Normal Tissue Structures Research Articles

Thyme oil alleviates Ova-induced bronchial asthma through modulating Th2 cytokines, IgE, TSLP and ROS

Bronchial asthma (BA) is a heterogeneous allergic respiratory disease with diverse inflammatory symptoms, pathology, and responses to treatment. Thyme is a natural product which is consisted of multiple phenolic compounds of therapeutic significance for treatment of cough and bronchitis. This study evaluated the efficacy of thyme oil against ovalbumin (OVA)-induced BA in an experimental rabbit model. Forty male rabbits were divided into four equal groups [control group (G1), OVA (G2), thyme oil (G3), and OVA plus thyme oil (G4)]. Animals were treated for 30 days, and clinical, histopathological (HP), histochemical (HC), immunohistochemical (IHC), morphometric, biochemical and flow cytometry methods were performed, followed by statistical analysis. All used methods revealed normal structure of the lung tissues in rabbits of G1 and G3. In contrast, the clinical examination of G2 rabbits revealed an obvious increase in the respiratory rate, sneezing and wheezing, whereas the HP, HC and IHC techniques exhibited substantial inflammatory changes in the peribronchio-vascular lung tissues with thinning, degeneration, apoptosis (using the TUNEL assay), necrosis, and shedding of the airway epithelium. Furthermore, the morphometric results confirmed significant increases in the numbers of inflammatory cells, goblet cells, eosinophils and apoptotic cells from (12, 0, 2, 2 cells) to (34,10, 16, 18 cells) respectively, as well as the area percentage of collagen fiber deposition and immunoexpression of eotaxin-1/10 high power fields. Additionally, the biochemical results revealed significant increases in the serum levels of TSLP, IL-4, IL-5, IL-9, IL-13, IgE and eotaxin-1 cytokines from (140, 40, 15, 38, 120, 100, 48) pg./ml to (360, 270, 130, 85, 365, 398, 110) pg./ml respectively, while analysis of ROS by flow cytometry revealed remarkable oxidative stress effects in G2 rabbits. On the other hand, treatment of rabbits with thyme oil in G4 substantially alleviated all OVA-induced alterations. Overall, our findings indicate for the first time that thyme oil can ameliorate OVA-induced BA via its immunomodulatory, anti-inflammatory, antiapoptotic, and antioxidant effects on the lung tissues of rabbits.

Study The protective Effects of Cichorium intybus L. Root Extract Against Carbon Tetrachloride-Induced Hepatotoxicity in Broiler Chickens

An existing survey was performed to assess the hepatoprotective effects of C. intybus root extract on carbon tetrachloride-induced hepatotoxicity in broiler chickens. A total of 240 one-day-old broiler chickens were divided into diverse groups of control, carbon tetrachloride (1 mL/kg body weight IM injection), C. intybus root extract (500 mg/kg body weight/daily orally) and finally both C. intybus root extract and carbon tetrachloride. Liver samples were dissected and examined histopathologically at the day 31 of maintenance. Numerical grading of histopathological findings was performed according to the types of lesions at different criteria. Liver samples of carbon tetrachloride-treated group harbored moderate fatty degeneration and necrosis. Those treated with C. intybus extract showed normal cellular and tissue structure. Chicks faced with carbon tetrachloride and treated with C. intybus extract exhibited mild fatty degeneration and normal tissue structure. Chicks treated with C. intybus extract displayed the lowermost scores of necrosis (1.08±0.28), degeneration (1.33±0.49), inflammation (1.16±0.38) and total pathologic indexes (3.58±0.79). Broilers faced with carbon tetrachloride displayed the uppermost scores of necrosis (2.83±0.57), degeneration (3.66±0.49), inflammation (2.16±0.38) and total pathologic indexes (8.66±0.98). C. intybus extract application to broilers faced with carbon tetrachloride caused statistically significant decrease in the scores give to necrosis, degeneration, inflammation and total pathologic indexes (P <0.05). Findings suggested that 10 days administration of C. intybus extract caused significant decrease in the formation of centrilobular hepatic necrosis, fatty changes, inflammation and degeneration of the hepatic cells of broilers faced with CCl4-induced hepatotoxicity.

