Organs Liver Research Articles

Gambaran Patologi Anatomi dan Histopatologi Organ Visceral Kambing Kacang (Capra aegagrus hircus) Yang Terinfeksi Sistiserkus

The demand for kacang goat (Capra aegagrus hircus)in Kupang City is very high in the local market, especially before the sacrificial festival. Although the goat population growth is high, there are several reasons that cause low productivity, namely parasitic infection.worms Taenia infect carnivores (as well as humans) as the definitive host and involve an intermediate host which will develop into a cysticercus. The purpose of this study was to determine the anatomical pathology and histopathology of the visceral organs of kacang goats infected with cysticercus. This study used 6 samples of visceral organs of kacang goats consisting of 4 liver organs, 1 rumen organ and 1 colon organ from 6 kacang goats infected with cysticercus, in Pasir Panjang Village, Kupang City. Macroscopic observations, tissue fixation in 10% formalin, tissue processing and HE staining were carried out. The results of the study on liver organs infected with cysticerci showed pathological changes in the form of fibrosis, while in the rumen and colon only cysticerci were formed. Histopathological changes in the liver organs of kacang goat infected with cysticercus in the form of mononuclear and polymorphonuclear inflammatory cell infiltration, necrosis, congestion, hemorrhage, hydropic degeneration, widening of sinusoids and fibrous tissue. Meanwhile, changes that occur in the rumen and colon organs are in the form of infiltration of mild inflammatory cells.

CRISPR/Cas12a-powered CLASA towards OTA ultrasensitive detection in cereal samples

Ochratoxin A (OTA) is classified as a Class 2B carcinogens and poses a significant risk bto the liver, kidney and other organs, potentially leading to carcinogenic and teratogenic effects. Accurate monitoring of OTA content in food is crucial for safeguarding human and animal health. Here, a novel approach called the CRISPR/Cas12a enzyme-linked aptamer-sorbent assay (CLASA) was developed, which integrates the high-performance trans-cleavage ability of CRISPR/Cas12a with the cost-effective and high-affinity properties of aptamer for ultra-sensitive OTA detection. In this strategy, we incubated aptamers on microwell plates, and used the fluorescence intensity changes caused by OTA and crRNA competitively bind OTA-specific aptamer to achieve the quantitative detection. Our sensitive CLASA method not only solves the problems of poor repeatability and relatively low sensitivity of fluorescence based-CRISPR/Cas12a reaction in solution, but also solves the defects of expensive antibody and false positive result in traditional ELISA method, achieving a limit of detection (LOD) as low as 171 fg·mL−1 with a broad linear range from 1 pg·mL−1 to 1000 pg·mL−1. The presented CLASA approach was validated successfully by using commercial ELISA kit on rice and oat samples as well. Furthermore, by strategically modifying the sequences of aptamer and crRNA, our CLASA platform can be flexibly customized to detect a wide range of small molecular targets. This adaptability allows for the extension of our framework beyond nucleic acid substances, enabling the detection of non-nucleic acid compounds using the CRISPR-Cas12a system. As a result, our CLASA approach holds great promise as a versatile sensing kit with applications in various fields requiring sensitive and specific detection of diverse analytes.

Comparison of in-gel and in-solution proteolysis in the proteome profiling of organ perfusion solutions

PurposeThe organ perfusion solution (perfusate), collected at clinically and temporally significant stages of the organ preservation and transplantation process, provides a valuable insight into the biological status of an organ over time and prior to reperfusion (transplantation) in the recipient. The objective of this study was to assess two bottom-up proteomics workflows for the extraction of tryptic peptides from the perfusate.Experimental designTwo different kinds of perfusate samples from kidney and liver trials were profiled using liquid chromatography–mass spectrometry (LC-MS/MS). The preparation of clean peptide mixtures for downstream analysis was performed considering different aspects of sample preparation; protein estimation, enrichment, in-gel and urea-based in-solution digestion.ResultsIn-solution digestion of perfusate allowed identification of the highest number of peptides and proteins with greater sequence coverage and higher confidence data in kidney and liver perfusate. Key pathways identified by gene ontology analysis included complement, coagulation and antioxidant pathways, and a number of biomarkers previously linked to ischemia-reperfusion injury were also observed in perfusate.ConclusionsThis study showed that in-solution digestion is a more efficient method for LC-MS/MS analysis of kidney and liver organ perfusion solutions. This method is also quicker and easier than in-gel digestion, allowing for greater sample throughput, with fewer opportunities for experimental error or peptide loss.

