Detoxifying bacterial genes for deoxynivalenol epimerization confer durable resistance to Fusarium head blight in wheat.

Fusarium head blight (FHB) and the presence of mycotoxin deoxynivalenol (DON) pose serious threats to wheat production and food safety worldwide. DON, as a virulence factor, is crucial for the spread of FHB pathogens on plants. However, germplasm resources that are naturally resistant to DON and DON-producing FHB pathogens are inadequate in plants. Here, detoxifying bacteria genes responsible for DON epimerization were used to enhance the resistance of wheat to mycotoxin DON and FHB pathogens. We characterized the complete pathway and molecular basis leading to the thorough detoxification of DON via epimerization through two sequential reactions in the detoxifying bacterium Devosia sp. D6-9. Epimerization efficiently eliminates the phytotoxicity of DON and neutralizes the effects of DON as a virulence factor. Notably, co-expressing of the genes encoding quinoprotein dehydrogenase (QDDH) for DON oxidation in the first reaction step, and aldo-keto reductase AKR13B2 for 3-keto-DON reduction in the second reaction step significantly reduced the accumulation of DON as virulence factor in wheat after the infection of pathogenic Fusarium, and accordingly conferred increased disease resistance to FHB by restricting the spread of pathogenic Fusarium in the transgenic plants. Stable and improved resistance was observed in greenhouse and field conditions over multiple generations. This successful approach presents a promising avenue for enhancing FHB resistance in crops and reducing mycotoxin contents in grains through detoxification of the virulence factor DON by exogenous resistance genes from microbes.

The QTL and Candidate Genes Regulating the Early Tillering Vigor Traits of Late-Season Rice in Double-Cropping Systems.

Rice effective panicle is a major trait for grain yield and is affected by both the genetic tiller numbers and the early tillering vigor (ETV) traits to survive environmental adversities. The mechanism behind tiller bud formation has been well described, while the genes and the molecular mechanism underlying rice-regulating ETV traits are unclear. In this study, the candidate genes in regulating ETV traits have been sought by quantitative trait locus (QTL) mapping and bulk-segregation analysis by resequencing method (BSA-seq) conjoint analysis using rice backcross inbred line (BIL) populations, which were cultivated as late-season rice of double-cropping rice systems. By QTL mapping, seven QTLs were detected on chromosomes 1, 3, 4, and 9, with the logarithm of the odds (LOD) values ranging from 3.52 to 7.57 and explained 3.23% to 12.98% of the observed phenotypic variance. By BSA-seq analysis, seven QTLs on chromosomes 1, 2, 4, 5, 7, and 9 were identified using single-nucleotide polymorphism (SNP) and insertions/deletions (InDel) index algorithm and Euclidean distance (ED) algorithm. The overlapping QTL resulting from QTL mapping and BSA-seq analysis was shown in a 1.39 Mb interval on chromosome 4. In the overlap interval, six genes, including the functional unknown genes Os04g0455650, Os04g0470901, Os04g0500600, and ethylene-insensitive 3 (Os04g0456900), sialyltransferase family domain containing protein (Os04g0506800), and ATOZI1 (Os04g0497300), showed the differential expression between ETV rice lines and late tillering vigor (LTV) rice lines and have a missense base mutation in the genomic DNA sequences of the parents. We speculate that the six genes are the candidate genes regulating the ETV trait in rice, which provides a research basis for revealing the molecular mechanism behind the ETV traits in rice.

Effects of short-term supplementation with DHA-enriched phosphatidylcholine and phosphatidylserine on lipid profiles in the brain and liver of n-3 PUFA-deficient mice in early life after weaning.