Radiotherapy plan evaluation indices

To classify the available plan evaluation indices and compare the dosimetric suitability of these indices. Available published plan evaluation indices were categorized. Conformity index (CI) into two groups, one group contains those CI formulas which do not consider critical structure and other group contains those CI formulas which consider planning target volume (PTV) coverage, normal tissue and critical structure sparing simultaneously. Various homogeneity index (HI) formulas extracted from literature. Structure data sets of 25 patients were taken under consideration comprising of various sites. For each patient, two plans were created using Volumetric Arc Therapy technique. First type of plan (Plan-A) were generated considering all tissue objectives for targets and Organ at Risks (OARs) whereas second type of plan (Plan-B) were generated considering only targets tissue objectives and excluding OARs tissue objectives during plan optimization and dose calculation. Planning evaluation parameters were compared between Plan-A and Plan-B. CI calculated by various formulas in two different scenarios presented <2% variation. Any commonly used CI formula failed to differentiate the two different planning situations. On comparison between HI of two different scenario, it is observed that there are four formulas of HI which showed negligible variation but two formulae: S-index and HI (D) showed marginal variation. It is also observed that when OARs are removed from optimization dose homogeneity improved which is specifically pointed by sigma index formula. CI, which has assimilated the presence of OAR in their formulation, shows more reliability in plan evaluation. Sigma index was found to be more efficient formula while evaluating homogeneity of a treatment plan.

Tensins - emerging insights into their domain functions, biological roles and disease relevance.

Tensins are a family of focal adhesion proteins consisting of four members in mammals (TNS1, TNS2, TNS3 and TNS4). Their multiple domains and activities contribute to the molecular linkage between the extracellular matrix and cytoskeletal networks, as well as mediating signal transduction pathways, leading to a variety of physiological processes, including cell proliferation, attachment, migration and mechanical sensing in a cell. Tensins are required for maintaining normal tissue structures and functions, especially in the kidney and heart, as well as in muscle regeneration, in animals. This Review discusses our current understanding of the domain functions and biological roles of tensins in cells and mice, as well as highlighting their relevance to human diseases.

Mechanistic insights into the protective effect of paracetamol against rotenone-induced Parkinson’s disease in rats: Possible role of endocannabinoid system modulation

Parkinson’s disease (PD) is a disabling progressive neurodegenerative disease. So far, PD’s treatment remains symptomatic with no curative effects. Aside from its blatant analgesic and antipyretic efficacy, recent studies highlighted the endowed neuroprotective potentials of paracetamol (PCM). To this end: the present study investigated: (1) Possible protective role of PCM against rotenone-induced PD-like neurotoxicity in rats, and (2) the mechanisms underlying its neuroprotective actions including cannabinoid receptors’ modulation. A dose-response study was conducted using three doses of PCM (25, 50, and 100 mg/kg/day, i.p.) and their effects on body weight changes, spontaneous locomotor activity, rotarod test, tyrosine hydroxylase (TH) and α-synuclein expression, and striatal dopamine (DA) content were evaluated. Results revealed that PCM (100 mg/kg/day, i.p.) halted PD motor impairment, prevented rotenone-induced weight loss, restored normal histological tissue structure, reversed rotenone-induced reduction in TH expression and striatal DA content, and markedly decreased midbrain and striatal α-synuclein expression in rotenone-treated rats. Accordingly, PCM (100 mg/kg/day, i.p.) was selected for further mechanistic investigations, where it ameliorated rotenone-induced oxidative stress, neuro-inflammation, apoptosis, and disturbed cannabinoid receptors’ expression. In conclusion, our findings imply a multi-target neuroprotective effect of PCM in PD which could be attributed to its antioxidant, anti-inflammatory and anti-apoptotic activities, in addition to cannabinoid receptors’ modulation.