Abstract 17336: A Hepato-Cardiac FGF21 Signaling Axis Promotes Cardiac Hypertrophy

FGF21 is expressed mainly in the liver and other organs, including the heart. The role of FGF21 is controversial, with potential benefits for obesity and certain heart conditions, but also associations with heart failure and increased mortality. We found higher serum FGF21 levels (2.5-fold) in left ventricular hypertrophy patients (N=31) compared to those without hypertrophy (N=45). Similarly, mice subjected to Transverse Aortic Constriction (TAC) had elevated plasma FGF21 levels and hepatic expression. Surprisingly, a time course experiment showed that liver FGF21 production peaked 3 days post-TAC (prior to the onset of hypertrophy), while an unexpected increase of cardiac FGF21 expression was observed 2 weeks post-TAC, coinciding with hypertrophy and dysfunction. FGF21 expression in skeletal muscle did not change. As in mice, hypertensive individuals (N=6) showed a 14-fold increase in cardiac FGF21 mRNA levels compared to normotensive (N=6). To delineate the role of hepatic and cardiac FGF21 in hypertrophy, TAC was performed on mice with hepatocyte- (HEP-FGF21-KO) or cardiomyocyte-specific (CM-FGF21-KO) FGF21 ablation. Both HEP-FGF21-KO and CM-FGF21-KO mice were protected from hypertrophy, pro-hypertrophic signaling, fibrosis, and cardiac dysfunction. Notably, hepatocyte FGF21 deletion prevented cardiac FGF21 upregulation with TAC, suggesting control of CM FGF21 expression by liver-derived FGF21 and highlighting the role of CM FGF21 in driving cardiac hypertrophy. This was confirmed by treatment of AC16 human cardiomyocytes with recombinant FGF21 that increased endogenous FGF21 expression and cell size. RNAseq analysis revealed attenuation of cardiac fibrosis- and hypertrophy-related transcriptome in both HEP-FGF21-KO and CM-FGF21-KO mice. To explore if FGF21 increase is a cause and not a consequence of cardiac hypertrophy, we developed anti-sense oligonucleotides against FGF21 and administered them in C57BL/6 mice with TAC. ASO-FGF21 treatment attenuated cardiac hypertrophy and fibrosis and improved cardiac function. Thus, FGF21 emerges as a therapeutic target for pathological cardiac hypertrophy.

Effect of ethanolic leaf extracts of Medicago sativa, Gongronema latifolium and Pterocarpus sanalinoides on the liver integrity of alloxan-induced diabetic albino rats

The study investigated the effects of ethanolic leaf extracts of Medicago sativa (MS), Pterocarpus santalinoides (PS) and Gongronema latifolium (GL) on the liver function profile and organ histology integrity of alloxan-induced diabetic albino rats. Sixty male rats were divided into 10 groups, made up of 1 group each of normal, diabetic, and positive controls, 3 treatment groups each of the single and pairwise extract combinations, and 1 group of the ternary extracts combination. Hyperglycaemia was induced in the treatment groups by a single intraperitoneal injection of alloxan at 150 mg/kg body weight. The positive control was treated with metformin (100 mg/kg), while the extracts were administered via oral intubation to the single (200 mg/kg of each extract), double (combination of 2 extracts at 100 mg/kg each) and ternary (combination of the 3 extracts at 66.7 mg/kg each) treatment groups for a total period of 4 weeks. Induction of diabetes significantly (p<0.05) increased AST, ALT and ALP activities and total bilirubin concentration, but treatment with metformin and the plants’ extracts significantly (p<0.05) reduced the enzymes activities and total bilirubin concentration to levels comparable to those of the normal control. Generally, the combination therapies had non-significantly stronger effects than the single extract treatments. Histological evaluation confirmed that combinatorial compared to individual extracts treatment reverted more the damage to the liver organ caused by alloxan induction. Thus, Medicago sativa, Pterocarpus santalinoides and Gongronema latifolium are possible lead plants for potential production of hepatoprotective agents.

