Comparison of the immunogenicity of nasal-spray rVSV vector, adenovirus vector, and inactivated COVID-19-based vaccines in rodent models.

Intranasal (i.n.) vaccines can induce mucosal and systemic immunity against respiratory pathogens. Previously, we demonstrated that the recombinant vesicular stomatitis virus (rVSV)-based COVID-19 vaccine rVSV-SARS-CoV-2, with poor immunogenicity via the intramuscular route (i.m.), is more suitable for i.n. administration in mice and nonhuman primates. Here, we found that the rVSV-SARS-CoV-2 Beta variant was more immunogenic than the wild-type strain and other variants of concern (VOCs) in golden Syrian hamsters. Furthermore, the immune responses elicited by rVSV-based vaccine candidates via the i.n. route were significantly higher than those of two licensed vaccines: the inactivated vaccine KCONVAC delivered via the i.m. route and the adenovirus-based Vaxzevria delivered i.n. or i.m. We next assessed the booster efficacy of rVSV following two i.m. doses of KCONVAC. Twenty-eight days after receiving two i.m. doses of KCONVAC, hamsters were boosted with a third dose of KCONVAC (i.m.), Vaxzevria (i.m. or i.n.), or rVSVs (i.n.). Consistent with other heterologous booster studies, Vaxzevria and rVSV elicited significantly higher humoral immunity than the homogenous KCONVAC. In summary, our results confirmed that two i.n. doses of rVSV-Beta elicited significantly higher humoral immune responses than commercial inactivated and adeno-based COVID vaccines in hamsters. As a heterologous booster dose, rVSV-Beta induced potent, persistent, and broad-spectrum humoral and mucosal neutralizing responses against all VOCs, highlighting its potential to be developed into a nasal-spray vaccine.

Biomarkers for Bile Acid Malabsorption in Diarrhea-predominant Irritable Bowel Syndrome: A Systematic Review and Meta-analysis.

BACKGROUND AND AIM: A clear relationship of biological indexes between bile acid malabsorption (BAM) and diarrhea-predominant irritable bowel syndrome (IBS-D) has not been well analyzed. This meta-analysis aimed to establish a more convenient method to diagnose BAM in IBS-D patients by comparing the differences in biomarkers between IBS-D patients and healthy people. METHODS: Multiple databases were searched for relevant case-control studies. Indicators used to diagnose BAM included 75 Se-homocholic acid taurine (SeHCAT), 7α-hydroxy-4-cholesten-3-one(C4), fibroblast growth factor-19 and 48-hour fecal bile acid (48FBA). The rate of BAM (SeHCAT) was calculated by using a random-effect model. The levels of C4, FGF19, and 48FBA were compared, and the overall effect size was combined by a fixed effect model. RESULTS: The search strategy identified 10 relevant studies comprising 1034 IBS-D patients and 232 healthy volunteers. The pooled rate of BAM in IBS-D patients was 32% (according to SeHCAT; 95% CI: 24%-40%). The level of C4 in IBS-D patients was significantly higher than that in the control group (2.86 ng/mL; 95% CI: 1.09, 4.63); The level of FGF19 was significantly lower than that in the control group (-33.97 pg/mL; 95% CI: -51.13, -16.82); The level of 48FBA was significantly higher than that in the control group (0.059; 95% CI: 0.41, 0.77). CONCLUSIONS: The results mainly concluded serum C4 and FGF19 levels in IBS-D patients. Most of the studies have different normal cutoff points of serum C4 and FGF19 levels; the performance of each test should be further estimated. By comparing the levels of these biomarkers, BAM in patients with IBS-D could be identified more accurately, which would lead to more effective treatment.

Venous malformations of the lower limb with severe localized intravascular coagulopathy treated with radiofrequency ablation and resection.

Diffuse venous malformations (VMs) are relatively rare, especially the lesions locting special anatomical sites, and they are prone to casuse localized intravascular coagulopathy (LIC). Diffuse VMs can also cause bleeding and life-threatening disseminated intravascular coagulopathy (DIC) from trauma, surgery, and improper treatments. Thus, the treatment of diffuse VMs with LIC is quite tough. We report of a diffuse VMs with severe LIC that was treated with the combined use of minimally invasive treatment and open surgery.

