Loss of pod strings in common bean is associated with gene duplication, retrotransposon insertion, and overexpression of PvIND

Regulation of fruit development has been central in the evolution and domestication of flowering plants. In common bean (Phaseolus vulgaris L.), a major global staple crop, the two main economic categories are distinguished by differences in fiber deposition in pods: a)dry beans with fibrous and stringy pods; and b) stringless snap/green beans withreduced fiber deposition, but which frequently revert to the ancestral stringy state. To better understand control of this important trait, we first characterized developmental patterns of gene expression in four phenotypically diverse varieties. Then, using isogenic stringless/revertant pairs of six snap bean varieties, we identified strong overexpression of the common bean ortholog of INDEHISCENT (PvIND) in non-stringy types compared to their string-producing counterparts. Microscopy of these pairs indicates that PvIND overexpression is associated with overspecification of weak dehiscence zone cells throughout the entire pod vascular sheath. No differences in PvIND DNA methylation were correlated with pod string phenotype. Sequencing of a 500 kb region surrounding PvIND in the stringless snap bean cultivar Hystyle revealed that PvIND had been duplicated into two tandem repeats, and that a Ty1-copia retrotransposon was inserted between these tandem repeats, possibly driving PvIND overexpression. Further sequencing of stringless/revertant isogenic pairs and diverse materials indicated that these sequence features had been uniformly lost in revertant types and were strongly predictive of pod phenotype, supporting their role in PvIND overexpression and pod string phenotype.

Activation of the Unfolded Protein Response (UPR) Is Associated with Cholangiocellular Injury, Fibrosis and Carcinogenesis in an Experimental Model of Fibropolycystic Liver Disease

Fibropolycystic liver disease is characterized by hyperproliferation of the biliary epithelium and the formation of multiple dilated cysts, a process associated with unfolded protein response (UPR). In the present study, we aimed to understand the mechanisms of cyst formation and UPR activation in hepatocytic c-Jun N-terminal kinase 1/2 (Jnk1/2) knockout mice. Floxed JNK1/2 (Jnkf/f) and Jnk∆hepa animals were sacrificed at different time points during progression of liver disease. Histological examination of specimens evidenced the presence of collagen fiber deposition, increased α-smooth muscle actin (αSMA), infiltration of CD45, CD11b and F4/80 cells and proinflammatory cytokines (Tnf, Tgfβ1) and liver injury (e.g., ALT, apoptosis and Ki67-positive cells) in Jnk∆hepa compared with Jnkf/f livers from 32 weeks of age. This was associated with activation of effectors of the UPR, including BiP/GRP78, CHOP and spliced XBP1. Tunicamycin (TM) challenge strongly induced ER stress and fibrosis in Jnk∆hepa animals compared with Jnkf/f littermates. Finally, thioacetamide (TAA) administration to Jnk∆hepa mice induced UPR activation, peribiliary fibrosis, liver injury and markers of biliary proliferation and cholangiocarcinoma (CCA). Orthoallografts of DEN/CCl4-treated Jnk∆hepa liver tissue triggered malignant CCA. Altogether, these results suggest that activation of the UPR in conjunction with fibrogenesis might trigger hepatic cystogenesis and early stages of CCA.

Cardiac Effects of Treadmill Running at Different Intensities in a Rat Model

Purpose: In this study, we investigated the effect of treadmill exercise training on cardiac hypertrophy, collagen deposition, echo parameters and serum levels of cardiac troponin I (cTnI) in rats, and how they differ with various exercise intensities, hence exploring potential signal transduction.Methods: Male Sprague-Dawley rats were randomly divided into sedentary (SED), low-intensity running (LIR), medium-intensity running (MIR), and high-intensity running (HIR) groups. Each exercise group had 3 subgroups that were sacrificed for cardiac tissue analyses at 1, 4, and 8 weeks, respectively, and all rats participated in a daily 1 h treadmill routine 5 days per week. Echocardiographic measurements were performed 24 h after the last exercise session. Additionally, myocardium samples and blood were collected for histological and biochemical examinations. Changes in the extracellular signal-regulated kinases 1/2 (ERK1/2) signal pathway were detected by Western blotting.Results: After a week of running, ventricular myocyte size and the phosphorylation of ERK1/2 increased in the HIR group, while left ventricular (LV) diastolic diameter values and LV relative wall thickness increased in the LIR and MIR groups. In addition, we observed heart enlargement, cTnI decrease, and ERK1/2 signal activation in each of the exercise groups after 4 weeks of running. However, the HIR group displayed substantial rupture and increased fibrosis in myocardial tissue. In addition, compared with the LIR and MIR groups, 8 weeks of HIR resulted in structural damage, fiber deposition, and increased cTnI. However, there was no difference in the activation of ERK1/2 signaling between the exercise and SED groups.Conclusion: The effect of running on cardiac hypertrophy was intensity dependent. In contrast to LIR and MIR, the cardiac hypertrophy induced by 8 weeks of HIR was characterized by potential cardiomyocyte injury, which increased the risk of pathological development. Furthermore, the ERK signaling pathway was mainly involved in the compensatory hypertrophy process of the myocardium in the early stage of exercise and was positively correlated with exercise load. However, long-term exercise may attenuate ERK signaling activation.

