Effect of Brassica rapa var. rapifera on Insulin Resistance and Inflammatory Analysis of Visceral Adipose Tissue of Obese Wistar Rats Under Glucolipotoxicity Condition / Efecto de Brassica rapa var. rapifera sobre la Resistencia a la Insulina y el Análisis Inflamatorio del Tejido Adiposo Visceral de Ratas Wistar Obesas en Condiciones de Glucolipotoxicidad

SUMMARY: Obesity-related pathophysiologies such as insulin resistance and the metabolic syndrome show a markedly increased risk for type 2 diabetes and atherosclerotic cardiovascular disease. This risk appears to be linked to alterations in adipose tissue function, leading to chronic inflammation and the dysregulation of adipocyte-derived factors. Brassica rapa have been used in traditional medicine for the treatment of several diseases, including diabetes. This study aimed to investigate the effect of nutritional stress induced by a high-fat and high-sucrose diet on the pathophysiology of visceral adipose tissue and the therapeutic effect of Brassica rapa in male Wistar rats. We subjected experimental rats to a high-fat (10 %) high-sucrose (20 %)/per day for 11 months and treated them for 20 days with aqueous extract Br (AEBr) at 200 mg/kg at the end of the experiment. At the time of sacrifice, we monitored plasma and tissue biochemical parameters as well as the morpho-histopathology of visceral adipose tissue. We found AEBr corrected metabolic parameters and inflammatory markers in homogenized visceral adipose tissue and reduced hypertrophy, hyperplasia, and lipid droplets. These results suggest that AEBr enhances anti-diabetic, anti-inflammatory and a protective effect on adipose tissue morphology in type 2 diabetes and obesity.

La fisiopatología relacionadas con la obesidad, como la resistencia a la insulina y el síndrome metabólico, muestran un riesgo notablemente mayor de diabetes tipo 2 y enfermedad cardiovascular aterosclerótica. Este riesgo parece estar relacionado con alteraciones en la función del tejido adiposo, lo que lleva a una inflamación crónica y a la desregulación de los factores derivados de los adipocitos. Brassica rapa se ha utilizado en la medicina tradicional para el tratamiento de varias enfermedades, incluida la diabetes. Este estudio tuvo como objetivo investigar el efecto del estrés nutricional inducido por una dieta rica en grasas y sacarosa sobre la fisiopatología del tejido adiposo visceral y el efecto terapéutico de Brassica rapa en ratas Wistar macho. Sometimos a ratas experimentales a una dieta rica en grasas (10 %) y alta en sacarosa (20 %)/por día durante 11 meses y las tratamos durante 20 días con extracto acuoso de Br (AEBr) a 200 mg/kg al final del experimento. En el momento del sacrificio, monitoreamos los parámetros bioquímicos plasmáticos y tisulares, así como la morfohistopatología del tejido adiposo visceral. Encontramos parámetros metabólicos corregidos por AEBr y marcadores inflamatorios en tejido adiposo visceral homogeneizado y reducción de hipertrofia, hiperplasia y gotitas de lípidos. Estos resultados sugieren que AEBr mejora el efecto antidiabético, antiinflamatorio y protector sobre la morfología del tejido adiposo en la diabetes tipo 2 y la obesidad.

Método indirecto para la verificación del intervalo de referencia del perfil lipídico / Indirect method for the verification of the lipid profile reference range

Introducción: La dislipidemia es uno de los problemas más frecuentes en los niños y adolescentes y su estudio es importante debido a su fuerte correlación con la enfermedad cardiovascular aterosclerótica en adultos. Muchos países desarrollaron valores de referencia nacionales investigando los lípidos séricos utilizando datos basados en la población nacional propia. Nuestro objetivo fue verificar el intervalo de referencia del perfil lipídico calculando las curvas de percentiles a través del método indirecto en nuestra población pediátrica. Materiales y métodos: Se analizaron los resultados de nuestra base de datos utilizando el método indirecto. Luego de aplicar filtros y criterios de exclusión se calcularon los percentiles 25, 50, 75, 95 y 99 para colesterol total (CT), colesterol HDL (C-HDL), colesterol no HDL (C-no-HDL), triglicéridos (TG) y colesterol LDL (C-LDL) y para el C-HDL además se calculó el percentil 10. El valor de referencia para el cambio (RCV) se utilizó para determinar si existía diferencia clínicamente significativa entre los valores de percentiles obtenidos y los utilizados en el consenso de la SAP. Resultados: No se evidenció diferencia clínicamente significativa contra los valores propuesto por la SAP, excepto para los TG para las edades 1,5,7 años en el percentil 95 y para la edad de 8 años en el percentil 75 y 95; para el C-HDL en el percentil 10 para las edades 1,16 y 17 años. Discusión: Se obtuvieron los percentiles de los lípidos y se compararon con los valores de referencia utilizados por el consenso en el que están basados las guías (AU)