Can Purple Sweet Potato Water Extract (Ipomoea batatas L.) Induce Steatosis at Toxic Doses in Rat?

Purple sweet potato (Ipomoea batatas L.) has a secondary metabolite that contains a lot of antioxidants. Some of the secondary metabolites in purple sweet potato have a hepatotoxic effect. Objective: To described the toxic effects of purple sweet potato water extract on steatosis in rats. Methods: This descriptive study was conducted on 29‒30 June 2019 in the Biomedical Laboratory of the Faculty of Medicine, Islamic Bandung University, with an in-vivo experimental design with random allocation techniques and using the proposed new method on 11 rats. One of the control rats was not given extract, and ten other rats were given a dose of purple sweet potato water extract 50, 200, 400, 800, 1000, 1500, 2000, 3000, 4000, and 5000 mg/KgBW/PO. The liver organ was harvested after 24 hours, and then slides were made at the Pathology Anatomy Laboratory of Padjajaran University. Results: The histopathological view did not find any steatosis either in macrovesicular or microvesicular, but other features were found in ballooning degeneration, sinusoidal dilation, and inflammation. Conclusion: Steatosis was not found because purple sweet potato contains anthocyanins and tannins.Keywords: purple sweet potato, steatosis, tannin

Antiapoptotic and chemotaxis-stimulating effects of poly (d, l-lactide-co-glycolide)-chitosan and whey proteins against aflatoxicosis-induced splenic and thymic atrophy

BackgroundAflatoxin B (AFB) induces toxicological effects on the liver and immune organs. The whey proteins can modulate the immune response during aflatoxicosis. Our work evaluates the novel polylactic acid-glycolic acid-chitosan-encapsulated bovine and camel whey proteins against AFB-induced thymic and splenic atrophy in rats.Methods and resultsSeventy adult male Wister albino rats were divided into a control healthy group (G1) and six AFB1-intoxicated groups (G2–G7). One of the following supplements: distilled water, camel whey proteins (CWP), bovine whey proteins, poly (d, l-lactide-co-glycolide) (PLGA)- chitosan-loaded with camel whey protein microparticles (CMP), PLGA-chitosan loaded with bovine whey protein microparticles (BMP), and PLGA-chitosan nanoparticles were administered as prophylactic supplements to AFB1-intoxicated groups. The AFB-treated group showed significantly higher hepatic levels of oxidative stress and lower levels of antioxidants. In the aflatoxicated group, atrophy of the splenic lymphatic nodules and disfigurement in the organisation with an apparent decrease in the thickness of the cortex in the thymus were observed, as well as a decrease in splenic and thymic CD4+T and CD8+T lymphocytes. Moreover, CXCL12 levels were downregulated, whereas tumour necrosis factor-alpha, nuclear factor kappa B, and cleaved caspase-3 levels were upregulated. CWP, BMP, and CMP supplements markedly decreased oxidative stress, inflammation, and apoptosis, as well as significantly raised CXCL12, CD4+T, and CD8+T cells.ConclusionsThe CWP, BMP, and CMP supplements rescue the liver and immune tissues from the toxic effects of AFB through their antioxidant, antiapoptotic, anti-inflammatory, and chemotaxis-enhancing roles.

Changes of insulin receptors in high fat and high glucose diet mice with insulin resistance

ABSTRACT This study aimed to observe the expression of insulin-signaling molecules in different organs of mice with insulin resistance (IR). Firstly, mice were fed a high-fat and high-sugar diet (HF group) to establish an IR model, and the controls (NF group) were fed with a normal diet. Next, the weight, fasting blood glucose (FBG), serum insulin and insulin tolerance were detected. Pathological changes of liver tissues were observed by H&E staining. The expressions of INSR, IRS-1 and IRS-2 in the liver, skeletal muscle and ovary were measured by qRT-PCR and western blotting. As a result, compared with the NF group, the HF group mice had increased weight, FBG, insulin and IR index after 6-week of feeding as well as a worse performance in the insulin tolerance test and H&E staining showed fatty liver-like changes after 12-week of feeding, exhibited lower expression of INSR, IRS-1 and IRS-2 in the liver of mice at 6 and 12 weeks. The expression of INSR and IRS-1 in skeletal muscle tissues exhibited the same trend, while those in ovary organs showed the opposite trend. These results suggested that the insulin signaling alters in the liver, skeletal muscle and ovary organs with the progress of IR.

