Search Results (90)

Background: Dietary protein optimization is an important nutritional strategy for improving growth and physiological responses, and antioxidant homeostasis in fish. Methods: In this study, 540 black carp (initial body weight: 10.50 ± 1.00 g) were randomly assigned into recirculating tanks (500 L) fed with six dietary protein levels (30–44% crude protein) for an 8-week feeding trial with triplicates per treatment and 30 fish per replicate. After the trial, fish body, blood, hepatopancreas, and intestinal samples were collected for body composition, serum biochemical parameters, metabolism, and antioxidant indices’ analyses. Results: Results showed fish fed 38% protein (PT38) exhibited the highest weight gain (p < 0.05), with no further improvement at higher protein levels. Compared with PT30 group, PT38 group significantly promoted protein deposition by upregulating transcript levels of insulin-like growth factors (IGFs) via activating mechanistic target of rapamycin (mTOR) signaling pathway. PT38 could improve fatty acid oxidation by heightening levels of carnitine palmitoyl transferase 1α (CPT1α), peroxisome proliferator-activated receptor α (PPARα) and PPARδ. Meanwhile, PT38-PT41 significantly inhibit expression of fatty acid synthesis and lipid droplet deposition-related genes, including acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and perilipin 2 (p < 0.05). PT38 significantly enhanced antioxidant homeostasis by increasing levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) via activating nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Conclusions: Overall, Under the current experimental conditions, 38% dietary protein is suitable for promoting growth performance, improving protein and lipid metabolism, and enhancing antioxidant homeostasis in black carp. Full article

The renin–angiotensin system (RAS) regulates inflammation, tissue homeostasis, and barrier integrity in lung and colon epithelial cells. Beyond classical pathways, non-canonical components including angiotensin-converting enzyme 2 (ACE2), epidermal growth factor receptor (EGFR), insulin-like growth factor 2 receptor (IGF2R) and aminopeptidase N (ANPEP) are implicated in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and bacterial sepsis due to their roles in tissue repair and signaling. Despite their similar inflammatory and coagulopathic features, their impact on RAS-associated non-immune gene expression in epithelial tissues remains unclear. This study investigates the regulation of these targets in lung (BEAS-2B) and colon (CRL-1831) cells following exposure to recombinant SARS-CoV-2 spike protein N-terminal domain fragment (S1-NTD) and Pseudomonas aeruginosa-derived lipopolysaccharide (LPS). Cells were treated with 100 ng/mL of S1-NTD or LPS for 12–72 h. Viability was assessed via XTT assays, and molecular changes were analyzed through qRT-PCR and Western blotting. Both stimuli induced a time and dose-dependent decrease in metabolic activity. ACE2 was significantly downregulated in lung cells, while transient upregulation occurred in colon cells at 24 h. EGFR expression increased in colon cells following LPS exposure but decreased in lung cells after S1-NTD treatment. Both IGF2R and ANPEP were upregulated by S1-NTD in lung cells at 72 h, whereas colon cells showed earlier upregulation at 24–48 h. Our findings reveal that viral and bacterial stimuli elicit distinct, tissue-specific regulatory patterns in RAS-associated pathways. These alterations may contribute to epithelial barrier dysfunction and inflammation, highlighting these proteins as potential targets for managing secondary bacterial infections and inflammatory lung–gut complications in COVID-19. Full article

An eight-week feeding trial was conducted to investigate methionine and lysine supplementation on the growth performance, body composition, antioxidant index and protein synthesis-related gene expression of the FFCR No. 2 strain common carp (Cyprinus carpio). The experiment included five groups: the CON group (basal diet), CM group (supplemented with 0.6% crystalline methionine), CML group (supplemented with 0.6% crystalline methionine and 0.3% crystalline lysine), HM group (supplemented with 0.6% coated methionine), and HML group (supplemented with 0.6% coated methionine and 0.3% coated lysine). The results showed that the WG (weight gain), SGR (specific growth rate) and CF (condition factor) of the HML group were significantly increased (p < 0.05), and the activities of amylase, lipase, and protease in the intestine of those belonging to the HML group were significantly higher than those in the CON group (p < 0.05). The whole-body crude lipid, SOD (superoxide dismutase), GOT (glutamic oxaloacetic transaminase) activity, and BUN (urea nitrogen) levels in serum were reduced significantly in the HM and HML groups than in the CON group (p < 0.05). Additionally, in the HML group the gene expression levels of IGF-1 (insulin-like growth factor-1), IGFBP (insulin-like growth factor binding protein), 4EBP1(recombinant eukaryotic translation initiation factor 4E binding protein 1), and S6K1 (ribosomal protein s6 kinase 1) in the muscle were significantly higher than those in the CON group. In summary, supplementing coated methionine and lysine improved amino acid utilization, enhanced growth performance, and upregulated the expression of genes associated with growth and protein synthesis. Full article