Introduction: Dyslipidemia is one of the most common problems in children and adolescents and its study is important because of its strong correlation with atherosclerotic cardiovascular disease in adulthood. Many countries have developed national reference values investigating serum lipids using data based on their own national population. Our aim was to verify the lipid profile reference range by calculating percentile curves through the indirect method in our pediatric population. Materials and methods: The results of our database were analyzed using the indirect method. After applying filters and exclusion criteria, the 25th, 50th, 75th, 95th, and 99th percentiles were calculated for total cholesterol (TC), HDL cholesterol (HDL-C), non-HDL cholesterol (non-HDL-C), triglycerides (TG), and LDL cholesterol (LDL-C); for HDL-C, the 10th percentile was also calculated. The reference change values (RCV) were used to determine whether there was a clinically significant difference between the percentile values obtained and those used in the consensus of the Argentine Association of Pediatrics (SAP). Results: There was no clinically significant difference with the values proposed by the SAP, except for TG for ages 1, 5, and 7 years at the 95th percentile and for age 8 years at the 75th and 95th percentile; and for HDL-C at the 10th percentile for ages 1, 16, and 17 years. Discussion: Lipid percentiles were obtained and compared with the reference values used by the consensus on which the guidelines are based (AU)

Formulación de galletas fortificadas por sustitución parcial de harina de moringa y suero lácteo / Formulation of fortified cookies by partial substitution of moringa flour and whey

El suero lácteo y la moringa poseen alto valor nutricional; sin embargo, su uso en la elaboración de productos alimenticios es una alternativa viable pero poco utilizada. Objetivo. Elaborar una galleta fortificada por sustitución parcial de harina de moringa (HM) y polvo de suero lácteo (PSL). Materiales y métodos. Durante septiembre-diciembre 2021, se desarrollaron cuatro formulaciones con sustitución parcial de harina de trigo por HM y PSL (F0=100:0:0; F1=90:5:5; F2=80:10:10; F3=70:15:15). La aceptación del producto se determinó mediante una evaluación sensorial considerando los atributos sabor, olor, color, textura y aceptación general. Se realizó el análisis químico proximal a la HM, al PSL, a la formulación de mayor aceptación y a F0. Se compararon los distintos parámetros químico proximales y de aceptación mediante una anova de una vía, seguido de una prueba de comparación de medias de Tukey (p<0,05). Resultados. Conforme se incrementa el porcentaje de sustitución de harina de trigo por HM y PSL se obtiene menor aceptación de las galletas, siendo F1 la más aceptada. F1 registró un contenido proteico de 6,90±0,04%, significativamente mayor al observado en F0. Conclusiones. La buena aceptabilidad de F1 indica que la sustitución parcial por HM y PSL no influyen en su aceptación; además, F1 mostró un enriquecimiento de proteinas, lípidos y cenizas, así como contenido adecuado de humedad y carbohidratos(AU)

Introduction. Whey and moringa have high nutritional value; however, their use in the production of food products is a viable but rarely used alternative. Objective. To make a biscuit fortified by partial substitution of moringa flour (MF) and whey powder (WP). Materials and methods. During September-December 2021, four formulations were developed with different degrees of partial substitution of wheat flour for MF and WP (F0=100:0:0; F1=90:5:5; F2=80:10:10; F3=70:15:15). The acceptance of the product was determined through a sensory evaluation considering the attributes taste, odor, color, texture and general acceptance. A proximal chemical analysis was performed on the MF, WP, the most widely accepted formulation and F0. Proximal chemical parameters and acceptance attributes were compared using a one-way anova, followed by a Tukey mean comparison test (p<0.05). Results. As the percentage of substitution of wheat flour by MF and WP increases less acceptance of the biscuits is obtained, with F1 as the most accepted formulation. F1 registered a protein content of 6.90±0.04%, significantly higher than that observed in F0. Conclusions: The good acceptability of F1 indicates that the partial substitution of wheat flour for MF and WP do not influence its acceptance; in addition, F1, showed an enrichment of protein, lipid and ash, as well as adequate moisture and carbohydrate content(AU)

El ayuno intermitente y sus efectos en la salud metabólica en humanos / Intermittent fasting and human metabolic health

Intermittent fasting (IF) has gained increasing scientific and general attention. Most studied forms of IF include alternate-day fasting, modified alternate-day fasting, and time-restricted eating (TRE). Several cardiometabolic effects of IF have been described in animal models and, to a lesser extent, in humans. This review analyzes the impact of IF on weight loss, glucose metabolism, blood pressure, and lipid profile in humans. A literature search was conducted in the Pubmed/Medline, Scopus, and Google Scholar databases. Controlled observational or interventional studies in humans, published between January 2000 and June 2021, were included. Studies comparing IF versus religious fasting were not included. Most studies indicate that the different types of IF have significant benefits on body composition, inducing weight loss and reducing fat mass. Changes in cardiometabolic parameters show more divergent results. In general, a decrease in fasting glucose and insulin levels is observed, together with an improved lipid profile associated with cardiovascular risk. High heterogeneity in study designs was observed, particularly in studies with TRE, small sample sizes, and short-term interventions. Current evidence shows that IF confers a range of cardiometabolic benefits in humans. Weight loss, improvement of glucose homeostasis and lipid profile, are observed in the three types of IF protocols evaluated.

Persistent organic pollutants distribution in plasma lipoprotein fractions / Distribuição persistente de poluentes orgânicos em frações de lipoproteínas plasmáticas

Abstract This study determines the associations among serum lipid profiles, risk of cardiovascular disease, and persistent organic pollutants. Using Gas chromatography technique, the intensity of toxic pollutant residues in serum samples of Hypertensive patients were measured. Based on statistical analysis, the effects of different covariates namely pesticides, age, systolic blood pressure, diastolic blood pressure, and lipid profile duration was checked using the logistic regression model. Statistical computation was performed on SPSS 22.0. The P-values of F-Statistic for each lipid profile class are greater than 0.01 (1%), therefore we cannot reject the null hypothesis for all cases. The estimated coefficients, their standard errors, Wald Statistic, and odds ratio of the binary logistic regression model for different lipid profile parameters indicate if pesticides increase then the logit value of different lipid profile parameters changes from -0.46 to -0.246 except LDL which increases by 0.135. The study reports a significantly increased threat of cardiovascular disease with increased concentrations of toxic pollutants.

