Integrated grade-wise profiling analysis reveals potential plasma miR-373-3p as prognostic indicator in Prostate Cancer & its target KPNA2.

Background: Plasma microRNAs (miRNAs) have recently garnered attention for their potential as stable biomarkers in the context of Prostate Cancer (PCa), demonstrating established associations with tumor grade, biochemical recurrence (BCR), and metastasis. This study seeks to assess the utility of plasma miRNAs as prognostic indicators for distinguishing between high-grade and low-grade PCa, and to explore their involvement in PCa pathogenesis. Methodology: We conducted miRNA profiling in both plasma and tissue specimens from patients with varying PCa grades. Subsequently, the identified miRNAs were validated in a substantial independent PCa cohort. Furthermore, we identified and confirmed the gene targets of these selected miRNAs through Western blot analysis. Results: In our plasma profiling investigation, we identified 98, 132, and 154 differentially expressed miRNAs (DEMs) in high-grade PCa vs. benign prostatic hyperplasia (BPH), low-grade PCa vs. BPH, and high-grade PCa vs. low-grade PCa, respectively. Our tissue profiling study revealed 111, 132, and 257 statistically significant DEMs for the same comparisons. Notably, miR-373-3p emerged as the sole consistently dysregulated miRNA in both plasma and tissue samples of PCa. This miRNA displayed significant overexpression in plasma and tissue samples, with fold changes of 3.584 ± 0.5638 and 8.796 ± 1.245, respectively. Furthermore, we observed a significant reduction in KPNA2 protein expression in PCa. Conclusion: Our findings lend support to the potential of plasma miR-373-3p as a valuable biomarker for predicting and diagnosing PCa. Additionally, this miRNA may contribute to the progression of PCa by inhibiting KPNA2 expression, shedding light on its role in the disease.

Prenatal arsenic exposure alters keratinocyte stem cell fate through persistent activation of IGF2R-MAPK cascade leading to aggravated skin carcinogenesis in mice offspring.

Chronic exposure to arsenic (As) promotes skin carcinogenesis in humans and potentially disturbs resident stem cell dynamics, particularly during maternal and early life exposure. In the present study, we demonstrate how only prenatal arsenic exposure disturbs keratinocyte stem cell (KSC) conditioning using a BALB/c mice model. Prenatal As exposure alters the normal stemness (CD34, KRT5), differentiation (Involucrin), and proliferation (PCNA) program in skin of offspring with progression of age as observed at 2, 10, and 18 weeks. Primary KSCs isolated from exposed animal at Day-2 showed increased survival (Bax:Bcl-xL, TUNEL assay), proliferation (BrdU), and differentiation (KRT5, Involucrin) potential through the activation of pro-carcinogenic IGF2R-MAPK cascade (IGF2R-G(α)q-MEK1-ERK1/2). This was associated with reduced enrichment of histone H3K27me3 and its methylase, EZH2 along with increased binding of demethylase, KDM6A at Igf2r promoter. Altered KSCs conditioning through disturbed Igf2r imprint contributed to impaired proliferation and differentiation and an aggravated tumor response in offspring.

Inhibition of autocrine HGF maturation overcomes cetuximab resistance in colorectal cancer.

Although amplifications and mutations in receptor tyrosine kinases (RTKs) act as bona fide oncogenes, in most cancers, RTKs maintain moderate expression and remain wild-type. Consequently, cognate ligands control many facets of tumorigenesis, including resistance to anti-RTK therapies. Herein, we show that the ligands for the RTKs MET and RON, HGF and HGFL, respectively, are synthesized as inactive precursors that are activated by cellular proteases. Our newly generated HGF/HGFL protease inhibitors could overcome both de novo and acquired cetuximab resistance in colorectal cancer (CRC). Conversely, HGF overexpression was necessary and sufficient to induce cetuximab resistance and loss of polarity. Moreover, HGF-induced cetuximab resistance could be overcome by the downstream MET inhibitor, crizotinib, and upstream protease inhibitors. Additionally, HAI-1, an endogenous inhibitor of HGF proteases, (i) was downregulated in CRC, (ii) exhibited increased genomic methylation that correlated with poor prognosis, (iii) HAI-1 expression correlated with cetuximab response in a panel of cancer cell lines, and (iv) exogenous addition of recombinant HAI-1 overcame cetuximab resistance in CC-HGF cells. Thus, we describe a targetable, autocrine HAI-1/Protease/HGF/MET axis in cetuximab resistance in CRC.