Antimicrobial films fabricated with myricetin nanoparticles and chitosan derivation microgels for killing pathogenic bacteria in drinking water

Pathogenic bacteria in drinking water threaten human health and life. In the work, antimicrobial films composed of myricetin@tannic acid (My@TA) nanoparticles (NPs) and chitosan derivation microgels were developed to kill pathogenic bacteria in drinking water. Hydrophobic My was first made into water soluble My@TA NPs using a solvent exchange method with TA as stabilizer. Polymeric microgels of carboxymethyl chitosan (CMCS)/hydroxypropyltrimethyl ammonium chloride chitosan (HACC) were then fabricated with a blending method. CMCS&HACC/My@TA multilayer films were further deposited on the internal surface of PET bottles by using a layer-by-layer (LbL) assembly technique. The PET bottles coated with the films could effectively kill pathogenic bacteria in water such as S. aureus, E. coli, Staphylococcus epidermidis, Pseudomonas fluorescens, Listeria monocytogenes and methicillin resistant Staphylococcus aureus (MRSA). In addition, CMCS&HACC/My@TA films displayed good antioxidant activity, water resistance, and in vivo biocompatibility with heart, liver, spleen, lung and kidney organs. We believe that the container coated with CMCS&HACC/My@TA films can be applied to prevent microbial contamination of drinking water.

Enterohepatocentrism as the basis of human psychosomatic pathology

The gut microbiota regulates critical processes in host metabolism and physiology. Understanding the formation of relationships between the gut microbiome, liver, and other organs under physiological conditions, as well as under the influence of microbiota-damaging factors, provides important insights into the pathophysiology of not only liver diseases, but also the complex level of communication and the role of the microbiome in the gut-liver-brain, gut-liver-kidney, gut-liver-lung, and gut-liver-heart axes.

EXPERIMENTAL TOXOCARIASIS IN RABBITS

Toxocariasis as a zoonosis represents a medical and veterinary problem. In the structure of human larval helminthiases, toxocariasis accounts for more than 60%. In non-specific hosts, including humans, toxocara larvae undergo visceral larva migrans, primarily damaging the liver, lungs, and other organs and tissues. Constant reinvasion accumulates second and third-stage larvae in the bodies of nonspecific (paratenic) hosts. In our research, we considered the problem of soil parasitological contamination on rabbit farms and the risks of rabbit infection, emphasising the need to study the involvement of rabbits as paratenic hosts in toxocariasis. We selected rabbits of the Soviet chinchilla breed as experimental animals. Toxocara eggs were administered orally to the animals. Hematological studies were conducted using commonly accepted methods. To detect specific IgG class antibodies, rabbit serum was analysed by enzyme-linked immunosorbent assay (ELISA). The presence of IgG class antibodies in the blood serum of rabbits at a positive titer (1:100) in ELISA allows us to conclude that rabbits, along with other animals, serve as paratenic hosts for Toxocara canis. Haematological research results indicated the absence of significant differences and remained within the physiological norm throughout the entire experiment.

The protective effects of curcumin against cigarette smoke-induced toxicity: A comprehensive review.

