Sarcopenia in Liver Transplantation: an Update

Purpose of Review: Patients undergoing liver transplantation (LT) are at high risk of sarcopenia and associated physical frailty. This review summarises advances in our knowledge of the definition, assessment, clinical implications and management of sarcopenia in LT. Recent Findings: Sarcopenia is associated with increased mortality, morbidity, physical disability and poor quality of life both before and after LT. Assessment tools have evolved from solely relying on imaging (i.e. muscle area only) to reproducible measures of function and physical performance status (i.e. liver frailty index). The multi-faceted management of sarcopenia is heavily reliant on nutrition (protein &gt; 1.5 g/kg/day) and exercise (combined aerobic and resistance) advice. Summary: There is an increased awareness of the clinical implications, assessment tools and management for patients with sarcopenia awaiting LT. Future studies need to investigate the role of specific nutritional supplements, pharmaco-/behavioural therapy and the long-term outcomes (e.g. survival) of reversing sarcopenia in this patient population.</p

Urinary and serum neutrophil gelatinase-associated lipocalin as a biomarker in Egyptian systemic lupus erythematosus patients: Relation to lupus nephritis and disease activity

AbstractBackgroundNeutrophil gelatinase-associated lipocalin (NGAL) is an excellent structural biomarker for the early diagnosis of acute kidney injury, prognosis, dialysis requirement and mortality in several common clinical scenarios.Aim of the workThe aim of this work is to detect the levels of both urinary and serum NGAL in SLE patients with and without lupus nephritis (LN) and to correlate their levels with renal biopsy class and disease activity.Patients and methodsThe study included 35 SLE patients; 22 with LN and 13 without as well as 30 matched controls. The SLE Disease Activity Index (SLEDAI) was assessed and the renal biopsy class determined. Urinary and serum levels of NGAL were assessed by ELISA.ResultsThe 35 patients had a median age of 30years and disease duration of 4years. They were 31 females and 4 males. The SLE patients had an elevated urinary NGAL (UNGAL) (median 19ng/ml, IQR 8–87) as compared to controls (median 2ng/ml, IQR 1–18.3) (p<0.006). Levels of UNGAL were higher in patients with LN than those without (p<0.023). In patients with LN, serum levels of NGAL were not significantly different from controls (p=0.6). The UNGAL level significantly correlated with the renal score of SLEDAI (r=0.54, p=0.001) but serum NGAL level did not (r=0.25, p=0.15). UNGAL significantly correlated with grade III and IV of renal biopsy (r=0.67, p=0.009). The sensitivity of UNGAL levels for the diagnosis of LN was 85.7%, with a specificity of 80%.ConclusionUrinary NGAL is a sensitive marker of proliferative nephritis in SLE and disease activity

Association of GH gene polymorphism with growth and semen traits in rabbits

[EN] Although growth hormone (GH) gene mutations are described in several species, the studies concerning their variabilities and associations with economic traits in rabbits are scarce, particularly associations with semen traits. A total of 149 rabbit bucks from five populations (V-line=36, Moshtohor line=28, APRI line=42, cross ½A½M=23, and Gabali=20) were used in the present study to identify polymorphism of c.-78 C&gt;T single nucleotide polymorphism (SNP) of GH gene among these populations and to investigate the association of GH gene polymorphism with body weight (BW), daily weight gain (DG) and semen traits. DNA was extracted from blood samples for genotyping of c.-78 C&gt;T SNP of GH gene based on polymerase chain reaction with the restriction fragment length polymorphism (PCR-RFLP) technique. The genetic diversity of SNP C&gt;T of GH gene was assessed in terms of genotypic and allelic frequencies, effective number of alleles (Ne), observed (Ho) and expected (He) heterozygosity, Hardy-Weinberg equilibrium (HWE), reduction in heterozygosity due to inbreeding (FIS) and polymorphism information content (PIC). Three genotypes of TT, CC and TC of PCR product of 231 bp of GH gene were detected and all the populations were in HWE in terms of GH gene. The highest Ne was obtained for the Moshtohor line (1.978), while the lowest allelic numbers were obtained for V-line (1.715) and Gabali breed (1.800). The highest genotype frequency of GH gene was 0.48 in TT genotype of V-line, 0.21 in CC genotype of Moshtohor line, 0.67 and 0.56 in TC genotype of ½A½M and Gabali rabbits (P&lt;0.05). The highest frequency for C allele was recorded by Moshtohor line (0.45) and the lowest frequency by Gabali (0.32). The genetic diversity scores for GH gene were intermediate (Ho=0.551, He=0.471, PIC=0.358). The values of Ho ranged from 0.444 in V-line to 0.667 in ½A½M cross, while the values of He were 0.425 in V-line and 0.508 in Moshtohor line. The values of PIC were moderate and ranged from 0.332 in V-line to 0.375 in M-line. The highest FIS was observed in Moshtohor line (0.042) and the lowest value was observed in ½A½M cross (–0.413). The CT genotype of GH gene showed the highest and significant values for body weights at 4, 8, 10 and 12 wk (542, 1131, 1465 and 1861 g) and daily gains at intervals of 4-6 and 8-10 wk (23.1 and 26.5 g). Additionally, the CT genotype recorded the highest and significant values for volume of ejaculate (1.1 mL), sperm motility (57.6%), live sperm (85.6%), normal sperm (93.1%) and sperm concentration in semen (611×106/mL), along with the lowest and significant values for dead sperms (14.4%) and abnormal sperms (6.9%).The authors are very grateful to the Central Laboratory of the Faculty of Veterinary Medicine, Benha University, Egypt for the help and support in molecular genetic analyses. This work was financially supported by the research project entitled “Genetic improvement of local rabbit breeds by using molecular genetic techniques” from the Scientific Research Fund (SRF), Benha University, Egypt.Khalil, MHE.; Zaghloul, AR.; Iraqi, MM.; El Nagar, AG.; Ramadan, SI. (2021). Association of GH gene polymorphism with growth and semen traits in rabbits. 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PROTECTIVE EFFECT OF AQUEOUS EXTRACT POMEGRANATE PEEL AGAINST STERIGMATOCYSTIN TOXICITY IN RAT

