLUSIONS: Expression levels of the TNF-a, TGF-b, and IFN-g cytokines play an important role in PNH. The GC and CC genotypes, as well as the C allele of the IL-6 gene may protect the Han people of Northern China against PNH. Additionally, the TC/GG genotype of the TGF-b gene may be the protective allele. In contrast, the TA genotype and the T allele for the IFN-g gene, as well as the C allele of TGF-b may be susceptible to PNH. However, SNPs in the TNF-a and IL-10 genes did not correlate with PNH development. Alternatively, the increased plasma concentrations of TNF-a, TGF-b, and IFN-g in PNH patients may also be related to PNH development.