Cigarette smoking (CS) is a crucial modifiable risk of developing several human diseases and cancers. It causes lung, bladder, breast, and esophageal cancers, respiratory disorders, as well as cardiovascular and metabolic diseases. Because of these adverse health effects, continual efforts to decrease the prevalence and toxicity of CS are imperative. Until the past decades, the impacts of natural compounds have been under investigation on the harmful effects of CS. Turmeric (Curcuma longa), a rhizomatous herbaceous perennial plant that belongs to the Zingiberaceae family, is the main source of curcumin. This review is an attempt to find out the current knowledge on CS's harmful effects and protective potential of curcumin in the pulmonary, liver, brain, gastrointestinal, and testis organs. According to the present review, simultaneous consumption of curcumin and CS can attenuate CS toxicities including chronic obstructive pulmonary disease, gastrointestinal toxicity, metabolic diseases, testis injury, and neurotoxicity. Moreover, curcumin suppresses carcinogenesis in the skin, liver, lungs, breast, colon, and stomach. Curcumin mediates these protective effects through antioxidant, anti-inflammatory, anti-apoptotic, and anti-carcinogenicity properties.

Stem cells from human exfoliated deciduous teeth rejuvenate the liver in naturally aged mice by improving ribosomal and mitochondrial proteins

Background aimsAging is accompanied by a decline in cellular proteome homeostasis, mitochondrial, and metabolic function. Mesenchymal stromal cell (MSC) therapies have been reported to extend lifespan and delay some age-related pathologies, yet the anti-aging rate and mechanisms remain unclear. Here, we investigated the effects and mechanism by transplantation of stem cells from human exfoliated deciduous teeth (SHED) into the naturally aged mice model. MethodsSHED were cultured in vitro and injected into mice by caudal vein. The in vivo imaging uncovered that SHED labeled by DiR dye mainly migrated to the liver, spleen, and lung organs of wild-type mice. As the main metabolic organ and SHED homing place, the liver was selected for proteomics and aging clock algorithm (LiverClock) analysis, which was constructed to estimate the proteomic pattern related to liver age state. ResultsAfter 6 months of continuous SHED injections, the liver proteomic pattern was reversed from senescent (∼30 months) to a youthful state (∼3 months), accompanied with upregulation of hepatocytes marker genes, anti-aging protein Klotho, a global improvement of liver functional pathways proteins, and a dramatic regulation of ribosomal and mitochondrial proteins, including upregulation of translation elongation and ribosome-sparing proteins Rpsa and Rplp0; elongation factors Eif4a1, Eef1b2, Eif5a; protein-folding chaperones Hsp90aa and Hspe1; ATP synthesis proteins Atp5b, Atp5o, Atp5j; and downregulation of most ribosomal proteins, suggesting that the proteome homeostasis destruction and mitochondria dysfunction in the aged mice liver might be relieved after SHED treatment. ConclusionsSHED treatment could dramatically relieve the senescent state of the aged liver, affect ribosome component proteins and upregulate the ribosomal biogenesis proteins in the aged mice liver. These results may help understand the improvements and mechanisms of SHED treatment in anti-aging.

The Physiological and Pathological Role of Acyl-CoA Oxidation.

Fatty acid metabolism, including β-oxidation (βOX), plays an important role in human physiology and pathology. βOX is an essential process in the energy metabolism of most human cells. Moreover, βOX is also the source of acetyl-CoA, the substrate for (a) ketone bodies synthesis, (b) cholesterol synthesis, (c) phase II detoxication, (d) protein acetylation, and (d) the synthesis of many other compounds, including N-acetylglutamate-an important regulator of urea synthesis. This review describes the current knowledge on the importance of the mitochondrial and peroxisomal βOX in various organs, including the liver, heart, kidney, lung, gastrointestinal tract, peripheral white blood cells, and other cells. In addition, the diseases associated with a disturbance of fatty acid oxidation (FAO) in the liver, heart, kidney, lung, alimentary tract, and other organs or cells are presented. Special attention was paid to abnormalities of FAO in cancer cells and the diseases caused by mutations in gene-encoding enzymes involved in FAO. Finally, issues related to α- and ω- fatty acid oxidation are discussed.

Quercetagetin alleviates zearalenone-induced liver injury in rabbits through Keap1/Nrf2/ARE signaling pathway.