Resumo Este estudo determina as associações entre o perfil lipídico sérico, o risco de doença cardiovascular e os poluentes orgânicos persistentes. Por meio da técnica de cromatografia gasosa, mediu-se a intensidade dos resíduos de poluentes tóxicos em amostras de soro de pacientes hipertensos. Com base na análise estatística, os efeitos de diferentes covariáveis ​​- ou seja, pesticidas, idade, pressão arterial sistólica, pressão arterial diastólica e duração do perfil lipídico - foram verificados usando o modelo de regressão logística. O cálculo estatístico foi realizado no SPSS 22.0. Os valores P da estatística F para cada classe de perfil lipídico são maiores que 0,01 (1%), portanto não podemos rejeitar a hipótese nula para todos os casos. Os coeficientes estimados, seus erros padrão, estatística de Wald e odds ratio do modelo de regressão logística binária para diferentes parâmetros do perfil lipídico indicam se os pesticidas aumentam, então o valor logit de diferentes parâmetros do perfil lipídico muda de -0,46 para -0,246, exceto LDL, que aumenta em 0,135. O estudo relata um aumento significativo da ameaça de doença cardiovascular com aumento das concentrações de poluentes tóxicos.

Effect of protein and lipids levels in a growth diet on adult whitebait Galaxias maculatus (Jenyns 1842) / Efeito dos níveis de proteína e lipídio em uma dieta de crescimento em whitebait Galaxias maculatus adulto (Jenyns 1842)

Abstract Galaxias maculatus aquaculture objectives is to produce millions of eggs. Wild females are small (2 g), have quick sexual maturity and low mean fecundity (500 eggs/female), requiring larger fishes with higher fecundity. This study aim is to evaluate experimentally the effect of the levels of protein, lipid and dietary energy on weight increases in adults. Five independent experiments were performed at different sequential time periods at the UCT hatchery, Chile. Specimens were obtained from a) Crystalline sea return specimen catches in the Tolten estuary (4 -6 cm, 0.3-0.4 g.). b) Hatchery cultured fish. Fish were fed by hand ad libitum. In experiments 1 to 4, pelleted diets were prepared with 3 to 5 levels of protein (treatments 27 up to 57%), crumble size, three 100 L fibre ponds replicates. In experiment 5 the effect of two lipid levels (8 and 21%) was evaluated with commercial extruded Salmon Nutra Starter isoproteic crumble 1 diet at 63%, replicated in 4 ponds. The results show: A tendency to increased weight in all sizes with an increased protein level in the pelleted diet.A maximal adult growth is obtained with a diet containing a minimum of 37% crude protein, with 40% the optimal value. A higher % protein in the diet or growth in weight lower feed conversion ratio. The feed conversion ratio in the extruded diet reaches up to 0.5 and in the pelleted vary from 0.7 to 1.5. Fish 0.6 g fed with 63% protein, extruded commercial diet with two different lipid levels (8 and 21%, 20.40 and 23.84 MJ kg-1, PE/TE 0.62 and 0.71) increased weight the first month 67 and 105% each. It has been established that high-energy diets with optimal levels of protein and lipid are a good short-term solution to obtain G. maculatus of higher weight.

Resumo O objetivo da aquicultura de Galaxias maculatus é produzir milhões de ovos. As fêmeas selvagens são pequenas (2 g) e têm maturidade sexual rápida e fecundidade média baixa (500 ovos/fêmea), necessitando de peixes maiores e com fecundidade superior. O objetivo deste estudo é avaliar experimentalmente o efeito dos níveis de proteínas, lipídios e energia da dieta sobre o aumento de peso em adultos. Cinco experimentos independentes foram realizados em diferentes períodos sequenciais de tempo no incubatório UCT, Chile. Os espécimes foram obtidos a partir de: a) capturas de espécimes de retorno do mar cristalino no estuário de Tolten (4-6 cm, 0,3-0,4 g); b) peixes de cultura em incubatório. Os peixes foram alimentados à mão ad libitum. Nos experimentos de 1 a 4, dietas peletizadas foram preparadas com três a cinco níveis de proteína (tratamentos 27 a 57%), tamanho do crumble, três repetições de tanques de fibra de 100 L. No experimento 5, o efeito de dois níveis de lipídios (8 e 21%) foi avaliado com dieta comercial isoproteica crumble 1 de Salmon Nutra Starter extrusada a 63%, replicada em quatro tanques. Os resultados mostram: uma tendência ao aumento de peso em todos os tamanhos, com um aumento do nível de proteína na dieta peletizada; um crescimento adulto máximo com uma dieta contendo um mínimo de 37% de proteína bruta, com 40% do valor ideal; uma porcentagem maior de proteína na dieta ou crescimento em peso com menor taxa de conversão alimentar. A taxa de conversão alimentar na dieta extrusada chega a 0,5, e na peletizada varia de 0,7 a 1,5. Peixes de 0,6 g alimentados com 63% de proteína e dieta comercial extrusada com dois níveis lipídicos diferentes (8 e 21%; 20,40 e 23,84 MJ kg-1; PE / TE 0,62 e 0,71) aumentaram de peso no primeiro mês em 67 e 105% cada, respectivamente. Foi estabelecido que dietas de alta energia com níveis ótimos de proteínas e lipídios são uma boa solução de curto prazo para obter G. maculatus de peso mais alto.