Insulin-like growth factor 2 (IGF2) plays a pivotal role in regulating growth and development; however, its functional involvement in skeletal muscle satellite cells (SMSCs) remains incompletely understood. To elucidate the regulatory role of IGF2, goose SMSCs were engineered to overexpress IGF2 via lentiviral transduction, followed by comprehensive transcriptomic profiling. Comparative analysis revealed 2802 differentially expressed genes (DEGs) in IGF2-overexpressing cells relative to controls, comprising 1202 upregulated and 1600 downregulated genes. IGF2 overexpression markedly activated fibrogenic programs, as evidenced by the upregulation of AP-1 complex components (FOS, JUN), extracellular matrix-related genes (COL1A1, COL5A3), and Wnt signaling receptors (FZD1, FZD7). In contrast, genes involved in myogenic differentiation and contractile function were broadly suppressed, including key myogenic transcription factors (MEF2C, MEF2D), sarcomeric structural proteins (MYBPC1, ACTN2, MYOM3), and metabolic enzymes. Through the construction of protein–protein interaction networks coupled with functional enrichment analysis, we observed a concerted suppression of myogenic regulatory networks critical for myofiber formation. Quantitative real-time PCR validation further confirmed the reliability of the transcriptomic data. Collectively, these findings suggest that overexpression of IGF2 induces a phenotypic shift from myoblasts toward a fibroblast-like state, uncoupling proliferation from differentiation while enhancing fibrogenic identity. This study provides novel insights into IGF2-mediated regulatory mechanisms underlying skeletal muscle development and fibrotic processes. Full article

This study investigated the physiological benefits of probiotic supplementation during refeeding after short-term fasting in Nile tilapia (Oreochromis niloticus). A total of 180 fish were assigned to three groups: continuously fed control or subjected to 5 days of fasting followed by 15 days of refeeding with either a basal or probiotic-enriched diet containing Bacillus subtilis, B. licheniformis, and B. pumilus. Growth performance indices (body weight, length, weight gain, specific growth rate, condition factor, relative feed intake, and feed conversion ratio) were measured. Muscle samples were collected for histomorphological evaluation and quantitative real-time PCR analysis of antioxidant genes catalase (cat) and superoxide dismutase 2 (sod-2), growth-related genes insulin-like growth factor 1 (igf-1) and suppressor of cytokine signaling 2 (soc-2), anti-inflammatory gene transforming growth factor beta (tgf-β), and myostatin genes. Fasting significantly reduced (p < 0.05) body weight compared to control, confirming the impact of nutrient deprivation. Upon refeeding, fish on the basal diet showed partial growth recovery but remained below control levels, whereas probiotic-fed fish exhibited superior recovery, surpassing both control and basal groups in body weight, length and weight gain. Condition factor exhibited insignificant changes among all groups after fasting and upon refeeding. Specific growth rate of the entire experiment was highest in the probiotic group, while insignificant. Relative feed intake decreased in both refed groups, yet feed conversion ratio improved, particularly with probiotics. Gene expression analysis revealed fasting-induced upregulation of antioxidant (cat and sod-2) and myostatin (p < 0.05), alongside downregulation of growth-related (igf-1 and soc-2) and anti-inflammatory (tgf-β) genes (p < 0.05). Basal refeeding restored most expressions, whereas probiotics enhanced antioxidant, growth, and anti-inflammatory genes while normalizing myostatin (p > 0.05 vs. control). Histological evaluation showed fasting-induced muscle atrophy, which was most effectively reversed by probiotics. Overall, probiotics accelerated recovery, highlighting their potential to optimize post-fasting growth in aquaculture. Full article

