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SUMMARY OBJECTIVE: There are limited data on non-alcoholic fatty liver disease in chronic hepatitis B virus infection. We aimed to determine the predictors for non-alcoholic fatty liver disease in patients with treatment-naïve chronic hepatitis B virus infection. METHODS: All consecutive treatment-naïve patients with chronic hepatitis B virus infection at the Haseki Training and Research Hospital between October 1, 2021, and September 31, 2022, were retrospectively enrolled. Chronic hepatitis B virus infection is defined by positive serum hepatitis B surface antigen for 6 months or more. Patients with significant alcohol consumption, prolonged steatogenic drug use, malignancy, monogenic hereditary disorders, patients co-infected with hepatitis D virus, hepatitis C virus infection, or human immunodeficiency virus were excluded. Demographic characteristics, anthropometric determinants, laboratory findings, and virological parameters were retrospectively collected from patients' charts and electronic medical records. RESULTS: A total of 457 patients with treatment-naïve chronic hepatitis B virus infection were included in the study. The three multivariate regression models revealed that age (p<0.028), body mass index (p=0.046), diabetes mellitus (p=0.030), hemoglobin (p=0.008), platelet (p=0.012), and triglyceride (p=0.002) in Model 1; body mass index (p=0.033), diabetes mellitus (p<0.001), hemoglobin (p=0.008), platelet (p=0.004), LDL (p=0.023), and HDL (p=0.020) in Model 2; and age (p<0.001), body mass index (p=0.033), hemoglobin (p=0.004), platelet (p=0.004), and HDL (p=0.007) in Model 3 were independent predictors. CONCLUSION: Non-alcoholic fatty liver disease was observed in about one-third of patients with chronic hepatitis B virus infection and was positively associated with older age, higher body mass index, presence of comorbid conditions including diabetes mellitus, increased levels of metabolic laboratory parameters, especially serum triglyceride and LDL, and decreased HDL.
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Background: The common cause of mortality in India is related to complications of cardiovascular disease which has direct relation with the hyperlipidemia, diabetes mellitus, and hypertension. Rosuvastatin more efficacious than other statins in lesser dosage and having good safety profile. Aim and Objective: The present study was undertaken to evaluate the safety, efficacy of rosuvastatin 10 mg daily dose versus alternate day dose in hyperlipidemia patients. Materials and Methods: A total of 50 individuals with hyperlipidemia were selected in this prospective open label research. Patients were grouped as Group D with rosuvastatin daily dose and Group A with alternate day dose. Fasting plasma lipid profile was assessed in both groups on the 1st, 4th, and 6th weeks. Results: There is significant reduction in total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and elevation of high-density lipoprotein (HDL) after 4 weeks and 6 weeks of the treatment in both the groups compared to baseline. The mean percentage reduction of total cholesterol was by 24% and 21.60% (P < 0.05) in Group D and Group A, respectively. The mean percentage reduction of LDL-C was by 33.50% and 31% (P < 0.05) Group D and Group A, respectively. The mean percentage improvement of HDL-cholesterol was by 19.89% and 17.09% (P < 0.05) in Group D and Group A, respectively. The mean percentage of reduction of TG was by 36.70% and 41.33% (P < 0.05) Group D and Group A. Conclusion: Rosuvastatin 10 mg on alternate days had the same efficacy in lowering cholesterol levels as taking it every day, also it may be a cost-effective alternative without sacrificing therapeutic benefits or side effects.
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【Objective】 To investigate the improvement of motor function recovery and the activation of endogenous neural stem cells (eNSCs) via voluntary exercise in mice with hyperlipidemia after intracerebral hemorrhage (ICH). 【Methods】 Four-month-old male Nestin-CreERT2: tdTomato transgenic mice were fed with high-fat diet (HFD) for eight weeks. Type Ⅳ collagenase was micro-injected into the corpus striatum to construct mouse ICH model with the help of stereotaxic apparatus. Voluntary exercise (wheel running) was initiated on the second day after ICH and monitored daily for seven days. Neurological severity score (NSS) and beam walking test were applied to evaluate motor function and coordination. Liver and brain tissues were collected at day 9 after ICH and sliced for staining. Then the Nestin-labeled cells, Ki67+, and doublecortin (DCX)+ in subventricular zone (SVZ) were counted to evaluate eNSCs activation. 【Results】 ① Compared with those of mice fed by chow diet (CD), the body weight, blood glucose level, concentration of lipid metabolism factors and the number of Nile Red positive cells in liver tissue were significantly higher in HFD-fed mice, confirming hyperlipidemia. ② Compared with the sham group, NSS score increased and the distance of cross-beam walking of ICH mice significantly decreased, showing the deficiency of motor function. It could be rescued by 7-day wheel running, as shown by a lower NSS score and a longer cross-beam walking distance. ③ Compared with the sham group, the number of Nestin+/Ki67+ cells decreased and Nestin+/DCX+ cells increased after ICH. After 7-day voluntary exercise, the number of Nestin+/Ki67+ cells decreased but that of Nestin+/DCX+ cells further increased significantly. However, compared with ICH, the increase of Nestin+/DCX+ cells in ICH+Ex was not significant. 【Conclusion】 Short-term voluntary exercise during the acute stage of ICH improved the recovery of motor function and enhance the proliferation of eNSCs in mice with hyperlipidemia. This provides a new idea for further developing ICH accelerated rehabilitation strategy based on eNSCs.