Curcumin loaded polycaprolactone-/polyvinyl alcohol-silk fibroin based electrospun nanofibrous mat for rapid healing of diabetic wound: An in-vitro and in-vivo studies

Electrospinning is emerging as a versatile technique nanofibers fabrication because due to their unique properties such as large surface area to volume ratio, porosity and maintaining moist wound environment, the nanofibers are able to deliver sustained drug release and oxygen to the wound for rapid healing of diabetic wound. The present work was aimed to prepare and evaluate silk fibroin-curcumin based nanofiber in combination with polycaprolactone (PCL) and polyvinyl alcohol (PVA) which helped to strengthen the wound healing properties of nanofiber. Silk fibroin is a naturally occurring polymer was selected one polymer for making nanofibrous mat due to its unique properties such as biodegradability, permeability, oxygen supply and maintain moisture content in the wound. SEM results showed diameters of fibers varied in the range between 200 and 350 nm and their tensile strength ranged from 12.41 to 16.80 MP. The nanofibers were causing sustained release of curcumin for many hours. The in-vivo wound healing studies in streptozotocin-induced diabetic mice showed rapid wound healing efficacy as compared to conventional formulations. Furthermore, the histopathological studies evidenced its ability to restore the normal skin structure and histological conditions of tissues. The silk fibroin-based nanofiber wound dressing, therefore appears to be an ideal preparation, in combination with curcumin, because it blends the anti-oxidant, anti-inflammatory properties of curcumin. Therefore, it was concluded that the silk fibroin-based nanofiber loaded with curcumin has great healing potential in diabetic wound.

Interpreting signals from the peripheral nerve in amyloidosis: a call for action

Systemic amyloidosis includes a group of disorders, characterized by deposition of insoluble aggregates of amyloid fibrils in various tissues that lead to disruption of normal tissue structure and impaired function. They are currently categorized as hereditary and secondary. Peripheral neuropathy is a frequent complication of systemic amyloidosis. The most common phenotype is a length-dependent sensorimotor polyneuropathy with autonomic dysfunction, but there are many atypical presentations that often lead to delayed diagnosis. In this review, we emphasize the neurological clinical aspects that induce a suspicion of amyloidosis, the possible differential diagnosis and the diagnostic pitfalls. An early diagnosis of the disease is crucial for rapid initiation of appropriate treatment that may change the course and the progression of the disease.

Symmetric-Constrained Irregular Structure Inpainting for Brain MRI Registration with Tumor Pathology.

Deformable registration of magnetic resonance images between patients with brain tumors and healthy subjects has been an important tool to specify tumor geometry through location alignment and facilitate pathological analysis. Since tumor region does not match with any ordinary brain tissue, it has been difficult to deformably register a patient's brain to a normal one. Many patient images are associated with irregularly distributed lesions, resulting in further distortion of normal tissue structures and complicating registration's similarity measure. In this work, we follow a multi-step context-aware image inpainting framework to generate synthetic tissue intensities in the tumor region. The coarse image-to-image translation is applied to make a rough inference of the missing parts. Then, a feature-level patch-match refinement module is applied to refine the details by modeling the semantic relevance between patch-wise features. A symmetry constraint reflecting a large degree of anatomical symmetry in the brain is further proposed to achieve better structure understanding. Deformable registration is applied between inpainted patient images and normal brains, and the resulting deformation field is eventually used to deform original patient data for the final alignment. The method was applied to the Multimodal Brain Tumor Segmentation (BraTS) 2018 challenge database and compared against three existing inpainting methods. The proposed method yielded results with increased peak signal-to-noise ratio, structural similarity index, inception score, and reduced L1 error, leading to successful patient-to-normal brain image registration.

Controlled release of KGF-2 for regulation of wound healing by KGF-2 complexed with "lotus seedpod surface-like" porous microspheres.

