Accumulation of neurotoxic bilirubin due to a transient neonatal or persistent inherited deficiency of bilirubin glucuronidation activity can cause irreversible brain damage and death. Strategies to inhibit bilirubin production and prevent neurotoxicity in neonatal and adult settings seem promising. We evaluated the impact of Bvra deficiency in neonatal and aged mice, in a background of unconjugated hyperbilirubinemia, by abolishing bilirubin production. We also investigated the disposal of biliverdin during fetal development. In Ugt1^−/− mice, Bvra deficiency appeared sufficient to prevent lethality and to normalize bilirubin level in adults. Although biliverdin accumulated in Bvra-deficient fetuses, both Bvra^−/− and Bvra^−/−Ugt1^−/− pups were healthy and reached adulthood having normal liver, brain, and spleen histology, albeit with increased iron levels in the latter. During aging, both Bvra^−/− and Bvra^−/−Ugt1^−/− mice presented normal levels of relevant hematological and metabolic parameters. Interestingly, the oxidative status in erythrocytes from 9-months-old Bvra^−/− and Bvra^−/−Ugt1^−/− mice was significantly reduced. In addition, triglycerides levels in these 9-months-old Bvra^−/− mice were significantly higher than WT controls, while Bvra^−/−Ugt1^−/− tested normal. The normal parameters observed in Bvra^−/−Ugt1^−/− mice fed chow diet indicate that Bvra inhibition to treat unconjugated hyperbilirubinemia seems safe and effective.

The present study explored the ameliorative potency of aqueous extract of Capsicum annum (AqCA), against oxidative imbalance and renal toxicity induced by ethanol. Randomly grouped male Wistar rats (n = 6), were marked as ethanol-treated (2 g/kg bw, i.p.), CA₁₂₅ (125 mg/kg bw, i.p.), CA₂₅₀ (250 mg/kg bw, i.p.), ethanol pre-treated with CA (similar doses), and control (0.5 ml normal saline, i.p.), and treated for 30 consecutive days. Biochemical analysis of tissue and serum parameters was performed, along with histopathological and histochemical studies. Also, we performed TUNEL assay and western blotting for our experimental groups. Statistical analysis revealed significant (p ≤ .001) alteration in the levels of antioxidant enzymes, serum urea, creatinine, pro-inflammatory cytokines, and cleaved caspases, along with histopathological alterations in the ethanol-treated group. Prior treatment with AqCA prevented ethanol-induced alterations in tissue and serum parameters. These findings indicate that the extract of CA can protect renal cells from ethanol-induced damage by inhibiting oxidative stress, inflammatory response, and apoptosis. PRACTICAL APPLICATIONS: Chronic alcohol consumption is a major public health concern that leads to various diseases and social problems as well. It affects both the affluent and non-affluent society equally. Alcohol (ethanol) is a renowned hepato-toxicant and a well-documented risk factor for oxidative stress, with less known effect on the kidney. Thus, it is essential to investigate the effect of alcohol metabolism on the kidney to find a remedy to prevent it. The present investigation depicts the anti-oxidative and anti-inflammatory role of Capsicum annum against ethanol-induced renal damage. The outcome of this study can be utilized in the future for phytotherapeutic herbal drug formulation. Besides, the bioactive components identified in the study can be further explored by researchers or pharmaceutical corporates for potential therapeutic purpose against renal impairment.

Epidemiological data of HIV affected individuals of aged 50 years and above in India are lacking for various reasons. Diagnosing HIV infection among the elderly is challenging as chronic HIV/AIDS can mimic those typically associated with aging in parallel to the myth that elderly individuals lead asexual lives. In this study, low-literate, poor, urban men were the major group. The most common presentation at diagnosis was frailty or unexpected weight loss and neurocognitive impairment, whereas the incidence of TB was much less. Policy makers and social workers should be aware of this descriptive analysis in order to address the emerging issue of HIV among geriatrics and to create a broader awareness programme and more liberal HIV testing among this group. This study also highlights the need for a larger population based study involving elderly HIV infected persons in India.

Bilirubin is a heme catabolite and Ugt1a1 is the only enzyme involved in the biological elimination of bilirubin. Partially functional or non-functional Ugt1a1 may result in neuronal damage and death due to the accumulation of unconjugated bilirubin in the brain. The understanding of the role of alternative bilirubin detoxification mechanisms that can reduce bilirubin toxicity risk is crucial for developing novel therapeutic strategies. To provide a proof-of-principle showing whether activation of alternative detoxification pathways could lead to life-compatible bilirubin levels in the absence of Ugt1a1 activity, we used Ugt1^−/− hyperbilirubinemic mice devoid of bilirubin glucuronidation activity. We treated adult Ugt1^−/− mice with TCPOBOP, a strong agonist of the constitutive androstane receptor (CAR). TCPOBOP treatment decreased plasma and liver tissue bilirubin levels by about 38%, and resulted in the transcriptional activation of a vast array of genes involved in bilirubin transport and metabolism. However, brain bilirubin level was unaltered. We observed ~40% degradation of bilirubin in the liver microsomes from TCPOBOP treated Ugt1^−/− mice. Our findings suggest that, in the absence of Ugt1a1, the activation of alternative bilirubin clearance pathways can partially improve hyperbilirubinemic conditions. This therapeutic approach may only be considered in a combinatorial manner along with other treatments.

Hyaluronan, an important constitutent of the extracellular matrix (ECM) is known to have multifaceted regulations through its different ligands like hyaluronic acid binding protein1 (HABP1). It has been purified, cloned and shown to be present in human chromosome 17p13.3. Sequence analysis confirmed its multifunctionlity as it is identical with p32, the protein associated with alternate splicing factor SF2 and the receptor of gC1Q. Interestingly its differential cellular compartmentalization in several cell lines and nuclear translocation with viral transformation raises its different activities residing in specific compartments. In order to search for its function, we have made the following approaches. We have transformed normal fibroblast with HABP1 gene and found it undergoes into apoptosis due to generation of reactive oxygen species by the mitochondrial accumulation of HABP1. In parallel, we investigated the probable pathway of cell cycle modulation in which expression of HABP1 has been down regulated by siRNA. In continuation as being an ECM component HA is known to promote anchorage independent growth and invasiveness, the mark of malignant phenotype. Thus we studied the effect of HABP1 supplementation in the medium and found enhanced expression and secretion of matrix metalloproteases which can be correlated with NF‐êB activation. Finally we would like to discuss earlier clinical reports on the level of HABP1 in carcinoma and papiloma with our present data on defined functions of HABP1 gene.