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Objective To detecte the expressions of phosphorylated p38 MAPK (p-p38 MAPK), Bax and Bcl-2 in the cerebral cortex of hyperlipidemia rats after cerebral ischemia-reperfusion (I/R) injury and the effect of SB203580 on the expressions of p-p38 MAPK, Bax and Bcl-2, to explore the effect of p38 MAPK activation on the expressions of Bax and Bcl-2 in hyperlipidemia cerebral I/R injury. Methods After the hyperlipidemia model was established, the rats were randomly divided into 3 groups: sham operation group, operation group (I/R) and SB203580 treatment group (SB+I/R), with 10 rats in each group. The focal cerebral I/R model in hyperlipemia rats was established with thread embolism of the left middle cerebral artery. The neurobehavioral score was used to observe the symptoms of neurobehavioral injury. The 2, 3, 5-triphenyltetrazolium chloride (TTC) staining was used to detect the volume of cerebral infarction, and the TUNEL staining was used to observe apoptotic cells. The relative expression levels of p-p38 MAPK, Bax and Bcl-2 were analyzed by immunohistochemistry. Results Compared with the sham group, the infarct volume, apoptosis index and neurobehavioral score of rats in the I/R group increased significantly, and the expressions of p-p38 MAPK and Bax increased significantly, and the expression of Bcl-2 decreased significantly (P<0. 05). Compared with the I/R group, rats in the SB+I/R group had less brain damage, the infarct volume and the apoptosis index were significantly reduced, the expressions of p-p38 MAPK reduced significantly, Bax expression decreased while Bcl-2 expression increased. The differences were statistically significant (P<0. 05). Neurobehavioral scores were lower in SB+I/R group than in I/R group, but the difference was not statistically significant. Conclusion In the process of cerebral I/R injury in hyperlipidemiarats, activation of p38 MAPK can regulate the expression of Bax and Bcl-2.
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Objective To observe the effect of polyinosinic-polycytidylic acid ( Poly-IC ) treatment on the expressions of Bcl-2 and Bax after cerebral ischemia-reperfusion ( I / R ) injury in fryperlipidemia rats, and to detect the cerebral infarction, blood-brain barrier permeability and behavioral injury symptoms, to explore the neuroprotective effect of Poly-IC treatment on cerebral I /R injury in fryperlipidemia rats. Methods Hyperlipidemia rats were randomly divided into cerebral I /R group, Poly-IC pretreatment group, Poly-IC post-treatment group and sham operation group, 20 rats in each group. Neurobehavioral performance of rats in each group was recorded according to neurobehavioral score of 0-4 points. Blood-brain barrier permeability of rats in each group was detected by Evans blue staining. TTC staining was used to observe the cerebral infarction in each group. Apoptotic cells in the cerebral cortex of rats in each group was observed by TUNEL staining. The relative expression levels of Bcl-2 and Bax were determined by Western blotting. Results Compared with the sham group, the symptoms of neurobehavioral damage in the I/R group were serious and the score increased significantly (P<0. 05). The scores of Poly-IC pretreatment and post-treatment groups were significantly lower than that of I/R group (P<0. 05). Evans blue staining result showed that the blood-brain barrier permeability of the I/R group was significantly higher than that of the sham group (P<0. 05) , and Poly-IC pretreatment or post-treatment could significantly reduce the blood-brain barrier permeability ( P < 0. 05 ) . No infarct was observed in the sham group with uniform red staining, while white infarct was observed in the brain tissue of the I/R group. Compared with the I/R group, the volume of infarct in both Poly-IC pretreatment and post-treatment groups reduced significantly (P<0. 05). The apoptosis index in cerebral cortex of rats in I/R group was significantly higher than that in sham group ( P < 0 .05 ) , while the apoptosis index in Poly-IC pretreatment or post-treatment group was significantly lower than that in I/R group(P<0. 05 ) . The result of Western blotting showed that, compared with the sham group, the expression of Bax in the I/R group was significantly increased(P<0. 05) , the expression of Bcl-2 was significantly decreased(P<0. 05). Compared with the I/R group, the expression of Bax in the Poly-IC pretreatment or post-treatment group reduced significantly ( P < 0. 05 ) , the expression of Bcl-2 increased significantly(P<0. 05). Conclusion Poly-IC pretreatment or post-treatment can improve the symptoms of neurobehavioral injury, reduce the damage of blood-brain barrier, reduce the volume of cerebral infarction, decrease the apoptosis index of nerve cells, play a neuroprotective effect on cerebral ischemia reperfusion injury in rats with hyperlipidemia, and this protective effect may be related to the change of Bcl-2 and Bax expression levels.