BACKGROUND: Lack of n-3 polyunsaturated fatty acids during the period of maternity drastically lowers the docosahexaenoic acid (DHA) level in the brain of offspring and studies have demonstrated that different molecular forms of DHA are beneficial to brain development. The aim of this study was to investigate the effect of short-term supplementation with DHA-enriched phosphatidylserine (PS) and phosphatidylcholine (PC) on DHA levels in the liver and brain of congenital n-3-deficient mice. RESULTS: Dietary supplementation with DHA significantly changed the fatty acid composition of various phospholipid molecules in the cerebral cortex and liver while DHA-enriched phospholipid was more effective than DHA triglyceride (TG) in increasing brain and liver DHA. Both DHA-PS and DHA-PC could effectively increase the DHA levels, but DHA in the PS form was superior to PC in the contribution of DHA content in the brain ether-linked PC (ePC) and liver lyso-phosphatidylcholine molecular species. DHA-PC showed more significant effects on the increase of DHA in liver TG, PC, ePC, phosphatidylethanolamine (PE) and PE plasmalogen (pPE) molecular species and decreasing the arachidonic acid level in liver PC plasmalogen, ePC, PE and pPE molecular species compared with DHA-PS. CONCLUSION: The effect of dietary interventions with different molecular forms of DHA for brain and liver lipid profiles is different, which may provide theoretical guidance for dietary supplementation of DHA for people. © 2024 Society of Chemical Industry.

Supplementation of n-3 PUFAs in Adulthood Attenuated Susceptibility to Pentylenetetrazol Induced Epilepsy in Mice Fed with n-3 PUFAs Deficient Diet in Early Life.

The growth and development of the fetus and newborn throughout pregnancy and lactation are directly related to the nutritional status of the mother, which has a significant impact on the health of the offspring. The purpose of this experiment was to investigate the susceptibility of n-3 polyunsaturated fatty acid deficiency in early life to seizures in adulthood. The n-3 PUFAs-deficient mice's offspring were established and then fed with α-LNA diet, DHA-enriched ethyl ester, and DHA-enriched phospholipid-containing diets for 17 days at the age of eight weeks. During this period, animals received intraperitoneal injections of 35 mg/kg of pentylenetetrazol (PTZ) every other day for eight days. The results showed that dietary n-3 PUFA-deficiency in early life could aggravate PTZ-induced epileptic seizures and brain disorders. Notably, nutritional supplementation with n-3 PUFAs in adulthood for 17 days could significantly recover the brain n-3 fatty acid and alleviate the epilepsy susceptibility as well as raise seizure threshold to different levels by mediating the neurotransmitter disturbance and mitochondria-dependent apoptosis, demyelination, and neuroinflammation status of the hippocampus. DHA-enriched phospholipid possessed a superior effect on alleviating the seizure compared to α-LNA and DHA-enriched ethyl ester. Dietary n-3 PUFA deficiency in early life increases the susceptibility to PTZ-induced epilepsy in adult offspring, and nutritional supplementation with n-3 PUFAs enhances the tolerance to the epileptic seizure.

N-3 PUFA Deficiency Aggravates Streptozotocin-Induced Pancreatic Injury in Mice but Dietary Supplementation with DHA/EPA Protects the Pancreas via Suppressing Inflammation, Oxidative Stress and Apoptosis.

It has been reported that dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential for the preservation of functional ß-cell mass. However, the effect of dietary n-3 PUFA deficiency on pancreatic injury and whether the supplementation of n-3 PUFA could prevent the development of pancreatic injury are still not clear. In the present study, an n-3 PUFA deficiency mouse model was established by feeding them with n-3 PUFA deficiency diets for 30 days. Results showed that n-3 PUFA deficiency aggravated streptozotocin (STZ)-induced pancreas injury by reducing the insulin level by 18.21% and the HOMA ß-cell indices by 31.13% and the area of islet by 52.58% compared with the STZ group. Moreover, pre-intervention with DHA and EPA for 15 days could alleviate STZ-induced pancreas damage by increasing the insulin level by 55.26% and 44.33%, the HOMA ß-cell indices by 118.81% and 157.26% and reversed the area of islet by 196.75% and 205.57% compared to the n-3 Def group, and the effects were significant compared to γ-linolenic acid (GLA) and alpha-linolenic acid (ALA) treatment. The possible underlying mechanisms indicated that EPA and DHA significantly reduced the ration of n-6 PUFA to n-3 PUFA and then inhibited oxidative stress, inflammation and islet ß-cell apoptosis levels in pancreas tissue. The results might provide insights into the prevention and alleviation of pancreas injury by dietary intervention with PUFAs and provide a theoretical basis for their application in functional foods.

