This study aimed to investigate the association between hepatic VNN1 expression and carcass traits in Mahuang chickens as well as to identify polymorphisms in the upstream and downstream regions of VNN1 that could potentially be associated with these carcass traits. The study revealed that VNN1 expression levels in liver correlated with various carcass traits such as dressed weight, eviscerated weight, and abdominal fat weight. A total of 39 polymorphic sites were identified, among which 23 were found to be associated with 15 different carcass traits. These polymorphic sites were organized into three distinct haplotype blocks, with BLOCK2 and BLOCK3 being associated with various eviscerated weight percentages, thigh weight, breast muscle weight, wing weight, and other traits. The study underscores the significant role of VNN1 in influencing the carcass traits of Mahuang chickens and sheds light on the genetic foundations of these traits. The findings provide valuable insights that could inform breeding strategies aimed at optimizing traits relevant to market demands and slaughtering efficiency.

Naringenin, a natural dihydrochalcone flavonoid, exhibits diverse pharmacological properties. This study investigates the hypolipidemic effects of Nar-NPs on obese mice. The characteristics of Nar-NPs, including morphology, particle size, zeta potential, UV-vis, and FT-IR spectra, were examined. The anti-obesity properties of Nar-NPs were evaluated in obese rats, considering LD50, 1/20 LD50, and 1/50 LD50 for treatment preparation. Results indicated that synthesized Nar-NPs were uniform, spherical, and well-dispersed, with a size of 130.06 ± 1.98 nm and with a zeta potential of -25.6 ± 0.8 mV. Nar-NPs exhibited enhancement in the cumulative release of naringenin (56.87 ± 2.45 %) as compared to pure naringenin suspension 87.83 ± 1.84 % in 24 h of the study. The LD50 of Nar-NPs was determined as 412.5 mg/kg.b.w. HFD induced elevated glycemic, oxidative stress, and inflammatory biomarkers while reducing HDL-C, GSH, and superoxide dismutase (SOD) levels. Administration of Nar-NPs significantly mitigated body weight, glucose, insulin, leptin, TC, TG, SREBP1c, pAMPK, PPAR-α, as well as vanin-1, MCP-1, and iNOS mRNA gene expression. Histological investigations supported the biochemical and PCR findings. In a nutshell, the study suggests that the Nar-NPs could serve as a promising and viable pharmacological strategy for the treatment of obesity-related disorders.

BACKGROUND: Energy-dissipating brown adipocytes have significant potential for improving systemic metabolism. Vanin-1, a membrane-bound pantetheinase, is involved in various biological processes in mice. However, its role in BAT mitochondrial function is still unclear. In this study, we aimed to elucidate the impact of Vanin-1 on BAT function and contribution during overnutrition-induced obesity.
METHODS: Vanin-1 expression was analyzed in different adipose depots in mice. The cellular localization of Vanin-1 was analyzed by confocal microscopy and western blots. Mice lacking Vanin-1 (Vanin-1-/-) were continuously fed either a chow diet or a high-fat diet (HFD) to establish an obesity model. RNA-seq analysis was performed to identify the molecular changes associated with Vanin-1 deficiency during obesity. BAT-specific Vanin-1 overexpression mice were established to determine the effects of Vanin-1 in vivo. Cysteamine treatment was used to examine the effect of enzymatic reaction products of Vanin-1 on BAT mitochondria function in Vanin-1-/- mice.
RESULTS: The results indicate that the expression of Vanin-1 is reduced in BAT from both diet-induced and leptin-deficient obese mice. Study on the subcellular location of Vanin-1 shows that it has a mitochondrial localization. Vanin-1 deficiency results in increased adiposity, BAT dysfunction, aberrant mitochondrial structure, and promotes HFD induced-BAT whitening. This is attributed to the impairment of the electron transport chain (ETC) in mitochondria due to Vanin-1 deficiency, resulting in reduced mitochondrial respiration. Overexpression of Vanin-1 significantly enhances energy expenditure and thermogenesis in BAT, renders mice resistant to diet-induced obesity. Furthermore, treatment with cysteamine rescue the mitochondrial dysfunction in Vanin-1-/- mice.
CONCLUSIONS: Collectively, these findings suggest that Vanin-1 plays a crucial role in promoting mitochondrial respiration to counteract diet-induced obesity, making it a potential therapeutic target for obesity.