Keratinocyte growth factor-2 (KGF-2) can regulate the proliferation and differentiation of keratinocyte, which plays a remarkable role in maintaining normal tissue structure and promoting wound healing. As an effective strategy, KGF-2 solution is widely used in the treatment of wounds in clinical applications. However, KGF-2 in solution cannot achieve sustained release, which results in drug loss and unnecessary waste. Polysaccharide hemostasis microspheres (PHMs) are an ideal drug loading platform due to their special "lotus seedpod surface-like" morphology and structure. Herein, to realize the controllable release of KGF-2, PHMs loaded with KGF-2 (KGF-2@PHMs) were prepared. It was found that the bioavailability of KGF-2 was improved greatly. Most importantly, KGF-2@PHMs can reduce inflammation and accelerate the wound healing process due to the controlled release of KGF-2. KGF-2@PHMs might be a potential alternative strategy for wound healing in future clinical applications.

Vascular Heterogeneity With a Special Focus on the Hepatic Microenvironment.

Utilizing single-cell sequencing, recent studies were able to analyze at a greater resolution the heterogeneity of the vasculature and its complex composition in different tissues. Differing subpopulations have been detected, distinguishable only by their transcriptome. Designed to provide further insight into the heterogeneity of the functional vascular tissue, endothelial cells have been the main target of those studies. This review aims to present a synopsis of the variability of the different vascular beds, their endothelial variety, and the supporting cells that allow the vessels to serve their various purposes. Firstly, we are going to chart vascular tissue heterogeneity on a cellular level, describing endothelial diversity as well as stromal microenvironmental variety and interaction in a physiological setting. Secondly, we will summarize the current knowledge of pathological vessel formation in the context of cancer. Conventional anti-tumor therapeutic targets as well as anti-angiogenetic therapy is frequently limited by poor response of the tumor tissue. Reasons for moderate response and resistance to treatment can be found through different drivers of angiogenesis, different mechanisms of blood supply, but also in poorly understood tissue diversity. Based on this, we are comparing how pathologies alter the normal structure of vascular tissues highlighting the involved mechanisms. Lastly, illustrating the concept above, we will focus on the hepatic microenvironment, an organ of frequent metastatic spreading (e.g., from colorectal, breast, and lung cancers). We will address how the hepatic vasculature usually develops and subsequently we will describe how common liver metastases vary in their vasculature and the way they supply themselves (e.g., angiogenesis versus vessel co-option).

Comparative Dosimetric Analysis of Combined Intracavitary and Interstitial Needles Placement vs. Intracavitary Alone for Cervical Cancer