Lipid extract from blue mussel (Mytilus edulis) improves glycemic traits in Chinese type 2 diabetic mellitus patients: a double-blind randomized controlled trial.

BACKGROUND: Studies have shown that blue mussel lipid extract (BMLE) has strong anti-inflammatory activity in both rheumatoid arthritis patients and animal arthritis models. Chronic inflammation was closely related to type 2 diabetes mellitus (T2DM). Though the beneficial effects cannot be completely attributed to n-3 polyunsaturated fatty acids, the aim of this study was to investigate whether BMLE can improve glycemic traits of T2DM patients. METHOD: In a double-blind randomized controlled trial, 133 Chinese T2DM participants were randomized to either fish oil (FO, n = 44), BMLE (n = 44), or corn oil (CO, n = 45) groups for 60 days. The participants were asked to take the corresponding oil capsules (two capsules per day, 0.8 g per capsule), which provided 1.6 g day-1 of FO (29.9% eicosapentaenoic acid + 20.4% docosahexaenoic acid), BMLE (20.7% eicosapentaenoic acid + 26.7% docosahexaenoic acid), or CO (53.5% linoleic acid). RESULTS: The fasting serum concentration of insulin (P = 0.005) and the homeostasis model of insulin resistance (P = 0.026) were significantly decreased in the BMLE group, whereas no significant change was found in the FO or CO groups. There was no significant difference between groups on serum glycosylated hemoglobin. Tumor necrosis factor-α was significantly decreased in the BMLE group (P = 0.003), but not in the FO or CO groups. A significant decrease of interleukin-1ß was observed in the BMLE and CO groups (P = 0.004 and P = 0.011 respectively), but not in the FO group. The total cholesterol was significantly decreased in the BMLE and CO groups (P < 0.001 and P < 0.001 respectively), but not in the FO group. Triacylglycerol was significantly decreased in the BMLE group (P = 0.007), but not in the FO or CO groups. High-density lipoprotein cholesterol was significantly lower in the BMLE and CO groups than in the FO group (P = 0.003). CONCLUSION: Blue mussel lipid supplements improved glycemic traits, inflammatory cytokines, and lipids profile in Chinese T2DM patients (Chinese Clinical Trial Registration number: ChiCTR1900025617). © 2022 Society of Chemical Industry.

Attention-Based Spatial-Temporal Convolution Gated Recurrent Unit for Traffic Flow Forecasting.

Accurate traffic flow forecasting is very important for urban planning and traffic management. However, this is a huge challenge due to the complex spatial-temporal relationships. Although the existing methods have researched spatial-temporal relationships, they neglect the long periodic aspects of traffic flow data, and thus cannot attain a satisfactory result. In this paper, we propose a novel model Attention-Based Spatial-Temporal Convolution Gated Recurrent Unit (ASTCG) to solve the traffic flow forecasting problem. ASTCG has two core components: the multi-input module and the STA-ConvGru module. Based on the cyclical nature of traffic flow data, the data input to the multi-input module are divided into three parts, near-neighbor data, daily-periodic data, and weekly-periodic data, thus enabling the model to better capture the time dependence. The STA-ConvGru module, formed by CNN, GRU, and attention mechanism, can capture both temporal and spatial dependencies of traffic flow. We evaluate our proposed model using real-world datasets and experiments show that the ASTCG model outperforms the state-of-the-art model.

Venous malformations with severe localized intravascular coagulopathy treated with microwave ablation.

