Synthesis of nimbolide and its analogues and their application as poly(ADP-ribose) polymerase-1 trapping inducers.

Nimbolide, a ring seco-C limonoid natural product, was recently found to inhibit the poly(ADP)-ribosylation (PARylation)-dependent ubiquitin E3 ligase RNF114. In doing so, it induces the 'supertrapping' of both PARylated PARP1 and PAR-dependent DNA-repair factors. PARP1 inhibitors have reshaped the treatment of cancer patients with germline / mutations partly through the PARP1 trapping mechanism.

Nimbolide targets RNF114 to induce the trapping of PARP1 and synthetic lethality in -mutated cancer.

Recent studies have pointed to PARP1 trapping as a key determinant of the anticancer effects of PARP1 inhibitors (PARPi). We identified RNF114, as a PARylation-dependent, E3 ubiquitin ligase involved in DNA damage response. Upon sensing genotoxicity, RNF114 was recruited, in a PAR-dependent manner, to DNA lesions, where it targeted PARP1 for degradation.

Palladium-Catalyzed Dearomative syn-1,4-Oxyamination.

A palladium-catalyzed dearomative syn-1,4-oxyamination protocol using non-activated arenes has been developed. This one-pot procedure utilizes arenophile chemistry, and the corresponding para-cycloadducts are treated with oxygen nucleophiles via formal allylic substitution, providing direct access to syn-1,4-oxyaminated products. The reaction conditions permit a range of arenes, as well as different O-nucleophiles, such as oximes and benzyl alcohols.

Relationship between the rs2596542 polymorphism in the MICA gene promoter and HBV/HCV infection-induced hepatocellular carcinoma: a meta-analysis.

Background & Aims: Various studies have investigated the relationship between the polymorphism, rs2596542, in the promoter of the major histocompatibility complex class I-related gene A (MICA) gene with susceptibility to hepatitis B virus (HBV)/ hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC); however, the results are inconclusive. This meta-analysis was conducted to investigate the relationship between rs2596542 and HCV/HBV-induced HCC.

Methods: Three electronic scientific publication databases (MEDLINE, Web of Science, and Embase) were screened using specific search terms and relevant literature identified using literature traceability methods.

Hepatic splenosis: Rare yet important - A case report and literature review.

Hepatic splenosis is an uncommon condition that occurs following traumatic splenic rupture or splenectomy. The case of a 41-year-old male patient with multiple isolated liver masses indistinguishable from primary and metastatic liver tumours is reported. Following laparotomy, the liver lesions were resected and histopathology confirmed a diagnosis of hepatic splenosis.

Asymmetric Total Synthesis of (+)-Majusculoic Acid via a Dimerization-Dedimerization Strategy and Absolute Configuration Assignment.

The first total synthesis of (+)-majusculoic acid, the enantiomer of naturally occurring antifungal cyclopropane fatty acid (-)-majusculoic acid, was accomplished in 13 steps, leading to the assignment of the absolute configuration of the natural product. The synthesis featured a ring closing metathesis dimerization, a conformationally controlled cyclopropanation, a dedimerization, and a bromoolefination.

Everolimus in de novo liver transplant recipients: a systematic review.

Background: Everolimus has no nephrotoxicity and is used to treat patients with post-liver transplant chronic renal insufficiency. The present systematic review was to evaluate the efficacy and safety of everolimus in de novo liver transplant patients.

Data Sources: Randomized controlled trials comparing everolimus for de novo liver transplant in PubMed, the Cochrane Library, and ScienceDirect published up to March 31, 2014 were searched by two independent reviewers.

p53 gene therapy-based transarterial chemoembolization for unresectable hepatocellular carcinoma: A prospective cohort study.

Background And Aim: Transarterial chemoembolization (TACE) is used for treating unresectable hepatocellular carcinoma (HCC), but its efficacy still needs to be improved. Recombinant adenovirus p53 (rAd-p53) injection is a gene therapeutic agent that could improve the prognosis of HCC patients. This study aimed to evaluate the efficacy and safety of rAd-p53-based TACE for treating unresectable HCC.