A Comparative Study about the Neuroprotective Effects of DHA-Enriched Phosphatidylserine and EPA-Enriched Phosphatidylserine against Oxidative Damage in Primary Hippocampal Neurons.

Nerve damage caused by accumulated oxidative stress is one of the characteristics and main mechanisms of Alzheimer's disease (AD). Previous studies have shown that phosphatidylserine (PS) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) plays a significant role in preventing and mitigating the progression of AD. However, whether DHA-PS and EPA-PS can directly protect primary hippocampal neurons against oxidative damage has not been studied. Here, the neuroprotective functions of DHA-PS and EPA-PS against H2O2/t-BHP-induced oxidative damage and the possible mechanisms were evaluated in primary hippocampal neurons. It was found that DHA-PS and EPA-PS could significantly improve cell morphology and promote the restoration of neural network structure. Further studies showed that both of them significantly alleviated oxidative stress-mediated mitochondrial dysfunction. EPA-PS significantly inhibited the phosphorylation of ERK, thus playing an anti-apoptotic role, and EPA-PS significantly increased the protein expressions of p-TrkB and p-CREB, thus playing a neuroprotective role. In addition, EPA-PS, rather than DHA-PS could enhance synaptic plasticity by increasing the expression of SYN, and both could significantly reduce the expression levels of p-GSK3ß and p-Tau. These results provide a scientific basis for the use of DHA/EPA-enriched phospholipids in the treatment of neurodegenerative diseases, and also provide a reference for the development of related functional foods.

The synergistic effect of sea cucumber saponins and caffeine on preventing obesity in high-fat diet-fed mice by extending the action duration of caffeine.

BACKGROUND: Sea cucumber saponins (SCSs) exhibit a unique structure and high bioactivities and might have specialized implications on caffeine metabolic process by altering the activity of N-demethylation enzyme CYP1A2. The present study aimed to clarify the effects of SCS on caffeine metabolism in vivo and in vitro, as well as the synergistic anti-obesity effect of SCS and caffeine on high-fat diet-induced obese mice. RESULTS: Results found that SCS administration significantly postponed the elimination rate of caffeine and its metabolites in vivo, and further study found CYP1A2-mediated caffeine metabolism was remarkably inhibited in a dose-dependent manner in vitro. The synergistic effect of the SCS and caffeine combination could decrease the total weight of white adipose tissue by 52% compared with high-fat diet-treated group. CONCLUSION: SCS could prolong caffeine action time, and the combination of the two substances exhibited joint action on high-fat diet-induced obese mice. These findings might provide a basis for the development of functional foods and potential application using the combination of SCS and caffeine. © 2022 Society of Chemical Industry.

Phosphatidylglucose alleviates atherosclerosis by increasing cholesterol alienation to bile acids and cholesterol efflux in ApoE-/- mice.

BACKGROUND: Phosphatidylcholine (PC) is considered to be the major dietary source for choline, which is associated with atherosclerosis progress. Thus, phosphatidylglucose (PG) was prepared by enzymatic modification of PC to investigate the effects on atherosclerosis in apolipoprotein E deficient (ApoE-/- ) mice, as well as to investigate its dose-response relationship. RESULTS: The results showed that dietary PG significantly decreased the atherosclerotic lesion area in a dose-dependent manner. Further studies found that intervention with a 0.8 g kg-1 and 2 g kg-1 PG diet for 4 months significantly decreased free cholesterol level and thus reduced total cholesterol levels in serum. The results of cholesterol distribution among lipoproteins showed that dietary PG significantly decreased low-density lipoprotein levels in ApoE-/- mice. In addition, only administration of high-dose PG significantly reduced total cholesterol levels in liver tissues by 31.2%. Furthermore, mice treated with high-dose PG had an expanded bile acid pool and increased the ratio of conjugated bile acids to unconjugated bile acids in the liver, serum and gallbladder by increasing hepatic gene expression of primary and conjugated bile acid synthesis. Additionally, low-dose and high-dose PG significantly increased total fecal sterols by 20.8% and 11.9%, respectively, by increasing sitosterol and ethylcoprostanol levels. CONCLUSION: These results indicate that PG alleviated atherosclerosis in a dose-dependent manner by increasing cholesterol alienation to bile acids and cholesterol efflux. © 2023 Society of Chemical Industry.

