Nephroprotective Effect of Garlic Chives (Allium Tuberosum) on Bun and Creatinine Levels of Wistar Rats Induced by Doxorubicin

Cancer is the most leading disease that cause of death. Doxorubicin chemotherapy is often used in cancer treatment, because of its effectiveness. Although doxorubicin has a positive effect for killing cancer cell, doxorubicin has many side effects, one of which doxorubicin can cause kidney damage through the process of interstitial fibrosis. Utilization garlic chives extract as co chemotherapy to reduce renal damage induced by doxorubicin is a prospective opportunities. This study aimed to analyze the effect of garlic chives extract as a nephroprotective on levels of BUN and creatinine of wistar rats induced by doxorubicin. The research method was quasi experimental design with post test only randomized controlled group. The results showed that extracts of garlic chives can reduce levels of BUN and creatinine (p <0.05) in the group that only induced by doxorubicin. In conclusion, extract of garlic chives has nephroprotecive effects on wistar rats which were induced by doxorubicin

Seasonal and predator-prey effects on circadian activity of free-ranging mammals revealed by camera traps

Endogenous circadian and seasonal activity patterns are adapted to facilitate effective utilisation of environmental resources. Activity patterns are shaped by physiological constraints, evolutionary history, circadian and seasonal changes and may be influenced by other factors, including ecological competition and interspecific interactions. Remote-sensing camera traps allow the collection of species presence data throughout the 24 h period and for almost indefinite lengths of time. Here, we collate data from 10 separate camera trap surveys in order to describe circadian and seasonal activity patterns of 10 mammal species, and, in particular, to evaluate interspecific (dis)associations of five predator-prey pairs. We recorded 8,761 independent detections throughout Northern Ireland. Badgers, foxes, pine martens and wood mice were nocturnal; European and Irish hares and European rabbits were crepuscular; fallow deer and grey and red squirrels were diurnal. All species exhibited significant seasonal variation in activity relative to the timing of sunrise/sunset. Foxes in particular were more crepuscular from spring to autumn and hares more diurnal. Lagged regression analyses of predator-prey activity patterns between foxes and prey (hares, rabbits and wood mice), and pine marten and prey (squirrel and wood mice) revealed significant annual and seasonal cross-correlations. We found synchronised activity patterns between foxes and hares, rabbits and wood mice and pine marten and wood mice, and asynchrony between squirrels and pine martens. Here, we provide fundamental ecological data on endemic, invasive, pest and commercially valuable species in Ireland, as well as those of conservation importance and those that could harbour diseases of economic and/or zoonotic relevance. Our data will be valuable in informing the development of appropriate species-specific methodologies and processes and associated policies

Gene domain-specific DNA methylation episignatures highlight distinct molecular entities of ADNP syndrome.

BACKGROUND:ADNP syndrome is a rare Mendelian disorder characterized by global developmental delay, intellectual disability, and autism. It is caused by truncating mutations in ADNP, which is involved in chromatin regulation. We hypothesized that the disruption of chromatin regulation might result in specific DNA methylation patterns that could be used in the molecular diagnosis of ADNP syndrome. RESULTS: We identified two distinct and partially opposing genomic DNA methylation episignatures in the peripheral blood samples from 22 patients with ADNP syndrome. The epi-ADNP-1 episignature included ~ 6000 mostly hypomethylated CpGs, and the epi-ADNP-2 episignature included ~ 1000 predominantly hypermethylated CpGs. The two signatures correlated with the locations of the ADNP mutations. Epi-ADNP-1 mutations occupy the N- and C-terminus, and epi-ADNP-2 mutations are centered on the nuclear localization signal. The episignatures were enriched for genes involved in neuronal system development and function. A classifier trained on these profiles yielded full sensitivity and specificity in detecting patients with either of the two episignatures. Applying this model to seven patients with uncertain clinical diagnosis enabled reclassification of genetic variants of uncertain significance and assigned new diagnosis when the primary clinical suspicion was not correct. When applied to a large cohort of unresolved patients with developmental delay (N = 1150), the model predicted three additional previously undiagnosed patients to have ADNP syndrome. DNA sequencing of these subjects, wherever available, identified pathogenic mutations within the gene domains predicted by the model. CONCLUSIONS: We describe the first Mendelian condition with two distinct episignatures caused by mutations in a single gene. These highly sensitive and specific DNA methylation episignatures enable diagnosis, screening, and genetic variant classifications in ADNP syndrome

Diagnostic Utility of Genome-wide DNA Methylation Testing in Genetically Unsolved Individuals with Suspected Hereditary Conditions.