Introduction and Aim: Sterigmatocystin (Stg) a mycotoxin with mutagenic and carcinogenic properties is commonly found as the contaminant in grains and animal feeds. Pomegranate peel is a rich source of antioxidants, flavonoids and other phenolic compounds. So the aim of the current study was to evaluate the protective effects of aqueous extract of red Pomegranate peel against Stg toxicity in liver, kidney, intestine and lung as well as final body weight using male rats. Methods: Forty eight Sprague-Dawley male rats were divided into six groups (8rats/group) including the control group that fed on a standard diet and water without any treatment, group 2 fed on standard diet plus aqueous extract of RPP (250 mg/rat/day), group 3 fed on standard diet plus aqueous extract of RPP (500 mg/ rat/day), group 4 fed on a standard diet and orally Stg. dissolved at a dose (18µg/rat/day), group 5 fed on a standard diet and Stg  plus aqueous extract of RPP (250mg/day) and group 6 fed on a standard diet and Stg. plus aqueous extract of RPP (500mg/day). At the end of the experimental period, blood samples were collected for serum biochemical analyses. After collecting the blood samples all animals were scarified and dissected samples of liver, kidney, intestine and lung were collected for histological examination. Results: The total phenols and total flavonoids, compounds in aqueous extract of RPP were 1.38 mg/ml and 680.28 mg/ml, respectively. However, the antioxidant activity amounted to 68.0% in the determination of radical DPPH scavenging activity. On the other hand, results indicated that rat orally Stg plus aqueous extract of RPP with low dose and high doses showed a significant improvement in final body weight compared with group administrated of Stg alone. While, the effect of aqueous extract of RPP on kidney and liver function of rats, the results indicated that the rat orally Stg alone caused significant increased in urea, creatinine and uric acid compared with the control group. The aqueous extract of RPP alone at the two tested doses did not induce any significant changes in the biochemical parameters or the histological picture. The combined treatment showed significant improvements in all tested parameters and histological pictures in the liver tissues. Moreover, this improvement was more pronounced in the group received the high dose of aqueous extract of RPP. Conclusion: From results it can be concluded that u the aqueous extract of RPP has a potent antioxidant activity and a protective effect against Stg toxicity and this protection was dose dependent. Keywords: Sterigmatocystin, Red pomegranate peels (RPP), aqueous extract, liver and kidney

The Effect Of Graphene On Catalytic Performance Of Palladium Nanoparticles Decorated With Fe3O4, Co3O4, And Ni (OH)2: Potential Efficient Catalysts Used For Suzuki Cross—Coupling