Vitamin D3 Prevents the Deleterious Effects of Testicular Torsion on Testis by Targeting miRNA-145 and ADAM17: In Silico and In Vivo Study

Testicular torsion (TT) is the most common urological emergency in children and young adults that can lead to infertility in many cases. The ischemia-reperfusion (IR) injury due to TT has been implicated in the pathogenesis of testicular damage. The main pathological mechanisms of contralateral injury after ipsilateral TT are not fully understood. In the presented study, we investigated the molecular and microscopic basis of ipsilateral and contralateral testicular injury following ipsilateral testicular torsion detorsion (T/D) and explored the possible protective role of vitamin D3. The biochemical analysis indicated that IR injury following T/D significantly decreased the activity of testicular glutathione peroxidase (GPx) enzyme, level of serum testosterone, serum inhibin B, and expression of testicular miRNA145, while increased the activity of testicular myeloperoxidase (MPO) enzyme, level of testicular malondialdehyde (MDA), level of serum antisperm-antibody (AsAb), and expression of ADAM-17. The histological and semen analysis revealed that torsion of the testis caused damages on different tissues in testis. Interestingly, administration of vitamin D3 prior to the IR injury reversed the deterioration effect of IR injury on the testicular tissues as indicated by biochemical and histological analysis which revealed normal appearance of the seminiferous tubules with an apparent decrease in collagen fiber deposition in both ipsilateral and contralateral testes. Our results revealed that the protective effect of vitamin D3 treatment could be attributed to target miRNA145 and ADAM17 protein. To further investigate these findings, we performed a detailed molecular modelling study in order to explore the binding affinity of vitamin D3 toward ADAM17 protein. Our results revealed that vitamin D3 has the ability to bind to the active site of ADAM17 protein via a set of hydrophobic and hydrophilic interactions with high docking score. In conclusion, this study highlights the protective pharmacological application of vitamin D3 to ameliorate the damages of testicular T/D on the testicular tissues via targeting miRNA145 and ADAM17 protein.

Effect of Usage of the Proton Pump Inhibitor Omeprazole on the Structure of the Kidney of Male Albino Rats

Introduction Recent clinical observational studies claimed that long term use of proton pump inhibitors (PPIs) might lead to kidney injury that might progress to end-stage renal disease. Aim of the work Was to verify these claims by an in vivo experimental study in the rat. Materials &methods Fourty two adult male albino rats were assigned in four groups Control group (I) in which rats were not administrated any treatment . In groups IIa, IIb, IIc rats received daily oral omeprazole in dose of 0.75mg per kg. for 2,4,or 6 weeks successively. At the end of experiment, blood samples were collected for serum creatinine and blood urea nitrogen (BUN) measurement. Then animals were sacrificed and kidney specimens were processed into paraffin blocks, sectioned and stained with H&E, Mallory trichrome &PAS. Stained sections and image analysis were used to count vacuolated cells, pyknotic nuclei, tubular casts and area precent of collagen fiber deposition then data was subjected to statistical analysis. Results Histological examination of renal sections from omeprazole treated group showed sectional kidney injury in renal corpuscle, renal tubules and sever vascular congestion with inflammatory cell infiltrate in renal interstitium . Thickening of basement membrane was seen by PAS, while progressive increase in collagen fiber deposition was detected by Mallory trichrome stain . Morphometry, image analysis statistical analysis confirmed histological findings. Statistical significant increase in number of vacuolated cells, pyknotic nuclei, hyaline casts and area percent of collagen fiber deposition compared with control group. Clear deterioration of renal function tests was observed across the 3 time points of the study compared with the control with highly significant rise of serum creatinine in 4 & 6 weeks group compared with the control. Results of the study were time -dependent with the worst damage in the 6 week group (IV). Conclusion The present study declared that long term use of omeprazole resulted in structural damage of rat renal tissue with associated deterioration of renal function in a time dependent manner. Extreme caution should be taken with clinical prescription of omeprazole and close monitoring of renal function is highly recommended.

The Histopathological Correlate of Peri-Vascular Adipose Tissue Attenuation on Computed Tomography in Surgical Ascending Aorta Aneurysms: Is This a Measure of Tissue Inflammation?

On computed tomography (CT) imaging, a peri-vascular adipose tissue attenuation (pVAT) measure has been proposed as a non-invasive correlate of inflammation in the coronary artery vessels, and a single research group provided histopathological demonstration of this radiological/pathological correspondence. Our group has shown that patients with surgical-grade ascending aorta (AA) aneurysm display higher pVAT compared with patients with smaller aneurysms or normal AA. Based on histopathological studies on coronary arteries, we speculated that this correlation may be related to a non-otherwise specified aortic inflammatory process. However, since adipose tissue around the AA is often scant, and there are no histopathological studies confirming such hypothesized association between higher pVAT and inflammation around the AA, we cannot exclude that this pVAT change is secondary to different mechanisms, unrelated to the actual presence of peri-vascular inflammation. We performed a retrospective clinical/radiological/pathological study in 78 patients who underwent AA surgery with the aim to correlate pre-operatory pVAT on CT with histopathological findings from the surgical specimens. Histopathological review and immunohistochemistry were performed on the surgical aortic samples. The AA adventitial/periadventitial adipose tissue had higher pVAT by an increasing collagen fiber deposition, which progressively makes the fat hypotrophic and, in the late stages of this process, it replaces the normal soft tissue composition in this location. In the ascending aorta, pVAT on CT imaging is probably not a proxy for the presence of current vascular inflammation, although it may track changes involving the progressive substitution of perivascular adipose cells by higher-pVAT tissues, mainly fibrotic replacement.