Emerging role of miRNA in prostate cancer: A future era of diagnostic and therapeutics.

Prostate cancer (PCa) is the most common cancer in men (20%) and is responsible for 6.8% (1/5) of all cancer-related deaths in men around the world. The development and spread of prostate cancer are driven by a wide variety of genomic changes and extensive epigenetic events. Because of this, the MicroRNA (miRNA) and associated molecular mechanisms involved in PCa genesis and aggressive were only partially identified until today. The miRNAs are a newly discovered category of regulatorsthat have recently been recognized to have a significant role in regulating numerous elements of cancer mechanisms, such as proliferation, differentiation, metabolism, and apoptosis. The miRNAs are a type of small (22-24 nucleotides), non-coding, endogenous, single-stranded RNA and work as potent gene regulators. Various types of cancer, including PCa, have found evidence that miRNA genes, which are often located in cancer-related genetic regions or fragile locations, have a role in the primary steps of tumorigenesis, either as oncogenes or tumorsuppressors. To explain the link between miRNAs and their function in the initiation and advancement of PCa, we conducted a preliminary assessment. The purpose of this research was to enhance our understanding of the connection between miRNA expression profiles and PCa by elucidating the fundamental processes of miRNA expression and the target genes.

Fabrication, characterization and in vivo assessment of cardiogel loaded chitosan patch for myocardial regeneration.

Cell therapy is one of the promising approaches for cardiac repair, subsequently after infarction or injury. However, contemporary mesenchymal stromal/stem cell (MSCs) delivery strategies result in low retention and poor engraftment of donor cells, thus limiting the therapeutic efficacy. Here, we developed an engineered biomimetic cardiogel patch (EBCP) comprising of the native decellularized cardiac extracellular matrix (ECM) "cardiogel" and chitosan, leading to the efficient regeneration of injured myocardium. We also developed novel bio-adhesive that is capable of suture-free epicardial placement of EBCP to injured myocardium. We have illustrated the potential of the mussels-inspired bioadhesive system, which comprises gelatin catechol and partially oxidized chitosan, which relies on self-crosslinking capability, to promote wet adhesion. In vitro studies with isolated cardiogel promoted cell proliferation, adhesion, and migration while aiding cardiomyogenic differentiation. The EBCP's ability to protect cells from abrasion due to surrounding tissues in the myocardial infarction (MI) rat model makes it more desirable. Furthermore, the epicardial implantation of the EBCP loaded with MSCs improves the initial retention of cells and subsequent functional cardiac recovery with enhanced myocardial tissue restoration. Histological examination showed the presence of EBCP and infiltration of cells to the infarcted heart tissue. The fast and facile synthesis of bioadhesive and major therapeutic benefits of EBCP make it a potential candidate for recuperating the ailing heart.

Fluid shear stress in a logarithmic microfluidic device enhances cancer cell stemness marker expression.

Fluid shear stress (FSS) is crucial in cancer cell survival and tumor development. Noteworthily, cancer cells are exposed to several degrees of FSS in the tumor microenvironment and during metastasis. Consequently, the stemness marker expression in cancer cells changes with the FSS signal, although it is unclear how it varies with different magnitudes and during metastasis. The current work explores the stemness and drug resistance characteristics of the cervical cancer cell line HeLa in a microfluidic device with a wide range of physiological FSS. Hence, the microfluidic device was designed to achieve a logarithmic flow distribution in four culture chambers, realizing four orders of biological shear stress on a single chip. The cell cycle analysis demonstrated altered cell proliferation and mitotic arrest after FSS treatment. In addition, EdU staining revealed increased cell proliferation with medium to low FSS, whereas high shear had a suppressing effect. FSS increased competence to withstand higher intracellular ROS and mitochondrial membrane potential in HeLa. Furthermore, stemness-related gene (Sox2, N-cadherin) and cell surface marker (CD44, CD33, CD117) expressions were enhanced by FSS mechanotransduction in a magnitude-dependent manner. In summary, these stemness-like properties were concurrent with the drug resistance capability of HeLa towards doxorubicin. Overall, our microfluidic device elucidates cancer cell survival and drug resistance mechanisms during metastasis and in cancer relapse patients.

Prenatal exposure to arsenic promotes sterile inflammation through the Polycomb repressive element EZH2 and accelerates skin tumorigenesis in mouse.