Introduction: This study aimed to assess the alleviative effect of quercetagetin (QG) on zearalenone (ZEN)-induced liver injury in rabbits. Methods: Ninety 41-day-old healthy Hyla rabbits were randomly assigned into three groups, including a control (fed with basic diet), ZEN addition group (fed with basic diet + 600μg/kg ZEN), and ZEN + QG addition group (fed with basic diet + 600μg/kg ZEN + 100mg/kg QG), with 30 rabbits per group. The duration of the experiment was 28days. Results: The results revealed no significant differences in the average daily gain, average daily feed intake, the gain to feed ratio and the liver, kidney and spleen organ indexes (p > 0.05) between the rabbits across the three groups. However, the sacculus rotundus index of the rabbits in the control group was significantly higher than that in the ZEN + QG group (p < 0.05). The intake of ZEN-contaminated diet also significantly increased the activities or levels of alanine transaminase, alkaline phosphatase, total bile acid (TBA), total bilirubin, malondialdehyde, and interleukin-4 (IL-4) and enhanced the abundance of kelch-like ECH-associated protein 1 (Keap1), heat shock protein 70 (HSP70) and cysteine-aspartic acid protease-3 (Caspase-3) mRNA in the blood or liver tissue in ZEN group, compared to the control group (p < 0.05). On the contrary, the activities or levels of immunoglobulin A, complement 3, total antioxidant capacity, glutathione peroxidase (GSH-Px), superoxide dismutase, interleukin-10, and the abundance of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA were significantly decreased (p < 0.05). Supplementing the diet with QG still maintained significantly higher levels of TBA and IL-4, and the abundance of GSH-Px, HSP70, IL-4, and Caspase-3 mRNA in the blood and liver of rabbits in the ZEN + QG group than in the control group (p < 0.05). At the same time, the other indicators were restored to levels in the control group (p > 0.05). Discussion: In conclusion, QG alleviated the ZEN-induced oxidative damage and liver injury caused by inflammatory reaction through the Keap1-Nrf2-antioxidant response element (ARE) signal pathway, which protected the liver. This study revealed the alleviative effect of QG on the hepatotoxicity of ZEN in rabbits for the first time, providing a new perspective for applying QG and developing a ZEN antidote.

Protective effects of tanshinone ⅡA on sepsis-induced multiple organ dysfunction: a literature review.

TanshinoneⅡA (TanⅡA) is a noteworthy lipophilic diterpene compound derived from the dried roots of the Traditional Chinese Medicine Danshen () that has various pharmacological properties, including anti-inflammatory, antibacterial, and antioxidative effects. Sepsis is a life-threatening organ dysfunction induced by a dysregulated host response to infection. Recently, increasing attention has been paid to sepsis-induced dysfunction of the intestine, car-diovascular system, lungs, kidneys, liver, and other organs. Experimental studies have shown that TanⅡA has therapeutic potential for sepsis-induced organ dysfunction owing to its anti-inflammatory, anti-apoptotic and regulatory effects on multiple signalling pathways. The purpose of this article is to evaluate the potential multiorgan protective effects of TanⅡA in sepsis.

Dosimetric Analysis of Patients Treated with Stereotactic Body Radiation Therapy for Malignant Portal Vein Tumor Thrombosis Using MRI-Guided vs. CT-Guided Linear Accelerator

