Effect of enzymatically produced tuna oil acylglycerol on the characteristics of gelatin O/W emulsion during microencapsulation using complex coacervation

Complex coacervation is an effective process to deliver ingredients for functional food applications. A stable oil-in-water (O/W) emulsion with desired characteristics significantly affects the complex coacervation and the quality of final microcapsules. In this study, tuna oil was partially hydrolyzed using TL100 and ADL lipases to produce acylglycerols TL100-AC and ADL-AC, respectively. These lipids were subsequently stabilized by gelatin in the O/W emulsion, followed by the complex coacervation with sodium hexametaphosphate. The effect of lipids on emulsion properties, such as interfacial properties, rheological properties, protein conformation and microcapsule formation during complex coacervation, was investigated. Compared with tuna oil-based emulsion, acylglycerol-based ones exhibited reduced droplet size (75%). These changes were beneficial to the formation of coagulant and flocculant so that gelatin-stabilized acylglycerol-based O/W emulsion resulted in improved complex coacervation between gelatin and sodium hexametaphosphate. This study provides a scientific basis for designing specific gelatin O/W emulsions and microencapsulation for the stabilization and delivery of omega-3 fatty acids

Osteocalcin has a muscle-protective effect during weight loss in men without metabolic syndrome: a multicenter, prospective, observational study

ObjectiveWeight reduction often accompanies muscle loss. Existing studies highlight the involvement of osteocalcin (OC) in energy metabolism and its potential to prevent age-related muscle loss. Nevertheless, these studies predominantly involve individuals with hyperglycemia, yielding conflicting research outcomes. This study investigated the protective role of OC against muscle loss during weight reduction in individuals without metabolic syndrome (MetS).MeasuresWe enrolled 130 overweight or obese individuals without MetS in a 4-month high-protein, energy-restricted dietary weight management program conducted at two clinic centers. Body composition and laboratory tests were assessed both before and after weight loss. Correlation and regression analysis were made between the changes in metabolic indicators and muscle mass during weight loss.ResultsFollowing weight loss, there was a decrease in body mass index (BMI), percentage of body fat (PBF), visceral fat area (VFA), fasting insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c), and lipid profile, and increase in the percentage of skeletal muscle (PSM) and vitamin D. There was no change in osteocalcin (OC) during the intervention. Correlation analysis of the relative changes in all metabolic indicators revealed a positive correlation between OC and PSM (r=0.383, p=0.002). Multiple linear regression analysis found that OC has a significant protective effect on muscles during weight loss in males after adjusting for confounding factors (β=0.089, p=0.017).ConclusionHigh-protein, energy-restricted diets demonstrate efficacy in enhancing metabolic indicators within the weight-loss population. Furthermore, OC exhibits a protective effect on muscle mass during weight reduction in individuals without MetS, with this effect being particularly evident in males

Single-Cell Spatial Transcriptomics Unveils Platelet-Fueled Cycling Macrophages for Kidney Fibrosis.

With the increasing incidence of kidney diseases, there is an urgent need to develop therapeutic strategies to combat post-injury fibrosis. Immune cells, including platelets, play a pivotal role in this repair process, primarily through their released cytokines. However, the specific role of platelets in kidney injury and subsequent repair remains underexplored. Here, the detrimental role of platelets in renal recovery following ischemia/reperfusion injury and its contribution to acute kidney injury  to chronic kidney disease transition is aimed to investigated. In this study, it is shown that depleting platelets accelerates injury resolution and significantly reduces fibrosis. Employing advanced single-cell and spatial transcriptomic techniques, macrophages as the primary mediators modulated by platelet signals is identified. A novel subset of macrophages, termed cycling M2, which exhibit an M2 phenotype combined with enhanced proliferative activity is uncovered. This subset emerges in the injured kidney during the resolution phase and is modulated by platelet-derived thrombospondin 1 (THBS1) signaling, acquiring profibrotic characteristics. Conversely, targeted inhibition of THBS1 markedly downregulates the cycling M2 macrophage, thereby mitigating fibrotic progression. Overall, this findings highlight the adverse role of platelet THBS1-boosted cycling M2 macrophages in renal injury repair and suggest platelet THBS1 as a promising therapeutic target for alleviating inflammation and kidney fibrosis

The effect of honokiol on pulmonary artery endothelium cell autophagy mediated by cyclophilin A in hypoxic pulmonary arterial hypertension