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Objective To study the effect of simulated high altitude hypoxia on the pharmacokinetics and pharmacodynamics of atorvastatin calcium in hyperlipidemia rats. Methods The wistar rats with hyperlipidemia induced by high-fat diet were divided into normoxia group and hypoxia group. Rats in the hypoxia group received a 14-day chronic hypoxia exposure at simulated an altitude of 5, 500 m. The two groups were given atorvastatin calcium(20 mg•kg
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Through the non-targeted metabolomics study of endogenous substances in the liver and serum of hyperlipidemia rats, the biomarkers related to abnormal lipid metabolism in hyperlipidemia rats were found, and the target of ginsenoside Rb_1 in improving hyperlipidemia was explored and its mechanism was elucidated. The content of serum biochemical indexes of rats in each group was detected by the automatic biochemical analyzer. The metabolite profiles of liver tissues and serum of rats were analyzed by HPLC-MS. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to compare and analyze the metabolic data in the normal group, the hyperlipidemia group, and the ginsenoside Rb_1 group, and screen potential biomar-kers. The related metabolic pathways were further constructed by KEGG database analysis. The results showed that hyperlipemia induced dyslipidemia in rats, which was alleviated by ginsenoside Rb_1. The non-targeted metabolomics results showed that there were 297 differential metabolites in the liver tissues of hyperlipidemia rats, 294 differential metabolites in the serum samples, and 560 diffe-rential metabolites in the hyperlipidemia rats treated by ginsenoside Rb_1. Perillic acid and N-ornithyl-L-taurine were common metabolites in the liver and serum samples, which could be used as potential biomarkers for ginsenoside Rb_1 in the improvement of hyperlipidemia. As revealed by pathway enrichment in the liver and serum, ginsenoside Rb_1 could participate in the metabolic pathway of choline in both the liver and serum. In addition, ginsenoside Rb_1 also participated in the ABC transporter, alanine, aspartic acid, and glutamate metabolism, protein digestion and absorption, β-alanine metabolism, taurine and hypotaurine metabolism, caffeine metabolism, valine, leucine, and isoleucine biosynthesis, arachidonic acid metabolism, and methionine and cysteine metabolism to improve dyslipidemia in rats.
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Ratas , Animales , Hiperlipidemias/tratamiento farmacológico , Metaboloma , Ginsenósidos/metabolismo , Metabolismo de los Lípidos , Metabolómica/métodos , Hígado/metabolismo , Biomarcadores , TaurinaRESUMEN
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.