Cost-effectiveness of artificial intelligence screening for diabetic retinopathy in rural China.

BACKGROUND: Diabetic retinopathy (DR) has become a leading cause of global blindness as a microvascular complication of diabetes. Regular screening of diabetic retinopathy is strongly recommended for people with diabetes so that timely treatment can be provided to reduce the incidence of visual impairment. However, DR screening is not well carried out due to lack of eye care facilities, especially in the rural areas of China. Artificial intelligence (AI) based DR screening has emerged as a novel strategy and show promising diagnostic performance in sensitivity and specificity, relieving the pressure of the shortage of facilities and ophthalmologists because of its quick and accurate diagnosis. In this study, we estimated the cost-effectiveness of AI screening for DR in rural China based on Markov model, providing evidence for extending use of AI screening for DR. METHODS: We estimated the cost-effectiveness of AI screening and compared it with ophthalmologist screening in which fundus images are evaluated by ophthalmologists. We developed a Markov model-based hybrid decision tree to analyze the costs, effectiveness and incremental cost-effectiveness ratio (ICER) of AI screening strategies relative to no screening strategies and ophthalmologist screening strategies (dominated) over 35 years (mean life expectancy of diabetes patients in rural China). The analysis was conducted from the health system perspective (included direct medical costs) and societal perspective (included medical and nonmedical costs). Effectiveness was analyzed with quality-adjusted life years (QALYs). The robustness of results was estimated by performing one-way sensitivity analysis and probabilistic analysis. RESULTS: From the health system perspective, AI screening and ophthalmologist screening had incremental costs of $180.19 and $215.05 but more quality-adjusted life years (QALYs) compared with no screening. AI screening had an ICER of $1,107.63. From the societal perspective which considers all direct and indirect costs, AI screening had an ICER of $10,347.12 compared with no screening, below the cost-effective threshold (1-3 times per capita GDP of Chinese in 2019). CONCLUSIONS: Our analysis demonstrates that AI-based screening is more cost-effective compared with conventional ophthalmologist screening and holds great promise to be an alternative approach for DR screening in the rural area of China.

A Comparative Study of the Anti-Obesity Effects of Dietary Sea Cucumber Saponins and Energy Restriction in Response to Weight Loss and Weight Regain in Mice.

Dietary supplementation of sea cucumber saponins and calorie restriction have been proved to be effective in alleviating obesity, but the differences of anti-obesity effects between sea cucumber saponins and energy restriction during weight loss and weight regain are still unknown. In the present study, high-fat-induced obesity mice were randomly divided into three groups, including a high-fat diet group (HF), an energy restriction by 40% group (HF-L), and a sea cucumber saponins group (HF-S), to compare the effects of dietary sea cucumber saponins and energy restriction on the weight, glucose, and lipid metabolism of obese mice during weight loss and weight regain. The results showed that dietary 0.06% sea cucumber saponins and limiting energy intake by 40% had the same weight loss effect. Interestingly, sea cucumber saponins could alleviate impaired glucose tolerance and insulin resistance caused by obesity. In addition, the inhibited SREBP-1c mediated lipogenesis might lead to the alleviation of weight regain after resuming the high-fat diet even when sea cucumber saponins were no longer supplemented. In contrast, limiting energy intake tended to promote lipid synthesis in the liver and white adipose tissue after restoring a high-fat diet, and inflammation was also induced. The findings indicated that sea cucumber saponins could replace calorie restriction to prevent obesity and might be used as a functional food or drug to resist obesity and related diseases caused by obesity.