OBJECTIVES: To evaluate the safety and feasibility of microwave ablation for treating venous malformations (VMs) with severe localized intravascular coagulopathy (LIC). PATIENTS AND METHODS: Data for patients with the diagnosis of VMs coupled with severe LIC who underwent color Doppler-guided microwave dynamic ablation between January 2017 and June 2019 were retrospectively reviewed and analyzed. All patients had previously received sclerotherapy or other treatments with poor outcomes and gradual aggravation of coagulation abnormalities. Microwave treatment with "dynamic ablation" was performed with real-time color Doppler monitoring and was repeated if necessary after 3 months. Low-molecular-weight heparin (LMWH) was used to control consumptive coagulopathy. The therapeutic efficacy including coagulation function and lesion size was evaluated using the four-level scale developed by Achauer. RESULTS: Among 15 patients with extensive diffuse or multiple VMs, 10 patients presented with lesions in a single lower extremity, one in both lower extremities and the perineum, one in both upper extremities and the trunk, and three with multiple lesions. The patients underwent a total of 74 microwave ablation sessions, with an average of 4.9 sessions per person. Coagulation abnormalities were temporarily aggravated in 59 sessions within the first seven days post-ablation but improved to grade II (fair) a week later. From six months to three years after the ablation, the lesions improved to grade IV (excellent) in one patient, grade III (good) in six patients, and grade II (fair) in eight patients. Moreover, the coagulation function improved to grade IV in four patients, grade III in eight patients, and grade II in three patients, resulting in an efficiency rate of 80% (12/15). Post-ablation complications included fever, hemoglobinuria, and elevations in aspartate aminotransferase, lactate dehydrogenase, and alanine aminotransferase. The patients with fever and hemoglobinuria recovered after specific therapeutic measures, but elevations in aspartate aminotransferase, lactate dehydrogenase, and alanine aminotransferase recovered spontaneously without further interventions. CONCLUSIONS: Ablation coupled with anticoagulation can effectively treat VMs in patients with severe LIC and improve the long-term coagulation function.

Analysis of 18 complex diffuse arteriovenous malformation cases treated with percutaneous radiofrequency ablation.

BACKGROUND: The aim of the present study is to evaluate the short-term efficacy and feasibility of radiofrequency ablation in the treatment of complex diffuse arteriovenous (AV) malformations. METHODS: The data of 18 patients (8 male and 10 female) with complex AV malformations treated between December 2014 and June 2019 were analyzed retrospectively. The lesion area was 10 × 7 cm ~ 28 × 30 cm. Under duplex ultrasound guidance, the site with the most abundant blood flow signals in the lesion was percutaneously punctured with the radiofrequency ablation needle (electrode). The impedance automatic adjustment mode was adopted, and ablation was monitored usingduplex ultrasoundduring the entire process. RESULTS: Of the included patients, 1 had a high fever after two rounds of treatment, 2 had transient hemoglobinuria, and 1 had tissue necrosis in the original ruptured tumor area as well as a penetrating defect in the cheek, which was repaired with a pedicled trapezius myocutaneous flap. In 9 patients who experienced bleeding, the bleeding stopped after one round of treatment. During the follow-up period of 1-5 years, there were 0 grade I (poor) cases, 0 grade II (medium) cases, 7 grade III (good) cases, and 11 grade IV (excellent) cases. CONCLUSION: The "high power and continuous" radiofrequency ablation technique conducted under real-time duplex ultrasoundmonitoring can completely destroy the deep core lesions of AV malformations and effectively control life-threatening massive hemorrhage; it is an effective alternative treatment method for complex diffuse AV malformations in which interventional embolization, sclerotherapy, and surgery are ineffective.

Integration of an interpretable machine learning algorithm to identify early life risk factors of childhood obesity among preterm infants: a prospective birth cohort.

BACKGROUND: The early life risk factors of childhood obesity among preterm infants are unclear and little is known about the influence of the feeding practices. We aimed to identify early life risk factors for childhood overweight/obesity among preterm infants and to determine feeding practices that could modify the identified risk factors. METHODS: A total of 338,413 mother-child pairs were enrolled in the Jiaxing Birth Cohort (1999 to 2013), and 2125 eligible singleton preterm born children were included for analyses. We obtained data on health examination, anthropometric measurement, lifestyle, and dietary habits of each participant at their visits to clinics. An interpretable machine learning-based analytic framework was used to identify early life predictors for childhood overweight/obesity, and Poisson regression was used to examine the associations between feeding practices and the identified leading predictor. RESULTS: Of the eligible 2125 preterm infants (863 [40.6%] girls), 274 (12.9%) developed overweight/obesity at age 4-7 years. We summarized early life variables into 25 features and identified two most important features as predictors for childhood overweight/obesity: trajectory of infant BMI (body mass index) Z-score change during the first year of corrected age and maternal BMI at enrollment. According to the impacts of different BMI Z-score trajectories on the outcome, we classified this feature into the favored and unfavored trajectories. Compared with early introduction of solid foods (≤ 3 months of corrected age), introducing solid foods after 6 months of corrected age was significantly associated with 11% lower risk (risk ratio, 0.89; 95% CI, 0.82 to 0.97) of being in the unfavored trajectory. CONCLUSIONS: The trajectory of BMI Z-score change within the first year of life is the most important predictor for childhood overweight/obesity among preterm infants. Introducing solid foods after 6 months of corrected age is a recommended feeding practice for mitigating the risk of being in the unfavored trajectory.