Prenatal and postnatal life stress could be a potent programmer of phenotype or disease state of an individual in the later life. Prenatal arsenic exposure has been shown to promote developmental defects, low birth weight, immunotoxicity and is associated with various cancers including skin cancer in adulthood. To investigate the association between prenatal arsenic exposure and adult life skin carcinogenesis, we used a two-stage cutaneous carcinogenesis model in which BALB/c mice were prenatally exposed to 0.04 mg/kg and 0.4 mg/kg arsenic (As). Exposure to arsenic was sufficient to shorten the tumor latency period and promote epidermal hyperplasia in the offspring upon challenge with dimethylbenz[a]/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA). The levels of inflammatory and tissue microenvironment remodeling factors such as IL-1α and TNF-α were persistently elevated in the skin, and their inhibition through diacerein led to a significant decrease in the tumor response, suggesting their role in tumorigenesis. While there was overexpression of multiple epigenetic regulators at tissue level, we found decreased enrichment of Polycomb repressive complex 2 (PRC2) member EZH2 and H3K27me3 mark at the upstream of the affected inflammatory genes. The higher expression of the inflammatory genes suggests the gene specific selective nature of EZH2 repression which was also associated with increased binding of the activator KDM6a (demethylase). Further, arsenic conditioned basal keratinocytes cells (BKCs) showed increased migration and proliferation along with higher expression of tumor associated cytokines. Inhibition of EZH2 in the BKCs lead to their further upregulation suggesting that BKCs might be the potential cell type for the interaction of EZH2 and inflammatory cytokines. The present study provides new evidence for the role of PRC2 group regulators in inflammatory conditioning and development of skin cancer in offspring prenatally exposed to arsenic.

Recent Advances in Cardiac Tissue Engineering for the Management of Myocardium Infarction.

Myocardium Infarction (MI) is one of the foremost cardiovascular diseases (CVDs) causing death worldwide, and its case numbers are expected to continuously increase in the coming years. Pharmacological interventions have not been at the forefront in ameliorating MI-related morbidity and mortality. Stem cell-based tissue engineering approaches have been extensively explored for their regenerative potential in the infarcted myocardium. Recent studies on microfluidic devices employing stem cells under laboratory set-up have revealed meticulous events pertaining to the pathophysiology of MI occurring at the infarcted site. This discovery also underpins the appropriate conditions in the niche for differentiating stem cells into mature cardiomyocyte-like cells and leads to engineering of the scaffold via mimicking of native cardiac physiological conditions. However, the mode of stem cell-loaded engineered scaffolds delivered to the site of infarction is still a challenging mission, and yet to be translated to the clinical setting. In this review, we have elucidated the various strategies developed using a hydrogel-based system both as encapsulated stem cells and as biocompatible patches loaded with cells and applied at the site of infarction.

Recent trends in biodegradable polyester nanomaterials for cancer therapy.

Biodegradable polyester nanomaterials-based drug delivery vehicles (DDVs) have been largely used in most of the cancer treatments due to its high biological performance and wider applications. In several previous studies, various biodegradable and biocompatible polyester backbones were used which are poly(lactic acid) (PLA), poly(ε-caprolactone) (PCL), poly(propylene fumarate) (PPF), poly(lactic-co-glycolic acid) (PLGA), poly(propylene carbonate) (PPC), polyhydroxyalkanoates (PHA), and poly(butylene succinate) (PBS). These polyesters were fabricated into therapeutic nanoparticles that carry drug molecules to the target site during the cancer disease treatment. In this review, we elaborately discussed the chemical synthesis of different synthetic polyesters and their use as nanodrug carriers (NCs) in cancer treatment. Further, we highlighted in brief the recent developments of metal-free semi-aromatic polyester nanomaterials along with its role as cancer drug delivery vehicles.

Injectable hydrogel for co-delivery of 5-azacytidine in zein protein nanoparticles with stem cells for cardiac function restoration.