Abnormal autophagy plays critical roles in the structure and function of the pulmonary vasculature. Cyclophilin A (CyPA) can be secreted from cells in response to hypoxia and oxidative stress, which are involved in inducing autophagy and regulating the function of endothelial cells in pulmonary arterial hypertension. Honokiol is a small molecule natural compound; it has many bioactivities, such as antitumor, anti-inflammatory, antioxidant and antiangiogenic properties, but how honokiol mediates autophagy in pulmonary arterial hypertension is unclear. Rat' lungs gavaged with honokiol were examined for autophagy via western blot and fluorescence microscopy. In addition, western blot, quantitative RT-PCR and immunofluorescence were employed to test the expression of CyPA and autophagy markers in pulmonary artery endothelial cells (PAECs). Small interfering RNA targeting CyPA (si-CyPA) was used to knockdown the expression of CyPA, and then autophagy was tested with mRFP-GFP-LC3 fluorescence microscopy and western blot. We found that honokiol could reduce the expression of CyPA and autophagy markers in vivo and in vitro. Furthermore, autophagy was also down-regulated by si-CyPA. Taken together, we revealed a novel mechanism by which honokiol regulates autophagy. The results revealed that honokiol can alleviate autophagy and pulmonary arterial hypertension regulated by CyPA in PAECs. Keywords: Honokiol, Autophagy, Cyclophilin A, Pulmonary arterial hypertension, Pulmonary artery endothelial cell

Association between trimester-specific gestational weight gain and childhood obesity at 5 years of age: results from Shanghai obesity cohort

Abstract Background It is still unclear if and at which trimester gestational weight gain is related to childhood adiposity. Thus we aimed to evaluate the association between trimester-specific gestational weight gain and body-fat compositions in Chinese children. Methods Maternal gestational weight were measured by trained nurses every 2 to 4 weeks from the first prenatal care, and body-fat compositions of 407 children from the Shanghai Obesity Cohort at 5 years of age were measured by nutritionist through bioelectrical impedance analysis. Overweight/obesity of children was defined according to the criteria of International Obesity Task Force. Logistic and linear regression models adjusted for potential confounders were conducted to evaluate the associations of gestational weight gains with childhood obesity and body-fat compositions. Two-sided P-value < 0.05 was considered statistically significant. Results Greater gestational weight gain in the 1st-trimester was significantly associated with a higher risk of childhood overweight/obesity [OR: 1.40 (95% CI: 1.06, 1.86)], fat mass index [β: 0.25 (95% CI: 0.12, 0.38)], body fat percentage [β: 1.04 (95% CI: 0.43, 1.65)], and waist-to-height ratio [β: 0.005 (95% CI: 0.002, 0.008)]. A positive but nonsignificant association was found between greater 3rd-trimester gestational weight gain and a higher risk of offspring overweight/obesity, and we speculated that the association between 2nd-trimester gestational weight gain and offspring overweight/obesity is the “U” type. Conclusions Weight gain in the first trimester gestation is positively correlated with the risk of childhood overweight/obesity and with body adiposity distributions of children at 5 years of age. Weight gain should be well controlled and monitored from early pregnancy

Comparative Lipidomics Profiling of Acylglycerol from Tuna Oil Selectively Hydrolyzed by Thermomyces Lanuginosus Lipase and Candida Antarctica Lipase A

Lipase hydrolysis is an effective method to develop different functional types of lipids. In this study, tuna oil was partially hydrolyzed at 30% and 60% by Thermomyces lanuginosus lipase (TL 100 L) and Candida Antarctica lipase A (ADL), respectively, to obtain lipid-modified acylglycerols. The lipidomic profiling of the acylglycerols was investigated by UPLC-Q-TOF-MS and GC–MS to clarify the lipid modification effect of these two lipases on tuna oil. The results showed that 247 kinds of acylglycerols and 23 kinds of fatty acids were identified in the five samples. In the ADL group, the content of triacylglycerols (TAG) and diacylglycerols (DAG) increased by 4.93% and 114.38%, respectively, with an increase in the hydrolysis degree (HD), while there was a decreasing trend in the TL 100 L group. TL 100 L had a better enrichment effect on DHA, while ADL was more inclined to enrich EPA and hydrolyze saturated fatty acids. Cluster analysis showed that the lipids obtained by the hydrolysis of TL 100 L and ADL were significantly different in the cluster analysis of TAG, DAG, and monoacylglycerols (MAG). TL 100 L has strong TAG selectivity and a strong ability to hydrolyze acylglycerols, while ADL has the potential to synthesize functional lipids containing omega-3 PUFAs, especially DAG