Goat reproductive performance is a key determinant of the productivity and economic value of goat farming, especially in meat and milk production. In a previous study, to investigate the genetic basis of prolificacy, we divided goats into groups according to their consistent reproductive performance (producing either single kids or twins) over five consecutive kidding cycles, and performed whole-genome resequencing and RNA-seq analysis on their ovarian tissues. Through integrated analysis, we identified three candidate genes—IGF2BP1 (insulin-like growth factor 2 mRNA-binding protein 1), CDC25A (cell division cycle 25A), and RXFP2 (relaxin family peptide receptor 2)—as potential key regulators of reproductive capacity. Using goat ovarian granulosa cells, we systematically assessed the impact of each gene through gain- and loss-of-function experiments. Overexpression of IGF2BP1 promoted cell proliferation and suppressed apoptosis, underscoring its role in maintaining cellular viability. Conversely, its knockdown significantly impeded growth and induced cell death. Similarly, CDC25A enhanced granulosa cell proliferation, whereas its knockdown led to marked growth impairment and increased apoptosis. Proliferation was also enhanced by RXFP2 overexpression but impaired upon its knockdown, suggesting that RXFP2 is functionally important for follicular development. Collectively, these findings establish IGF2BP1, CDC25A, and RXFP2 as fundamental regulators of granulosa cell dynamics and ovarian follicular development, providing crucial functional insights and promising targets for genetic selection to enhance reproductive efficiency in goats. Full article

Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is an RNA-binding protein known to play critical roles in metabolism, cell proliferation, and tumorigenesis. Although its involvement in muscle development has been documented in several species, the function of goose IGF2BP2 remains largely unexplored. In this study, we cloned and characterized the full-length cDNA and genomic DNA sequences of goose IGF2BP2. The cDNA is 2957 bp in length and contains a 1662 bp open reading frame encoding a 553-amino acid protein with five conserved RNA-binding domains. The genomic sequence spans 12,183 bp and consists of 12 exons and 11 introns. A total of 60 genetic variants were identified, including a deletion of a G base at position 2299 (g.2299delG) that results in a frameshift mutation. Expression analysis revealed high levels of IGF2BP2 mRNA in the liver, heart, and muscle tissues of female geese across embryonic (E25d), growing (A70d), and laying (L270d) stages, consistent with a potential role in muscle development (p < 0.05). Functionally, overexpression of IGF2BP2 in skeletal muscle satellite cells (SMSCs) was associated with significant changes in the expression of several genes linked to muscle development and signaling pathways, including upregulation of IGF1, EGFR, FGF19, BMP6, BMP2, ACVR1C and WNT5A and downregulation of MYBPC3, NODAL, HOXD13, TNXB, and ADD2 (Padj < 0.01). Furthermore, protein–protein interaction (PPI) network analysis of these genes suggests that IGF2BP2 may coordinate key genes, contributing to its potential role in skeletal muscle development in geese. Full article

Background: Type 2 diabetes mellitus (T2DM) is a rapidly expanding worldwide health issue associated with impairments in memory and executive functions. The bioactive sphingolipid sphingosine-1-phosphate (S1P) regulates cell death/survival and the inflammatory response by acting on S1P receptors (S1PRs). Unfortunately, the role of S1PRs signaling in the T2DM brain remains elusive. Methods: The effect of fingolimod (FTY720, S1PRs modulator) on the behavior and expression profile of genes encoding S1PRs, sphingosine kinases (SPHK1 and 2), glucose transporters, proteins engaged in insulin signaling, sirtuin 1 (SIRT1), and proinflammatory cytokines in the brain cortex and hippocampus of diabetic mice was examined. Results: We observed a significant reduction in S1pr1, Sirt1, and insulin-like growth factor-1 (Igf1) gene expression that was accompanied by elevation of Sphk2, S1pr3, Il6, and Tnf in T2DM mice. Moreover, animals showed anxiety-like behavior and memory deficits. Fingolimod administration recovered downregulated S1pr1, Sirt1, and Igf1 expression and upregulated Slc2a4 (GLUT-4) and Ide (insulin-degrading enzyme). Furthermore, FTY720 reduced the elevated expression of Il6 and Tnf. Fingolimod also exerted an anxiolytic effect in T2DM. Conclusions: Results indicate an important role of S1PR modulation in T2DM. Moreover, fingolimod affected mRNA levels of proteins engaged in glucose metabolism/insulin signaling and improved the behavior of diabetic mice. Full article

