Palmitic acid (PA) is a 16-carbon long-chain saturated fatty acid (SFA) in the human body and a major component of dietary SFAs. PA plays a significant regulatory role in the pathogenesis and progression of various diseases, particularly cardiovascular diseases (CVD). The human body acquires PA through endogenous de novo synthesis and exogenous dietary intake, and its concentration in plasma is relatively stable; however, the concentration of PA can increase several-fold in the plasma of patients with CVD. This review focuses on the biosynthetic pathways of PA and its mechanistic involvement in atherosclerosis (AS), ischemic heart disease (IHD), and ischemic stroke (IS). Elucidating the mechanistic contributions of PA to these disease processes may provide critical insights for developing novel targeted therapies.

Cryptococcus neoformans (C. neoformans) is a pathogenic fungus that can cause life-threatening meningitis, particularly in individuals with compromised immune systems. The current standard treatment involves the combination of amphotericin B and azole drugs, but this regimen often leads to inevitable toxicity in patients. Therefore, there is an urgent need to develop new antifungal drugs with improved safety profiles. We screened antimicrobial peptides from the hemolymph transcriptome of Blaps rhynchopetera (B. rhynchopetera), a folk Chinese medicine. We found an antimicrobial peptide named blap-6 that exhibited potent activity against bacteria and fungi. Blap-6 is composed of 17 amino acids (KRCRFRIYRWGFPRRRF), and it has excellent antifungal activity against C. neoformans, with a minimum inhibitory concentration (MIC) of 0.81 μM. Blap-6 exhibits strong antifungal kinetic characteristics. Mechanistic studies revealed that blap-6 exerts its antifungal activity by penetrating and disrupting the integrity of the fungal cell membrane. In addition to its direct antifungal effect, blap-6 showed strong biofilm inhibition and scavenging activity. Notably, the peptide exhibited low hemolytic and cytotoxicity to human cells and may be a potential candidate antimicrobial drug for fungal infection caused by C. neoformans.

The development of effective anticoagulants remains a critical need in modern medicine, particularly for preventing and treating thromboembolic disorders, such as arterial thrombosis and deep vein thrombosis (DVT), as well as complications like ischemic stroke. This study identifies a cysteine-knotted peptide GC38 (sequence: GCSGKGARCAPSKCCSGLSCGRHGGNMYKSCEWNWKTG) derived from the venom gland transcriptome of the Macrothele sp. spider, which exerts thrombus-inhibitory effects by potentiating activated protein C (APC) activity. In vitro assays reveal that GC38 enhances APC activity, prolongs plasma clotting time, and shows no significant cytotoxicity or hemolytic activity. Mechanistically, GC38 interacts allosterically with APC; biolayer interferometry (BLI) confirms this direct interaction, with a dissociation constant K_D of 6.16 μM. Additionally, three in vivo thrombosis models (FeCl₃-induced arterial occlusion, stasis-induced DVT, and cortical photothrombotic stroke) consistently demonstrated that GC38 was effective in alleviating thrombus formation, with tail-bleeding assays confirming its low hemorrhagic risk. Collectively, our findings position GC38 as a pioneering spider venom-derived lead molecule that addresses dual arterial and venous antithrombotic actions. This opens new avenues for developing spider venom-derived peptides as therapeutic agents targeting intravascular coagulation in arteries and veins.

For many years, excessive intake of SFAs has been recognized as a principal cause of cardiovascular disease (CVD). Despite the prevalence of guidelines recommending the restriction of SFAs intake, particularly among patients with atherosclerotic cardiovascular disease and dyslipidemia, some researchers have pointed out a new connection between SFAs intake and cardiovascular health. This review explores the sources of SFAs in humans and the controversy surrounding the link between different chain lengths of SFAs and CVD risk by analyzing the available evidence, focusing on the effects of SFAs carbon chain heterogeneity. Based on the latest mechanistic studies and epidemiological data, it offers evidence-informed recommendations for clinical practice and dietary guideline amendments. In the authors’ view, the cardiovascular effects of SFAs depend not only on chain length but also on the food matrix in which they are consumed and the nutrients they displace.