Hui Luo

Caudatin ( 1 ) represents one of major C ₂₁ ‐steroids isolated from Cynanchum otophyllum . Thirty‐one novel caudatin derivatives with arylacryloyl ( 1a–1w ) and quinolyl ( 2a–2h ) substituents were synthesized and structurally characterized by spectroscopic analysis. Their anticancer activities were evaluated against four human cancer cell lines (MCF‐7, H1299, HeLa, and HepG2). Most compounds exhibit significant antiproliferative effects, among which 1b and 2h demonstrated broad‐spectrum activity with IC ₅₀ values of 8.54–12.12 and 11.43–14.25 uM, respectively. Further mechanistic studies showed that 1b induced marked apoptosis in HepG2 cells and modulated cell cycle distribution, with a higher percentage of cells accumulating in the G0/G1 phase at increased concentrations. Overall, these findings indicate that caudatin derivatives bearing arylacryloyl and quinolyl moieties constitute a preliminary chemical framework for the development of antitumor candidates for caudatin‐like natural products.

Postmenopausal osteoporosis is characterized by a disruptive bone‑fat imbalance, yet effective therapies remain limited. Here, for the first time, we link the traditional use of fish maw heat‑treated with clam shell powder (CPFM) to the restoration of bone‑fat balance. Using INFOGEST simulated digestion followed by LC‑MS/MS analysis, we found that CPFM peptides were predominantly low‑molecular‑weight species (84.6% below 1 kDa), with heptapeptides as the most abundant fraction (20%). In ovariectomized mice, CPFM peptides reduced bone marrow fat accumulation and improved bone microstructure (increased BV/TV and BMD). In bone marrow stromal cells (BMSCs), they concurrently inhibited adipogenic differentiation (reduced Oil Red O‑positive area) and promoted osteogenesis (enhanced ALP activity and mineralization). From CPFM digests, we systematically screened and identified an absorbable tetrapeptide, FLLL, based on its high relative abundance (37.8%), predicted bioactivity (PeptideRanker >0.5), cell‑penetrating ability (CPPpred >0.33), and favorable ADMET properties. In cultured BMSCs, FLLL recapitulated the dual effects of CPFM, promoting osteogenesis while suppressing adipogenesis. Mechanistically, both CPFM and FLLL downregulated adipogenic factors (PPARγ, FABP4, FASN) and upregulated osteogenic markers (RUNX2, COL1α2, BGLAP). Surface plasmon resonance confirmed direct binding of FLLL to RUNX2 (KD = 32.5 μM), and rescue experiments indicated that FLLL regulates the bone‑fat balance in association with the PPARγ/RUNX2 axis. Collectively, this study establishes a chain of evidence spanning peptide profiling, in vivo efficacy, active component identification, and mechanistic insight. These findings support CPFM as a promising dietary candidate and identify FLLL with well-defined in vitro bioactivity.

Phytochemical investigation on the stems of Nerium oleander led to the isolation of four previously undescribed polyene pregnane steroids, namely neristerone A‐D ( 1–4 ), together with six known analogues ( 5–10 ). Their structures were fully elucidated by extensive spectroscopic analysis (UV, IR, HR‐ESI‐MS, and NMR) and electronic circular dichroism (ECD) calculations. All isolates were evaluated for the inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)‐induced RAW264.7 macrophages. Notably, compounds 1 , 4 , and 10 exhibited significant inhibitory activity with IC ₅₀ values ranging from 11.27 ± 0.81 to 18.13 ± 1.25 µ mol/L, which were lower than that of the positive control dexamethasone (21.48 ± 0.83 µ mol/L). A preliminary structure–activity relationship analysis was also discussed. This study expands the chemical diversity of polyene pregnane steroids from N. oleander and provides new insights into their anti‑inflammatory potency.

Two previously undescribed highly oxygenated cembrane-type diterpenes, namely sarcocraol A (1) and sarcocraol B (2), along with five known compounds (3–7), have been isolated from the soft coral Sarcophyton crassocaule collected off Ximao Island in the South China Sea. Their structures were determined through comprehensive spectroscopic analysis, QM-NMR calculations, TDDFT-ECD computation, X-ray diffraction analysis, and by comparison with literature data. Plausible biosynthetic pathways for these compounds were also proposed. All compounds were evaluated for peroxisome proliferator-activated receptors (PPARs) transcriptional activity using luciferase assay. The bioassay results demonstrated that compound 1 exhibits selective PPAR-γ agonistic activity. Furthermore, it promoted glucose uptake in HepG2 cells by 1.18-, 1.45-, and 1.90-fold at concentrations of 2.5, 5, and 10 μM, respectively, whereas rosiglitazone (10 μM) produced a 2.47-fold increase over the induced control. Compound 1 at 10 μM induced mild lipid accumulation in 3T3-L1 cells, showing a 1.63-fold increase relative to the control, which was much lower than the 3.28-fold increase observed in rosiglitazone (10 μM) group indicating its potential antidiabetic properties. These findings suggested that compound 1 could be a promising lead for the development of antidiabetic agents.