EPA-Enriched Phospholipids Alleviate Renal Interstitial Fibrosis in Spontaneously Hypertensive Rats by Regulating TGF-ß Signaling Pathways.

Hypertensive nephropathy is a chronic kidney disease caused by hypertension. Eicosapentaenoic acid (EPA) has been reported to possess an antihypertensive effect, and our previous study suggested that EPA-enriched phospholipid (EPA-PL) had more significant bioactivities compared with traditional EPA. However, the effect of dietary EPA-PL on hypertensive nephropathy has not been studied. The current study was designed to examine the protection of EPA-PL against kidney damage in spontaneously hypertensive rats (SHRs). Treatment with EPA-PL for three weeks significantly reduced blood pressure through regulating the renin-angiotensin system in SHRs. Moreover, dietary EPA-PL distinctly alleviated kidney dysfunction in SHRs, evidenced by reduced plasma creatinine, blood urea nitrogen, and 24 h proteinuria. Histology results revealed that treatment of SHRs with EPA-PL alleviated renal injury and reduced tubulointerstitial fibrosis. Further mechanistic studies indicated that dietary EPA-PL remarkably inhibited the activation of TGF-ß and Smad 3, elevated the phosphorylation level of PI3K/AKT, suppressed the activation of NF-κB, reduced the expression of pro-inflammatory cytokines, including IL-1ß and IL-6, and repressed the oxidative stress and the mitochondria-mediated apoptotic signaling pathway in the kidney. These results indicate that EPA-PL has potential value in the prevention and alleviation of hypertensive nephropathy.

Dietary n-3 PUFA Deficiency Increases Vulnerability to Scopolamine-Induced Cognitive Impairment in Male C57BL/6 Mice.

BACKGROUND: DHA (22:6n-3), a long-chain n-3 PUFA, is essential for normal brain development and function. Our previous study demonstrated that DHA significantly improves scopolamine-induced dementia. However, there are no reports on the relation between n-3 PUFA deficiency and scopolamine-induced cognitive impairment. OBJECTIVES: The aim of this study was to evaluate whether n-3 PUFA deficiency increases vulnerability to scopolamine-induced cognitive impairment. METHODS: Male and female C57BL/6 mice were mated and fed an n-3 PUFA-adequate [containing 2.88% α-linolenic acid (ALA; 18:3n-3)] or -deficient (containing 0.09% ALA) diet for 2 consecutive generations. The corresponding second-generation male offspring were kept on the same diet as their mothers after weaning, and were randomly assigned to 2 subgroups at 7 wk of age, in which they were intraperitoneally injected with saline [fed n-3 PUFA-adequate (Con) or -deficient (Def) diet] or scopolamine [5 mg/kg body weight; fed n-3 PUFA-adequate (Sco) or -deficient (Def + Sco) diet] once per day for 7 d before killing. Behavioral performance was analyzed using the Morris Water Maze test. Fatty acid composition, protein expression, and indicators of cholinergic and oxidative stress in the brain were measured. RESULTS: The Def group showed lower brain DHA (-63.7%, P ≤ 0.01) and higher n-6 PUFA (+65.5%, P ≤ 0.05) concentrations than the Con group. The Def + Sco group and the Sco group showed poorer spatial learning and memory (escape latency on the sixth day: +60.3% and +36.8%; platform crossings: -43.9% and -28.2%, respectively) and more obvious cholinergic dysfunction (acetylcholine: -47.6% and -27.7%, respectively), oxidative stress (glutathione peroxidase: -64.2% and -32.5%, respectively), apoptosis [B-cell lymphoma 2 (BCL2)-associated X protein/BCL2: +230.8% and +153.8%; phosphorylated P38/P38: +232% and +130%, phosphorylated c-Jun N-terminal kinase (JNK)/JNK: +104.5% and +58.8%, respectively], neuroinflammation (IL-1ß: +317.6% and +95%, respectively), and neurodevelopmental delay (brain-derived neurotrophic factor: -54.4% and -7.25%, respectively) than their corresponding saline-treated controls. CONCLUSIONS: Dietary n-3 PUFA deficiency significantly decreases brain DHA concentrations and increases vulnerability to scopolamine-induced cognitive impairment in C57BL/6 male mice.