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Ratas , Animales , Proteínas Quinasas Activadas por AMP/metabolismo , Ratas Sprague-Dawley , LDL-Colesterol , Fermentación , Acuaporina 2/metabolismo , Metabolismo de los Lípidos , Hígado , Lípidos , Hiperlipidemias/genética , Adenosina Trifosfato/farmacología , Dieta Alta en Grasa/efectos adversosRESUMEN
Objective To explore the pharmacokinetic properties of curcumin nano emulsion and its pharmacodynamic effects on hyperlipidemia in rats. Methods The method for determination of curcumin was established by HPLC-MS. The pharmacokinetics characteristics of curcumin nano emulsion oral administration system were investigated. SD rats were used as model animals to establish hyperlipidemia animal models, and the pharmacodynamic effects of curcumin nano emulsion on hyperlipidemia induced by high fat diet was preliminarily investigated. Results The results of pharmacokinetic studies in vivo showed that the relative bioavailability of curcumin nano emulsion was 313.47% with bulk drug group as the reference preparation. The relative bioavailability of curcumin nano emulsion was 279.52 % with tablets as reference preparation. Cmax of curcumin nano emulsion group was 201.48 % of that of bulk drug group and 193.02 % of that of tablet group, and had higher MRT value (183.52 % of that of bulk drug group and 154.21 % of that of tablet group) than bulk drug group and tablet group. Pharmacodynamics research results showed that curcumin nano emulsion oral administration system could significantly reduce the levels of triglyceride and LDL-c in serum of model rats, and relieve liver lipid deposition and liver injury caused by high-fat diet in model animals. Conclusion The oral administration system of curcumin nano emulsion could effectively improve the bioavailability of curcumin, which has a good hypolipidemic effect. It also could control the weight gain of hyperlipidemia rats and improve the changes of liver coefficient caused by lipid metabolism disorder.
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Cholesterol is an important precursor of many endogenous molecules. Disruption of cholesterol homeostasis can cause many pathological changes, leading to liver and cardiovascular diseases. CYP1A is widely involved in cholesterol metabolic network, but its exact function has not been fully elucidated. Here, we aim to explore how CYP1A regulates cholesterol homeostasis. Our data showed that CYP1A1/2 knockout (KO) rats presented cholesterol deposition in blood and liver. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats. Further studies found that the lipogenesis pathway (LXRα-SREBP1-SCD1) of KO rats was activated, and the key protein of cholesterol ester hydrolysis (CES1) was inhibited. Importantly, lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A. Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.
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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.
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Humanos , Hiperlipidemias/tratamiento farmacológico , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión , Farmacología en Red , Nutrientes , Aterosclerosis/prevención & control , Lípidos , Medicamentos Herbarios Chinos/farmacología , Simulación del Acoplamiento MolecularRESUMEN
ObjectiveTo evaluate the lipid-lowering activity of Quansanqi tablets（QSQ）， an innovative new drug of Panax notoginseng. MethodMice and golden hamsters were used to establish a hyperlipidemia model by injecting egg yolk milk and feeding high-fat diets. The levels of total cholesterol （TC），triglyceride （TG），low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected， and liver function indicators ［alanine aminotransferase （ALT）， aspartate amino-transferase （AST）， and alkaline phosphatase （ALP）］ of golden hamsters were detected. Hematoxylin-eosin （HE） staining was used to observe the degree of liver injury. In the experiments， a normal group， a model group， an atorvastatin calcium group， and low-， medium-， and high-dose QSQ groups （0.32， 0.64， 1.28 g·kg-1 for mice， and 0.16， 0.32， 0.64 g·kg-1 for golden hamsters） were set up. ResultCompared with the normal group， the acute hyperlipidemia model mice showed increased TC， TG， and LDL-C levels （P<0.01）， and the hyperlipidemia model mice showed increased TC and LDL-C levels （P<0.01）. Additionally， the hyperlipidemia model golden hamsters showed increased serum TC， TG， LDL-C， ALT， AST， and ALP levels （P<0.05， P<0.01）. HE staining indicated the presence of fat accumulation in the liver， accompanied by inflammatory reactions. Compared with the model group， QSQ of various doses could reduce TC， TG， and LDL-C levels in acute hyperlipidemia model mice （P<0.05， P<0.01）， and the high-dose QSQ could reduce TC and LDL-C levels （P<0.01） and increase HDL-C level （P<0.05） in hyperlipidemia model mice， as well as reduce TC， TG， and LDL-C levels in hyperlipidemia model golden hamsters （P<0.05， P<0.01）， especially in the first two weeks. In addition， atorvastatin calcium could further increase ALT， AST， and ALP levels （P<0.05， P<0.01） and aggravate liver function damage， while low-dose QSQ could reduce ALT， AST， and ALP （P<0.05）， and medium- and high-dose QSQ did not cause further liver function damage. ConclusionQSQ have a significant lipid-lowering effect on different hyperlipidemia model animals and can improve liver function and liver injury.
