MicroRNA expression profile and lipid metabolism characteristics in liver of rat undergoing high-fat diet

This study aimed to investigate the microRNA expression profile and the characteristics of lipid metabolism in the livers of rats undergoing a high-fat diet. Fifty male Sprague-Dawley (SD) rats were divided into a standard chow group (C group, N = 10) and a high-fat diet group (H group, N = 40). After 12 weeks, the rat body weight, body length, fat mass, and serum lipid concentration were measured. The expression profile of microRNAs and the gene and protein expression levels involved in lipid metabolism in rat liver were detected. Body fat and serum lipid concentrations were all significantly higher in the H group than those in the C group (p < 0.05 or p < 0.01). The expression of 10 microRNAs showed significant differences in the liver (p < 0.05). In particular, the let-7 family expression levels significantly increased (p < 0.05) in the H group compared with those in the C group. Compared with the C group, the high-fat diet resulted in low FAS, CPT1A, and ApoAI mRNA expression levels (p < 0.05 or p < 0.01) and high PPARα and FAT/CD36 mRNA expression levels in the H group rat liver (p < 0.01). Meanwhile, the protein PPARα, FAS, CPT1A, FAT/CD36, and ApoAI expression levels were all significantly lower in the H group than those in the C group (p < 0.05 or p < 0.01). In conclusion, the high-fat diet increased the body fat and serum lipid levels and altered the 10 microRNA expression levels in the liver. The high-fat diet may affect hepatic carbohydrate metabolism and increase ectopic fat accumulation through let-7 family overexpression. The high-fat diet for 12 weeks decreased lipid metabolism level in the liver, thereby decreasing fatty acid synthesis, oxidation, and transport by down-regulating the PPARα, FAS, CPT1A, FAT/CD36, and ApoAI protein levels.     

Thermal properties of duck fatty liver (foie gras) products

Thermal properties of duck fatty liver (foie gras), foie gras emulsion and fatty liver fat, as well as regular duck fat, were determined as a function of temperature. Density of foie gras and foie gras fat and emulsion at 20°C was measured as 947, 836, and 928 kg/m³, respectively. Differential scanning calorimetry thermograms for foie gras fat resulted in melting points ranging from –20 to 40°C. Values for the specific heat at 65°C for the fatty liver, its emulsion and fat, and duck fat were 1.79, 2.38, 1.71, and 2.48 J/g°C, respectively. Thermal conductivity of foie gras (organ) and its emulsion at 40°C was determined as 0.330 and 0.428 W/m°C, respectively. Mathematical models based on composition and temperature were developed for all the thermal properties obtained in this work.     

Health burden of road traffic accidents,an analysis of clinical data on disability and mortality exposure rates in Flanders and Brussels

Statistics on road traffic accidents (RTAs) mainly come from police records. The police reported RTA statistics however are known to have a large degree of under-registration, underestimating the true risk of being injured in traffic accidents. The use of medical based datasets can provide a more accurate estimate of the actual traffic accident health risk. Exposure-based rates of the actual burden from Flanders and Brussels were calculated, comparing differences between road user, age, gender and type of injury sustained. Minimal Clinical Data (MCD) was selected for the years 2003–2007, as well as data from the mortality statistics. Disability Adjusted Life Years (DALY) were calculated and put into perspective with the passenger kilometres travelled.     

Vehicle mass and injury risk in two-car crashes: A novel methodology

This paper introduces a novel methodology based on disaggregate analysis of two-car crash data to estimate the partial effects of mass, through the velocity change, on absolute driver injury risk in each of the vehicles involved in the crash when absolute injury risk is defined as the probability of injury when the vehicle is involved in a two-car crash. The novel aspect of the introduced methodology is in providing a solution to the issue of lack of data on the speed of vehicles prior to the crash, which is required to calculate the velocity change, as well as a solution to the issue of lack of information on non-injury two-car crashes in national accident data. These issues have often led to focussing on relative measures of injury risk that are not independent of risk in the colliding cars. Furthermore, the introduced methodology is used to investigate whether there is any effect of vehicle size above and beyond that of mass ratio, and whether there are any effects associated with the gender and age of the drivers. The methodology was used to analyse two-car crashes to investigate the partial effects of vehicle mass and size on absolute driver injury risk. The results confirmed that in a two-car collision, vehicle mass has a protective effect on its own driver injury risk and an aggressive effect on the driver injury risk of the colliding vehicle. The results also confirmed that there is a protective effect of vehicle size above and beyond that of vehicle mass for frontal and front to side collisions.     