Comparative evaluation of phosphatidylcholine and phosphatidylserine with different fatty acids on nephrotoxicity in vancomycin-induced mice.

Phospholipids reportedly alleviate drug-induced acute kidney injury. However, no study has compared the effect of phospholipids with different fatty acids and polar heads on drug-induced nephrotoxicity. In the present study, we aimed to compare the possible nephroprotection afforded by phosphatidylcholine and phosphatidylserine with different fatty acids in a mouse model of vancomycin-induced nephrotoxicity. Pretreatment with phospholipids rich in docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) doubled the survival time when compared with the model group. Moreover, phospholipids rich in DHA/EPA significantly reduced the serum levels of renal function biomarkers and ameliorated kidney pathologies. In terms of alleviating renal damage, no significant differences were observed between different polar heads in DHA-enriched phospholipids, while phosphatidylserine from soybean was better than phosphatidylcholine in mitigating renal injury. Furthermore, DHA/EPA-enriched phospholipids inhibited vancomycin-induced nephrotoxicity mainly by inhibiting apoptosis and oxidative stress. These results provide a scientific basis for phospholipids as potential ingredients to prevent acute kidney injury.

Docosahexaenoic Acid-Acylated Astaxanthin Esters Exhibit Superior Renal Protective Effect to Recombination of Astaxanthin with DHA via Alleviating Oxidative Stress Coupled with Apoptosis in Vancomycin-Treated Mice with Nephrotoxicity.

Prevention of acute kidney injury caused by drugs is still a clinical problem to be solved urgently. Astaxanthin (AST) and docosahexaenoic acid (DHA) are important marine-derived active ingredients, and they are reported to exhibit renal protective activity. It is noteworthy that the existing forms of AST in nature are mainly fatty acid-acylated AST monoesters and diesters, as well as unesterified AST, in which DHA is an esterified fatty acid. However, no reports focus on the different bioactivities of unesterified AST, monoesters and diesters, as well as the recombination of DHA and unesterified AST on nephrotoxicity. In the present study, vancomycin-treated mice were used to evaluate the effects of DHA-acylated AST monoesters, DHA-acylated AST diesters, unesterified AST, and the recombination of AST and DHA in alleviating nephrotoxicity by determining serum biochemical index, histopathological changes, and the enzyme activity related to oxidative stress. Results found that the intervention of DHA-acylated AST diesters significantly ameliorated kidney dysfunction by decreasing the levels of urea nitrogen and creatinine, alleviating pathological damage and oxidative stress compared to AST monoester, unesterified AST, and the recombination of AST and DHA. Further studies revealed that dietary DHA-acylated AST esters could inhibit the activation of the caspase cascade and MAPKs signaling pathway, and reduce the levels of pro-inflammatory cytokines. These findings indicated that the administration of DHA-acylated AST esters could alleviate vancomycin-induced nephrotoxicity, which represented a potentially novel candidate or therapeutic adjuvant for alleviating acute kidney injury.

Heparin versus 0.9% saline solution to maintain patency of totally implanted venous access ports in cancer patients: A systematic review and meta-analysis.

AIM: The use of heparin and 0.9% saline solution is always controversial for central venous catheters. However, there is no systematic review or guideline about whether saline solution can replace heparin solution in adult cancer patients with totally implantable venous access ports (TIVAPs). The purpose of this review is to evaluate whether saline solution can replace heparin saline to lock TIVAPs. METHODS: The following databases were searched: PubMed, the Cochrane Library, Web of Science, Embase, CINAHL and Ovid (January 1, 1982, and February 21, 2020). All statistical analyses of the meta-analysis were completed using the Review Manager 5.3. RESULTS: A total of 201 studies were identified from these databases after initial review, and four studies met inclusion criteria, including 2652 cases. There was little heterogeneity among the included studies (I2 < 30%), and all analyses were conducted by the fixed-effects model. The total complications, catheter occlusions, catheter-related bloodstream infections and other complication rates in the heparin solution group were higher than in the saline solution group. In the subgroup analysis of heparin concentration, total complication rates in the saline solution group were higher than with 50 U of heparin and lower than with 100 U of heparin. However, the differences in these complications were small, and no significant difference was observed (all P > 0.05). CONCLUSIONS: Based on existing clinical studies, we recommend that saline solution can replace 50 or 100 U/ml of heparin as a safe and effective flush solution for TIVAPs.