Econutrition, brown and beige fat tissue and obesity.

BACKGROUND AND OBJECTIVES: Obesity is caused by excessive fat accumulation or abnormal fat distribution and has become one of the biggest health challenges worldwide. Considering the high thermogenic ability of brown fat tissue (BAT) and the plasticity of fat tissue, to induce the browning of white fat tissue (WAT), so increasing BAT activity provides an attractive option for the prevention and resolution of obesity. The aim of the present narrative review was to understand the relationship between diet, BAT, and obesity. METHODS AND STUDY DESIGN: PubMed and Embase databases were searched to identify eligible studies. RESULTS: Although cold exposure has long been known to be effective in the browning of WAT and activation of BAT, it is societally impractical for everyday body weight management aside from the tolerance of ambient temperature. An alternative is to identify specific dietary components with similar effects to cold exposure on BAT. Current evidence indicates that capsaicin and capsinoids, catechins, curcumin, quercetin, berberine, lipoic acid, polyunsaturated fatty acids, royal jelly, and some natural sweeteners are effective promoters of WAT browning, increase BAT activity and improve obesity related traits. However, only capsaicin, capsinoids, and catechins have demonstrated efficacy in clinical trials. Evidence for effects of curcumin, quercetin, berberine, lipoic acid, polyunsaturated fatty acids, royal jelly and natural sweeteners on BAT have only been observed in animal or in vitro studies, with clinical trials awaited for verification. CONCLUSIONS: Several dietary components can induce WAT browning and activate BAT, offering potential targets for obesity prevention and management.

Effects of EPA and DHA on blood pressure and inflammatory factors: a meta-analysis of randomized controlled trials.

The present study aimed to clarify whether eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have differential effects on blood pressure and inflammatory mediators. A systematic literature search was conducted in PubMed and Scopus updated to Apr. 2018. The mean changes in risk factors of chronic diseases were calculated as weighted mean difference (WMD) by using a random-effects model. Twenty randomized controlled trials (RCTs) were included. The summary estimate showed that EPA intervention significantly reduced systolic blood pressure (SBP) (-2.6 mmHg; 95%confident interval (CI): -4.6, -0.5 mmHg), especially in subjects with dyslipidemia (-3.8 mmHg; 95%CI: -6.7, -0.8 mmHg). The pooled effect indicated that supplemental DHA exerted a significant reduction in diastolic blood pressure (DBP) in subjects with dyslipidemia (-3.1 mmHg; 95%CI: -5.9, -0.2 mmHg). Both EPA (-0.56 mg/L; 95%CI: -1.13, 0.00) and DHA (-0.5 mg/L; 95%CI: -1.0, -0.03) significantly reduced the concentrations of C-reactive protein (CRP), respectively, especially in subjects with dyslipidemia and higher baseline CRP concentrations. Given that limited trials have focused on EPA or DHA intervention on concentrations of interleukin (IL)-6 and tumor necrosis factor (TNF)-α, further RCTs should be explored on these inflammatory factors. The present meta-analysis provides substantial evidence that EPA and DHA have independent (blood pressure) and shared (CRP concentration) effects on risk factors of chronic diseases, and high-quality RCTs with multi-center and large simple-size should be performed to confirm the present findings.

Relationship between retinol and risk of diabetic retinopathy: a case-control study.