Antimicrobial peptides (AMPs) come from various sources and exhibit unique antimicrobial properties. Their rapid action, effectiveness, and resistance to resistance development make them promising alternatives to combat antibiotic resistance. In addition to its excellent antibacterial properties, AMPs have superior immunomodulatory, antitumor, and antiviral activities. In recent years, the demand for AMPs has continued to increase in many fields, especially in the medical field, and the prospects are extensive. However, AMPs have the disadvantages of expensive development cost, higher hemolysis, short half-life, susceptibility to degradation by protein hydrolases, low bioavailability, toxic side effects, and other disadvantages, which seriously limit the wide application of AMPs. Therefore, fewer AMPs have been approved for marketing or are undergoing clinical trials. The review covers the period from 2001 to 2025 and provides a detailed discussion by searching databases such as Google Scholar and Web of Science. This paper reviews the progress of research on AMPs sources, structures, optimization strategies, biological activities, mechanisms of action, and applications. In general, the development approaches and the number of new AMPs have increased significantly. The improvement technologies for AMPs high hemolysis, poor stability, low bioavailability and high cost have increased significantly. The development cost of AMPs is still high, but many AMPs have been widely used in clinical, food, livestock, poultry, cosmetics and other fields. This article focuses on the commonly used optimization strategies and main activities of AMPs, aiming to effectively respond to challenges and provide a theoretical basis for expanding their application range.

A better understanding of the characteristic serum metabolites and microbiota from the gut and oral cavity in centenarians could contribute to elucidating the mutual connections among them and would help provide information to achieve healthy longevity. Here, we have recruited a total of 425 volunteers, including 145 centenarians in Suixi county — the first certified “International Longevity and Health Care Base” in China. An integrative analysis for the serum metabolites, gut, and oral microbiota of centenarians (aged 100–120) was compared with those of centenarians' lineal relatives (aged 24–86), the elderly (aged 65–88) and young (aged 23–54). Strikingly distinct metabolomic and microbiological profiles were observed within the centenarian signature, longevity family signature, and aging signature, underscoring the metabolic and microbiological diversity among centenarians and their lineal relatives. Within the centenarian between healthy and frail individuals, significant differences in metabolite profiles and microbiota compositions are observed, suggesting that healthy longevity is associated with unique metabolic and microbiota patterns. Through an integrative analysis, the tryptophan pathway has been revealed to be an important potential mechanism for individuals to achieve healthy longevity. Specifically, a key tryptophan metabolite, 5‐methoxyindoleacetic acid (5‐MIAA), was revealed to be associated with the genus Christensenellaceae R‐7 group, and it exhibited effects of delaying cell senescence, promoting lifespan, and alleviating inflammation. Our characterization of the extensive metabolomic and microbiota remodeling in centenarians may offer new scientific insights for achieving healthy longevity.

Invasive micropapillary carcinoma of the breast (IMPC) exhibits a unique micropapillary structure and “inside-out” growth pattern. Despite its extremely low incidence, IMPC has attracted considerable attention owing to its poor prognosis. Since Siriaunkgul and Tavassoli first proposed the term IMPC in 1993 to describe its morphological characteristics, with tumor cell clusters arranged in a pseudopapillary structure within the glandular cavity, its diagnostic rate has substantially increased. Based on the in-depth study of IMPC, a more comprehensive understanding of its epidemiology, clinicopathological features, and diagnostic criteria has been achieved in recent years. The pathogenesis and specific therapeutic targets of IMPC remain unclear. However, numerous studies have delved into its high-risk biological behavior. This review discusses the opportunities and challenges associated with IMPC.

The pursuit of extreme longevity is a popular topic. Advanced technologies such as metabolomics and proteomics have played a crucial role in unraveling complex molecular interactions and identifying novel longevity-related biomarkers in long-lived individuals. This review summarizes key longevity-related biomarkers identified through metabolomics, including high levels of omega-3 polyunsaturated fatty acids (PUFAs), short-chain fatty acids (SCFAs) and sphingolipids, as well as low levels of tryptophan. Proteomics analyses have highlighted longevity-related proteins such as apolipoprotein E (APOE) and pleiotrophin (PTN), along with lower S-nitrosylated and higher glycosylated proteins found from post-translational modification proteomics as potential biomarkers. We discuss the molecular mechanisms that could support the above biomarkers' potential for healthy longevity, including metabolic regulation, immune homeostasis maintenance, and resistance to cellular oxidative stress. Moreover, multi-omics studies of various long-lived cohorts are encompassed, focusing on how the integration of various omics technologies has contributed to the understanding of longevity. This comprehensive review aims to provide new biological insights and pave the way for promoting health span.