Aged Skeletal Muscle Retains the Ability to Remodel Extracellular Matrix for Degradation of Collagen Deposition after Muscle Injury

Aging causes a decline in skeletal muscle function, resulting in a progressive loss of muscle mass, quality, and strength. A weak regenerative capacity is one of the critical causes of dysfunctional skeletal muscle in elderly individuals. The extracellular matrix (ECM) maintains the tissue framework structure in skeletal muscle. As shown by previous reports and our data, the gene expression of ECM components decreases with age, but the accumulation of collagen substantially increases in skeletal muscle. We examined the structural changes in ECM in aged skeletal muscle and found restricted ECM degradation. In aged skeletal muscles, several genes that maintain ECM structure, such as transforming growth factor β (TGF-β), tissue inhibitors of metalloproteinases (TIMPs), matrix metalloproteinases (MMPs), and cathepsins, were downregulated. Muscle injury can induce muscle repair and regeneration in young and adult skeletal muscles. Surprisingly, muscle injury could not only efficiently induce regeneration in aged skeletal muscle, but it could also activate ECM remodeling and the clearance of ECM deposition. These results will help elucidate the mechanisms of muscle fibrosis with age and develop innovative antifibrotic therapies to decrease excessive collagen deposition in aged muscle.     

The Role of CTLA4 and Its Polymorphisms in Solid Organ and Haematopoietic Stem Cell Transplantation

HLA matching, transplantation technique, or underlying disease greatly influences the probability of long-term transplantation success. It has been hypothesised that genetic variation affecting antigen presentation also contributes to the outcomes of both solid organ transplantation and allogeneic haematopoietic stem cell transplantation (AHSCT). Those genes, along with those responsible for innate and adaptive immunity, have become targets of investigation. In this review, we focus on the role of CTLA4 in the process of acute graft rejection and summarise the progress in our understanding of its role in predicting the outcome. We present the results of the latest studies investigating the link between CTLA4 gene variability and AHSCT, as well as organ transplantation outcomes. While some studies found a link between +49 A/G and −318 C/T and transplantation outcomes, comprehensive meta-analyses have failed to present any association. The most recent field reviews suggest that the −1772 T/C (rs733618) CC genotype is weakly associated with a lower risk of acute graft rejection, while +49 A/G might be clinically meaningful when investigated in the context of combinations with other polymorphisms. Studies verifying associations between 12 CTLA4 gene SNPs and AHSCT outcomes present inexplicit results. Some of the most commonly studied polymorphisms in this context include +49 A/G (rs231775) and CT60 A/G (rs3087243). The results signify that, in order to understand the role of CTLA4 and its gene polymorphisms in transplantology, further studies must be conducted.     

Systemic Inflammation and the Breakdown of Intestinal Homeostasis Are Key Events in Chronic Spinal Cord Injury Patients

Our aim was to investigate the subset distribution and function of circulating monocytes, proinflammatory cytokine levels, gut barrier damage, and bacterial translocation in chronic spinal cord injury (SCI) patients. Thus, 56 SCI patients and 28 healthy donors were studied. The levels of circulating CD14^+highCD16⁻, CD14^+highCD16⁺, and CD14^+lowCD16⁺ monocytes, membrane TLR2, TLR4, and TLR9, phagocytic activity, ROS generation, and intracytoplasmic TNF-α, IL-1, IL-6, and IL-10 after lipopolysaccharide (LPS) stimulation were analyzed by polychromatic flow cytometry. Serum TNF-α, IL-1, IL-6 and IL-10 levels were measured by Luminex and LPS-binding protein (LBP), intestinal fatty acid-binding protein (I-FABP) and zonulin by ELISA. SCI patients had normal monocyte counts and subset distribution. CD14^+highCD16⁻ and CD14^+highCD16⁺ monocytes exhibited decreased TLR4, normal TLR2 and increased TLR9 expression. CD14^+highCD16⁻ monocytes had increased LPS-induced TNF-α but normal IL-1, IL-6, and IL-10 production. Monocytes exhibited defective phagocytosis but normal ROS production. Patients had enhanced serum TNF-α and IL-6 levels, normal IL-1 and IL-10 levels, and increased circulating LBP, I-FABP, and zonulin levels. Chronic SCI patients displayed impaired circulating monocyte function. These patients exhibited a systemic proinflammatory state characterized by enhanced serum TNF-α and IL-6 levels. These patients also had increased bacterial translocation and gut barrier damage.     

Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl₄)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl₄-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway.     

The Tumor Microenvironment in Liver Metastases from Colorectal Carcinoma in the Context of the Histologic Growth Patterns

Colorectal carcinoma (CRC) is the third most common cancer. Likewise, it is a disease that has a long survival if it is prematurely detected. However, more than 50% of patients will develop metastases, mainly in the liver (LM-CRC), throughout the evolution of their disease, which accounts for most CRC-related deaths. Treatment it is certainly a controversial issue, since it has not been shown to increase overall survival in the adjuvant setting, although it does improve disease free survival (DFS). Moreover, current chemotherapy combinations are administered based on data extrapolated from primary tumors (PT), not considering that LM-CRC present a very particular tumor microenvironment that can radically condition the effectiveness of treatments designed for a PT. The liver has a particular histology and microenvironment that can determine tumor growth and response to treatments: double blood supply, vascularization through fenestrated sinusoids and the presence of different mesenchymal cell types, among other particularities. Likewise, the liver presents a peculiar immune response against tumor cells, a fact that correlates with the poor response to immunotherapy. All these aspects will be addressed in this review, putting them in the context of the histological growth patterns of LM-CRC, a particular pathologic feature with both prognostic and predictive repercussions.     

Nephrotoxicity as a Complication of Chemotherapy and Immunotherapy in the Treatment of Colorectal Cancer,Melanoma and Non-Small Cell Lung Cancer

Acute kidney injury is a common complication of many medical procedures, including those used in cancer treatment. Both chemotherapy and immunotherapy may result in deterioration of kidney function, which may lead to an increase in mortality among patients with cancer. Antineoplastic agents can affect any element of the nephron, leading to the appearance of clinical symptoms such as proteinuria, hypertension, electrolyte disorders, glomerulonephritis, acute and chronic interstitial nephritis and acute kidney injury. The medical literature describing renal complications occurring during chemotherapeutic and immunotherapeutic treatment in neoplasms, such as colorectal cancer, non-small cell lung cancer and melanoma, was analysed. The immune system plays an important role in controlling the development of neoplasms and fighting them. Oncological treatment algorithms include immunotherapy as monotherapy, combined with chemotherapy or chemotherapy as monotherapy. In the treatment of the above-mentioned neoplasms immunotherapeutics are used, such as checkpoint inhibitors (CPI) (i.e., ipilimumab, pembrolizumab, nivolumab, atezolizumab), vascular endothelial growth factor (VEGF) inhibitors (i.e., bevacizumab, ramucirumab) and a variety of chemotherapeutic agents (irinotecan, capecitabine, oxaliplatin, gefitinib, erlotinib, gemcitabine, cisplatin, paclitaxel, carboplatin, doclitaxel, vinorelbine, topotecan, etoposide). In our article, we focused on the number and type of renal complications as well as on the time of their manifestation when using specific treatment regimens. Our analysis also includes case reports. We discussed treatment of immunological complications and adjustments of the dose of chemotherapeutic agents depending on the creatinine clearance. Analysing the data from the literature, when two immunotherapeutic agents are used together, the number of recorded renal complications increases. Bevacizumab and ramucirumab are the cause of the largest number of renal complications among the immunotherapeutic agents described above. Cisplatin is the best-described substance with the greatest nephrotoxic potential among the chemotherapeutic agents. Crucial for renal complications are also cancer stage, previous chemotherapy and other risk factors of AKI such as age, comorbidities and medications used. Due to the described complications during oncological treatment, including kidney damage, it seems necessary to elaborate standards of cooperation between oncologists and nephrologists both during and after treatment of a patient with cancer. Therefore, it is necessary to conduct further research and develop algorithms for management of a cancer patient, especially during such an intensive progress in oncology.