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ObjectiveTo explore the effect and possible mechanism of electroacupuncture （EA） at Fenglong （ST40） on liver lipid synthesis and insulin resistance （IR） in hyperlipidemic （HLP） rats. MethodEighteen rats were randomly divided into three groups， blank group， model group， and EA group， each consisting of six rats. The blank group rats were with fed a basic diet， while those in the model group and EA group were fed high-fat diet for 8 weeks. After modeling， the rats in the EA group received bilateral EA treatment at “Fenglong” （ST 40）. The rats in the model group underwent daily binding treatment， once a day， continuously 5 days a week， for a total of 4 weeks. Following the intervention， the levels of triglycerides （TG） and free fatty acids （FFA） in liver tissue was determined using ELISA. Serum TG， FFA， fasting insulin （FINS）， alanine transaminase （ALT）， aspartate Transaminase （AST）， tumor necrosis factor-ɑ （TNF-ɑ）and interleukin 6 （IL-6） were also measured. The fasting plasma glucose （FBG） assessed using a glucose meter and the homeostatic model assessment of insulin resistance （HOMA-IR） was calculated. Liver pathology was examined through HE staining and oil red O staining. The expression of hepatic sterol regulator binding protein 1c （SREBP1c）， recombinant fatty acid synthase （FASN） and stearoyl-CoA desaturase 1 （SCD1） were detected through immunofluorescence. The protein expression levels of liver insulin receptor substrate 1 （IRS1） and tyrosine-phosphorylated insulin receptor substrate 1 （p-IRS1-Tyr） were determined via Western blot. ResultsWhen compared to the blank group， the model group of rats exhibited elevated serum and liver tissue levels of TG and FFA， as well as increased serum levels of AST， ALT， TNF-α， IL-6， FBG， FINS， and HOMA-IR （P＜0.05）. HE staining revealed disordered arrangements of liver cells， indicating widespread fatty degeneration. Oil red O staining showed abundant bright red lipid droplets within liver cell cytoplasm， indicating severe lipid accumulation. The average fluorescence intensity of SREBP1c， FASN， and SCD1 in liver tissue significantly increased （P＜0.05）， while p-IRS1-Tyr protein expression levels significantly decreased （P＜0.05）. In comparison to the model group， the EA group of rats showed significantly reduced serum and liver tissue levels of TG and FFA， along with decreased serum levels of AST， ALT， TNF-α， IL-6， FBG， FINS， and HOMA-IR （P＜0.05）. HE staining indicated more regular arrangements of liver cells， and oil red O staining revealed a significant reduction in liver cell lipid droplets， indicating a less severe degree of lipid accumulation. The average fluorescence intensity of SREBP1c， FASN， and SCD1 in liver tissue significantly decreased （P＜0.05）， while p-IRS1-Tyr protein expression levels significantly increased （P＜0.05）， with no significant difference in IRS1 protein expression （P＞0.05）. ConclusionEA at “Fenglong” （ST 40） can significantly decrease serum lipid in HLP rats， improves liver fat accumulation， and also ameliorate insulin resistance. The mechanism may be related to the inhibition of hepatic lipid synthesis molecule expression， reduced serum inflammatory factors， and an increase in insulin substrate receptor phosphorylation levels.
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Hyperlipidemia is a dyslipidemia caused by dyslipidemia of lipid metabolism， which can be divided into primary and secondary types. The current clinical diagnostic criteria are mainly changes in lipid levels， which are the inducers of high-risk cardiovascular diseases such as atherosclerosis， pancreatitis and coronary heart disease. As a key target in lipid metabolism， peroxisome proliferator-activated receptor α （PPARα） is involved in a variety of metabolic activities， including fatty acid degradation， synthesis， transport， storage， lipoprotein metabolism， etc. Activation of PPARα can maintain the balance of lipid metabolism through a variety of ways， which is an important way to treat hyperlipidemia. At present， chemical drugs such as statins and bettes are mainly used in the clinical treatment of hyperlipidemia. Although they can slow down the disease to a certain extent， there are many adverse reactions and drug resistance. By reviewing the literature in recent years， the author found that the activation of PPARα pathway by traditional Chinese medicine in the treatment of hyperlipidemia has significant effect and small adverse reactions. The lipid-lowering active ingredients include flavonoids， alkaloids， phenols， terpenoids and other compounds. These active components mainly affect the expression of downstream effectors through the activation of PPARα pathway， thereby inhibiting the synthesis of total cholesterol and promoting fatty acid oxidation， and play a role in the treatment of hyperlipidemia. In this paper， we systematically reviewed the structure types and mechanism of active components of traditional Chinese medicine that activate PPARα pathway， so as to provide guidance for the rational development and clinical application of lipid-lowering traditional Chinese medicine new drugs.
