BVR-A deficiency leads to autophagy impairment through the dysregulation of AMPK/mTOR axis in the brain—Implications for neurodegeneration

Biliverdin reductase-A (BVR-A) impairment is associated with increased accumulation of oxidatively-damaged proteins along with the impairment of autophagy in the brain during neurodegenerative disorders. Reduced autophagy inhibits the clearance of misfolded proteins, which then form neurotoxic aggregates promoting neuronal death. The aim of our study was to clarify the role for BVR-A in the regulation of the mTOR/autophagy axis by evaluating age-associated changes (2, 6 and 11 months) in cerebral cortex samples collected from BVR-A knock-out (BVR-A−/−) and wild-type (WT) mice. Our results show that BVR-A deficiency leads to the accumulation of oxidatively-damaged proteins along with mTOR hyper-activation in the cortex. This process starts in juvenile mice and persists with aging. mTOR hyper-activation is associated with the impairment of autophagy as highlighted by reduced levels of Beclin-1, LC3β, LC3II/I ratio, Atg5–Atg12 complex and Atg7 in the cortex of BVR-A−/− mice. Furthermore, we have identified the dysregulation of AMP-activated protein kinase (AMPK) as a critical event driving mTOR hyper-activation in the absence of BVR-A. Overall, our results suggest that BVR-A is a new player in the regulation of autophagy, which may be targeted to arrive at novel therapeutics for diseases involving impaired autophagy

A Genome-Wide Association Study of Total Bilirubin and Cholelithiasis Risk in Sickle Cell Anemia

Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5×10−8). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08×10−25). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15×10−4). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities

Bilirubin links heme metabolism to neuroprotection by scavenging superoxide (Vasavda et al., 2019)

Source code associated with &quot;Bilirubin links heme metabolism to neuroprotection by scavenging superoxide&quot; by Vasavda et al. (2019

Intravenous Immunoglobulin as a treatment for SLE with severe, refractory cutaneous involvement requiring hospitalization (Sengupta et al., 2023)

Supplemental Figures and Tables reporting patient demographics and clinical characteristics and dermatologic findings.Supplemental Figure 1. Acute cutaneous lupus erythematosus requiring hospitalization (Case 1). Supplemental Figure 2. Acute cutaneous lupus erythematosus requiring hospitalization (Case 3).Supplemental Table 1. Patient summary and clinical characteristics.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Bilirubin links heme metabolism to neuroprotection by scavenging superoxide (Vasavda et al., 2019)

Source code associated with &quot;Bilirubin links heme metabolism to neuroprotection by scavenging superoxide&quot; by Vasavda et al. (2019)THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Identification of the NRF2 transcriptional network as a therapeutic target for trigeminal neuropathic pain (Vasavda et al., 2022)

Table S1. Compound Connectivity Scores for Nfe2l2-derived and Keap1-derived transcriptome signatures.Table S2. Differential gene expression in primary human dermal fibroblasts treated with vehicle or JQ-1.Table S3. Gene ontology analysis of JQ-1-dependent differential gene expression.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Asymmetric patterns of patient access to in-person and teledermatologic healthcare during the COVID-19 pandemic (Vasavda et al., 2022)

Supplemental Materials related to report, &quot;Asymmetric patterns of patient access to in-person and teledermatologic healthcare during the COVID-19 pandemic&quot;Teledermatology-Vasavda et al-Supplemental DiscussionTeledermatology-Vasavda et al-Supplemental MethodsVasavda et al-Teledermatology-Table S1Vasavda et al-Teledermatology-Table S2Vasavda et al-Teledermatology-Table S3THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV