Search Results (212)

Polycystic ovary syndrome (PCOS) is frequently accompanied by visceral obesity, insulin resistance, low-grade chronic inflammation, and metabolic syndrome (MetS). These alterations promote significant dysfunction in adipose tissue and liver metabolism through cytokine production. Growing evidence indicates that the interaction between hepatokines and adipokines plays a central role in the development of metabolic and hepatic abnormalities in women with PCOS. This narrative review was conducted to analyze the relationship between adipose tissue dysfunction and liver metabolic impairment in women with PCOS, emphasizing the involvement of hepatokines and adipokines in insulin resistance, inflammation, hepatic steatosis, hepatic fibrosis and MetS. From this perspective, contemporary clinical, biochemical, and molecular studies were reviewed to evaluate how adipocyte-derived factors and hepatocyte-derived cytokines influence metabolic homeostasis in the liver and adipose tissue in women with PCOS. Increased visceral adiposity in PCOS enhances the release of free fatty acids (FFAs) to the liver, resulting in hepatotoxicity, oxidative stress, and hepatic inflammation. Several hepatokines, including fetuin-A, angiopoietin-like protein 3 (ANGPTL3), selenoprotein P(Sep-P), and hepassocin (HPS), show abnormal circulating levels in PCOS and are strongly associated with insulin resistance, dyslipidemia, and progression to hepatic steatosis. In contrast, fibroblast growth factor 21 (FGF-21), follistatin, and interleukin (IL-6) may exert dual effects. Adipokines, such as resistin, visfatin, apelin, and retinol-binding protein 4 (RBP-4), contribute to chronic inflammation, impaired glucose metabolism, androgen excess, and hepatic steatosis and fibrosis. Some of these adipokines, such as leptin and vaspin, may exert both beneficial and detrimental effects, while others, including chemerin and omentin, appear to play predominantly beneficial roles in metabolism. Reduced adiponectin-to-leptin levels further aggravate metabolic dysfunction. These changes indicate that adipose tissue–liver crosstalk is a key mechanism linking PCOS and MetS. Overall, metabolic disturbances in PCOS are strongly mediated by dysregulated communication between adipose tissue and the liver. Altered hepatokine and adipokine profiles contribute to insulin resistance, liver dysfunction, hypertension and the development of MetS in women with PCOS. Understanding these intricate interactions may support the early identification of high-risk patients and the development of targeted therapeutic strategies. Full article

Cancer remains a major global health challenge, with persistent limitations in early diagnosis, metastatic disease control, and the achievement of durable therapeutic responses with acceptable toxicity. These challenges highlight the need for more precise biomarkers and more effective therapeutic strategies. Increasing evidence implicates dysregulated lipid metabolism as a central contributor to tumor development and progression. In recent years, proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein 3 (ANGPTL3), and cholesteryl ester transfer protein (CETP) have gained particular attention due to their roles in cholesterol homeostasis, oncogenic signaling, and immune modulation within the tumor microenvironment (TME). This narrative review evaluates the potential of these lipid-regulatory mediators as diagnostic biomarkers and therapeutic targets in oncology. The majority of available evidence derives from preclinical and epidemiological studies, with PCSK9 representing the most extensively investigated target. Findings are sometimes contradictory and strongly influenced by tumor type, disease stage, and biological context, which currently precludes the clinical applicability of these molecules as reliable biomarkers. Similar limitations apply to their translational potential as actionable therapeutic targets. Nevertheless, emerging preclinical evidence suggests that modulation of these glycoproteins may enhance the efficacy of chemotherapy, targeted therapies, and immunotherapy, including nanomedicine-based approaches. Of note, clinical research investigating the role of PCSK9 inhibition in oncology is currently ongoing, whereas comparable studies focusing on ANGPTL3 and CETP remain scarce. Overall, further mechanistic, translational, and prospective clinical investigations are warranted to elucidate the involvement of these lipid-regulatory proteins in cancer biology and to define their potential integration into future oncologic diagnostic and therapeutic strategies. Full article

Residual cardiovascular risk arises from dysregulated expression of genes encoding apolipoprotein(a) (LPA), apolipoprotein C-III (APOC3), angiopoietin-like gene 3 (ANGPTL3), and proprotein convertase subtilisin/kexin type 9 (PCSK9). RNA-based therapies, small interfering RNAs (siRNAs), and antisense oligonucleotides (ASOs) modulate these targets at the post-transcriptional level through RNA interference and RNase H-mediated degradation, respectively. This scoping review maps the molecular mechanisms, target involvement, and pharmacodynamic outcomes of RNA therapies for managing residual cardiovascular risk, with contextual comparison to traditional lipid-lowering agents. A systematic search of PubMed, Embase, Web of Science, and Scopus was performed from 2020 to February 2026. Of the 1088 records identified, 30 studies met the inclusion criteria. RNA therapies have demonstrated potential for engagement, with 80–98% reductions in Lp(a) (pelacarsen, olpasiran, zerlasiran, lepodisiran), 50–80% reductions in triglycerides (olezarsen, plozasiran, volanesorsen), and 36–44% reductions in low-density lipoprotein cholesterol (LDL-C). Mechanistically, siRNAs achieve gene silencing through RISC-mediated mRNA cleavage, with sustained pharmacodynamic effects (3–6 months) because of Argonaute-2 stability, while gapmer ASOs recruit RNase H1 for mRNA degradation. Conjugation with GalNAc allows for hepatocyte-specific delivery with a subcutaneous bioavailability of 70–85%. Safety profiles were favorable, with injection site reactions (4–12%) being the most common adverse event. This analysis maps the emerging molecular landscape of RNA therapies, highlighting their substantial precision for targeting residual cardiovascular risk pathways that cannot be addressed by traditional agents. Full article

Breast cancer remains the most frequently diagnosed malignancy among women worldwide, while metabolic dysfunction-associated steatotic liver disease (MASLD) represents the leading cause of chronic liver disease, reflecting a global burden of metabolic dysfunction. Increasing evidence suggests that MASLD is associated with breast cancer development and progression; however, whether this relationship reflects an independent effect of hepatic metabolic dysfunction or the broader metabolic environment remains uncertain. This review synthesizes current epidemiological, clinical, and mechanistic data linking hepatic metabolic dysfunction to breast carcinogenesis. Population-based studies consistently demonstrate an association between hepatic steatosis and increased breast cancer incidence, particularly in postmenopausal and metabolically vulnerable populations, as well as poorer oncological outcomes. Mechanistically, MASLD promotes a systemic pro-tumorigenic environment through interconnected pathways, including insulin resistance, hormonal dysregulation with increased estrogen bioavailability, chronic inflammation, oxidative stress, lipid metabolic reprogramming, and gut–liver axis disruption. Hepatokines, particularly fibroblast growth factor 21 (FGF21), emerge as key mediators of tumor progression and potential biomarkers of metabolic vulnerability, while Fetuin-A and angiopoietin-like protein 8 (ANGPTL8) further support the liver’s endocrine role in oncogenic signaling. Preclinical evidence highlights fatty acid oxidation as a metabolic dependency in aggressive breast cancer subtypes, suggesting novel therapeutic targets. Despite consistent associations, causality remains unproven. Future prospective studies are needed to determine whether targeting metabolic dysfunction can improve breast cancer prevention and outcomes. Full article

In this paper, we review the literature regarding metformin’s action on blood lipid concentrations in metformin-treated diabetic patients. Published data indicate that metformin reduces serum total cholesterol (T-C), LDL-cholesterol (LDL-C) and triacylglycerol (TAG) concentrations and raises serum HDL-cholesterol (HDL-C) concentrations in diabetic patients. The beneficial effect of metformin on serum lipid profiles in diabetic patients can result from (a) its action on AMP-activated protein kinase, which inhibits lipogenesis and cholesterol synthesis and stimulates fatty acid oxidation; (b) decreased plasma TAG concentrations, via promoting VLDL-TAG clearance by brown adipose tissue; (c) the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression, affecting lipid profile in diabetic patients; (d) the inhibition of the expression of genes encoding proprotein convertase subtilisin/kexin 9 (PCSK9) and lipogenic enzymes; (e) the downregulation of carbohydrate-response element-binding protein (ChREBP), which affects liver TAG and cholesterol synthesis from acetate formed by gut microbiota; (f) the inhibition of angiopoietin-like 3 protein (ANGPTL3) gene expression, and consequent effects on plasma TAG concentrations; (g) the activation of AMPK, which inhibits LXRα activity; and (h) reverse cholesterol transport. In conclusion, one can assume that beyond its primary antihyperglycemic effect, metformin exerts pleiotropic effects that modulate lipid metabolism and blood lipid profile in T2D patients. These beneficial effects of metformin on blood lipid profile may play a role in the reduction in cardiovascular risk in diabetic patients. Full article

Silver Pomfret is increasingly threatened by many diseases under intensive artificial culturing conditions, yet conserved host biomarkers across different infections remain poorly defined. In this study, we integrated transcriptomic datasets from independent infections with Cryptocaryon irritans, Nocardia seriolae, and Photobacterium damselae subsp. damselae to identify shared host-response genes. By combining differential expression analysis with weighted gene co-expression network analysis, we prioritized six candidate genes associated with cross-pathogen infection responses. Random Forest and support vector machine analysis further supported their classification potential across the three infection models. Phylogenetic and structural analyses provided additional evidence for the conserved annotation of these proteins. GSVA-based signature analysis supported the cross-pathogen discriminatory capacity of the six-gene panel and suggested context-dependent contributions of individual genes across infection models. Immune signature analysis indicated distinct host immune response patterns under different pathogenic challenges, and candidate genes showed positive associations with inferred T cell-related signatures. Upstream regulatory prediction identified CTCF and the miR-17/20/93 family as potential regulators of these genes. Quantitative real-time PCR of the kidney further highlighted canx, rnd3, and angptl4 as the most robust infection-responsive candidates, with consistent temporal expression patterns observed from 0 to 24 h post-infection. These findings suggest a potential cross-pathogen host-response pattern in Silver Pomfret and provide preliminary support for future exploration of molecular markers for disease monitoring in aquaculture. Full article

Background/Objectives: Angiopoietin-like proteins 4 and 8 (ANGPTL4 and ANGPTL8) are key regulators of lipid metabolism and inflammatory processes, with a potential role in the pathogenesis of type 2 diabetes mellitus (T2DM) and its complications. This monocentric observational study evaluated serum levels of ANGPTL4 and ANGPTL8 in 160 participants (93 patients with T2DM and 67 controls without carbohydrate disturbances) and their associations with peripheral and cardiac autonomic neuropathy. Methods: This is a monocentric, cross-sectional, observational study conducted at the Endocrinology and Metabolic Disorders Clinic of Alexandrovska Hospital in Sofia, involving 160 participants and approved by the Ethics Committee of Medical University–Sofia, with all subjects providing written informed consent in accordance with the Declaration of Helsinki. The main methods included detailed clinical and anthropometric assessments, diagnosis of peripheral neuropathy via the Neuropathy Disability Score (NDS), evaluation of cardiac autonomic neuropathy using heart rate variability analysis and Ewing cardiovascular reflex tests, comprehensive laboratory investigations with fasting blood samples, measurement of serum ANGPTL4 and ANGPTL8 levels by ELISA kits, and statistical analysis performed with IBM SPSS version 25, using parametric and non-parametric tests, correlations, logistic regression, and ROC curves. Results: ANGPTL4 levels were significantly lower in patients with T2DM (12.6 ± 23.1 ng/mL vs. 21.5 ± 29.3 ng/mL; p = 0.033). In a multivariate model, higher values remained associated with lower odds of T2DM (OR per 1 SD = 0.634; p = 0.0424). ANGPTL8 demonstrated moderate discriminatory ability for cardiac autonomic neuropathy (AUC = 0.678; p = 0.007) in unadjusted analysis, but the association did not persist after covariate adjustment. ANGPTL4 showed inverse correlations with body weight, basal metabolic rate, and GGT. Conclusions: The results support the role of ANGPTL4 as a potential biomarker in metabolic disturbances and complications in T2DM, while ANGPTL8 remains mainly insignificant after correction for potential confounding factors. Full article

Acute mountain sickness (AMS) arises from hypobaric hypoxia at high altitude and still lacks effective pharmacological treatments. Although hypoxic preconditioning via gradual ascent prevents AMS, the underlying molecular adaptations have not yielded therapeutics. Here, inspired by metabolic reprogramming during stepwise altitude adaptation, we screened for anti-hypoxia compounds and identified H0802 (N-(pyridin-2-yl) pyridine-2-carbothioamide) as the most promising candidate. H0802 markedly enhances hypoxic tolerance in mice, prolongs survival under acute hypoxia, improves survival during simulated high-altitude exposure, and attenuates hypoxia-induced lung injury, accompanied by combined anti-inflammatory and antioxidant effects. Transcriptomic profiling shows that H0802 elicits a gene expression signature resembling hypoxia, including key hypoxia-related genes (Edn1, Angptl4, Mt1, Gdf15, Slc7a5, and Hif-3α) involved in glucose and oxygen metabolism. Mechanistically, H0802 stabilizes endogenous hypoxia-inducible factor (HIF) proteins under normoxia by preventing ubiquitin-dependent degradation, thereby activating hypoxia-responsive genes. In vivo, H0802 pretreatment lowers circulating glucose and hepatic glycogen while increasing brain glucose uptake, suggesting a metabolic shift that preserves cerebral energy during acute hypoxic stress; it also modulates whole-body oxygen consumption. H0802 represents a candidate for anti-AMS therapy, and phenotypic optimization of H0802 provides a potential route for drug discovery. Full article

Hypertriglyceridemia is a well-recognized contributor to residual atherosclerotic cardiovascular disease risk and a predisposing factor for acute pancreatitis. Despite the availability of pharmacologic agents and lifestyle interventions, patients with severe and refractory hypertriglyceridemia often fail to achieve adequate control. Recent advances in the molecular understanding of triglyceride metabolism have driven the development of targeted therapies that selectively modulate key regulatory pathways. This study sought to provide an overview of triglyceride regulation, the atherogenic role of remnant lipoproteins, and clinical evidence of emerging triglyceride-lowering therapies. Lipoprotein metabolism is regulated by a complex network of regulatory proteins that include lipoprotein lipase (LPL), apolipoproteins such as apolipoprotein C-III (ApoC-III), and angiopoietin-like proteins (ANGPTLs). Targeting these proteins in the metabolic cascade has shown promising results in reducing triglyceride levels. Emerging therapies such as antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) directed against ApoC-III (volanesorsen, olezarsen, and plozasiran), inhibitors of ANGPTL3 (evinacumab and zodasiran), and fibroblast growth factor 21 (FGF-21) analogs (pegozafermin) have demonstrated substantial triglyceride-lowering efficacy. These agents have achieved reductions in triglyceride levels of up to 80% in clinical trials. Additionally, preliminary evidence suggests that these agents may also reduce the incidence of acute pancreatitis and improve cardiometabolic risk profiles, although dedicated trials are still needed to confirm these outcomes. The therapeutic landscape for hypertriglyceridemia is rapidly evolving. Integrating these novel agents into clinical practice will require individualized treatment plans, sustained lifestyle modification, and careful safety monitoring. Full article

Background/Objectives: Prostate cancer (PCa) cells are known to heavily depend on lipids to support their growth. We hypothesized that hyperlipidemic factors, for which inhibitors are already available and used to treat cardiovascular disease, would be dysregulated in metastatic PCa (mPCa). The goal of this case-control study, including 35 men per group, was to compare the levels of PCSK9, ANGPTL3, Apo CIII, leptin, and the lipid profile in patients with mPCa versus localized Gleason 8/9 PCa (lPCa) and patients at risk of developing PCa (controls). Methods: Protein levels were assessed using ELISAs, while lipids were measured using the Roche Cobas analytical platform. Results: The following circulating analytes were higher in mPCa: triglycerides (in mmol/L; controls 1.7 ± 1.2, lPCa 1.5 ± 0.7, mPCa 2.3 ± 1.2, p = 0.0004), Apo CIII (in µg/mL; control 110.7 ± 55.7, lPCa 115.0 ± 57.64, mPCa 159.9 ± 96.7, p = 0.0179), ANGPTL3 (in ng/mL; controls 41.7 ± 20.0, lPCa 42.8 ± 24.1, mPCa 57.3 ± 26.9, p = 0.0390), and leptin (in ng/mL, controls 9.6 ± 9.1, lPCa 8.2 ± 7.9, mPCa 17.7 ± 17.8, p < 0.0001). Surprisingly, PCSK9 levels were negatively correlated with LDL in the entire cohort. Conclusions: In this cohort of men, whole-body lipid metabolic rewiring is a feature restricted to the metastatic phase of prostate cancer, suggesting it may play a significant role in the progression toward more aggressive cancer forms. Given the availability of drugs targeting ANGPTL3 and Apo CIII, the therapeutic potential of these drugs should be evaluated in metastatic PCa. Full article

Respiratory syncytial virus (RSV), a member of the genus Orthopneumovirus, is an etiological agent in infant lower respiratory tract infections (LRTIs) producing substantial global morbidity. Here, secretoglobin (Scgb1a1)-derived progenitors play a primary role in triggering innate, inflammatory, and cell state transitions in response to RSV LRTIs. Whether RSV activation of innate signaling in this epithelial sentinel population leads to chronic airway disease is unknown. To understand the role of innate signaling in Scgb1a1-derived progenitors, a model of RSV post-viral disease (PVLD) was developed and studied in the presence or absence of RelA conditional knockout (CKO). Single-cell RNA sequencing (scRNA-seq) studies showed that RSV-PVLD induced a transition of atypical, differentiation-intermediate, alveolar type 2 (aAT2) cells characterized by tumor protein 63 (TRP63), aquaporin 3 (AQP3), and Itgβ4 expression, as well as changes in PDGFRβ mesenchyme. A single-cell trajectory analysis and lineage-tracing experiments using Scgb1a1 CreER^TM X mTmG mice demonstrated that the Scgb1a1+ populations were precursors to the aAT2 population. Mechanistically, we found that the formation of the aAT2 population was prevented by RelA CKO. A differential gene expression analysis revealed that RSV-PVLD coordinately upregulates nuclear receptor subfamily 1 group D (Nr1d1/2), clock and basic helix-loop-helix ARNT-like 1 (Bmal) genes both in the aAT2 cell and in its Pdgfrα+ mesenchymal niche in a RelA-dependent manner. A systematic analysis of intercellular epithelial–mesenchymal communication in the scRNA-seq data showed that the clock-dysregulated epithelial–mesenchymal niche produces aberrant ANGPTL4 expression. ANGPTL4 upregulation was confirmed by the measurement of both its mRNA and protein. Moreover, ANGPTL4 is biologically active in the BALF of RSV-PVLD mice, inhibiting lipoprotein lipase activity. We conclude that RSV-PVLD is mediated, at least in part, by RelA signaling in Scgb1a1-derived epithelial progenitors, dysregulating ANGPTL4 signaling in an epithelial–mesenchymal niche, resulting in persistence of atypical alveolar epithelial cells with dysregulated of clock gene expression. Full article

Background/Objectives: Recent studies suggest that angiopoietin-like protein 2 (ANGPTL2) is one of the factors contributing to disease progression in distant organs associated with periodontitis. We previously reported that periodontitis promotes hepatocellular carcinoma and that ANGPTL2 may be involved in tumor progression. Based on these findings, we herein investigated the role of periodontitis-induced ANGPTL2 in the progression of colorectal cancer (CRC) in mice. Methods: Male C57BL/6 mice were divided into control and periodontitis groups. Colorectal tumors were induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). Periodontitis was induced by silk ligation. In addition, the model was enhanced by repeated gingival administration of lipopolysaccharide (LPS) derived from Porphyromonas gingivalis, a periodontal pathogen, to better mimic clinical conditions. Tumor development and ANGPTL2 expression in periodontal tissues, colorectal tumors, and serum were assessed by histology, immunostaining, and enzyme-linked immunosorbent assay. Results: Ligation and administration of P. gingivalis LPS resulted in significant alveolar bone resorption. The periodontitis group exhibited a significantly increased colorectal tumor burden compared with the control group. ANGPTL2 expression was markedly elevated in periodontal tissues, serum, and colorectal tumors in the periodontitis group. Histological analysis revealed increased tumor cell proliferation and enhanced inflammation in the periodontitis group relative to controls. These findings suggest a possible association between periodontitis-associated inflammation, elevated ANGPTL2 levels, and CRC progression in this experimental model. Conclusions: In this experimental model, experimental periodontitis was accompanied by concurrent increases in both local and systemic ANGPTL2 expression and accelerated growth of colorectal tumors. These findings suggest a potential association between periodontal inflammation, increased ANGPTL2 levels, and colorectal tumor progression. Full article

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and can lead to severe visual impairment. Based on disease severity, DR is classified into no clinically apparent diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Although nearly all retinal cell types are involved in DR progression, the dominant cell populations and their pathophysiological changes at each stage remain unclear. By integrating bulk and single-cell transcriptomic data from human and mouse retinas, this study revealed the following: (1) In the NDR stage, photoreceptors exhibit significant changes in ribosomal pathways. (2) In the NPDR stage, endothelial cells and pericytes show marked transcriptional alterations, accompanied by enhanced LAMININ signaling in cell-cell communication. (3) At the PDR stage, neural and glial cells are extensively involved in disease progression, with notable changes in ANGPTL signaling. Additionally, this study observed DR-specific subtypes of endothelial cells and pericytes and potentially identifies gene signatures in macroglia cells that correlate with disease duration. The altered expression of several key genes in early diabetic retina was confirmed by qPCR. These findings may offer a comprehensive view of the cellular and molecular landscape underlying DR and may suggest potential targets. Full article

Background: The body maintains homeostasis by inflammation, and arthritis is related to autoimmunity or inflammation. Angiogenesis contributes to synovitis through angiogenic factors and proteolytic enzymes, while different inflammatory arthritis conditions, such as osteoarthritis and rheumatoid arthritis, share similar cytokine networks and immune cell populations. Notably, progressive joint damage can occur despite effective systemic immunosuppression, suggesting that local stromal–immune interactions within the joint microenvironment may sustain inflammation and tissue destruction. Methods: We conducted an exploratory single-cell RNA-sequencing analysis using publicly available datasets from the NCBI GEO database, including synovial tissue and synovial fluid samples. Cell–cell communication and transcriptional regulatory networks were inferred using CellChat and SCENIC. Results: Computational analyses suggested that, in RA, macrophage-associated signaling shifts from TNF-related pathways toward SPP1-associated patterns, coinciding with transcriptional features of MMP3⁺ fibroblast-like synoviocytes (FLS). FLS–FLS interactions were associated with FGF-related signaling across disease contexts. ANGPTL-related signaling patterns differed among arthritis subtypes, with ANGPTL4 more prominent in OA and PsA and ANGPTL2 more frequently in RA-related transcriptional programs. Conclusions: These findings provide an exploratory framework for stromal–immune interactions and ANGPTL-associated signaling across inflammatory arthritis. The therapies for PsA may focus on systemic immune modulation and preservation of joint structural integrity. For OA and RA, the highlight may target ANGPTL4 and ANGPTL2 in the early and late stages of disease progression. Given the reliance on computational inference, the results warrant further experimental validation. Full article

Fetal growth restriction (FGR) is a major contributor to perinatal morbidity and mortality, most commonly arising from placental dysfunction, with increasing evidence implicating aberrant DNA methylation in its pathogenesis. To identify robust epigenetic alterations associated with FGR, we analyzed placental chorionic villi from an in-house early-onset FGR cohort and compared them with a publicly available dataset (GSE100197). DNA methylation profiling was performed using Illumina EPIC (in-house) and 450K (public) arrays, processed with identical normalization and quality-control pipelines, including adjustment for gestational age and estimation of placental cell-type composition. Differentially methylated positions (DMPs) were identified using linear regression models, revealing 10,427 DMPs in the in-house cohort and 7467 in the public dataset, with 108 shared DMPs showing consistent direction of change across both cohorts. Promoter-associated DMPs were mapped to genes involved in angiogenesis, morphogenesis, immune regulation, and transcriptional control, including EPHA1, ANGPTL6, ITGAX, BCL11B, and CYP19A1, while additional novel candidates such as SLC39A12, YEATS4, and MIR515 family members were also identified. Functional annotation suggests that these methylation changes may influence pathways essential for placental vascular development and structural organization. Overall, this cross-cohort comparison highlights reproducible epigenetic signatures of FGR and underscores the need for standardized approaches to clarify the molecular mechanisms underlying placental insufficiency. Full article