Heart failure is major cause of mortality associated with mostly Myocardial infarction (MI). Transplanting mesenchymal stem cells (MSC) have exhibited potential role in myocardial regeneration. Secretion of immune-modulatory cytokines and various growth factors after transplantation plays significant role in remodelling process of MI region. However, low retention, higher shear stress during administration and rejection at host infarct environment hinders therapeutic efficacy. Myocardial regeneration demands for accurate spatio-temporal delivery of MSCs with supportive vascular network that leads to improvement of cardiac function. In this study, injectable alginate based microporous hydrogel has been used to deliver 5-Azacytidine (5-Aza) in zein protein nanoparticle with MSCs for attenuating adverse cardiac remodelling after MI. Zein nanoparticles loaded with 5-Aza were prepared by liquid-liquid dispersion, and it was found that 35% of drug was released in 7 days supported with mathematical modelling. The presence of 5-Aza and zein in developed hydrogel supported in vitro MSC proliferation, migration and angiogenesis. Significant increased expression of cardiac specific markers, GATA4, MEF2C, MLC, SERCA and NKX2.5 was observed in vitro. 5-Aza loaded protein nanoparticle with MSCs encapsulated hydrogels in rat MI model also exhibited substantial improvement of functional cardiac parameters such as cardiac output and ejection fraction. Histopathological analysis showed reduced fibrosis, attenuated infarct expansion and cardiac tissue restoration and angiogenesis. In brief, we developed nanocarrier-hydrogel system a promising strategy for co-delivering 5-Aza as cardiac differentiation cue with MSCs to achieve higher cell retention and enhanced improvement in myocardial regeneration after MI.

Functional impact of allelic variations/haplotypes of TNF-α on reproductive tract infections in Indian women.

The aim of the present study is to investigate the functional role of TNF-α single-nucleotide polymorphisms/haplotypes in an association with reproductive tract infections (RTIs) in symptomatic and asymptomatic women. A total of 850 consecutive subjects consisting of 400 cases and 450 healthy controls, were screened for RTIs, along with their risk factors and associated symptoms. The propensity score matching was performed to reduce the confounding bias arise owing to covariates and to balance the data between two groups. A total of 211 pairs (1:1) have been created. Genotyping of rs1800629 (-308) and rs361525 (-238) SNPs of TNF-α was done by PCR-RFLP followed by sequencing. The functional implication of TNF-α SNPs in an association with RTIs was also checked by using ELISA. The frequency of -238A allele and -308A allele was found to be twofold (P < 0.0001) and threefold (P < 0.0001) higher in the presence of RTIs. AA haplotype emerged as a major player in an association with RTIs and elevated TNF-α expression. The present study revealed the functional role of rs1800629 (-308) and rs361525 (-238) of TNF-α in an association with RTIs. This information may be used to establish biomarkers for an inflammatory response during the persistence of RTIs.

Meniscal tissue engineering via 3D printed PLA monolith with carbohydrate based self-healing interpenetrating network hydrogel.

Failure of bioengineered meniscus implant after transplantation is a major concern owing to mechanical failure, lack of chondrogenic capability and patient specific design. In this article, we have, for the first time, fabricated a 3D printed scaffold with carbohydrate based self-healing interpenetrating network (IPN) hydrogels-based monolith construct for load bearing meniscus tissue. 3D printed PLA scaffold was surface functionalized and embedded with self-healing IPN hydrogel for interfacial bonding further characterized by micro CT. Using collagen (C), alginate (A) and oxidized alginate (ADA), we developed self-healing IPN hydrogels with dual crosslinking (Ca2+ based ionic crosslinking and Schiff base (A-A, A-ADA)) capability and studied their physicochemical properties. Further, we studied human stem cells behaviour and chondrogenic differentiation potential within these IPN hydrogels. In-vivo heterotopic implantation confirmed biocompatibility of the monolith showing the feasibility of using carbohydrate based IPN hydrogel embedded in 3D printed scaffold for meniscal tissue development.

Association of abnormal cervical cytology with coinfection of human papillomavirus and Chlamydia trachomatis.