To compare the target volume coverage and normal tissue avoidance for high-dose rate (HDR) brachytherapy boost for cervical cancer between intracavitary (IC) tandem and ovoid (T&O) with additional free-hand interstitial (IS) needles (IC-IS) vs. IC brachytherapy alone under ultrasound guidance. We reviewed IC T&O cases with free-hand IS needles for cervical cancer treatment from Nov 2018 to Oct 2019. Ultrasound guidance was used for applicator placement. Treatment planning was CT-based; high-risk clinical target volumes (HR-CTVs) and organs at risk (OARs) were delineated before each fraction. Minimum acceptable target coverage was 90% of the prescription dose delivered to the HR-CTV (D90). If these objectives were unmet with the standard IC applicator, IS needles were added at the discretion of the physician. For this analysis, each IC-IS case was re-planned (r) with IC alone and again with IC-IS, matching the dose-limiting normal tissue structure for that treatment. HR-CTV with D90 along with OARs D2cc means and 95% confidence intervals were evaluated between rIC-IS and rIC plans using a paired t-tests, p = 0.05. Acute side effects were evaluated using CTCAE v5.0 criteria. We identified 6 patients with 20 IC-IS treatments after whole pelvis radiation. Between two to six IS needles were placed for each treatment. All fractions were planned for 7 Gy. Mean D90 per fraction to the HR-CTV for iIC-IS, rIC, and rIC-IS needles was 7.6 Gy (6.3–9.4) vs. 7.1 Gy (4.9–9.3) vs. 7.8 Gy (6.3–9.8) (p = 0.0000008), respectively, with a relative percent-dose increase of 10.6% from rIC alone to rIC-IS. Regarding OARs, mean D2cc per fraction for iIC-IS, rIC alone, and rIC-IS were: Bladder - 5.3 Gy (3.7–6.4) vs. 5.5 (4.1–6.2) vs. 5.5 (3.93 – 6.19) (p = 0.78); Rectum - 3.1 Gy (2.2–4.2) vs. 3.2 (2.1–4.1) vs. 3.3 Gy (2.2–4.1) (p = 0.14); Sigmoid - 3.4 Gy (2.3–4.2) vs. 3.4 (2.5–4.2) vs. 3.4 (2.5– 4.2) (p = 0.49). Dosimetric results demonstrated in the table. All patients tolerated the procedure well without any CTCAE v5.0 Grade 3 to 5 adverse events. For appropriately selected patients, adding IS needless to IC HDR brachytherapy boost can improve dose coverage of HR-CTV for cervical cancer while not increasing dose to OARs. Long term follow-up is warranted for evaluating differences in clinical outcomes and associated toxicity.Tabled 1Abstract 2856; Table; Comparison of initial (i) IC + IS cases vs. re-planned (r) IC alone vs. rIC-IS (Gy)Patient Number (# fractions)iIC-IS D90 HRCTVrIC alone D90 HRCTVrIC-IS D90 HRCTViIC-IS D2cc BladderrIC alone D2cc BladderrIC-IS D2cc bladderiIC-IS D2cc RectumrIC alone D2cc RectumrIC-IS D2cc rectum1 (3)7.67.67.94.64.74.82.42.62.72 (4)7.77.98.34.54.94.72.82.72.83 (3)6.867.15.76.16.14.13.944 (4)8.7895.75.95.82.83.13.15 (3)75.46.96.25.55.83.73.93.96 (3)7.27.17.35.75.75.73.33.23.3Average (CI)7.6 (6.3–9.4)7.1 (4.9–9.3)7.8 (6.3–9.8)5.3 (3.7–6.4)5.5 (4.1–6.2)5.5 (3.9–6.2)3.1 (2.2–4.2)3.2 (2.1–4.1)3.3 (2.2-4.1)p - value0.0000080.780.14 Open table in a new tab

How C-Reactive Protein Structural Isoforms With Distinctive Bioactivities Affect Disease Progression.

C-reactive protein (CRP) is a widely known, hepatically synthesized protein whose blood levels change rapidly and pronouncedly in response to any tissue damaging event associated with an inflammatory response. The synthesis and secretion of CRP is stimulated by interleukin-6, an early pleiotropic cytokine released by macrophages, endothelial, and other cells that are activated when localized normal tissue structures are compromised by trauma or disease. Serum CRP levels can change rapidly and robustly from 10-100-fold within 6–72 h of any tissue damaging event. Elevated blood levels correlate with the onset and extent of both activated inflammation and the acute phase biochemical response to the tissue insult. Because its functional bioactivity as the prototypic acute phase reactant has eluded clear definition for decades, diagnosticians of various conditions and diseases use CRP blood levels as a simple index for ongoing inflammation. In many pathologies, which involves many different tissues, stages of disease, treatments, and responses to treatments, its interpretive diagnostic value requires a deeper understanding of the localized tissue processes and events that contribute signals which regulate protective or pathological host defense bioactivities. This report presents concepts that describe how local tissue activation events can lead to a non-proteolytic, conformational rearrangement of CRP into a unique isoform with distinctive solubility, antigenicity, binding reactivities and bioactivities from that protein widely known and measured in serum. By describing factors that control the expression, tissue localization, half-life and pro-inflammatory amplification activity of this CRP isoform, a unifying explanation for the diagnostic significance of CRP measurement in disease is advanced.

Unfulfilled Inflammatory Resolution: A Key Factor in the Pathogenesis of Psoriasis.