Improvement situation on indexes of the zebrafish disease model of non-alcoholic fatty liver disease with FGF21 analogues / 中华肝脏病杂志

Objective: To detect the therapeutic efficacy of FGF21 analogues on the zebrafish model of non-alcoholic fatty liver disease. Methods: A zebrafish model of non-alcoholic fatty liver disease was established by providing the normal diet fed to wild-type zebrafish three times daily. PF-05231023 was administered exogenously at a final concentration of 0.5 μmol/L. Body length, body weight, triglycerides, and other indexes were measured after 20 days. Pathological changes were evaluated in liver tissue sections by HE staining. Quantitative PCR was used to identify expressional changes in genes related to lipid metabolism, endoplasmic reticulum stress, and inflammation. Results: QPCR and immunofluorescence staining results showed that FGF21 was highly expressed in the zebrafish model group. The addition of the FGF21 analogue PF-05231023 significantly reduced the body length and body weight (P < 0.01), and the triglyceride content (P < 0.05) in the zebrafish model group. The liver HE staining results showed that PF-05231023 had alleviated the large and tiny bullae fat, lesions, and others in the zebrafish model group. The quantitative PCR results demonstrated that PF-05231023 reduced the expression of lipogenic factors (P < 0.01), inflammatory-related factors (P < 0.001), and genes related to endoplasmic reticulum stress (P < 0.05), but raised lipid-oxidation-related factors (P < 0.05) in the zebrafish model group. The addition of PF-05231023 reduced oleic acid-induced lipid and triglyceride levels in HepG2 cells. Conclusion: FGF21 analogue addition can improve indexes in the zebrafish disease model of non-alcoholic fatty liver disease.

Punicalagin inhibits hepatic lipid deposition in obese mice via AMPK/ACC pathway / 中国中药杂志

Hepatic lipid deposition is one of the basic manifestations of obesity, and nowadays pharmacological treatment is the most important tool. Punicalagin(PU), a polyphenol derived from pomegranate peel, is a potential anti-obesity substance. In this study, 60 C57BL/6J mice were randomly divided into a normal group and a model group. After establishing a model of simple obesity with a high-fat diet for 12 weeks, the successfully established rat models of obesity were then regrouped into a model group, an orlistat group, a PU low-dose group, a PU medium-dose group, and a PU high-dose group. The normal group was kept on routine diet and other groups continued to feed the high-fat diet. The body weight and food intake were measured and recorded weekly. After 8 weeks, the levels of the four lipids in the serum of each group of mice were determined by an automatic biochemical instrument. Oral glucose tole-rance and intraperitoneal insulin sensitivity were tested. Hemoxylin-eosin(HE) staining was applied to observe the hepatic and adipose tissues. The mRNA expression levels of peroxisome proliferators-activated receptor γ(PPARγ) and C/EBPα were determined by real-time quantitative polymerase chain reaction(Q-PCR), and the mRNA and protein expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), anterior cingulate cortex(ACC), and carnitine palmitoyltransferase 1A(CPT1A) were determined by Western blot. Finally, the body mass, Lee's index, serum total glyceride(TG), serum total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-C) levels were significantly higher and high-density lipoprotein cholesterol(HDL-C) levels were significantly lower in the model group as compared with the normal group. The fat deposition in the liver was significantly increased. The mRNA expression levels of hepatic PPARγ and C/EBPα and the protein expression level of ACC were increased, while the mRNA and protein expression levels of CPT-1α(CPT1A) and AMPK were decreased. After PU treatment, the above indexes of obese mice were reversed. In conclusion, PU can decrease the body weight of obese mice and control their food intake. It also plays a role in the regulation of lipid metabolism and glycometabolism metabolism, which can significantly improve hepatic fat deposition. Mechanistically, PU may regulate liver lipid deposition in obese mice by down-regulating lipid synthesis and up-regulating lipolysis through activation of the AMPK/ACC pathway.

Difference of lipid-lowering efficacy of "Xinjianqu" before and after fermentation and its mechanism based on LKB1-AMPK pathway and 16S rDNA sequencing technology / 中国中药杂志