INTRODUCTION: Chlamydia trachomatis (CT) and human papillomavirus (HPV) are considered to be major sexually transmitted infections (STIs) and likely health hazard among women. In addition, HPV and CT are considered as potential cofactors in the development of cervical intraepithelial neoplasia (CIN). OBJECTIVES: The main objective of this study was to investigate the association of HPV and CT infection with the presence of abnormal cervical cytology. MATERIALS AND METHODS: A cross-sectional study was carried out on 90 women with complaints of vaginal discharge attending STI clinic in a tertiary care hospital in New Delhi. Papanicolaou staining and polymerase chain reaction were done for the detection of HPV and CT. Statistical analyses were performed for comparison. RESULTS: Abnormal cervical cytology was observed in 42.2% of the study participants (41.1% low-grade squamous intraepithelial neoplasia and 1.1% high-grade intraepithelial neoplasia). HPV and CT were positive in 21.1% and 31.5% of participants with abnormal cervical cytology, respectively. Coinfection with HPV and CT was observed in 84.2% of participants with cervical atypia. Further, genital herpes was diagnosed in 18.9% of the studied population and a significant association was observed between genital herpetic ulcers and abnormal cervical cytology (P = 0.016). CONCLUSION: CT was found to be a significant risk factor for cervical cytological abnormalities in our study. HPV and CT coinfection were also associated with a higher prevalence of cervical atypia. As chlamydial infection is easily treatable, we recommend screening and treatment of all women of the reproductive age group for Chlamydia to decrease the risk of cervical dysplasia. LIMITATION: This is a single-center STI clinic-based study. Multicenter and community-based studies with a larger cohort will confirm the association.

Four percent formalin application for the management of radiation proctitis in carcinoma cervix patients: An effective, safe, and economical practice.

CONTEXT: Radiotherapy is a very effective treatment modality for pelvic malignancies such as carcinoma of the cervix. However, it is quite common for chronic radiation proctitis (CRP) to manifest after radical radiotherapy. CRP is a source of significant morbidity, and there is a lack of effective treatment modalities. There also exists a general lack of guidelines on management of CRP. AIMS: To assess the benefit from 4% formalin application for the treatment of Grade >2 CRP among patients previously treated with radical radiotherapy for cervical carcinoma. SETTINGS AND DESIGN: This retrospective descriptive study involved 29 eligible patients who were treated from November 2010 - November 2015 for CRP with 4% formalin application. MATERIALS AND METHODS: Of the 1864 patients of carcinoma cervix treated during the said patients, 29 patients fulfilled the eligibility criteria. Eligible patients were invited telephonically for follow-up and were assessed for response and complications of the procedure. RESULTS: The treatment of hemorrhagic radiation proctitis with local formalin instillation is effective, well tolerated and safe procedure. The procedure is inexpensive, technically simple and can be done on an outpatient basis. 62% patients had complete freedom from rectal bleed, while 34.5% patients had partial benefit. Only one patient required diversion colostomy for persistent bleeding.

Apolipoprotein A-V gene therapy for disease prevention / treatment: a critical analysis.

Apolipoprotein (apo) A-V is a novel member of the class of exchangeable apo's involved in triacylglycerol (TG) homeostasis. Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein lipase-mediated TG hydrolysis, another portion is recovered intracellularly, in association with cytosolic lipid droplets. Loss of apoA-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease. Single nucleotide polymorphisms (SNP) in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions. Likewise, rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction. Genetically engineered mouse models and human population studies suggest that, in certain instances, supplementation with wild type (WT) apoA-V may have therapeutic benefit. It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance. On the other hand, subjects with hypertriglyceridemia of independent origin (unrelated to apoA-V function) may not respond to apoA-V augmentation in this manner. Improvement in the ability to identify individuals predicted to benefit, advances in gene transfer technology and the strong connection between HTG and heart disease, point to apoA-V supplementation as a viable disease prevention / therapeutic strategy. Candidates would include individuals that manifest chronic TG elevation, have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.

Aberrant hetero-disulfide bond formation by the hypertriglyceridemia-associated p.Gly185Cys APOA5 variant (rs2075291).

OBJECTIVE: Apolipoprotein A-V (apoA-V) is a low-abundance plasma protein that modulates triacylglycerol homeostasis. Gene transfer studies were undertaken in apoa5 (-/-) mice to define the mechanism underlying the correlation between the single-nucleotide polymorphism c.553G>T in APOA5 and hypertriglyceridemia. APPROACH AND RESULTS: Adeno-associated virus (AAV) 2/8-mediated gene transfer of wild-type apoA-V induced a dramatic lowering of plasma triacylglycerol in apoa5 (-/-) mice, whereas AAV2/8-Gly162Cys apoA-V (corresponding to the c.553G>T single-nucleotide polymorphism: rs2075291; p.Gly185Cys when numbering includes signal sequence) had a modest effect. Characterization studies revealed that plasma levels of wild-type and G162C apoA-V in transduced mice were similar and within the physiological range. Fractionation of plasma from mice transduced with AAV2/8-G162C apoA-V indicated that, unlike wild-type apoA-V, >50% of G162C apoA-V was recovered in the lipoprotein-free fraction. Nonreducing SDS-PAGE immunoblot analysis provided evidence that G162C apoA-V present in the lipoprotein-free fraction, but not that portion associated with lipoproteins, displayed altered electrophoretic mobility consistent with disulfide-linked heterodimer formation. Immunoprecipitation followed by liquid chromatography/mass spectrometry of human plasma from subjects homozygous for wild-type APOA5 and c.553G>T APOA5 revealed that G162C apoA-V forms adducts with extraneous plasma proteins including fibronectin, kininogen-1, and others. CONCLUSIONS: Substitution of Cys for Gly at position 162 of mature apoA-V introduces a free cysteine that forms disulfide bonds with plasma proteins such that its lipoprotein-binding and triacylglycerol-modulation functions are compromised.