Structural basis of GABAB receptor–Gi protein coupling

International audienceG-protein-coupled receptors (GPCRs) have central roles in intercellular communication1,2. Structural studies have revealed how GPCRs can activate G proteins. However, whether this mechanism is conserved among all classes of GPCR remains unknown. Here we report the structure of the class-C heterodimeric GABAB receptor, which is activated by the inhibitory transmitter GABA, in its active form complexed with Gi1 protein. We found that a single G protein interacts with the GB2 subunit of the GABAB receptor at a site that mainly involves intracellular loop 2 on the side of the transmembrane domain. This is in contrast to the G protein binding in a central cavity, as has been observed with other classes of GPCR. This binding mode results from the active form of the transmembrane domain of this GABAB receptor being different from that of other GPCRs, as it shows no outside movement of transmembrane helix 6. Our work also provides details of the inter- and intra-subunit changes that link agonist binding to G-protein activation in this heterodimeric complex

Orthosteric and allosteric modulation of human HCAR2 signaling complex

Abstract Hydroxycarboxylic acids are crucial metabolic intermediates involved in various physiological and pathological processes, some of which are recognized by specific hydroxycarboxylic acid receptors (HCARs). HCAR2 is one such receptor, activated by endogenous β-hydroxybutyrate (3-HB) and butyrate, and is the target for Niacin. Interest in HCAR2 has been driven by its potential as a therapeutic target in cardiovascular and neuroinflammatory diseases. However, the limited understanding of how ligands bind to this receptor has hindered the development of alternative drugs able to avoid the common flushing side-effects associated with Niacin therapy. Here, we present three high-resolution structures of HCAR2-Gi1 complexes bound to four different ligands, one potent synthetic agonist (MK-6892) bound alone, and the two structures bound to the allosteric agonist compound 9n in conjunction with either the endogenous ligand 3-HB or niacin. These structures coupled with our functional and computational analyses further our understanding of ligand recognition, allosteric modulation, and activation of HCAR2 and pave the way for the development of high-efficiency drugs with reduced side-effects

Characterization of the Expression of the RNA Binding Protein eIF4G1 and Its Clinicopathological Correlation with Serous Ovarian Cancer

<div><p>Background</p><p>Ovarian cancer is the most lethal type of malignant tumor in gynecological cancers and is associated with a high percentage of late diagnosis and chemotherapy resistance. Thus, it is urgent to identify a tumor marker or a molecular target that allows early detection and effective treatment. RNA-binding proteins (RBPs) are crucial in various cellular processes at the post-transcriptional level. The eukaryotic translation initiation factor 4 gamma, 1(eIF4G1), an RNA-binding protein, facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. However, little is known regarding the characteristics of eIF4G1 expression and its clinical significance in ovarian cancer. Therefore, we propose to investigate the expression and clinicopathological significance of eIF4G1 in ovarian cancer patients.</p><p>Methods</p><p>We performed Real-time PCR in 40 fresh serous ovarian cancer tissues and 27 normal ovarian surface epithelial cell specimens to assess eIF4G1mRNA expression. Immunohistochemistry (IHC) was used to examine the expression of eIF4G1 at the protein level in 134 patients with serous ovarian cancer and 18 normal ovarian tissues. Statistical analysis was conducted to determine the correlation of the eIF4G1 protein levels with the clinicopathological characteristics and prognosis in ovarian cancer.</p><p>Results</p><p>The expression of eIF4G1 was upregulated in serous ovarian cancer tissues at both the mRNA (P = 0.0375) and the protein (P = 0.0007) levels. The eIF4G1 expression was significantly correlated with the clinical tumor stage (P = 0.0004) and omentum metastasis (P = 0.024). Moreover, patients with low eIF4G1 protein expression had a longer overall survival time (P = 0.026).</p><p>Conclusions</p><p>These data revealed that eIF4G1 is markedly expressed in serous ovarian cancer and that upregulation of the eIF4G1 protein expression is significantly associated with an advanced tumor stage. Besides, the patients with lower expression of eIF4G1 tend to have a longer overall survival time. Thus, eIF4G1 may contribute to the occurrence and metastasis of ovarian cancer and can serve as a potential therapeutic target for the treatment of ovarian cancer.</p></div