On the basis of establishing the prescription of Xinjianqu and clarifying the increase of the lipid-lowering active ingredients of Xinjianqu by fermentation, this paper further compared the differences in the lipid-lowering effects of Xinjianqu before and after fermentation, and studied the mechanism of Xinjianqu in the treatment of hyperlipidemia. Seventy SD rats were randomly divided into seven groups, including normal group, model group, positive drug simvastatin group(0.02 g·kg~(-1)), and low-dose and high-dose Xinjianqu groups before and after fermentation(1.6 g·kg~(-1) and 8 g·kg~(-1)), with ten rats in each group. Rats in each group were given high-fat diet continuously for six weeks to establish the model of hyperlipidemia(HLP). After successful modeling, the rats were given high-fat diet and gavaged by the corresponding drugs for six weeks, once a day, to compare the effects of Xinjianqu on the body mass, liver coefficient, and small intestine propulsion rate of rats with HLP before and after fermentation. The effects of Xinjianqu before and after fermentation on total cholesterol(TC), triacylglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), creatinine(Cr), motilin(MTL), gastrin(GAS), and the Na~+-K~+-ATPase levels were determined by enzyme-linked immunosorbent assay(ELISA). The effects of Xinjianqu on liver morphology of rats with HLP were investigated by hematoxylin-eosin(HE) staining and oil red O fat staining. The effects of Xinjianqu on the protein expression of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK), liver kinase B1(LKB1), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase(HMGCR) in liver tissues were investigated by immunohistochemistry. The effects of Xinjianqu on the regulation of intestinal flora structure of rats with HLP were studied based on 16S rDNA high-throughput sequencing technology. The results showed that compared with those in the normal group, rats in the model group had significantly higher body mass and liver coefficient(P<0.01), significantly lower small intestine propulsion rate(P<0.01), significantly higher serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2(P<0.01), and significantly lower serum levels of HDL-C, MTL, GAS, Na~+-K~+-ATP levels(P<0.01). The protein expression of AMPK, p-AMPK, and LKB1 in the livers of rats in the model group was significantly decreased(P<0.01), and that of HMGCR was significantly increased(P<0.01). In addition, the observed＿otus, Shannon, and Chao1 indices were significantly decreased(P<0.05 or P<0.01) in rat fecal flora in the model group. Besides, in the model group, the relative abundance of Firmicutes was reduced, while that of Verrucomicrobia and Proteobacteria was increased, and the relative abundance of beneficial genera such as Ligilactobacillus and Lachnospiraceae＿NK4A136＿group was reduced. Compared with the model group, all Xinjianqu groups regulated the body mass, liver coefficient, and small intestine index of rats with HLP(P<0.05 or P<0.01), reduced the serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2, increased the serum levels of HDL-C, MTL, GAS, and Na~+-K~+-ATP, improved the liver morphology, and increased the protein expression gray value of AMPK, p-AMPK, and LKB1 in the liver of rats with HLP and decreased that of LKB1. Xinjianqu groups could regulate the intestinal flora structure of rats with HLP, increased observed＿otus, Shannon, Chao1 indices, and increased the relative abundance of Firmicutes, Ligilactobacillus(genus), Lachnospiraceae＿NK4A136＿group(genus). Besides, the high-dose Xinjianqu-fermented group had significant effects on body mass, liver coefficient, small intestine propulsion rate, and serum index levels of rats with HLP(P<0.01), and the effects were better than those of Xinjianqu groups before fermentation. The above results show that Xinjianqu can improve the blood lipid level, liver and kidney function, and gastrointestinal motility of rats with HLP, and the improvement effect of Xinjianqu on hyperlipidemia is significantly enhanced by fermentation. The mechanism may be related to AMPK, p-AMPK, LKB1, and HMGCR protein in the LKB1-AMPK pathway and the regulation of intestinal flora structure.

Advances in gene editing and natural product synthesis of Rhodotorula toruloides / 生物工程学报

Rhodotorula toruloides is a non-conventional red yeast that can synthesize various carotenoids and lipids. It can utilize a variety of cost-effective raw materials, tolerate and assimilate toxic inhibitors in lignocellulosic hydrolysate. At present, it is widely investigated for the production of microbial lipids, terpenes, high-value enzymes, sugar alcohols and polyketides. Given its broad industrial application prospects, researchers have carried out multi-dimensional theoretical and technological exploration, including research on genomics, transcriptomics, proteomics and genetic operation platform. Here we review the recent progress in metabolic engineering and natural product synthesis of R. toruloides, and prospect the challenges and possible solutions in the construction of R. toruloides cell factory.

Therapeutic potential of alkaloid extract from Codonopsis Radix in alleviating hepatic lipid accumulation: insights into mitochondrial energy metabolism and endoplasmic reticulum stress regulation in NAFLD mice / 中国天然药物

Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine. This study aimed to investigate the therapeutic effects and underlying mechanisms of alkaloid extract from Codonopsis Radix (ACR) in ameliorating hepatic lipid accumulation in a mouse model of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD). The results revealed that ACR treatment effectively mitigated the abnormal weight gain and hepatic injury associated with HFD. Furthermore, ACR ameliorated the dysregulated lipid metabolism in NAFLD mice, as evidenced by reductions in serum triglyceride, total cholesterol, and low-density lipoprotein levels, accompanied by a concomitant increase in the high-density lipoprotein level. ACR treatment also demonstrated a profound anti-oxidative effect, effectively alleviating HFD-induced oxidative stress and promoting ATP production. These effects were achieved through the up-regulation of the activities of mitochondrial electron transfer chain complexes I, II, IV, and V, in addition to the activation of the AMPK/PGC-1α pathway, suggesting that ACR exhibits therapeutic potential in alleviating the HFD-induced dysregulation of mitochondrial energy metabolism. Moreover, ACR administration mitigated HFD-induced endoplasmic reticulum (ER) stress and suppressed the overexpression of ubiquitin-specific protease 14 (USP14) in NAFLD mice. In summary, the present study provides compelling evidence supporting the hepatoprotective role of ACR in alleviating lipid deposition in NAFLD by improving energy metabolism and reducing oxidative stress and ER stress. These findings warrant further investigation and merit the development of ACR as a potential therapeutic agent for NAFLD.

Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice / 中西医结合学报

OBJECTIVE@#Recent investigations have demonstrated that Polygonum perfoliatum L. can protect against chemical liver injury, but the mechanism behind its efficacy is still unclear. Therefore, we studied the pharmacological mechanism at work in P. perfoliatum protection against chemical liver injury.@*METHODS@#To evaluate the activity of P. perfoliatum against chemical liver injury, levels of alanine transaminase, lactic dehydrogenase, aspartate transaminase, superoxide dismutase, glutathione peroxidase and malondialdehyde were measured, alongside histological assessments of the liver, heart and kidney tissue. A nontargeted lipidomics strategy based on ultra-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry method was used to obtain the lipid profiles of mice with chemical liver injury and following treatment with P. perfoliatum; these profiles were used to understand the possible mechanisms behind P. perfoliatum's protective activity.@*RESULTS@#Lipidomic studies indicated that P. perfoliatum protected against chemical liver injury, and the results were consistent between histological and physiological analyses. By comparing the profiles of liver lipids in model and control mice, we found that the levels of 89 lipids were significantly changed. In animals receiving P. perfoliatum treatment, the levels of 8 lipids were significantly improved, relative to the model animals. The results showed that P. perfoliatum extract could effectively reverse the chemical liver injury and significantly improve the abnormal liver lipid metabolism of mice with chemical liver injury, especially glycerophospholipid metabolism.@*CONCLUSION@#Regulation of enzyme activity related to the glycerophospholipid metabolism pathway may be involved in the mechanism of P. perfoliatum's protection against liver injury. Please cite this article as: Peng L, Chen HG, Zhou X. Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice. J Integr Med. 2023; 21(3): 289-301.

Diacylated anthocyanins from purple sweet potato (Ipomoeabatatas L.) attenuate hyperglycemia and hyperuricemia in mice induced by a high-fructose/high-fat diet / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Studies have shown that targeting xanthine oxidase (XO) can be a feasible treatment for fructose-induced hyperuricemia and hyperglycemia. This study aimed to evaluate the dual regulatory effects and molecular mechanisms of diacylated anthocyanins from purple sweet potato (diacylated AF-PSPs) on hyperglycemia and hyperuricemia induced by a high-fructose/high-fat diet. The body weight, organ index, serum biochemical indexes, and liver antioxidant indexes of mice were measured, and the kidneys were observed in pathological sections. The relative expression levels of messenger RNAs (mRNAs) of fructose metabolism pathway enzymes in kidney were detected by fluorescent real-time quantitative polymerase chain (qPCR) reaction technique, and the expression of renal transporter protein and inflammatory factor pathway protein was determined by immunohistochemistry (IHC) technique. Results showed that diacylated AF-PSPs alleviated hyperuricemia in mice, and that this effect might be related to the regulation of liver XO activity, lipid accumulation, and relevant renal transporters. Diacylated AF-PSPs reduced body weight and relieved lipid metabolism disorder, liver lipid accumulation, and liver oxidative stress, thereby enhancing insulin utilization and sensitivity, lowering blood sugar, and reducing hyperglycemia in mice. Also, diacylated AF-PSPs restored mRNA levels related to renal fructose metabolism, and reduced kidney injury and inflammation. This study provided experimental evidence for the mechanisms of dual regulation of blood glucose and uric acid (UA) by diacylated AF-PSPs and their utilization as functional foods in the management of metabolic syndrome.

Lipid nanoparticle delivery of siRNA targeting Cyp2e1 gene attenuates subacute alcoholic liver injury in mice / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effect and mechanism of lipid nanoparticle (LNP) delivery of small interfering RNA (siRNA) targeting Cyp2e1 gene on subacute alcoholic liver injury in mice.@*METHODS@#siRNA targeting Cyp2e1 gene was encapsulated in LNP (si-Cyp2e1 LNP) by microfluidic technique and the resulting LNPs were characterized. The optimal dose of si-Cyp2e1 LNP administration was screened. Forty female C57BL/6N mice were randomly divided into blank control group, model control group, si-Cyp2e1 LNP group, LNP control group and metadoxine group. The subacute alcoholic liver injury mouse model was induced by ethanol feeding for 10 d plus ethanol gavage for the last 3 d. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and the superoxide dismutase (SOD) activity as well as malondialdehyde, reactive oxygen species, glutathione, triacylglycerol, total cholesterol contents in liver tissue were measured in each group, and liver index was calculated. The expression of genes related to oxidative stress, lipid synthesis and inflammation in each group of mice were measured by realtime RT-PCR.@*RESULTS@#Compared with the model control group, the levels of liver index, serum ALT, AST activities, malondialdehyde, reactive oxygen species, triacylglycerol, total cholesterol contents in liver tissue decreased, but the SOD activity as well as glutathione increased in the si-Cyp2e1 LNP group (all P<0.01). Hematoxylin-eosin staining result showed disorganized hepatocytes with sparse cytoplasm and a large number of fat vacuoles and necrosis in the model control group, while the si-Cyp2e1 LNP group had uniformly sized and arranged hepatocytes with normal liver tissue morphology and structure. Oil red O staining result showed si-Cyp2e1 LNP group had lower fat content of the liver compared to the model control group (P<0.01), and no fat droplets accumulated. Anti-F4/80 monoclonal antibody fluorescence immunohistochemistry showed that the si-Cyp2e1 LNP group had lower cumulative optical density values compared to the model control group (P<0.01) and no significant inflammatory reaction. Compared with the model control group, the expression of catalytic genes P47phox, P67phox and Gp91phox were reduced (all P<0.01), while the expression of the antioxidant enzyme genes Sod1, Gsh-rd and Gsh-px were increased (all P<0.01). The mRNA expression of the lipid metabolism genes Pgc-1α and Cpt1 were increased (all P<0.01) and the lipid synthesis-related genes Srebp1c, Acc and Fasn were decreased (all P<0.01); the expression of liver inflammation-related genes Tgf-β, Tnf-α and Il-6 were decreased (all P<0.01).@*CONCLUSIONS@#The si-Cyp2e1 LNP may attenuate subacute alcoholic liver injury in mice mainly by reducing reactive oxygen levels, increasing antioxidant activity, blocking oxidative stress pathways and reducing ethanol-induced steatosis and inflammation.