Vanin-1 is a pantetheinase that hydrolyzes pantetheine to pantothenic acid and cysteamine. Vanin-1 has become recognized to be associated with oxidative stress and inflammation. In animal models, vanin-1 was reported to accelerate atherosclerosis. However, no study has reported blood vanin-1 concentrations in patients with coronary artery disease (CAD). We investigated plasma vanin-1 concentrations in 388 patients undergoing elective coronary angiography for suspected CAD. Patients with acute coronary syndrome were excluded. Of the 388 study patients, CAD was found in 207 patients [1-vessel (1-VD), n = 88; 2-vessel (2-VD), n = 66; and 3-vessel disease (3-VD), n = 53]. Plasma vanin-1 concentrations were higher in patients with CAD than in those without CAD (median 0.59 vs. 0.46 ng/mL, P < 0.005). Vanin-1 concentrations in patients without CAD and those with 1-VD, 2-VD, and 3-VD were 0.46, 0.58, 0.57, and 0.61 ng/mL, respectively, and were highest in 3-VD (P < 0.05). A high vainin-1 concentration (> 0.48 ng/mL) was found in 46% of patients without CAD, 61% of 1-VD, 65% of 2-VD, and 66% of 3-VD (P < 0.01). Vanin-1 concentrations significantly correlated with the number of stenotic coronary segments (r = 0.14, P < 0.02). In the multivariate analysis, vanin-1 concentration was a significant factor associated with CAD independent of atherosclerotic risk factors. The odds ratio for CAD was 1.63 (95%CI = 1.04-2.55) for the high vanin-1 concentration of > 0.48 ng/mL. Thus, plasma vanin-1 concentrations in patients with CAD were found to be high and to be associated with the presence and severity of CAD.

UNASSIGNED: Cysteamine, a powerful endogenous antioxidant, is produced mostly by the vanin-1 with pantetheinase activity. With regard to glycemic, inflammatory, and redox factors, the current study sought to evaluate the association between the expression of the vanin-1 gene, oxidative stress, and inflammatory and iNOS signaling pathway in obese diabetic patients.
UNASSIGNED: We enrolled 67 male subjects with an average age of 53.5 ± 5.0 years, divided into 4 groups according to the WHO guideline. We determined their plasma levels of glucose, insulin, IRI, HbA1c, TC, TG, HDL-C, TNF- α, MCP-1, TGF-β1, SOD, CAT, and TBARs, as well as expression of the iNOS and Vanin1 genes.
UNASSIGNED: Overweight and obese class I and II diabetics had significantly higher levels of plasma glucose, insulin, HbA1c, TNF-α, MCP-1, TGF-β1, CAT, and TBAR as well as iNOS and vanin-1 gene expression compared to healthy control individuals. In addition, as compared to healthy control individuals, overweight obese class I and II diabetics\' plasma HDL-C levels and blood SOD activity were significantly lower. In addition, ultrasound and computed tomography showed that the presence of a mild obscuring fatty liver with mild hepatic echogenicity appeared in overweight, class I and II obese diabetic patients.
UNASSIGNED: These findings provide important information for understanding the correlation between Vanin 1 and glycemic, inflammatory, and redox factors in obese patients. Furthermore, US and CT analysis were performed to visualize the observed images of fatty liver due to obesity.

The mechanisms underlying acute kidney injury (AKI) and chronic kidney disease (CKD) progression include interstitial inflammation, cellular senescence, and oxidative stress (OS). Although vanin-1 (VNN1) plays an important role in OS, its contribution to the AKI-CKD transition remains unknown. Here, we explored the roles and mechanisms of VNN1 in the progression of the AKI-CKD transition. We observed that VNN1 expression was upregulated after ischemia/reperfusion (I/R) injury and high VNN1 expression levels were associated with poor renal repair after I/R injury. In VNN1 knockout (KO) mice, recovery of serum creatinine and blood urea nitrogen levels after I/R injury was accelerated and renal fibrosis was inhibited after severe I/R injury. Furthermore, in VNN1 KO mice, senescence of renal tubular cells was inhibited after severe I/R injury, as assessed by P16 expression and SA-β-Gal assays. However, our results also revealed that VNN1 KO renal tubular cells did not resist senescence when OS was blocked. To elucidate the mechanism underlying VNN1-mediated regulation of senescence during the AKI-CKD transition, retinoblastoma 1 (RB1) was identified as a potential target. Our results suggest that the reduced senescence in VNN1 KO renal tubular cells was caused by suppressed RB1 expression and phosphorylation. Collectively, our results unveil a novel molecular mechanism by which VNN1 promotes AKI-CKD transition via inducing senescence of renal tubular cells by activating RB1 expression and phosphorylation after severe renal injury. The present study proposes a new strategy for designing therapies wherein VNN1 can be targeted to obstruct the AKI-CKD transition.