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INTRODUCCIÓN: Para mitigar la propagación del SARS-CoV-2 se requirió de un confinamiento generalizado. Las autoridades argentinas impusieron aislamiento social preventivo durante 234 días (20 de marzo al 9 de noviembre de 2020), modificando el estilo de vida de la población. OBJETIVOS: Examinar la influencia de las medidas de bloqueo en el perfil metabólico de pacientes infectados por VIH en Argentina. PACIENTES Y MÉTODOS: Estudio de cohorte retrospectivo de 10.239 pacientes en seguimiento en una clínica de atención privada de personas con infección por VIH. Se incluyeron pacientes adultos con terapia antirretroviral (TARV) en curso que tuvieran una determinación de glucemia, colesterol total, colesterol HDL y trigliceridemia antes de la cuarentena (Pre-C: segundo semestre 2019) y una segunda determinación durante la misma (Intra-C: mayo 2020). Se excluyeron los pacientes con cambios en la TARV con impacto metabólico, los que iniciaron o suspendieron hipolipemiantes o hipoglucemiantes y mujeres embarazadas. Las variables categóricas se compararon mediante la prueba de la χ2 o la prueba exacta de Fisher y las continuas mediante la prueba t o la prueba de Mann-Whitney según correspondiera. Se consideró significativo un valor de p a dos colas < 0,05. RESULTADOS: Se incluyeron 540 individuos. La mediana de edad fue de 47 años y 74,6% fueron de sexo masculino. La mediana de índice de masa corporal fue 26,1 y 94,6% tenían bajo riesgo cardiovascular. Hubo un aumento significativo en el porcentaje de pacientes con hiperglucemia (Pre-C 5,2% vs Intra-C 8,5%, p 0,04), hipertrigliceridemia (Pre-C 33,9% vs Intra-C 40,7%, p 0,02) e hipercolesterolemia LDL (Pre-C 12,6% vs Intra-C 17,2%, p 0,04). CONCLUSIÓN: Nuestros resultados sugieren que la cuarentena, al menos en sus fases iniciales, puede tener un impacto negativo en el perfil metabólico de esta población.
BACKGROUND: The spread of SARS-CoV-2 required widespread lockdown to mitigate the pandemic. Argentine authorities imposed preventive social isolation for 234 days (March 20th to November 9th 2020). This measure led to major changes in the population's lifestyle. AIM: To examine the influence of COVID-19 lockdown measures on the metabolic profile of HIV-infected patients in Argentina. METHODS: Retrospective cohort study of 10,239 HIV-infected patients under follow up in a private clinic for HIV care. Adult patients with ongoing antiretroviral therapy (ART) and a baseline determination of blood glucose, total cholesterol, HDL-cholesterol and triglycerides done before lockdown (BL: second semester of 2019) and a second determination during lockdown (DL: May 2020) were included. Patients with recent changes in ART that may have metabolic impact, those starting lipid/glucose lowering agents and pregnant women were excluded. Categorical variables were compared using the χ2 test or Fisher's exact test, and continuous variables using the t-test or the Mann-Whitney test. A two-tailed value of p < 0.05 was considered significant. RESULTS: 540 individuals were included, median of age was 47 years and 74.6% were male. Median body mass index was 26.1 and 94.6% had low cardiovascular risk. There was a significant increase in the percentage of patients that met criteria for hyperglycemia (BL 4.8% and DL 8.5%, p < 0.001). We also observed significant (p < 0.001) increase in median (IQR) BL vs DL values in LDL-cholesterol [109 (90-128) vs 118 (97-139) mg/dL]; and triglycerides [120 (87-172) vs. 132 mg/dL (96-184)]. The proportion of patients with hyper-LDL cholesterolemia according to individual cardiovascular risk increased from 12.6 to 17.2% (p = 0.04). CONCLUSION: Our results suggest that quarantine, at least in its initial phases, may have a negative impact on the metabolic profile of this population.