A case of glycogen storage disease type Ⅰa with gout as the first manifestation / 浙江大学学报·医学版

A 24-year-old male was admitted due to recurrent redness, swelling, fever and pain in the ankle, frequently accompanied by hungry feeling. Dual energy CT scans showed multiple small gouty stones in the posterior edge of the bilateral calcaneus and in the space between the bilateral metatarsophalangeal joints. The laboratory examination results indicated hyperlipidemia, high lactate lipids, and low fasting blood glucose. Histopathology of liver biopsy showed significant glycogen accumulation. The results of gene sequencing revealed the compound heterozygous mutations of the G6PC gene c.248G>A (p.Arg83His) and c.238T>A (p.Phe80Ile) in the proband. The c.248G>A mutation was from mother and the c.238T>A mutation was from father. The diagnosis of glycogen storage disease type Ⅰa was confirmed. After giving a high starch diet and limiting monosaccharide intake, as well as receiving uric acid and blood lipids lowering therapy, the condition of the patient was gradually stabilized. After a one-year follow-up, there were no acute episodes of gout and a significant improvement in hungry feeling in the patient.

Association between early parenteral nutrition and the development of bronchopulmonary dysplasia in preterm infants / 中国当代儿科杂志

OBJECTIVES@#To study the relationship between early parenteral nutrient intake and the development of bronchopulmonary dysplasia (BPD) in preterm infants with gestational age less than 32 weeks who could not receive enteral nutrition within one week after birth.@*METHODS@#A retrospective study was conducted on preterm infants born between October 2017 and August 2022 with gestational age less than 32 weeks who were admitted to the Neonatal Intensive Care Unit in Children's Hospital of Soochow University within 24 hours after birth and relied solely on parenteral nutrition within the first week of life. The study population included 79 infants with BPD and 73 infants without BPD. Clinical data during hospitalization were compared between the two groups.@*RESULTS@#The proportions of infants with weight loss of more than 10% after birth, extrauterine growth retardation, and parenteral nutrition-associated cholestasis in the BPD group were higher than in the non-BPD group (P<0.05). The time to regain birth weight, time to achieve full enteral feeding, and corrected gestational age at discharge were longer in the BPD group than in the non-BPD group. The Z-scores of physical growth at corrected gestational age of 36 weeks were lower in the BPD group than in the non-BPD group (P<0.05). The BPD group had a higher fluid intake and a lower calories intake in the first week than the non-BPD group (P<0.05). The starting dose and total amount of amino acids, glucose, and lipids in the first week were lower in the BPD group than in the non-BPD group (P<0.05). The BPD group had a higher glucose-to-lipid ratio on the third day and higher energy-to-nitrogen and glucose-to-lipid ratios on the seventh day after birth than the non-BPD group (P<0.05).@*CONCLUSIONS@#Preterm infants with BPD had lower intake of amino acids and lipids and a lower proportion of calories provided by amino acids and lipids in the first week of life, which suggests an association between early parenteral nutrition intake and the development of BPD.

Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model / 中国中药杂志

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.

Correlation between serum cystatin C and lipid level in patients with chronic heart failure / 中南大学学报(医学版)

OBJECTIVES@#Serum cystatin C (Cys C) and blood lipid levels are related to the occurrence and development of chronic heart failure (CHF). However, there are few reports on the correlation between blood lipid level and serum Cys C level in patients with CHF. The aim of this study is to explore the correlation between serum Cys C level and blood lipid level in patients with CHF, and to provide valuable reference for clinical diagnosis and treatment of CHF.@*METHODS@#A total of 336 CHF patients who were hospitalized in the Department of Cardiovascular Medicine of Shaanxi Provincial People's Hospital from October 2017 to July 2018 were included and they were divided into a Cys C normal group (n=180) and a Cys C abnormal group (n=156) according to serum Cys C level of the patients. The general data, laboratory indicators, and cardiac ultrasound results were compared between the 2 groups. Pearson correlation analysis was used to detect the correlation between serum Cys C level and blood lipid level and other factors, and the data related to Cys C were further analyzed by multivariate logistic regression.@*RESULTS@#Compared with the Cys C normal group, patients in the Cys C abnormal group had lower left ventricular ejection fraction (LVEF) (P<0.001), older age (P=0.030), higher incidence rate of diabetes and smoking index (P=0.002 and P=0.003, respectively). The levels of serum creatinine (SCr), blood urea nitrogen (BUN), and total bilirubin (TBIL) were higher (all P<0.001), while the levels of high density lipoprotein (HDL), apolipoprotein (Apo) A, and albumin (ALB) were lower (P<0.001, P=0.001, and P=0.003, respectively) in the Cys C abnormal group. Pearson correlation analysis showed that serum Cys C level was negatively correlated with platelet count, HDL, Apo A, ALB, and LVEF. It was positively correlated with smoking index, mean platelet volume, neutrophil ratio, BUN, and TBIL (all P<0.05). The results of multivariate logistic regression analysis showed that the decreased HDL level was a risk factor for the abnormality of serum Cys C in patients with CHF (OR=0.119, P=0.003), while Apo A was not a risk factor for its abnormality (P=0.337).@*CONCLUSIONS@#HDL might be the only blood lipid index associated with abnormal serum Cys C in patients with CHF.