Recent literature has highlighted the importance of chronic inflammation in psoriasis pathogenesis. Non-resolving inflammation can trigger progressive tissue damage and inflammatory mediator release which in turn perpetuate the inflammatory cycle. Under normal conditions, inflammatory responses are tightly controlled through several mechanisms that restore normal tissue function and structure. Defects in regulatory mechanisms of the inflammatory response can result in persistent unresolved inflammation and further increases of inflammation. Therefore, this review focuses on defects in regulatory mechanisms of inflammatory responses that lead to uncontrolled chronic inflammation in psoriasis. Databases such as Pubmed Embase, ISI, and Iranian databases including Iranmedex, and SID were researched to identify relevant literature. The results of this review indicate that dysregulation of the inflammatory response may be a likely cause of various immune-mediated inflammatory disorders such as psoriasis. Based on current findings, advances in understanding the cellular and molecular mechanisms involved in inflammation resolution are not only improving our knowledge of the pathogenesis of chronic inflammatory diseases but also supporting the development of new therapeuticstrategies.

Multidisciplinary approach in the management of hATTR.

Amyloidosis is a disease with various clinical presentations characterized by deposition of insoluble, misassembled fibril proteins (amyloid) that disrupt normal tissue structure and function. Amyloidosis is caused by up to 30 different proteins, including immunoglobulin light chain and transthyretin (TTR).

Toxic effects of an organophosphate pesticide, envoy 50 SC on the histopathological, hematological, and brain acetylcholinesterase activities in stinging catfish (Heteropneustes fossilis)

BackgroundFreshwater fish in Bangladesh are adversely affected by the washed off pesticides, used in agriculture. The aim of this study was to evaluate the impacts of a commonly used organophosphate pesticide on freshwater stinging catfish, Heteropneustes fossilis, which envisioned that the possible threats might occur by this organophosphate group to other species in the wild.MethodologyTo study the potential hazards of Envoy 50 SC on H. fossilis, fry of the fish were exposed to the acute toxicity tests. Changes in the hematological parameters, organ-specific histomorphologies, and brain acetylcholinesterase (AChE) activities were determined by treating the fish with agricultural recommended dose and below that dose of 0.015 and 0.0075 ppm, respectively.ResultsLC50 of Envoy 50 SC for the fish was determined as 0.151 (0.014–0.198) ppm. Pesticide abruptly altered the normal tissue structures of the gill, liver, and kidney. The major alterations included were the gill lamellae missing, gill clubbing, hyperplasia, nuclear hypertrophy, vacuolation, glomerular expansion, increasing diameter of the renal tubules, hemorrhage, necrosis, and pyknosis. In blood cells, changes observed in the peripheral nuclear erythrocyte were large lymphocyte, dead cell, fusion of the cells, binucleated cells, tear-shaped cells, ghost cells, senile cells, and abnormal structures of the cells. Significantly lower (P < 0.05) red blood cell (RBC) count and AChE activities in fish brain due to the pesticide exposure suggested the reasons of abrupt behavior, increased oxygen consumption, and fish mortality at higher concentration of this organophosphate pesticide.ConclusionThe presence of pesticides, even at low concentrations, caused deleterious effects on the earlier life stages of a comparatively harder and robust fish, suggesting a wider range effect on the more sensitive wild life, in particular decrease in survival in their native environment. Therefore, measures should be taken to minimize the risk of contamination of the aquatic environment by such toxic chemicals.

Tadalafil alleviates cisplatin-induced reproductive toxicity through the activation of the Nrf2/HO-1 pathway and the inhibition of oxidative stress and apoptosis in male rats