BACKGROUND AND OBJECTIVES: The aim of the present study was to evaluate the relationship between retinol and risk of diabetic retinopathy in Chinese adults. METHODS AND STUDY DESIGN: Eighty-six subjects with type 2 diabetes mellitus (T2DM) and 40 healthy subjects (healthy comparison group, HCG) were recruited in Beijing Luhe Hospital. Of the 86 T2DM subjects, 43 subjects were diagnosed with diabetic retinopathy (DRG), and 43 subjects had no retinopathy (DNRG). RESULTS: Dietary intake of retinol (p<0.001) and retinol equivalent (p<0.05) was significantly higher but serum retinol and (p<0.001) retinol binding protein 4 (RBP4) (p<0.05) were significantly lower in DNRG compared with HCG. Dietary intake of retinol (p<0.05) and retinol equivalent (p<0.05) was significantly lower, and serum retinol and (p<0.01) retinol binding protein 4 (RBP4) (p<0.01) were significantly higher in DRG compared with DNRG. In T2DM subjects, per 100 µg/day higher dietary retinol intake was associated with 17% lower risk of diabetic retinopathy (odds ratio (OR), 0.83; 95% CI, 0.70 to 0.98; p=0.032), and after adjusting for potential confounding factors, the OR was 0.82 (95% CI, 0.69 to 0.99; p=0.036); per 100 µg/day higher in dietary retinol equivalent intake was associated with 12% lower risk of diabetic retinopathy (OR, 0.88; 95% CI, 0.79 to 0.97; p=0.010), and after adjusting for potential confounding factors, the OR was 0.88 (95% CI, 0.79 to 0.98; p=0.025). CONCLUSIONS: Higher dietary intake of retinol or retinol equivalent is associated with lower risk of diabetic retinopathy.

CD45RO regulates the HIV-1 gp120-mediated apoptosis of T cells by activating Lck.

CD45 has been reported to regulate the HIV-1 gp120-induced apoptosis of Jurkat cells. Here, we demonstrate that the extracellular domain of CD45 plays an important role in this function. We observed that CD45RO-transfected cells, but not cells transfected with other CD45 isoforms, underwent significant apoptosis induced by gp120. However, a CD45RA-transfected cell line treated with an O-glycan inhibitor was able to undergo apoptosis. The role of the extracellular domain of CD45 was further confirmed using CD45 isoform-transfected cell lines by analyzing the phosphorylation of Lck, which is a direct substrate of CD45 tyrosine phosphatase, and by using an Lck inhibitor. These results suggest that CD45RO modulates HIV-1 gp120-induced apoptosis by regulating the activity of Lck.

Clinical observations in mesh suture treatment for infants of Kasabach-Merritt phenomenon.

AIM: This study aims to evaluate the efficacy and adverse effects of the mesh suture treatment for infants of Kasabach-Merritt phenomenon and to report our treatment experience. METHODS: Of the three patients, two of the cases occurred in the scalp and one occurred in the back of the chest, with platelet counts < 40 × 109 /L before the treatment, reduced fibrinogen levels and increased D-dimer levels. All the three patients underwent the mesh suture treatment of the tumour area. Post-treatment observations were made regarding the surface colour and texture of the tumours, periodic routine blood examination results, fibrinogen and D-dimer levels. RESULTS: After treatment, the degree of swelling on the tumour surface was reduced, surface tension was decreased, the tumour colour turned pale red from dark red and the skin gradually returned to normal. Two days after treatment, the platelet counts increased to 70 × 109 /L or higher; the platelet count reached a normal level after 1 week in two cases. The fibrinogen level increased in varying degrees after treatment, whereas the D-dimer level was reduced. One case showed a small amount of exudate at the suture area, 1 month after the treatment; improvements were observed 3 days after changing the local dressing. All the patients were followed up for 6 months to 1 year, during which the patients showed complete regression of the lesion and relapse, normal platelet counts and normal fibrinogen and D-dimer levels. CONCLUSIONS: We recommend the mesh suture treatment as the first treatment of choice for paediatric Kasabach-Merritt phenomenon.

Interaction between Marine-Derived n-3 Long Chain Polyunsaturated Fatty Acids and Uric Acid on Glucose Metabolism and Risk of Type 2 Diabetes Mellitus: A Case-Control Study.