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Humanos , Masculino , Femenino , Embarazo , Adulto , Persona de Mediana Edad , Anciano , Infecciones por VIH/epidemiología , Cuarentena , COVID-19 , Argentina/epidemiología , Triglicéridos , Glucemia , Control de Enfermedades Transmisibles , Estudios Retrospectivos , Metaboloma , SARS-CoV-2 , HDL-ColesterolRESUMEN
Abstract Introduction Lipoprotein apheresis (LA) is an extracorporeal therapy which removes apolipoprotein B-containing particles from the circulation. We evaluated techniques and efficiency of lipoprotein apheresis procedures applied to patients with familial and non-familial hypercholesterolemia (FH) at our center. Methods We retrospectively evaluated 250 LA procedures applied to 27 patients with dyslipidemia between March 2011 and August 2019. Results A total of 27 patients, of whom 19 (70.4%) were male and 8 (29.6%), female, were included. Eighteen (66.7%), 6 (22.2%) and 3 (11.1%) patients were diagnosed with non-FH, homozygous FH (HoFH) and heterozygous FH (HeFH), respectively. Two different apheresis techniques, direct adsorption of lipoproteins (DALI) (48.8%) and double filtration plasmapheresis (DFPP) (51.2%), were used. The change in the serum total cholesterol (TC) level was the median 302 mg/dl (171-604 mg/dl) (60.4%) in HoFH patients, 305 mg/dl (194-393 mg/dl) (60.8%) in HeFH patients and 227 mg/dl (75-749 mg/dl) (65.3%) in non-FH patients. The change in the serum low-density lipoprotein (LDL) level was the median 275 mg/dl (109-519 mg/dl) (64.2%), 232 mg/dl (207-291 mg/dl) (64.5%) and 325 mg/dl (22-735 mg/dl) (70.9%) in patients with HoFH, HeFH and non-FH, respectively. A significantly effective reduction in serum lipid levels, including TC, LDL and triglycerides, was achieved in all patients, regardless of the technique, p< .001. The decrease in the serum TC and LDL levels was significantly higher in the DFPP, compared to the DALI, being 220 mg/dl (-300 to 771) vs 184 mg/dl (64-415), p< .001 and 196 mg/dl (11-712) vs 157 mg/dl (54-340), p< .001, respectively. Conclusions Our results showed that LA is a highly effective treatment in reducing serum lipid levels and safe, without any major adverse event.
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Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Eliminación de Componentes Sanguíneos , Lipoproteínas , HiperlipidemiasRESUMEN
Aim To investigate the expression of Foxos in human umbilical vein endothelial cells(HUVECs)with insulin resistance(IR)induced by high glucose and high fat(HG/HF)stress and its significance.Methods First, the IR model of endothelial cells was established by HG /HF stress.The differential expression of Foxos gene in normal(Ctrl )group and HG /HF group was observed, and the subtypes with the most significant changes in Foxos were screened out, such as Foxo6.Next, Foxo6 was silenced to observe its role in endothelial cell with IR.Finally, whether the mechanism of Foxo6-mediated IR was related to the interaction of NF-κB signaling was investigated.Results The expression increase of Foxo6 was the most significant among Foxos under the IR condition induced by HG/HF.Using a small RNA interference and plasmid transfection technique, we found that the silence effect of the siRNA3 fragments targeting Foxo6 was the most significant among the siRNAs.Moreover, the further study showed that silencing the Foxo6 gene could significantly reverse the endothelial IR induced by HG/HF, and the mechanism of the reversal effect was related to the interaction between the Foxo6 and NF-κB signal.Conclusions Foxo6 mediates the endothelial cell IR induced by the HG /HF stress.The underlying mechanism is that Foxo6 can interact with NF-κBp65 and activate NF-κB signaling pathway.Silencing Foxo6 can improve the IR of vascular endothelial cells induced by HG /HF stress.
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Aim To explore the ameliorative effects of Rosa roxburghii Tratt on hyperlipidemia and investigate the underlying mechanism by using experimental validation and network pharmacology.Methods The therapeutic effect of Rosa roxburghii Tratt on hyperlipidemia was investigated by constructing a hyperlipidemic rat model and measuring the serum lipid index and liver pathological changes.The literature search method was used to obtain active ingredients and targets of Rosa roxburghii Tratt,the target gene was collected from GeneCards,OMIM,DrugBank database,then generated herbal-active ingredient-potential target networks and protein-protein interactions(PPI)networks.The target GO function enrichment analysis and KEGG pathway enrichment analysis were analyzed by DAVID software.Molecular docking was carried out using AutoDock.Results Rosa roxburghii Tratt could significantly improve dyslipidemia and liver pathological damage in hyperlipidemic rats.Network pharmacology results showed that RXRA,AKT1,ESR1,PIK3R1 were key targets of Rosa roxburghii Tratt to lower blood lipids.Molecular docking showed that Roxburic acid and α-linolenic acid had good binding to RXRA,AKT1,ESR1,and PIK3R1.Conclusions Combined with pharmacodynamic experiments and network pharmacology-molecular docking,the therapeutic effect and possible mechanism of action of Rosa roxburghii Tratt on hyperlipidemia are preliminarily explored,which provides a certain basis for the in-depth study of pharmacodynamic substance basis,mechanism of action and clinical application.