Sea cucumbers-derived sterol sulfate alleviates insulin resistance and inflammation in high-fat-high-fructose diet-induced obese mice.

Sea cucumbers are widely consumed in traditional medicine and food. Sea cucumbers-derived sulfated sterol exhibits a sulfate group at C-3 position, which is different from phytosterol with a hydroxyl group. However, the effect of sterol sulfate on metabolic syndrome remains unknown. The purpose of the present study is to investigate the alleviation of sterol sulfate on high-fat-high-fructose diet (HFFD)-induced insulin resistance and inflammation. After 2 weeks feeding with HFFD, male C57BL/6J mice were continuously fed with HFFD plus 0.4 % (w/w) sterol sulfate or phytosterol for 6 weeks. The OGTT was carried out at 7 weeks. At the end of the experimental period, the changes of glycogen, circulating glucose, insulin, pro-inflammatory cytokine and adiponectin were measured. H&E staining was used to observe the morphological changes in adipose tissue. Furthermore, the underlying molecular mechanisms were investigated. Dietary sterol sulfate was superior to phytosterol in reducing body weight gain, adipocyte hypertrophy, and levels of circulating glucose and insulin, as well as increasing the glycogen content of tissues. Furthermore, sterol sulfate ameliorated insulin resistance mainly due to the inhibition of gluconeogenesis, the promotion of glycogen synthesis and GLUT4 translocation by activating PI3K/Akt signaling pathway. Additionally, sterol sulfate effectively attenuated inflammation by increasing serum adiponectin and reducing pro-inflammatory cytokine release. Sterol sulfate exhibited a more significant effect than phytosterol in alleviating HFFD -induced insulin resistance and inflammation, which might be closely related to the sulfate group. The results might provide insights into the prevention and alleviation of metabolic syndrome.

Recovery of brain DHA-containing phosphatidylserine and ethanolamine plasmalogen after dietary DHA-enriched phosphatidylcholine and phosphatidylserine in SAMP8 mice fed with high-fat diet.

BACKGROUND: Glycerophospholipids were the main components of cerebral cortex lipids, and there was a close association between lipid homeostasis and human health. It has been reported that dietary DHA-enriched phosphatidylcholine (DHA-PC) and phosphatidylserine (DHA-PS) could improve brain function. However, it was unclear that whether supplementation of DHA-PC and DHA-PS could change lipid profiles in the brain of dementia animals. METHODS: SAMP8 mice was fed with different diet patterns for 2 months, including high-fat diet and low-fat diet. After intervention with DHA-PC and DHA-PS for another 2 months, the lipid profile in cerebral cortex was determined by lipidomics in dementia mice. RESULTS: High-fat diet could significantly decrease the levels of DHA-containing PS/pPE, DPA-containing PS, and AA-containing PE, which might exhibit the potential of lipid biomarkers for the prevention and diagnosis of AD. Notably, DHA-PC and DHA-PS remarkably recovered the lipid homeostasis in dementia mice. These might provide a potential novel therapy strategy and direction of dietary intervention for patients with cognitive decline. CONCLUSIONS: DHA-PC and DHA-PS could recover the content of brain DHA-containing PS and pPE in SAMP8 mice fed with high-fat diet.

Efficacy and safety of Tripterygium wilfordii Hook F for CKD in Mainland China: A systematic review and meta-analysis.