The present case-control study explored the interaction between marine-derived n-3 long chain polyunsaturated fatty acids (n-3 LC PUFAs) and uric acid (UA) on glucose metabolism and risk of type 2 diabetes mellitus (T2DM). Two hundred and eleven healthy subjects in control group and 268 T2DM subjects in case group were included. Plasma phospholipid (PL) fatty acids and biochemical parameters were detected by standard methods. Plasma PL C22:6n-3 was significantly lower in case group than in control group, and was negatively correlated with fasting glucose (r = -0.177, p < 0.001). Higher plasma PL C22:6n-3 was associated with lower risk of T2DM, and the OR was 0.32 (95% confidence interval (CI), 0.12 to 0.80; p = 0.016) for per unit increase of C22:6n-3. UA was significantly lower in case group than in control group. UA was positively correlated with fasting glucose in healthy subjects, but this correlation became negative in T2DM subjects. A significant interaction was observed between C22:6n-3 and UA on fasting glucose (p for interaction = 0.005): the lowering effect of C22:6n-3 was only significant in subjects with a lower level of UA. In conclusion, C22:6n-3 interacts with UA to modulate glucose metabolism.

[Clinical analysis for treatment of 1 080 cases of infantile hemangiomas with oral propranolol].

OBJECTIVE: To explore the indications of hemangiomas of different types by observing the clinical efficacy of oral propranolol. METHODS: For this retrospective study from October 2009 to June 2013, a total of 1 080 cases were classified into 5 types according to their clinical characteristics. There were 338 males and 742 females. Their types were telangiectasis (n = 58), papular (n = 424), plump (n = 106), deep (n = 176) and mixed (n = 306). Propranolol was orally administered at a dose of 1.0 or 1.5 mg/kg daily (1.0 mg/kg for infants aged 2.5 months or under; 1.5 mg/kg for those aged 2.5 months or above). Dynamic observations of hemangioma size, texture or color change and adverse events during treatment were performed. Drug withdrawal was usually made after dosing for 1 year or under when there was a total regression of hemandiomas. The efficacy was evaluated on a 4-level scale. RESULTS: Rank test results showed no significant differences between 5 types during the changes of lesions (χ² = 1.738, P > 0.05). Changing of lesions occurred 8.0 (3.7, 16.2) hours after dosing in telangiectasis type, whereas 6.5 (4.1, 14.3) hours in papular type, 7.0 (5.5, 12.7) hours in plump type, 7.5 (3.8, 11.3) hours in deep type and 6.5 (4.2, 13.4) hours in mixed type. After a follow-up of 6 months to 2.5 years, there were 378 grade IV case (35.00%), 574 grade III case (53.15%), 120 grade II cases (11.11%) and 8 grade I cases (0.74%). And there were significant differences between patients of different types (P < 0.05). Patients of deep type had the best grade IV curative effect rate of 59.09% (104/176) , then papular type of 51.25% (162/316) and telangiectasis type of 26.41% (112/424). CONCLUSION: As a first-line treatment for hemangioma, propranolol shows excellent efficacies for patients of deep, mixed, plaque and papular types.

Mussel oil is superior to fish oil in preventing atherosclerosis of ApoE-/- mice.

Objectives: The present study aimed to explore the preventive effect of mussel oil (MO) on atherosclerosis and the potential mechanism in apolipoprotein E-null (ApoE-/-) mice. Methods: ApoE-/- mice were fed with a high-fat and high-cholesterol chow and given corn oil (CO), fish oil (FO), MO, or aspirin (ASP, dissolved in CO) by gavage for 12 weeks. The total n-3 polyunsaturated fatty acids (PUFAs) in MO (51.01%) and FO (46.82%) were comparable (mainly C22:6n-3 and C20:5n-3). Wild-type mice were fed with a normal chow and given equivalent CO as health control (CON). Results: Compared with the CON group, obvious atherosclerotic plaque appeared at aorta and aortic sinus in the CO group. Compared with the CO group, MO but not FO had a significantly smaller atherosclerotic plaque area in the aorta. The aortic atherosclerotic plaque area was comparable in the MO, CON, and ASP groups. The MO group had a significantly smaller atherosclerotic plaque area, lower lipid deposition, lower contents of smooth muscle cell (SMC), and slightly lower contents of macrophage at the aortic sinus than the FO group. Serum concentrations of IL-1ß, NF-κB, and VCAM-1 were comparable in the MO and FO groups and were significantly lower than the CO group. Compared with the CO group, the MO group but not FO group had significantly lower aortic protein levels of p65NF-κB, p38MAPK, and VCAM-1. The aortic protein levels of p-p65NF-κB and p-p38MAPK were significantly lower in the MO group than the FO group. Conclusion: In conclusion, MO is more potent than FO in preventing atherosclerosis, and the possible mechanism may be by downregulating p38MAPK/NF-κB signaling pathway, decreasing VCAM-1 and macrophage, and inhibiting proliferation and migration of SMC.

