Independent predictors for non-alcoholic fatty liver disease in patients with treatment-naïve chronic hepatitis B

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.

Evaluation of the therapeutic benefits of single daily dose versus alternate day dose of rosuvastatin in hyperlipidemia patients

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.

Lipid-lowering Activity of Quansanqi Tablets / 中国实验方剂学杂志

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.

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.

Discovery of biomarkers related to abnormal lipid metabolism in liver and serum and intervention mechanism of ginsenoside Rb_1 in hyperlipidemia rats based on non-targeted metabolomics / 中国中药杂志

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.

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.

Preparation, pharmacokinetics and pharmacodynamics of curcumin nano emulsion / 药学实践杂志

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.

Short-term voluntary exercise enhances the activation of endogenous neural stem cells inintracerebral hemorrhage mice with hyperlipidemia / 西安交通大学学报(医学版)

【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.

Effect of Electroacupuncture at “Fenglong”（ST 40） on Liver Lipid Synthesis and Insulin Resistance in Hyperlipidemic Model Rats / 中医杂志

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.

Research Progress of Active Components of Traditional Chinese Medicine in Treatment of Hyperlipidemia by Activating PPARα Pathway / 中国实验方剂学杂志

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.

The role of CYP1A1/2 in cholesterol ester accumulation provides a new perspective for the treatment of hypercholesterolemia

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.

Impacto de la cuarentena por COVID-19 en el perfil metabólico de personas con infección por VIH en Argentina / Impact of COVID-19 related lockdown on the metabolic profile of people with HIV infection in Argentina

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.

Lipoprotein apheresis efficacy and challenges: single center experience

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.

Lipid-lowering effect of Oroxylum indicum (L.) Kurz extract in hyperlipidemic mice

Objective: To investigate the effect of Oroxylum indicum fruit extract on high-fat diet-induced hyperlipidemic mice. Methods: The phytochemical composition of Oroxylum indicum fruit extract was determined by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry. Forty-two male mice were used. The mice were divided into six groups: normal control, high-fat diet control, simvastatin treatment (20 mg/kg BW/day), and Oroxylum indicum fruit extract (100, 200, 300 mg/kg BW/day) treatment groups. Food intake, body weight, serum parameters, lipid profile, and histopathological lesions of the kidney, liver, and epididymal fat were observed. Results: LC-MS/MS results revealed four major components of Oroxylum indicum fruit extract: luteolin, apigenin, baicalein, and oroxylin A. Twenty-seven volatile oils were identified from Oroxylum indicum fruit extract. Daily oral administration of Oroxylum indicum fruit extract at 100 to 300 mg/kg BW/day significantly reduced the body weight, total cholesterol, triglyceride, and low-density lipoprotein cholesterol level (P<0.05), whereas high-density lipoprotein cholesterol was higher than the high-fat diet control group. Treatment with 300 mg/kg BW/day Oroxylum indicum fruit extract reduced the pathological lesion and prevented fat accumulation in the kidney and liver. Conclusions: Oroxylum indicum fruit extract has hypolipidemic effect in hyperlipidemic mice, and the active ingredients of Oroxylum indicum fruit extract, both flavonoids and volatile oils, should be further explored as an antihyperlipidemic agent.

Anti-hyperlipidemic and anti-diabetic evaluation of ethanolic leaf extract of Catharanthus roseus alone and in combination therapy

The use of plants in disease treatment is cost effective and relatively safe. This study was designed to investigate anti-hyperlipidemic and anti-diabetic activity of ethanolic leaf extract of Catharanthus roseus alone and in combination therapy in hyperlipidemic & diabetic mice. Eight groups comprising five mice each were used. Group A was hyperlipidemic control, group B, C, D received atorvastatin (20 mg/kg), leaf extract (200 mg/kg) and leaf extract in combination with atorvastatin (200 mg/kg and 20 mg/kg) orally for 15 days. Group E was diabetic control. Group F, G, H received sitagliptin (40 mg/kg), leaf extract (200 mg/kg) and extract in combination with sitagliptin (200 mg/kg and 40 mg/kg) orally for 7 days. Blood cholesterol levels were measured at 1st, 5th, 10th and 15th day and fasting blood sugar levels were measured at 2, 12, 24, 72 and 168 hours during treatment. One-way ANOVA with tukey- kramer multiple comparison test was used. The chemical characterization of ethanolic extract of Catharanthus roseus leaves showed presence of alkaloids, saponins, tannins and flavonoids. Ethanolic extract of Catharanthus roseus has significant anti-hyperlipidemic & anti-diabetic effects (p<0.05, p<0.01) when compared with control but had not cause significantly increase in anti-hyperlipidemic effects of atorvastatin. While significantly increased the antidiabetic effect of sitagliptin (p<0.05)