Background: Breast cancer, particularly the luminal subtype, often responds to endocrine therapies. However, 20–30% of patients develop resistance, resulting in more aggressive disease. Long non-coding RNAs (lncRNAs) are implicated in cancer progression and treatment resistance. Objective: This study aimed to evaluate the role of the lncRNA insulin-like growth factor 2 antisense (IGF2-AS) in tamoxifen-resistant breast cancer and assess its potential as a therapeutic target. Methods: Two tamoxifen-resistant breast cancer cell lines (TAMR-V and TAMR-H) were used to assess IGF2-AS expression via qPCR. Knockdown experiments with siRNA evaluated the role of IGF2-AS in cell proliferation, invasion, and migration. Next-generation sequencing (NGS) analyzed gene expression differences between the cell lines. Kaplan–Meier survival analysis determined the clinical significance of IGF2-AS expression in breast cancer patients. Results: IGF2-AS expression was significantly upregulated in TAMR-V and TAMR-H cell lines compared to control MCF-7 cells. Knockdown of IGF2-AS reduced cell proliferation and invasion in TAMR-V cells but did not significantly affect TAMR-H cells, indicating a cell line-specific role in tamoxifen resistance. NGS revealed differential gene expression profiles between TAMR-V and TAMR-H cells, suggesting variability in resistance mechanisms. Survival analysis demonstrated that higher IGF2-AS expression was associated with poorer prognosis in breast cancer patients, including those with hormone-positive and triple-negative subtypes. Conclusions: IGF2-AS is upregulated in tamoxifen-resistant breast cancer and promotes cell proliferation and invasion in a cell line-specific manner. Its differential expression in TAMR-V and TAMR-H cells highlights the complexity of resistance mechanisms, suggesting IGF2-AS as a potential therapeutic target for overcoming tamoxifen resistance. Full article

Background/Objectives: Ovarian cancer is frequently diagnosed at advanced stages, during which ascites serves as a microenvironment conducive to cancer recurrence. This study aimed to identify factors in ascites specimens that could be targeted for the detection and prevention of recurrence of the most common and lethal histology type, high-grade serous ovarian cancer (HGSOC). Methods: Ascites specimens were collected from patients with HGSOC who provided informed consent. RNA was isolated from ascites cells, sequenced, and compared between ascites cells in two initial and four recurrent HGSOC samples using DRAGENv.4.2.4 to identify differentially expressed genes. Immune cell populations were estimated from the differentially expressed genes using deconvolution analysis. ELISA and antibody isotyping were used to evaluate cell-free ascitic fluid (N = 24) and banked serum (N = 23) collected from independent groups of patients with HGSOC who provided informed consent. Results: Transcriptomics analysis identified reduced expression of immunoglobulin variable chains in the recurrent ascites group. The primary immunoglobulin present in all ascites specimens was IgG1, whereas IgG2 and IgG3 appeared to be present at higher levels in recurrent ascites. Deconvolution analysis estimated a more suppressive immune cell population profile in the recurrent samples. The immunosuppressor insulin-like growth factor 2 (IGF2) was the most differentially expressed gene, with higher expression in recurrent ascites than in initial ascites. Significantly higher levels of IGF2 protein were measured in recurrent cell-free ascites fluid than in initial cell-free ascites fluid. Conclusions: In conclusion, IGF2 and suppressive immune cell populations were identified as candidate drug targets for prevention of ovarian cancer recurrence. Full article