Differential Effects of n-3 and n-6 Polyunsaturated Fatty Acids on Placental and Embryonic Growth and Development in Diabetic Pregnant Mice.

The present study aimed to investigate the differential effects of n-3 and n-6 polyunsaturated fatty acids (PUFAs) on placental and embryonic development. Pregnant mice were assigned to five groups: healthy control (HC), diabetes mellitus control (DMC), diabetes + low-dose n-3 PUFA (Ln-3), diabetes + high-dose n-3 PUFA (Hn-3), and diabetes + n-6 PUFA (n-6). On E12.5d, the Hn-3 group, but not the n-6 group, had a higher placenta weight. The weight ratio of embryo to placenta in the n-6 group was significantly lower than in the Hn-3 group but higher than in the DMC group. The Hn-3 group had significantly higher protein levels of VEGF, IGF-1, and IGFBP3, while the n-6 group had lower VEGF than the DMC group. Compared with the DMC group, embryonic Cer-16:0 was significantly higher in the Hn-3 group, while embryonic PC (36:6), PC (38:7), and PE (40:7) were significantly lower in the n-6 group. The embryo and placenta weights were positively correlated with placental VEGF, IGFBP3, and embryonic Cer-16:0, and they were negatively correlated with embryonic PC (36:6) and PE (40:7). The weight ratio of embryo to placenta was negatively correlated with embryonic PC (36:6). In addition, embryonic Cer-16:0 was positively correlated with placental VEGF and IGFBP3. In conclusion, n-3 PUFA and n-6 PUFA improved placental and embryonic growth through different mechanisms.

Hydrolyzed egg yolk peptide prevented osteoporosis by regulating Wnt/ß-catenin signaling pathway in ovariectomized rats.

Hydrolyzed egg yolk peptide (YPEP) was shown to increase bone mineral density in ovariectomized rats. However, the underlying mechanism of YPEP on osteoporosis has not been explored. Recent studies have shown that Wnt/ß-catenin signaling pathway and gut microbiota may be involved in the regulation of bone metabolism and the progression of osteoporosis. The present study aimed to explore the preventive effect of the YPEP supplementation on osteoporosis in ovariectomized (OVX) rats and to verify whether YPEP can improve osteoporosis by regulating Wnt/ß-catenin signaling pathway and gut microbiota. The experiment included five groups: sham surgery group (SHAM), ovariectomy group (OVX), 17-ß estradiol group (E2: 25 µg /kg/d 17ß-estradiol), OVX with low-dose YPEP group (LYPEP: 10 mg /kg/d YPEP) and OVX with high-dose YPEP group (HYPEP: 40 mg /kg/d YPEP). In this study, all the bone samples used were femurs. Micro-CT analysis revealed improvements in both bone mineral density (BMD) and microstructure by YPEP treatment. The three-point mechanical bending test indicated an enhancement in the biomechanical properties of the YPEP groups. The serum levels of bone alkaline phosphatase (BALP), bone gla protein (BGP), calcium (Ca), and phosphorus (P) were markedly higher in the YPEP groups than in the OVX group. The LYPEP group had markedly lower levels of alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and C-terminal telopeptide of type I collagen (CTX-I) than the OVX group. The YPEP groups had significantly higher protein levels of the Wnt3a, ß-catenin, LRP5, RUNX2 and OPG of the Wnt/ß-catenin signaling pathway compared with the OVX group. Compared to the OVX group, the ratio of OPG/RANKL was markedly higher in the LYPEP group. At the genus level, there was a significantly increase in relative abundance of Lachnospiraceae_NK4A136_group and a decrease in Escherichia_Shigella in YPEP groups, compared with the OVX group. However, in the correlation analysis, there was no correlation between these two bacteria and bone metabolism and microstructure indexes. These findings demonstrate that YPEP has the potential to improve osteoporosis, and the mechanism may be associated with its modulating effect on Wnt/ß-catenin signaling pathway.