Abstract: In this research, we report a scientific investigation of an efficient method used for the synthesis of highly active Palladium Nanoparticles decorated with Fe3O4, Co3O4, and Ni (OH)2 Supported on Graphene as Potential Efficient Catalysts for Suzuki Cross—Coupling. Pd/Fe3O4 nanoparticles supported on graphene nanosheets (Pd/Fe3O4/G) showed an excellent catalytic activity for Suzuki coupling reactions and recycled for up to four times without loss of catalytic activity. An efficient magnetic catalyst has been successfully synthesized using a simple, reproducible fast and reliable method using microwave irradiation conditions. The prepared catalysts are magnetic as in case of iron and cobalt oxides which is an advantage in the separation process of catalyst from the reaction medium via applying a strong external magnetic field. The synthesis approach is based on the Microwave (MW)-assisted simultaneous reduction of palladium and ferric nitrates in the presence of graphene oxide (GO) nanosheets using hydrazine hydrate as the reducing agent. The results provide a fundamental understanding of the system variables by comparing the catalytic activity and recyclability of different catalysts with different properties. The most active and recyclable catalyst was Pd–Fe3O4—supported on graphene which offers several added advantages including recyclability of up to seven times, mild reaction conditions, and short reaction times in an environmentally benign solvent system. Furthermore, the magnetic properties imparted by the Fe3O4 component of the catalyst enables the catalyst to be easily isolated and recycled, thus greatly simplifying the ability to purify the reaction products and increasing the economic value of the catalyst. The utility of these magnetic catalysts towards Suzuki cross coupling reaction was also demonstrated. The high activity and recyclability of these catalysts are attributed to a strong catalyst-support interaction where the defect sites in the reduced GO nanosheets act as nucleation centers for anchoring the Pd and Fe3O4 nanoparticles thus minimizing the potential of their agglomeration and the subsequent decrease in the catalytic activity. Graphical Abstract: [Figure not available: see fulltext.]

Expression of a pathogenic mutation of SOD1 sensitizes aprataxin-deficient cells and mice to oxidative stress and triggers hallmarks of premature ageing

Aprataxin (APTX) deficiency causes progressive cerebellar degeneration, ataxia and oculomotor apraxia in man. Cell free assays and crystal structure studies demonstrate a role for APTX in resolving 5'-adenylated nucleic acid breaks, however, APTX function in vertebrates remains unclear due to the lack of an appropriate model system. Here, we generated a murine model in which a pathogenic mutant of superoxide dismutase 1 (SOD1(G93A)) is expressed in an Aptx-/- mouse strain. We report a delayed population doubling and accelerated senescence in Aptx-/- primary mouse fibroblasts, which is not due to detectable telomere instability or cell cycle deregulation but is associated with a reduction in transcription recovery following oxidative stress. Expression of SOD1(G93A) uncovers a survival defect ex vivo in cultured cells and in vivo in tissues lacking Aptx. The surviving neurons feature numerous and deep nuclear envelope invaginations, a hallmark of cellular stress. Furthermore, they possess an elevated number of high-density nuclear regions and a concomitant increase in histone H3 K9 trimethylation, hallmarks of silenced chromatin. Finally, the accelerated cellular senescence was also observed at the organismal level as shown by down-regulation of insulin-like growth factor 1 (IGF-1), a hallmark of premature ageing. Together, this study demonstrates a protective role of Aptx in vivo and suggests that its loss results in progressive accumulation of DNA breaks in the nervous system, triggering hallmarks of premature ageing, systemically

Statin Use and Venous Thromboembolism in Cancer: A Large, Active Comparator, Propensity Score Matched Cohort Study

Background—Statins have been shown to have a protective effect for venous thromboembolism (VTE) in the general population. This study sought to assess the association between statins and the risk for cancer-associated deep vein thrombosis (DVT) and pulmonary embolism (PE). Methods—Patients with newly diagnosed cancer were followed for up to one year in a healthcare claims database (2010–2013). Three treatment groups included statin users, non-statin cholesterol lowering medication users, and an untreated group with pre-existing indications for statin therapy (hyperlipidemia, diabetes, or heart disease). Propensity score matched groups were compared using competing risks survival models for DVT and PE outcomes reporting the hazard ratios (HR) between the treatment groups. Sensitivity analyses assessed the influence of age and individual medications. Results—The total cohort included 170,459 patients, which, after matching, were similar on baseline characteristics. The overall model showed a statistically significant protective effect for statins compared to no treatment attributed only to leukemia for DVT (HR = 0.77, 95% CI 0.61–0.99) and colorectal cancers for PE (HR = 0.80, 95% CI 0.64–0.99) in stratified analyses. There were generally no differences in outcomes between statins and non-statins and no individual statin use showed results different from the class effect. Conclusions—In this propensity score matched sample of patients with cancer, statins were shown to have a small protective effect in some cancers for DVT or PE compared to no treatment and little difference compared to an active control group. The lack of effect was consistent across statins and was also not found for any of the sensitivity analyses included