BACKGROUND: The function of vascular non-inflammatory molecule 1 (Vanin-1), an enzyme essential for vitamin B5 synthesis, has not been studied yet in chronic obstructive pulmonary disease (COPD).
OBJECTIVE: In this study, we aimed to evaluate the expression of Vanin-1 in sera and lung tissues of COPD, and infer its possible roles in COPD.
METHODS: We collected blood and lung tissue specimens from 99 COPD patients and 62 non-COPD subjects. Enzyme-linked immunosorbent assay was used to determine levels of Vanin-1, pantothenic acid, interleukin-6 (IL-6), tumor necrotic factor α (TNFα), and reactive oxygen species (ROS). The receiver operating characteristics (ROC) curve was used for analysis of the diagnostic value of Vanin-1 in COPD patients. Pearson\'s correlation assay was used to determine the correlation between Vanin-1 and levels of inflammatory cytokines and ROS.
RESULTS: Vanin-1 expression was significantly higher in the sera and lung tissues of COPD patients compared to non-COPD subjects. ROC analysis showed that the area under the curve (AUC) was greater than 0.5 for both sera (AUC = 0.7342) and lung tissues (AUC = 0.9061). Pantothenic acid was also upregulated in COPD patients. IL-6, TNFα and ROS showed strong positive correlations to Vanin-1 levels in sera.
CONCLUSIONS: Vanin-1 upregulation in sera and lung tissue is a potentially valuable biomarker for COPD. Vanin-1 showed positive correlations to levels of pro-inflammatory cytokines and ROS. Together, our results support the further development of Vanin-1 as a new target for the diagnosis or treatment of COPD.

Fourteen novel vanin-1 inhibitors coded OMP-# were designed from RR6 and successfully synthesized by a nucleophilic addition-elimination reaction of the pantetheinic acid-derived Weinreb amide as a key step under Barbier conditions. The synthesized OMP compounds exhibited inhibitory activity against human serum vanin-1 in vitro. Among the synthesized compounds, OMP-7, which possesses a trifluoromethoxy group at the para-position on the phenyl ring, exhibited the most potent activity, approximately 20 times that of the mother compound RR6. OMP-7 was further subjected to an in vivo assay using a normal hamster. More potent activity was observed than that of RR6 against both serum and renal vanin-1. The activity lasted for 4 h after injection against serum vanin-1 and 1 h after injection against renal vanin-1, whereas RR6 did not show the desired activity.

This study aimed to evaluate the usefulness of vanin-1 and periostin in urine as markers of the autoimmune process in kidneys and renal fibrosis in IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAVN). From a group of 194 patients from the Department of Pediatrics and Nephrology, who were included in the Polish Pediatric Registry of IgAN and IgAVN, we qualified 51 patients (20 with IgAN and 31 with IgAVN) between the ages of 3 and 17, diagnosed based on kidney biopsy, for inclusion in the study. All of the patients received glucocorticosteroids, immunosuppressive drugs, or renoprotective therapy. The control group consisted of 18 healthy individuals. The concentration of vanin was significantly higher in the IgAN and IgAVN groups than in the control group. The concentration of vanin/creatinine correlates positively with the level of IgA and negatively with the serum level of C3 at the end of the observation. Urinary vanin-1 concentration may be useful as a marker of the active autoimmune process in IgAN and IgAVN in children, but the study needs confirmation on a larger group of children, along with evaluation of the dynamics of this marker. Urinary periostin is not a good marker for children with IgAN and IgAVN, especially in stage 1 and 2 CKD.

The main effect of Vanin-1/VNN1 is related to its pantetheinase sulfhydrylase activity, which can hydrolyze pantetheine into pantothenic acid and cysteamine. In recent studies, the enzymatic activity of vanin-1/VNN1 has been found to be essential in the development of many diseases. The study of specific vanin-1/VNN1 inhibitors can give us a deeper understanding of its role in the disease process. In this study, different skeletal inhibitors were designed and synthesized using pyrimidine amide compounds as lead compounds. In order to screen inhibitors intuitively, a fluorescent probe PA-AFC for in vitro evaluation of inhibitors was designed and synthesized in this study, which has good sensitivity and specificity. The bioluminescent probe PA-AL was then used for cellular level and in vivo inhibitor evaluation. This screening method was convenient, economical and highly accurate. Finally, these inhibitors were applied to a mouse colitis model, confirming that vanin-1 is useful in IBD and providing a new therapeutic direction.