Research advances in mechanism of lipid infiltration of coronary heart disease and simultaneous treatment of phlegm and blood stasis based on phlegm-blood stasis correlation theory / 中国中药杂志

Atherosclerosis(AS) is the key pathological basis of coronary heart disease(CHD), and lipid infiltration is a classical theory to explain the pathological mechanism of AS. The theory highlights that the occurrence and development of AS are closely related to abnormal lipid metabolism, with the essence of the pathological reaction caused by the invasion of lipids into arterial intima from plasma. Phlegm and blood stasis are physiologically homologous and subject to pathological co-existence. Phlegm-blood stasis correlation is the basic theory to explain the pathogenesis characteristics of CHD and has important guiding significance for revealing the mecha-nism of lipid infiltration of CHD. Phlegm is the pathological product of abnormal metabolism of Qi, blood, and body fluid, and a gene-ral summary of a series of abnormally expressed lipid substances. Among them, turbid phlegm invades the heart vessels, gradually accumulates, and condenses to achieve the qualitative change from "invisible pathogen" to "tangible pathogen", which corresponds to the mechanism of lipid migration and deposition in the intima of blood vessels, and is the starting factor of the disease. Blood stasis is the continuous development of phlegm, and it is a result of pathological states such as decreased blood fluidity, increased blood coagulation, and abnormal rheology. The fact that blood stasis caused by phlegm accords with the pathological process of "lipid abnormality-circulatory disturbance" and is the central link of the disease. Phlegm and blood stasis aggravate each other and lead to indissoluble cementation. The phlegm-blood stasis combination serves as common pathogen to trigger the disease, which is the inevitable outcome of the disease. Based on the phlegm-blood stasis correlation theory, the simultaneous treatment of phlegm and blood stasis is established. It is found that this therapy can simultaneously regulate blood lipid, reduce blood viscosity, and improve blood circulation, which can fundamentally cut off the biological material basis of the reciprocal transformation between phlegm and blood stasis, thus exerting a significant curative effect.

Mechanism of Didang Decoction in prevention of anti-atherosclerosis and hyperlipidemia by HPLC-Q-TOF-MS/MS and network pharmacology based on theory of "nutrients return to heart and fat accumulates in channels" / 中国中药杂志

Atherosclerosis(AS) is caused by impaired lipid metabolism, which deposits lipids in the intima, causes vascular fibrosis and calcification, and then leads to stiffening of the vascular wall. Hyperlipidemia(HLP) is one of the key risk factors for AS. Based on the theory of "nutrients return to the heart and fat accumulates in the channels", it is believed that the excess fat returning to the heart in the vessels is the key pathogenic factor of AS. The accumulation of fat in the vessels over time and the blood stasis are the pathological mechanisms leading to the development of HLP and AS, and "turbid phlegm and fat" and "blood stasis" are the pathological products of the progression of HLP into AS. Didang Decoction(DDD) is a potent prescription effective in activating blood circulation, removing blood stasis, resolving turbidity, lowering lipids, and dredging blood vessels, with the functions of dispelling stasis to promote regeneration, which has certain effects in the treatment of atherosclerotic diseases. This study employed high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS) to screen the main blood components of DDD, explored the targets and mechanisms of DDD against AS and HLP with network pharmacology, and verified the network pharmacological results by in vitro experiments. A total of 231 blood components of DDD were obtained, including 157 compounds with a composite score >60. There were 903 predicted targets obtained from SwissTargetPrediction and 279 disease targets from GeneCards, OMIM, and DisGeNET, and 79 potential target genes of DDD against AS and HLP were obtained by intersection. Gene Ontology(GO) analysis suggested that DDD presumably exerted regulation through biological processes such as cholesterol metabolism and inflammatory response, and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis suggested that signaling pathways included lipid and atherosclerosis, insulin resistance, chemo-carcinogenesis-receptor activation, and AGE-RAGE signaling pathways in diabetic complications. In vitro experiments showed that DDD could reduce free fatty acid-induced lipid accumulation and cholesterol ester content in L02 cells and improve cellular activity, which might be related to the up-regulation of the expression of PPARα, LPL, PPARG, VEGFA, CETP, CYP1A1, and CYP3A4, and the down-regulation of the expression of TNF-α and IL-6. DDD may play a role in preventing and treating AS and HLP by improving lipid metabolism and inflammatory response, and inhibiting apoptosis with multi-component, multi-target, and multi-pathway characteristics.