Gene-diet interaction in response to defatted flaxseed flour supplementation on obesity-related traits in Chinese overweight and obese adults: A randomized controlled trial.

Effects of dietary fiber on obesity-related traits in previous studies were inconsistent. The aim of the present study was to explore whether variants in genes related to satiety and appetite can modulate the effect of dietary fiber on obesity-related traits. Fifty-one overweight or obese adults were randomly allocated to two groups to consume control biscuits (n = 24) or biscuits containing defatted flaxseed flour (n = 27) at breakfast for 8 wk. Four single-nucleotide polymorphisms related to satiety and appetite were genotyped: rs11076023 on the FTO gene, rs16147 on the NPY gene, rs155971 on the PCSK1 gene, and rs6265 on the BDNF gene. A linear regression model was used to evaluate the gene-diet interaction between obesity-related traits. Compared with control biscuits, defatted flaxseed-flour biscuits significantly reduced body weight (P = 0.001) and body mass index (BMI) (P = 0.001) in A-allele carriers (AA + AT) of rs11076023 on the FTO gene but not in non-carriers (TT) (P for the interaction = 0.005 and 0.006) and decreased fasting serum glucose in participants with CC genotype (P = 0.019) but had less effect in T-allele carriers (TT + TC) (P = 0.021) of rs16147 on the NPY gene (P for the interaction = 0.002). Compared with the control biscuits, defatted flaxseed flour significantly reduced body weight (P < 0.001) in T-allele carriers (TT + TC) of rs155971 on the PCSK1 gene but not in non-carriers (CC) (P for the interaction = 0.041) and reduced body weight (P = 0.001) and BMI (P < 0.001) in A-allele carriers (AA + AG) of rs6265 on the BDNF gene but not non-carriers (GG) (P for the interaction = 0.017 and 0.018). Variants of genes related to satiety and appetite could modulate the effect of defatted flaxseed flour on obesity-related traits.

The preventive effect of mussel oil on gestational diabetes mellitus in pregnant mice fed by a high-fat and high-sucrose diet.

The present study aimed to investigate the preventive effect of mussel oil (MO) on gestational diabetes mellitus (GDM) in mice fed by a high-fat and high-sucrose (HFHS) diet. Pregnant mice were allocated to four groups: normal diet + corn oil (CO), HFHS + CO, HFHS + fish oil (FO), and HFHS + MO. The total n-3 polyunsaturated fatty acids (PUFAs) in MO (51.30%) and FO (48.25%) were comparable (mainly C22:6n-3 and C20:5n-3). HFHS + MO and HHFS + FO had a significantly lower area under the curve (AUC) for the oral glucose tolerance test (OGTT) than the HFHS + CO group. The HFHS + MO group but not HFHS + FO group had a significantly lower AUC for the insulin tolerance test (ITT) than the HFHS + CO group. The HFHS + MO group had significantly lower homeostasis model assessment-insulin resistance (HOMA-IR) and fasting serum insulin than the HHFS + FO and HFHS + CO groups. Liver sphingosine kinase 1 (SphK1) was significantly higher, while SphK2, Akt, and P-Akt were significantly lower in the HFHS + CO group compared with the normal diet + CO group. The HFHS + MO group but not the HFHS + FO group had significantly higher SphK2, Akt, and P-Akt than the HFHS + CO group. SphK2 had a strong negative correlation with the AUC for the OGTT (r = -0.759, p = 0.001) and insulin tolerance test (ITT) (r = -0.637; p = 0.008), fasting serum insulin (r = -0.594, p = 0.015), fasting blood glucose (r = -0.587, p = 0.017) and HOMA-IR (r = -0.629, p = 0.009) and a strong positive correlation with Akt (r = 0.594, p = 0.015) and P-Akt (r = 0.676, p = 0.004). In conclusion, mussel oil improved glucose intolerance and insulin resistance during mice pregnancy, which was superior to the effects of fish oil.