Tripterygium wilfordii Hook F (TwHF) is a promising Chinese traditional medicine used to significantly reduce proteinuria and improve renal function. However, its efficacy and safety in treatment of chronic kidney disease need to be further explored in order to promote its application in clinics. This review compared the efficacy and safety of TwHF with the placebo, conventional Western medicine and other immunosuppressive medicine in a range of kidney disorders. One hundred three randomized controlled trials were included. TwHF therapy decreased 24-hr proteinuria by 0.59 g/day (95% confidence interval [CI; -0.68, -0.50]), serum creatinine level by 1.93 µmol/L (95% CI [-3.69, -0.17]), and blood urea nitrogen level by 0.24 mmol/L (95% CI [-0.41, -0.07]); increased the total effective rate by 27% (95% CI [1.24, 1.30]); and decreased the incidence of adverse reactions by 19% (95% CI [0.68, 0.96]) overall. Meta regression results showed that the duration of therapy and mean age of participants were the major sources of high heterogeneity. Sensitivity analysis demonstrated that our statistic results were relatively stable and credible. The present findings suggested that TwHF possibly has nephroprotective effects by decreasing proteinuria, serum creatinine level, and blood urea nitrogen level and no more adverse reactions compared with control group in most kidney disorders. However, these findings still need to be further confirmed by high-quality trials.

The life cycle and development characteristics of Dermacentor everestianus (Acari: Ixodidae) under field conditions in Qinghai-Tibet Plateau.

The tick Dermacentor everestianus mainly distributed in Tibet, China and Nepal, and can transmit some pathogens causing great damages in Qinghai-Tibet Plateau. This study investigated the life cycle and development characteristics of D. everestianus under field conditions. The average duration of the whole life cycle of D. everestianus was 124.4 days, with the host available in the field plot. Under natural conditions, the mean feeding, preoviposition and oviposition period of female ticks were 6.1, 17.9 and 21.2 days, respectively. The incubation time of eggs was the longest phase in the life cycle of the ticks (26 days on average). Moreover, the weight of engorged females was highly positively correlated with the number of the eggs that were laid (r = 0.81, P < 0.05). The reproductive efficiency index and reproductive fitness index in females were 7.3 and 5.9, respectively. The above findings suggest that the tick D. everestianus have evolved well adaptability to the highland areas.

Betulin from Hedyotis hedyotidea ameliorates concanavalin A-induced and T cell-mediated autoimmune hepatitis in mice.

Hedyotis hedyotidea has been used in traditional Chinese medicine for the treatment of autoimmune diseases. However, the mechanisms underlying for the effect remain unknown. We previously showed that, among 11 compounds extracted from H hedyotidea, betulin produced the strongest suppressive effect on T cell activation. Here, we examined the hepatoprotective effects of betulin against acute autoimmune hepatitis in mice and the mechanisms underlying the effects. Freshly isolated mouse splenocytes were stimulated with concanavalin A (Con A, 5 µg/mL) in the presence of betulin, the cell proliferation was assessed with CSFE-dilution assay. Mice were injected with betulin (10, 20 mg·kg-1·d-1, ip) for 3 d. One hour after the last injection, the mice were injected with Con A (15 mg/kg, iv) to induce acute hepatitis. Blood samples and liver tissues were harvested at 10 h after Con A injection, and serum transaminase levels and liver histopathology were detected; serum levels of proinflammatory cytokines, hepatic T lymphocyte ratios, and functional statuses of conventional T and NKT cells were also analyzed. Betulin (16 and 32 µmol/L) dose-dependently suppressed the proliferation of Con A-stimulated mouse splenocytes in vitro. In Con A-challenged mice, preinjection with betulin (20 mg·kg-1·d-1) significantly decreased the levels of proinflammatory cytokines IFN-γ, TNF-α and IL-6, and ameliorated liver injury. Furthermore, pretreatment with betulin (20 mg·kg-1·d-1) significantly inhibited the Con A-induced activation of NKT and conventional T cells, and decreased production of proinflammatory cytokines IFN-γ, TNF-α and IL-6 in these two cell populations. Betulin has immunomodulatory effect on overly activated conventional T and NKT cells and exerts hepatoprotective action in mouse autoimmune hepatitis. The findings provide evidence for the use of H hedyotidea and its constituent betulin in the treatment of autoimmune diseases.