Fecal microbiota transplantation (FMT) promotes growth performance and intestinal development in yellow-feathered broilers, but whether the virome and metabolites contribute to its growth-promoting effect remains unclear. This study removed the microbiota from FMT filtrate using a 0.45 μm filter membrane, retaining the virome and metabolites to perform fecal virome transplantation (FVT), aiming to investigate its regulatory role in broiler growth. Healthy yellow-feathered broilers with high body weights (top 10% of the population) were used as FVT donors. Ninety-six 8-day-old healthy male yellow-feathered broilers (95.67 ± 3.31 g) served as FVT recipients. Recipient chickens were randomly assigned to a control group and an FVT group. The control group was gavaged with 0.5 mL of normal saline daily, while the FVT group was gavaged with 0.5 mL of FVT solution daily. Growth performance, immune and antioxidant capacity, intestinal development and related gene expression, and microbial diversity were measured. The results showed that FVT improved the feed utilization rate of broilers (the feed conversion ratio decreased by 3%; p < 0.05), significantly increased jejunal length (21%), villus height (69%), and crypt depth (84%) (p < 0.05), and regulated the jejunal barrier: insulin-like growth factor-1 (IGF-1) (2.5 times) and Mucin 2 (MUC2) (63 times) were significantly upregulated (p < 0.05). FVT increased the abundance of beneficial bacteria Lactobacillales. However, negative effects were also observed: Immunoglobulin A (IgA), Immunoglobulin G (IgG), Immunoglobulin M (IgM), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Interferon-gamma (IFN-γ) in broilers were significantly upregulated (p < 0.05), indicating immune system overactivation. Duodenal barrier-related genes Mucin 2 (MUC2), Occludin (OCLN), Claudin (CLDN1), and metabolism-related genes solute carrier family 5 member 1 (SLC5A1) and solute carrier family 7 member 9 (SLC7A9) were significantly downregulated (p < 0.05). The results of this trial demonstrate that, besides the microbiota, the gut virome and metabolites are also functional components contributing to the growth-promoting effect of FMT. The differential responses in the duodenum and jejunum reveal spatial heterogeneity and dual effects of FVT on the intestine. The negative effects limit the application of FMT/FVT. Identifying the primary functional components of FMT/FVT to develop safe and targeted microbial preparations is one potential solution. Full article

Genomic imprinting is critical for mammalian development, but its regulation varies across species. The insulin-like growth factor 2 receptor (IGF2R), which is a maternally expressed imprinted gene critical for cell proliferation and differentiation, as well as embryonic and placental development, is classically regulated by differentially methylated regions (DMRs) and lncRNA-Airn in mice. However, studies on this in equus are scarce, especially in terms of mechanistic studies. In the present study, heart, liver, spleen, lung, kidney, brain, and muscle samples were obtained from horses, donkeys, and hybrids, and gene expression and imprinting state were tested to investigate the imprinting regulation of Igf2r in these animals. Bisulfite sequencing combined with an allele-specific expression analysis revealed a tissue-specific loss of imprinting in the mule liver and hybrid brain tissues. Strikingly, we found that the maternal-specific expression of equine Igf2r did not rely on the canonical DMRs or lncRNA-Airn. Surprisingly, DNA methylation of a specific region called CpG island 2 (CpGI2) in the Igf2r promoter showed cis-acting inheritance, meaning that the DNA methylation patterns of the parental alleles are retained in hybrid tissues. Notably, the DNA methylation of CpGI2 correlated negatively with Igf2r expression in the spleen (R² = 0.8797, p = 6.46 × 10⁻⁶), lung (R² = 0.8569, p = 1.57 × 10⁻⁵), and kidney (R² = 0.8650, p = 3.85 × 10⁻⁶). Our findings suggest that imprinting may work differently in other species. This study provides a framework for understanding imprinting diversity in hybrids and shows that equine hybrids can be used to study how epigenetic inheritance works. Full article