Conventional genetic testing of individuals with neurodevelopmental presentations and congenital anomalies (ND/CAs), i.e., the analysis of sequence and copy number variants, leaves a substantial proportion of them unexplained. Some of these cases have been shown to result from DNA methylation defects at a single locus (epi-variants), while others can exhibit syndrome-specific DNA methylation changes across multiple loci (epi-signatures). Here, we investigate the clinical diagnostic utility of genome-wide DNA methylation analysis of peripheral blood in unresolved ND/CAs. We generate a computational model enabling concurrent detection of 14 syndromes using DNA methylation data with full accuracy. We demonstrate the ability of this model in resolving 67 individuals with uncertain clinical diagnoses, some of whom had variants of unknown clinical significance (VUS) in the related genes. We show that the provisional diagnoses can be ruled out in many of the case subjects, some of whom are shown by our model to have other diseases initially not considered. By applying this model to a cohort of 965 ND/CA-affected subjects without a previous diagnostic assumption and a separate assessment of rare epi-variants in this cohort, we identify 15 case subjects with syndromic Mendelian disorders, 12 case subjects with imprinting and trinucleotide repeat expansion disorders, as well as 106 case subjects with rare epi-variants, a portion of which involved genes clinically or functionally linked to the subjects\u27 phenotypes. This study demonstrates that genomic DNA methylation analysis can facilitate the molecular diagnosis of unresolved clinical cases and highlights the potential value of epigenomic testing in the routine clinical assessment of ND/CAs

BAFopathies\u27 DNA methylation epi-signatures demonstrate diagnostic utility and functional continuum of Coffin-Siris and Nicolaides-Baraitser syndromes.

Coffin-Siris and Nicolaides-Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B, SMARCB1, and SMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. We show that chromosome 6q25 microdeletion syndrome, harboring ARID1B deletions, exhibits a similar CSS/NCBRS methylation profile. Specificity of this epi-signature was confirmed across a wide range of neurodevelopmental conditions including other chromatin remodeling and epigenetic machinery disorders. We demonstrate that a machine-learning model trained on this DNA methylation profile can resolve ambiguous clinical cases, reclassify those with variants of unknown significance, and identify previously undiagnosed subjects through targeted population screening

When does priming justice promote forgiveness? On the importance of distributive and procedural justice for self and others

Two studies show that thinking about justice can both enhance and impede forgiveness, depending on whether thoughts about distributive and procedural justice for self and others are activated. In Study 1 (n = 197), participants expressed more forgiveness towards a prior transgressor when primed to think about justice for self or procedural justice for others, and less forgiveness when primed to think about distributive justice for others. Study 2 (n = 231) used an alternate priming method and replicated these effects by inducing an interpersonal transgression and measuring forgiveness intentions, emotions and behavior. Study 2 also showed that priming justice influences forgiveness especially when the perceived severity of an interpersonal offense is high. The current research shows that activating justice cognitions can enhance or impinge on forgiveness in predictable ways. We discuss contributions to emerging justice theory, potential implications, and future directions

One-year safety and efficacy of mitapivat in sickle cell disease: follow-up results of a phase 2, open-label study

Targeting the primary pathogenic event of sickle cell disease (SCD), the polymerization of sickle hemoglobin (HbS), may prevent downstream clinical events. Mitapivat, an oral pyruvate kinase (PK) activator, has therapeutic potential by increasing adenosine triphosphate (ATP) and decreasing 2,3-diphosphoglycerate (2,3-DPG), a glycolytic red blood cell (RBC) intermediate. In the previously reported 8-week dose-finding period of this phase 2, investigator-initiated, open-label study, mitapivat was well tolerated and showed efficacy in SCD. Here, the 1-year fixed-dose extension period is reported in which 9 of 10 included patients (90%) aged ≥16 years with SCD (HbSS, HbS/β0, or HbS/β+) continued with mitapivat. Mostly mild treatment-emergent adverse events (AEs) (most commonly, transaminase increase and headache) were still reported. Apart from the reported nontreatment-related serious AE (SAE) of a urinary tract infection in the dose-finding period, 1 nontreatment-related SAE occurred in the fixed-dose extension period in a patient who died of massive pulmonary embolism due to COVID-19. Importantly, sustained improvement in Hb level (mean increase, 1.1 ± 0.7 g/dL; P = .0014) was seen, which was accompanied by decreases in markers of hemolysis. In addition, the annualized rate of vaso-occlusive events reduced significantly from a historic baseline of 1.33 ± 1.32 to 0.64 ± 0.87 (P = .0489) when combining the dose-finding period and fixed-dose extension period. Cellularly, the ATP:2,3-DPG ratio and Hb-oxygen affinity significantly increased and RBC sickling (point of sickling) nonsignificantly reduced. Overall, this study demonstrated 1-year safety and efficacy of treatment with mitapivat in SCD, supporting further evaluation in ongoing phase 2/3 study (RISE UP, NCT05031780). This trial was registered at https://www.clinicaltrialsregister.eu/ as NL8517 and EudraCT 2019-003438-18