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Objective@#To investigate the characteristics of intestinal microflora among flying personnel with hyperlipidemia, so as to provide insights into prevention of hyperlipidemia among flying personnel. @*Methods @#Flying personnel diagnosed with hyperlipidemia in a sanatiorium from October 2020 to February 2021 were included in the hyperlipidemia group, while flying personnel with normal blood lipids during the same period served as controls. Subjects' age, family history, physical examinations and blood testing results were collected from both groups. Fecal samples were collected, and intestinal microflora was sequenced followed by bioinformatics analysis. The diversity and abundance of intestinal microflora were compared, and the key bacteria were screened using LEfSe analysis.@*Results@#There were 29 subjects in the hyperlipidemia group with a median age (interquartile range) of 34 (12) years and 25 subjects in the control group with a median age (interquartile range) of 30 (12) years, and all subjects were men. There were no significant differences between the two groups in terms of age, flight duration, smoking, family history of metabolic diseases and waist circumference (P>0.05). The Shannon diversity index of intestinal microflora was lower in the hyperlipidemia group than in the control group (Z=4.370, P=0.026), and there was a significant difference in the overall structure of intestinal flora between the two groups, which were clustered into two groups. LEfSe analysis identified Herbaspirillum, Atopobium and Eggerthella as key microorganisms in the hyperlipidemia group, and Agathobacter, Dialister, norank_Eubacterium_coprostanoligenes_group, Alloprevotella and unclassified Bacteroidales as key microorganisms in the control group.@*Conclusions@#The species diversity and relative abundance of intestinal microflora are lower in flying personnel with hyperlipidemia than in those with normal blood lipids. Herbaspirillum, Atopobium and Eggerthella may be the key bacteria contributing to hyperlipidemia among flying personnel.
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Objective:To explore the characteristics of T lymphocyte subsets and cytokines in hyperlipidemia-induced acute pancreatitis (HLAP) and its prognostic value.Methods:This study included 184 patients with acute pancreatitis (AP) admitted to the First Affiliated Hospital of Xiamen University from January 2018 to May 2021. Based on disease etiology, there were 92 HLAP cases and 92 non-hyperlipidemia-induced AP (NHLAP) cases. Stratified by disease severity according to 2012 Atlanta classification criteria, the patients were divided into the severe subgroup (SAP) and non-severe subgroup (NSAP). Peripheral venous blood samples were taken from all patients on day 1, 3, and 5 after admission. T lymphocyte subsets were determined by flow cytometry, and cytokines were detected by flow fluorometry. The number of CD4 +% and CD8 +% and the expression of cytokines were compared by Student’s t test or Mann-Whitney U analysis. Logistic regression analyses were performed to identify risk factors for severe AP, and a receiver operating characteristic (ROC) curve was constructed to predict severe AP. Statistical significance was taken as P<0.05. Results:Compared with the NHLAP group, patients in the HLAP group had lower CD4 +%, while higher levels of IL-2 on day 1 ( P<0.05), and had also lower CD4 +%, while higher levels of IL-4, IL-6, and IL-10 on day 3 ( P<0.05). Furthermore, IL-6 and IL-10 levels of the HLAP group were significantly increased compared to the NHLAP group on day 5 ( P<0.05). IL-10 levels in the SAP subgroup were significantly higher than those in the NSAP subgroup on day 1 ( P<0.05). Compared with the NSAP subgroup, the SAP subgroup had elevated levels of IL-2, IL-4, IL-6, IL-10 and IFN-γ on day 3 (all P<0.05), and had lower CD4 +%, while increased levels of IL-6 and IL-10 on day 5 (all P<0.05). Multivariate Logistic regression analysis showed that IL-10 was an immune indicator of independent risk factor for severe AP in the HLAP group on day 1 ( OR=1.139, 95% CI: 1.038-1.251, P<0.05). Finally, ROC analysis showed that the area under the curve of IL-10 to assess HLAP with severe AP was 0.772, and the best cut-off value for predicting severe AP was 5.6 pg/mL, with a sensitivity of 83.3% and a specificity of 68.8%. Conclusions:Changes of CD4 +% and cytokines are different between the HLAP and NHLAP groups. IL-10 can be used as a predictor of early disease severity in patients with HLAP.