Amygdalin isolated from Amygdalus mongolica protects against hepatic fibrosis in rats

The aim of this research was to investigate the effect of amygdalin on hepatic fibrosis in rats. Amygdalin was purified and identified from the seeds of Amygdalus mongo lica. Sprague Dawley rats in the control and model groups were administered water. Sprague Dawley rats were divided into the low-, middle-, and high-dose amygdalin groups that received 20, 40, and 80 mg kg−1 amygdalin, respectively. whereas the silymarin group was treated with 50 mg kg−1 silymarin. The control and model groups were administered water. Liver tissue analysis revealed significantly lower activities of ALT, AST, ALP, SOD, and MDA in the drug-treated groups compared to the model group. Serum analysis revealed significantly lower HYC and C-IV in the middle-dose amygdalin-treated group compared to the model group. The histopathological changes were less severe in the drug-treated groups as observed by the formation of pseudolobuli and decreased collagen fiber deposition. Hepatic fibrosis-related genes were expressed at significantly lower levels in the amygdalin-treated groups than in the model group. Amygdalin from A. mongolica represents a therapeutic candidate for hepatic fibrosis prevention and treatment.

Dwarf and Tall Elephantgrass Genotypes under Irrigation as Forage Sources for Ruminants: Herbage Accumulation and Nutritive Value

This two-year study evaluated the effect of Pennisetum purpureum genotypes under rainfed or irrigated conditions, during the dry and rainy seasons, on herbage, leaf, and stem dry matter (DM) accumulation rates, nutritive value, and carbohydrate and protein fractionation. Treatments were tall (Iri 381 and Elefante B) or dwarf (Mott and Taiwan A-146 2.37) genotypes under rainfed or irrigated conditions. Taiwan A-146 2.37 (146 kg DM ha per day) showed similar herbage accumulation rate (HAR) to tall genotypes during the rainy season (124 and 150 kg DM/ha per day, respectively). Dwarf genotypes showed differences in leaf accumulation rate (LAR) (66 and 49 kg DM/ha per day). Mott leaf had less neutral detergent fiber (NDF) (589 g/kg DM) than Taiwan A-146 2.37 (598 g/kg DM), and tall genotypes had generally greater NDF (668 g/kg DM) than the dwarf genotypes. Irrigation increased fiber deposition in the leaf. Stems of all genotypes had lower in vitro digestible dry matter (IVDDM) (378 g/kg DM) under rainfed conditions in the rainy season. Leaf from irrigated plots had 23% more carbohydrate C fraction (160 g/kg CHO) than those from rainfed plots (122 g/kg CHO). Dwarf genotypes had generally greater nutritive value than tall genotypes. These genotypes show promise under irrigation to fill forage gaps during dry periods.

Concurrent training remodels the subcutaneous adipose tissue extracellular matrix of people living with HIV: a non-randomized clinical trial

Evaluate the effect of 12wks of concurrent training (CT) in extracellular matrix (ECM) of subcutaneous adipose tissue (SAT) in people living with HIV/aids (PLWHA). To the non-randomized clinical trial 19 participants, 11 healthy (HIV-) and 18 PLWHA under the use of highly active antiretroviral therapy (HAART) for at least 1 year (HIV+). All participants engaged in a moderate-intensity CT program for 12 weeks, three times a week. Before and after CT, aerobic and strength performance were assessed, as well as anthropometry and biochemical blood profile. Also, SAT biopsies were carried out for histologic and morphometric analysis. The statistical analysis was carried out with R Studio, using descriptive and inferential analysis, ANOVA test and mixed-effect model were utilized (P<0.05). HIV+ showed higher levels of VLDL, TGL, and lower levels of HDL in baseline than HIV- (P<0.05). All groups improved aerobic and strength performance (P<0.05). Both groups presented reduced adipocyte sizes after CT (P<0,05). Lastly, HIV+ presented smaller adipocytes and higher elastic fiber deposition in baseline and decreased after training only in HIV+, matching similarly to HIV- group. Thus, CT in PLWHA promoted a decrease in size heterogeneity of adipocytes and elastic fiber deposition, remodeling ECM and improving SAT fibrosis profile. Brazilian Clinical Trials Registry (UTN: U1111-1214-3022) Novelty • Adipose tissue fibrosis is improved by training in people living with HIV. • Concurrent training remodels adipose tissue extracellular matrix.