This study was conducted to investigate the effects of replacing fish meal with either whole-fat or defatted krill powder on the growth, body color, immunity, and related gene expression of red–white koi carp. A total of 630 red–white koi carp with an initial body mass of 13.5 ± 0.05 g were randomly divided into seven groups with three replicates per group and 30 fish per replicate. The control group was fed a basic diet (C0). The other six diets were supplemented with different levels of whole krill meal or defatted krill meal as replacements (10% whole fat, 20% whole fat, 30% whole fat, 10% defatted, 20% defatted, and 30% defatted) in the experimental groups, named W10, W20, W30, D10, D20, and D30, respectively, for a total duration of 60 days. The growth, body color, immunity and gene expression indexes were measured in the koi after completion. The results indicate the following. (1) Compared with C0, the experimental groups of koi showed a significant increase in the specific growth rate (SGR) (p < 0.05), while the hepatosomatic index (HSI) and viscerosomatic ratio (VSI) decreased. Additionally, there was a significant increase in the relative expression level of insulin-like growth factor (IGF-1) in both the liver and muscle (p < 0.05). (2) The experimental groups of koi carp exhibited a significant increase in the carotenoid content in the scales and skin, as well as an elevated relative expression level of the tyrosinase (TYR) gene in the muscle (p < 0.05). (3) The lysozyme (LZM) and superoxide dismutase (SOD) activities were significantly increased in the experimental groups compared to C0 (p < 0.05). Additionally, the SOD activity was significantly higher in the defatted groups than in the whole-fat groups (p < 0.05). Furthermore, the liver alkaline phosphatase (AKP) activity was significantly lower in the D20 and D30 groups compared to the other five groups. (4) The expression level of LPL was significantly lower in the liver and muscle of the whole-fat group compared to the defatted group (p < 0.05). Tissue section observation revealed that the hepatocytes in the W20 and W30 groups exhibited a reduced size and an increased lipid droplet count, while the vacuolar degeneration of the hepatocytes increased in the D30 group. In conclusion, replacing fish meal with whole-fat or defatted krill powder or defatted Antarctic krill meal significantly improves the growth performance, body color, and immunity of red–white koi carp. However, excessive addition of krill meal can easily cause liver damage. The recommended replacement level for whole krill powder is 20% to 30%, while defatted krill powder should be replaced at a level of 10% to 20%. Full article

Background: Preeclampsia (PE) is a pregnancy-specific disorder and a leading cause of maternal and fetal morbidity and mortality. Impaired trophoblast invasion is a hallmark of PE, and alternative splicing (AS) is crucial for trophoblast differentiation and placental development. However, the exact mechanisms of AS in PE remain poorly understood. Methods: To elucidate AS-mediated regulatory pathways in PE, a total of 38 fresh-frozen placental samples, including 13 pre-eclampsia samples and 25 normal control samples, were collected from Renmin Hospital of Wuhan University between 1 February and 30 July 2022. We performed transcriptome sequencing of seven PE and seven normal placentas to identify differentially spliced events. After quality control and adapter trimming, raw sequencing reads were aligned to the human reference genome using STAR. Differential exon usage was analyzed using DEXSeq (version 1.36.0), and exons with an adjusted p-value < 0.05 and a fold change greater than 2 or less than 0.5 were considered significantly differentially spliced. Functional assays, including CCK8, colony formation, and cell cycle analyses, were conducted to assess trophoblast proliferation, whereas wound healing and Transwell assays were used to evaluate trophoblast migration and invasion using the HTR-8/SVneo cell line. RNA immunoprecipitation sequencing (RIP-seq) and RNA stability assays were employed to investigate mRNA interactions and stability. Results: Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) emerged as a key RNA-binding protein associated with alternative splicing regulation, intersecting both AS-related candidate genes and known splicing factors, although it is not a classical splicing factor itself. IGF2BP3 overexpression markedly enhanced HTR-8/SVneo trophoblast proliferation, migration, and invasion while suppressing ROS activation. RNA-seq, RIP-seq, and RNA stability assays revealed that IGF2BP3 directly interacts with and enhances the stability of PDE3A mRNA. Functional rescue experiments confirmed that PDE3A knockdown partially abrogated IGF2BP3-mediated trophoblast progression. Furthermore, miR-196a-5p was identified as a negative regulator of IGF2BP3 via miRNA inhibitor/mimic transfection, qRT-PCR, and functional assays, confirming that miR-196a-5p overexpression downregulates IGF2BP3, thereby impairing trophoblast migration and proliferation. Notably, restoring IGF2BP3 expression reversed these inhibitory effects. Conclusions: Our findings reveal a previously unrecognized regulatory axis in PE in which miR-196a-5p suppresses IGF2BP3 expression, leading to PDE3A mRNA destabilization and impaired trophoblast function. This study offers mechanistic insights into PE pathogenesis and identifies IGF2BP3 as a potential therapeutic target. Full article