Tyramine exerts hypolipidemic and anti-obesity effects in vivo

Abstract Obesity and dyslipidemia are conditions often associated with cardiovascular risk, inflammation, oxidative stress, and death. Thus, a new approach has been highlighted to promote research and development of pharmacological tools derived from natural sources. Among the most widely studied groups of substances, polyphenols such as tyramine stand out. This study investigated hypolipidemic and anti-obesity properties of tyramine. Oral toxicity evaluation, models of dyslipidemia and obesity were used. To induce dyslipidemia, Poloxamer-407 (P-407) was administered intraperitoneally. In the hypercholesterolemic and obesity model, specific diet and oral tyramine were provided. After 24h of P-407 administration, tyramine 2 mg/kg (T2) decreased triglycerides (TG) (2057.0 ± 158.5 mg/dL vs. 2838 ± 168.3 mg/dL). After 48h, TG were decreased by T2 (453.0 ± 35.47 vs. 760.2 ± 41.86 mg/dL) and 4 mg/kg (T4) (605.8 ± 26.61 760.2 ± 41.86 mg/dL). T2 reduced total cholesterol (TC) after 24h (309.0 ± 11.17 mg/dL vs. 399.7 ± 15.7 mg/dL); After 48h, 1 mg/kg (T1) (220.5 ± 12.78 mg/dL), T2 (205.8 ± 7.1 mg/dL) and T4 (216.8 ± 12.79 mg/dL), compared to P-407 (275.5 ± 12.1 mg/dL). The treatment decreased thiobarbituric acid reactive substances and nitrite in liver, increased superoxide dismutase, reduced the diet-induced dyslipidemia, decreasing TC around 15%. Tyramine reduced body mass, glucose, and TC after hypercaloric feed. Treatment with 5 mg/L (0.46 ± 0.04 ng/dL) and 10 mg/L (0.44 ± 0.02 ng/dL) reduced plasma insulin (1.18 ± 0.23 ng/dL). Tyramine increased adiponectin at 5 mg/L (1.02 ± 0.02 vs. 0.83 ± 0.02 ng/mL) and 10mg/L (0.96 ± 0.04 ng/mL). In conclusion, tyramine has low toxicity in rodents, has antioxidant effect, reduces plasma triglycerides and cholesterol levels. However, further studies should be conducted in rodents and non-rodents to better understand the pharmacodynamic and pharmacokinetic properties of tyramine

S-allyl Cysteine and Taurine revert peripheral metabolic and lipid profile in non-insulin-dependent diabetes mellitus animals: Combination vs Monotherapy

Abstract The present study was designed to evaluate the beneficial synergistic effects of S-allyl Cysteine (SAC) and Taurine (TAU) on hyperglycemia, lipid profile and renal damage markers in type 2 diabetes mellitus (T2DM) in rats. Experimental T2DM was developed by administering an intraperitoneal single dose of nicotinamide (NA; 230 mg/kg) and streptozotocin (STZ; 65 mg/ kg) in adult rats. Control and diabetic rats were treated with SAC (150 mg/kg); TAU (200 mg/ kg) or SAC and TAU (75+100 mg/kg) combination for four weeks. Measurements of traditional markers of kidney toxicity in serum, such as blood urea nitrogen (BUN), serum creatinine (Scr), and alkaline phosphatase (ALP), together with serum cholesterol/triglyceride such as serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) may yield a snapshot of renal damage and lipid profile in NA/STZ-treated rats. The variation in levels of fasting blood glucose, glycosylated hemoglobin, insulin and lipid profile was significantly augmented in SAC/TAU treatment group. The diabetic group showed elevated renal injury markers in serum, which were decreased significantly by SAC/TAU treatment. Thus the results of the experiment clearly indicate the potential of the SAC/TAU combination in improving diabetic complications.

Study on effects and mechanism of Tibetan medicine Shanhu qishiwei pill in lowering blood lipid of hyperlipidemia model rats / 中国药房

OBJECTIVE To study the effects of Tibetan medi cine Shanhu qishiwei pill in lowering blood lipid of hyperlipidemia（HLP）model rats ，and to explore its mechanism primarily. METHODS According to their body weigh ，60 SD rats were randomly divide into normal group ，model group ，simvastatin group （positive control ，20 mg/kg）and Shanhu qishiwei pill low-dose，medium-dose and high-dose groups （50，100，200 mg/kg），with 10 rats in each group. Normal group was given conventional diet ，and other groups were given high-lipid diet to induce HLP model ，for consecutive 4 weeks. Administration groups were given relevant medicine intragastrically at the same time of modeling ；normal group and model group were given equal volume of normal saline intragastrically ，once a day ，for consecutive 4 weeks. After last administration ，the serum levels of TC ，TG， LDL-C and HDL-C were determined ；pathological changes of liver tissue were observed ；the protein expressions of AMPK ， p-AMPK，LKB1，and HMGCR in liver tissue were detected in each group. RESULTS Low-dose，medium-dose and high-dose of Shanhu qishiwei pill could significantly reduce the serum levels of TC ，TG and LDL-C and protein expression of HMGCR in liver tissue（P＜0.05），while significantly increased serum level of HDL-C ，phosphorylation level of AMPK ，protein expression of LKB 1 in liver tissue in HLP model rats （P＜0.05）；the pathological changes of liver tissue in HLP model rats were improved to different extents. CONCLUSIONS Shanhu qishiwei pill can reduce the blood lipid level of HLP model rats ，and its mechanism may be related to inhibiting the transmission of LKB 1/AMPK signal pathway and regulating lipid metabolism.

Hyperlipidemia and intestinal microflora distributions among flying personnel / 预防医学

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.

Changes and significance of T lymphocyte subsets and cytokines in hyperlipidemia-induced acute pancreatitis / 中华急诊医学杂志

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.