👤 Nourhan Naji

Emerging lipid-lowering therapies, such as Plozasiran, target apolipoprotein C-III (APOC-III) by inhibiting its hepatic production at the mRNA level, presenting a novel approach to lipid regulation. However, the safety and efficacy of plozasiran have yet to be fully established. We searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL register of trials for studies comparing plozasiran to placebo in patients with dyslipidemic disorders. The primary outcomes were percentage changes from baseline in triglyceride (TG) and APOC-III levels at 24 weeks and the end of the study. Secondary outcomes included changes in other lipid parameters and safety outcomes at 24 weeks and the end of the study. A protocol was registered to PROSPERO under registration number [CRD420251026605]. Four studies encompassing 1,514 participants were included in our meta-analysis. Plozasiran significantly improved TGs, APOC-III, non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (ApoB) levels at both 24 weeks and study completion. Subgroup analyses based on dose and regimen revealed consistent findings. Quarterly administration of plozasiran at 10 mg, 25 mg, and 50 mg resulted in significant reductions in TGs, APOC-III, non-HDL-C, and HDL-C at both 24 weeks and study completion. For ApoB, all three doses produced significant reductions at 24 weeks; however, only the 25 mg and 50 mg quarterly regimens sustained these reductions through the end of the study. Regarding safety, patients receiving plozasiran experienced a higher incidence of any adverse events, headache, and mild rises in HbA1C levels. Subgroup analysis revealed a dose-dependent pattern for certain safety outcomes. While Plozasiran shows strong potential as a therapeutic option for severe dyslipidemic conditions, further studies are needed to compare its efficacy and safety with currently available treatments and, more importantly, evaluate its impact on clinical outcomes for implementation in clinical practice. Show less

Pancreatic endocrine neoplasms (PENs) are rare, mostly well-differentiated endocrine neoplasms, whose biology has been poorly characterized. Global expression microarrays can document abnormal pathways that impact on tumorigenesis and disease progression. RNA was extracted from eight well-differentiated PENs and three highly enriched pancreatic islet cell samples (80-90% purity), and examined using the Affymetrix U133A oligonucleotide microarray. Microarray data were normalized using dCHIP for identification of differentially expressed genes. PEN tissue microarrays were constructed from 53 archival PENs for immunohistochemical validation of microarray data. Sixty-six transcripts were overexpressed > or =3-fold in PENs compared with normal islet cells, including putative oncogenes (MLLT10/AF10), growth factors [insulin-like growth factor-binding protein 3 (IGFBP3)], cell adhesion and migration molecules (fibronectin), and endothelial elements (MUC18/MelCAM and CD31). A total of 119 transcripts were underexpressed < or =3-fold in PENs compared with normal islet cells, including cell cycle checkpoint proteins (p21/Cip1), the MIC2 (CD99) cell surface glycoprotein, putative metastasis suppressor genes (NME3), and junD, a MEN1-regulated transcription factor. Using PEN tissue microarrays, we confirmed the differential up-regulation of IGFBP3 (70%) and fibronectin (22%) and differential down-regulation of p21 (46%) and MIC2 (CD99; 91%) in PENs versus normal pancreatic islets. IGFBP3 overexpression was significantly more common in metastatic (93%) versus primary PEN lesions (60%), P=0.022. Fibronectin overexpression demonstrated a trend toward significance in lymphatic PEN metastases (55%) compared with primary PEN lesions (24%; P=0.14). Global expression analysis provides insight into tumorigenic pathways in PENs and may identify potential prognostic and therapeutic markers for these uncommon neoplasms. Show less