The use of MRI-guided linear accelerators (MRI-LINAC) for radiation therapy has allowed for increased treatment precision and real-time tumor tracking. We hypothesized that the use of an MRI-LINAC, recently acquired by our institution, would allow us to treat malignant portal vein tumor thromboses (PVTT) closer to the origin of the portal vein with similar doses to the liver and nearby GI organs and with similar treatment toxicities compared to patients treated using a CT-guided linear accelerator (CT-LINAC). We retrospectively assessed patients who received SBRT for treatment of PVTT within the UVA health system using the electronic medical record. We contoured the origin of the portal vein on the simulation scans (MRI or CT) for each patient. The shortest distance from the GTV to the portal vein origin and to organs at risk (OAR; duodenum, stomach or "other intestine") were measured. The PTV, volume of the liver receiving less than 18 Gy during treatment, and the Dmax to the portal vein origin and OAR were determined. The means for each variable were then compared between CT-LINAC and MRI-LINAC using independent samples t-tests. Treatment toxicities were graded using CTCAE version 5.0 guidelines. All plans met institutional dose constraints for SBRT. A total of 6 patients treated on CT-LINAC and 3 patients treated on MRI-LINAC were identified (mean dose CT 37.7 Gy [range 21-50] in 2-5 fractions; MRI 48.3 Gy [range 45-50] in 5 fractions). The GTV was significantly closer to the portal vein origin in the MRI-LINAC group (mean CT 92.75 mm ± 45.89; MRI 32.00 mm ± 29.46; p = 0.04). The GTV trended towards being closer to OAR in the MRI-LINAC group (mean CT 43.81 mm ± 37.09; MRI 4.36 mm ± 1.85; p = 0.059). The Dmax to both the portal vein origin (mean CT 0.58 Gy ± 0.33; MRI 22.49 Gy ±24.16; p = 0.024) and OAR (mean CT 13.38 Gy ± 5.98; MRI 36.23 Gy ± 5.38; p = <0.001) was significantly higher in the MRI-LINAC group. The PTV (mean CT 152.11 cc ± 169.94; MRI 122.47 cc ± 114.65; p = 0.398) or volume of liver receiving less than 18 Gy during treatment (mean CT 1287.87 cc ± 285.20; MRI 1743.88 cc ±961.94 = 3; p = 0.147) were not significantly different between the two groups. No patients in either the MRI-LINAC or CT-LINAC group reported acute toxicities greater than Grade 1. We found that patients with PVTT treated with MRI-LINAC SBRT at our institution were more likely to have central tumors near dose-limiting OAR. However, due to superior tumor delineation and dynamic tumor tracking, these patients were able to be treated without decreasing treatment dose or increasing acute GI toxicity compared to patients treated with CT-LINAC. A larger sample size and longer follow-up period is warranted to corroborate these initial findings.

L-Dopa decarboxylase modulates autophagy in hepatocytes and is implicated in dengue virus-caused inhibition of autophagy completion

The enzyme L-Dopa Decarboxylase (DDC) synthesizes the catecholamine dopamine and the indolamine serotonin. Apart from its role in the brain as a neurotransmitter biosynthetic enzyme, DDC has been detected also in the liver and other peripheral organs, where it is implicated in cell proliferation, apoptosis, and host-virus interactions. Dengue virus (DENV) suppresses DDC expression at the later stages of infection, during which DENV also inhibits autophagosome-lysosome fusion. As dopamine affects autophagy in neuronal cells, we investigated the possible association of DDC with autophagy in human hepatocytes and examined whether DDC mediates the relationship between DENV infection and autophagy. We performed DDC silencing/overexpression and evaluated autophagic markers upon induction of autophagy, or suppression of autophagosome-lysosome fusion. Our results showed that DDC favored the autophagic process, at least in part, through its biosynthetic function, while knockdown of DDC or inhibition of DDC enzymatic activity prevented autophagy completion. In turn, autophagy induction upregulated DDC, while autophagy reduction by chemical or genetic (ATG14L knockout) ways caused the opposite effect. This study also implicated DDC with the cellular energetic status, as DDC silencing reduced the oxidative phosphorylation activity of the cell. We also report that upon DDC silencing, the repressive effect of DENV on the completion of autophagy was enhanced, and the inhibition of autolysosome formation did not exert an additive effect on viral proliferation. These data unravel a novel role of DDC in the autophagic process and suggest that DENV downregulates DDC expression to inhibit the completion of autophagy, reinforcing the importance of this protein in viral infections.

Predictive Value of Tumor Volume on Local Control in Hepatocellular Carcinoma Treated with Image Guided Hypofractionated Radiation Treatment

