Momordica charantia (bitter melon) inhibits primary human adipocyte differentiation by modulating adipogenic genes

<p>Abstract</p> <p>Background</p> <p>Escalating trends of obesity and associated type 2 diabetes (T2D) has prompted an increase in the use of alternative and complementary functional foods. <it>Momordica charantia </it>or bitter melon (BM) that is traditionally used to treat diabetes and complications has been demonstrated to alleviate hyperglycemia as well as reduce adiposity in rodents. However, its effects on human adipocytes remain unknown. The objective of our study was to investigate the effects of BM juice (BMJ) on lipid accumulation and adipocyte differentiation transcription factors in primary human differentiating preadipocytes and adipocytes.</p> <p>Methods</p> <p>Commercially available cryopreserved primary human preadipocytes were treated with and without BMJ during and after differentiation. Cytotoxicity, lipid accumulation, and adipogenic genes mRNA expression was measured by commercial enzymatic assay kits and semi-quantitative RT-PCR (RT-PCR).</p> <p>Results</p> <p>Preadipocytes treated with varying concentrations of BMJ during differentiation demonstrated significant reduction in lipid content with a concomitant reduction in mRNA expression of adipocyte transcription factors such as, peroxisome proliferator-associated receptor γ (PPARγ) and sterol regulatory element-binding protein 1c (SREBP-1c) and adipocytokine, resistin. Similarly, adipocytes treated with BMJ for 48 h demonstrated reduced lipid content, perilipin mRNA expression, and increased lipolysis as measured by the release of glycerol.</p> <p>Conclusion</p> <p>Our data suggests that BMJ is a potent inhibitor of lipogenesis and stimulator of lipolysis activity in human adipocytes. BMJ may therefore prove to be an effective complementary or alternative therapy to reduce adipogenesis in humans.</p

NMDA Mediated Contextual Conditioning Changes miRNA Expression

We measured the expression of 187 miRNAs using quantitative real time PCR in the hippocampal CA1 region of contextually conditioned mice and cultured embryonic rat hippocampal neurons after neuronal stimulation with either NMDA or bicuculline. Many of the changes in miRNA expression after these three types of stimulation were similar. Surprisingly, the expression level of half of the 187 measured miRNAs was changed in response to contextual conditioning in an NMDA receptor-dependent manner. Genes that control miRNA biogenesis and components of the RISC also exhibited activity induced expression changes and are likely to contribute to the widespread changes in the miRNA profile. The widespread changes in miRNA expression are consistent with the finding that genes up-regulated by contextual conditioning have longer 3′ UTRs and more predicted binding sites for miRNAs. Among the miRNAs that changed their expression after contextual conditioning, several inhibit inhibitors of the mTOR pathway. These findings point to a role for miRNAs in learning and memory that includes mTOR-dependent modulation of protein synthesis

Medial unicompartmental knee arthroplasty in the ACL-deficient knee

Symptomatic osteoarthritis (OA) of the knee develops often in association with anterior cruciate ligament (ACL) deficiency. Two distinct pathologies should be recognised while considering treatment options in patients with end-stage medial compartment OA and ACL deficiency. Patients with primary ACL deficiency (usually traumatic ACL rupture) can develop secondary OA (typically presenting with symptoms of instability and pain) and these patients are typically young and active. Patients with primary end stage medial compartment OA can develop secondary ACL deficiency (usually degenerate ACL rupture) and these patients tend to be older. Treatment options in either of these patient groups include arthroscopic debridement, reconstruction of the ACL, high tibial osteotomy (HTO) with or without ACL reconstruction, unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA). General opinion is that a functionally intact ACL is a fundamental prerequisite to perform a UKA. This is because previous reports showed higher failure rates when ACL was deficient, probably secondary to wear and tibial loosening. Nevertheless in some cases of ACL deficiency with end-stage medial compartment OA, UKA has been performed in isolation and recent papers confirm good short- to mid-term outcome without increased risk of implant failure. Shorter hospital stay, fewer blood transfusions, faster recovery and significantly lower risk of developing major complications like death, myocardial infarction, stroke, deep vein thrombosis (as compared to TKA) make the UKA an attractive option, especially in the older patients. On the other hand, younger patients with higher functional demands are likely to benefit from a simultaneous or staged ACL reconstruction in addition to UKA to regain knee stability. These procedures tend to be technically demanding. The main aim of this review was to provide a synopsis of the existing literature and outline an evidence-based treatment algorithm

Modes of Aβ toxicity in Alzheimer’s disease

Alzheimer’s disease (AD) is reaching epidemic proportions, yet a cure is not yet available. While the genetic causes of the rare familial inherited forms of AD are understood, the causes of the sporadic forms of the disease are not. Histopathologically, these two forms of AD are indistinguishable: they are characterized by amyloid-β (Aβ) peptide-containing amyloid plaques and tau-containing neurofibrillary tangles. In this review we compare AD to frontotemporal dementia (FTD), a subset of which is characterized by tau deposition in the absence of overt plaques. A host of transgenic animal AD models have been established through the expression of human proteins with pathogenic mutations previously identified in familial AD and FTD. Determining how these mutant proteins cause disease in vivo should contribute to an understanding of the causes of the more frequent sporadic forms. We discuss the insight transgenic animal models have provided into Aβ and tau toxicity, also with regards to mitochondrial function and the crucial role tau plays in mediating Aβ toxicity. We also discuss the role of miRNAs in mediating the toxic effects of the Aβ peptide