Male reproductive toxicity is a well-known adverse effect of cisplatin (CIS), an important antineoplastic agent used to control several types of cancers. Tadalafil (TDF), is a long-acting phosphodiesterase-5 (PDE5) inhibitor commonly used as treatment for erectile dysfunction. The aim of this work was to study the possible protective effect of TDF against CIS-induced testicular toxicity in rats and the possible involvement of Nrf2/HO-1 pathway, which demonstrates antioxidant and inflammatory activities utilizing zinc protoporphyrin-IX (ZnPP) as HO-1 inhibitor. Results revealed that TDF attenuated the CIS-induced disturbances in sperm count and activities, normalized the serum testosterone level, improved the CIS-induced changes in epididymal and testicular weights and restored the normal structure of testicular tissues. In addition, TDF upregulated the gene expression levels of Nrf2 and HO-1 and the activity of HO-1 whereas, it reduced the CIS-induced changes in testicular oxidative stress markers and the levels of inflammatory mediators (TNF-α and iNOS). Furthermore, TDF antagonized the CIS-induced increase in testicular gene expression of apoptotic markers caspase-3 and Bax, and the decrease in Bcl-2. However, ZnPP co-administration significantly attenuated all TDF-mediated improvements in CIS-induced testicular toxicity, biochemical changes, and apoptosis. In conclusion, TDF exerts a protective effect against CIS-induced reproductive toxicity in males, through different mechanisms, besides its inhibitory action to PDE5, possibly mediated by the upregulation of Nrf2/HO-1, along with its antioxidant, anti-inflammatory, and anti-apoptotic effects. Hence, the use of TDF represents a promising therapeutic approach to protect the male reproductive system from the harmful toxic effects of CIS.

The Condition of the Rat Myocardium and Isolated Sheep Heart after Prolonged 24-Hour Hypothermic Preservation in a Pressurized Carbon Monoxide–Oxygen Gas Mixture

High organoprotective properties of a carbon monoxide (CO)–oxygen (O2) gas mixture were confirmed after prolonged (24-h) preservation of the papillary muscle and an isolated rat heart at 4°C. Hypothermic preservation in the high-pressure gas mixture (6 atm) provided efficient restoration of the contractile activity of the isolated rat heart after 24-h storage at 4°C. The isolated retrograde-perfused Langendorff heart performed physically relevant mechanical work, which was similar in duration to that of an intact control heart. Staining with triphenyltetrazolium chloride did not detect infarcted regions in the myocardium. After preservation, the heart tissue was highly capable of performing its function in a test for electrically stimulated contractile activity of papillary muscles. In the test group, The frequency–intensity relationship, the potentiation effect induced by a pause, and the response to stimulation with isoproterenol of test hearts generally corresponded to the parameters of a normal rat myocardium. A sheep heart, which is comparable in size and weight to a human heart, was for the first time successfully preserved using the gas mixture. Normal heartbeat was spontaneously restored after the start of perfusion in all experiments. Histology did not detect a significant difference between test and control sheep hearts. The normal tissue structure of the myocardium was preserved in the test hearts. The 24-h preservation achieved in the study was four times longer than the maximum allowable preservation time of standard static cold storage. The results obtained with the large laboratory animal heart model showed that the hypothermic preservation protocol is promising for prolonged storage of human hearts.

P0520EFFECT OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS ON SECONDARY ACUTE KIDNEY INJURY IN RATS WITH LIVER CIRRHOSIS