A case of extensive chromoblastomycosis from North India

A case of extensive chromoblastomycosis of the right leg and thigh with verruciform to nodular lesions evolving rapidly over five years duration is reported. The diagnosis was confirmed by visualizing pathognomonic pigmented muriform bodies with unique septate hyphae and mycological culture yielding Fonsecaea pedrosoi.

Gene transfer of apolipoprotein A-V improves the hypertriglyceridemic phenotype of apoa5 (-/-) mice.

OBJECTIVE: Apolipoprotein (apo) A-V is a low abundance protein with a profound influence on plasma triacylglycerol levels. In human populations, single nucleotide polymorphisms and mutations in APOA5 positively correlate with hypertriglyceridemia. As an approach to preventing the deleterious effects of chronic hypertriglyceridemia, apoA-V gene therapy has been pursued. METHODS AND RESULTS: Recombinant adeno-associated virus (AAV) 2/8 harboring the coding sequence for human apoA-V or a control AAV2/8 was transduced into hypertriglyceridemic apoa5 (-/-) mice. After injection of 1×10(12) viral genome AAV2/8-apoA-V, maximal plasma levels of apoA-V protein were achieved at 3 to 4 weeks, after which the concentration slowly declined. Complementing the appearance of apoA-V was a decrease (50±6%) in plasma triacylglycerol content compared with apoa5 (-/-) mice treated with AAV2/8-ß-galactosidase. After 8 weeks the mice were euthanized and plasma lipoproteins separated. AAV2/8-apoA-V-transduced mice displayed a dramatic reduction in very low-density lipoprotein triacylglycerol content. Vector generated apoA-V in plasma associated with both very low-density lipoprotein and high-density lipoprotein fractions. CONCLUSIONS: Taken together, the data show that gene transfer of apoA-V improves the severe hypertriglyceridemia phenotype of apoa5 (-/-) mice. Given the prevalence of hypertriglyceridemia, apoA-V gene therapy offers a potential strategy for maintenance of plasma triacylglycerol homeostasis.

Influence of apolipoprotein A-V on the metabolic fate of triacylglycerol.

PURPOSE OF REVIEW: Apolipoprotein (apo) A-V functions to modulate intracellular and extracellular triacylglycerol metabolism. The present review addresses molecular mechanisms underlying these effects. The relevance of apoA-V to human disease conditions is illustrated by the strong correlation between single nucleotide polymorphisms in APOA5, elevated plasma triacylglycerol and dyslipidemic disease. RECENT FINDINGS: Despite undergoing processing for secretion from hepatocytes, a portion of apoA-V escapes this destiny and accumulates as a component of cytosolic lipid droplets. Expression of recombinant apoA-V in hepatocarcinoma cells results in increased lipid droplet size and number at the expense of triacylglycerol secretion.ApoA-V modulates atherosclerosis in hypercholesterolemic apoE null mice. ApoE null/human apoA-V transgenic mice had reduced levels of triacylglycerol and cholesterol in plasma along with decreased aortic lesion size. SUMMARY: ApoA-V modulates triacylglycerol metabolic fate. Following its synthesis, apoA-V enters the endoplasmic reticulum and associates with membrane defects created by triacylglycerol accumulation. Association of apoA-V with endoplasmic reticulum membrane defects promotes nascent lipid droplets budding toward the cytosol. Despite its low concentration in plasma (∼150 ng/ml), apoA-V modulates lipoprotein metabolism by binding to glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. This interaction effectively localizes triacylglycerol-rich lipoproteins in the vicinity of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein1's other ligand, lipoprotein lipase.