External beam radiation treatment (EBRT) is an important local treatment in liver-confined hepatocellular carcinoma (HCC) patients who are not candidates for curative therapy. EBRT dose, technique and prognostic factors are evolving. We hypothesized that tumor volume to liver volume ratio can be a predictor of local control (LC) in patients treated with hypo-fractionated radiation (HFRT) in HCC MATERIALS/METHODS: We retrospectively reviewed 50 patients of HCC treated with HFRT at our institution. HFRT schedule was chosen such that the radiation dose to the remaining liver and other organs at risk (OAR) met the standard dosimetric constraints. Image guided techniques were used for motion management, internal target volume (ITV) and planning target volume (PTV) delineation. Tumor to Liver Ratio (TLR) was defined as ratio of PTV volume to whole liver volume. TLR ≤ 0.3 was considered as low volume disease and TLR > 0.3 was considered as high-volume disease. The radiation dose ranged from 45 Gy to 67.5 Gy in 5 - 15 fractions. The biologically equivalent dose (BED) for tumor ranged from 58.5 Gy10 to 100 Gy10. Local control (LC) was evaluated by Kaplan-Meier analysis, with log-rank test for groups stratified as per TLR. Multivariate Cox regression analysis was performed to identify additional prognostic factors. The mean duration of follow-up was 24 months. The median age was 69 years (range 50 - 90) and 76% were males. 32 patients had CP-A class cirrhosis while 17 had CP-B and 1 had CP-C class. BCLC stage A, B, C and D was seen in 2, 14, 33 and 2 patients, respectively. Portal vein thrombosis was present in 9 patients and prior trans-arterial chemo embolization (TACE) was done in 23 patients. The median volume of PTV was 551 cc (range 52 - 1990 cc). The TLR ranged from 0.04 - 0.67 with a median of 0.29. The median BED radiation dose was 78.4 Gy10 (range - 58.5 Gy10 to 100 Gy10). Nine patients had local recurrence with overall LC rate of 82%. The LC was better in low volume tumors, with the TLR cut-off of 0.3 as a significant factor associated with LC (p = 0.007). The 1-year actuarial LC with TLR ≤ 0.3 was 88% as compared 61% in TLR of > 0.3 (p = 0.007). BED ≥60 Gy10 was associated with better 1 year LC as compared to BED < 60 Gy10 (89% vs 62%; p = 0.11). ALBI grade 1 was associated with better 1 year LC as compared to ALBI grade 2 (80% versus 75%; p = 0.40). On multivariate analysis, high volume disease and TLR >0.3 were significant prognostic factor for LC. HFRT has good 1-year local control of 82% in carefully selected unresectable HCC. Radiation with BED greater than 60 Gy10 and ALBI grade 1 showed a trend towards better LC. Smaller tumors had better LC with a PTV to liver ratio (TLR) of < 0.3. This information can help in identifying the poor responders, intensifying the radiation treatment and adding additional therapy to improve the oncological outcomes.

Implementation of a vaccination clinic for adult solid organ transplant candidates: A single-center experience

Vaccination is an evidence-based strategy to prevent or reduce the severity of infectious diseases (ID). Here, we aimed to describe the experience of implementing a vaccination clinic specifically targeting liver, heart, lung, and combined dual organ transplantation at a single transplantation center in Denmark. In this cohort of 242 solid organ transplant (SOT) candidates, we investigated seroprotection and the proportion of recommended vaccinations documented before transplantation. Furthermore, we registered completed vaccinations after ID consultations. The median age in our cohort was 53 years (IQR, 42–60), 60% were males (n = 135), and liver transplants (n = 138; 57%) were the most frequently planned organ transplants. Before the consultation to the vaccination clinic, influenza and pneumococcal vaccines had the highest proportion of documented vaccination (58% and 37%, respectively). Serological protection was more frequently observed for measles, mumps, or rubella (MMR, approximately 90% for each), while only 30% (n = 72) of SOT candidates showed seroprotection against pneumococcal disease. All SOT candidates required at least one of the recommended vaccines, and over 90% required three or more. At least 10% of patients in our cohort needed a live attenuated vaccine for either MMR or yellow fever. The most frequently administered vaccine was the tetanus–diphtheria-acelullar pertussis (Tdap) booster (n = 217; 90%), influenza vaccination was either administered (n = 16; 7%) or recommended (n = 226; 93%), PCV13 was administered (n = 155; 64%) or recommended (n = 27; 11%), and PPSV23 was either administered (n = 18; 7.4%) or recommended (n = 140; 58%). All SOT candidates adhered completely to their vaccination schedules. Based on our findings, we recommend prioritizing vaccination before transplantation by providing ID consultations for SOT candidates.