Abstract Background and Aims Acute kidney injury( AKI) is one of the most common complications of decompensated cirrhosis, and it primarily presents as a sharp decrease in glomerular filtration rate, rapid increase in serum creatinine( SCr) and urea nitrogen. And the search for specific and safe treatment has been a research hot spot in recent years. In this article, the effect of human umbilical cord mesenchymal stem cells on carbon tetrachloride (CCl4)-induced liver fibrosis (HF) in rats with acute kidney injury and the possible mechanism are investigated. Method Human umbilical cord blood mesenchymal stem cells were sub-cultured by adherent method, and the cells were identified by morphological observation, cell phenotypic analysis and multi-directional differentiation potential analysis methods. WASTA rats were randomly divided into control group, cirrhosis model group and treatment group, with 10 rats in each group. Model group and treatment group were injected with CCl4-olive oil (1:1) solution 3 mL·kg -1, and the control group was given the same amount of olive oil for intervention, twice a week for 8 weeks. Rats in treatment group were administrated wth Human umbilical cord mesenchymal stem cells (2 × 109 /L) via the tail vein at the 5th week after injection of CCl4-olive oil solution, but the other rats were injected with 0.9% normal saline, once a week for 6 weeks. After the intervention, Serum, kidneys and 24 hours urine of rats in each group were collected, which were applied for a detection of serum creatinine and urea nitrogen, malondialdehyde (MDA), NO content and superoxide dismutase (SOD), as well as renal pathological examination. Results 1.In vitro, umbilical cord blood mesenchymal stem cells was passaged to the third generation, and the morphology was uniform and spiraled. Phenotypic analysis showed that the positive rates of stem cell markers CD29, CD44 and CD105 were all greater than 95%, the positive rate of HLA-DR (graft-versus-host disease-associated factor) less than 10%, and the positive rate of CD34 and CD45 lower than 20% (Figure 1). 2. Compared with the cirrhotic model group, MDA content of serum and kidney in model group significantly decreased under the effect of mesenchymal stem cell (p &amp;lt;0.01) (Table 1). 3. The normal group had normal liver tissue structure, ordered liver cells, no hepatic edema, and no lesions. In the model group, large-area lesions, including edema of liver cells, rupture of cell membranes, and infiltration of inflammatory cells, had appeared. Compared with the model group, Hepatocellular necrosis, edema, and inflammatory cell infiltration were significantly improved after transplanting Human umbilical cord mesenchymal stem cells (Figure 2). 4.In the model group, the rat renal tubules disappeared and the lumen was disordered. After injection of Human umbilical cord mesenchymal stem cells, renal tubular and renal interstitial damage is improved and the thickening of glomerular basement membrane is reduced (Figure 3). Conclusion In CCl4-induced liver cirrhosis model rats, human umbilical cord mesenchymal stem cells can protect the kidney by reducing free radicals and cellular lipid peroxidation in vivo.

Lipids and Lipid Mediators Associated with the Risk and Pathology of Ischemic Stroke.

Stroke is a severe neurological disorder in humans that results from an interruption of the blood supply to the brain. Worldwide, stoke affects over 100 million people each year and is the second largest contributor to disability. Dyslipidemia is a modifiable risk factor for stroke that is associated with an increased risk of the disease. Traditional and non-traditional lipid measures are proposed as biomarkers for the better detection of subclinical disease. In the central nervous system, lipids and lipid mediators are essential to sustain the normal brain tissue structure and function. Pathways leading to post-stroke brain deterioration include the metabolism of polyunsaturated fatty acids. A variety of lipid mediators are generated from fatty acids and these molecules may have either neuroprotective or neurodegenerative effects on the post-stroke brain tissue; therefore, they largely contribute to the outcome and recovery from stroke. In this review, we provide an overview of serum lipids associated with the risk of ischemic stroke. We also discuss the role of lipid mediators, with particular emphasis on eicosanoids, in the pathology of ischemic stroke. Finally, we summarize the latest research on potential targets in lipid metabolic pathways for ischemic stroke treatment and on the development of new stroke risk biomarkers for use in clinical practice.

Hormonal and Histopathological Fertility Assessments of Male Dogs in Kosovo

This study is aimed to evaluate the concentration of certain hormones (testosterone, LH and FSH), in male dogs from different regions of Kosovo and to histopathologically evaluate testicular tissue from these examined dogs. Testosterone, LH and FSH concentrations were determined by ELISA and testicular tissue samples were processed and subsequently stained with haematoxylin and eosin for histological examination with light microscopy. For mixed-breed dogs, higher testosterone levels were found in the Malisheva, while lower testosterone levels were recorded in the Vushtrria. LH levels in mixed-breed dogs were higher in the Malisheva and lower in the Kamenica. Furthermore, FSH levels in mixed-breed dogs were higher in the Malisheva and lower in the Kamenica. Histopathology revealed different histological changes in testicular tissues, ranging from normal tissue structure to mild, moderate and severe structural alterations. It can be concluded that hormone analyses and histopathological examinations could be considered for fertility assessments.