Prevention and treatment of lipoic acid-niacin on blue-light-induced retinal damage in rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the preventive effect and optimal drug dose of lipoic acid-niacin(N2L)against blue light-induced retinal damage in SD rats, and to explore its possible protective mechanism.METHODS: A total of 36 specific pathogen free-grade male SD rats of 150-200 g were selected and randomly divided into normal control group, blue light injury group, N2L low-dose group(1.0 mg/kg), N2L medium-dose group(2.5 mg/kg), N2L high-dose group(5.0 mg/kg), and physiological saline group, with 6 rats in each group. The normal control group was reared in a 12 h dark and light cycle, and the rest of the groups received 9 h of daily light exposure, 3 h of blue light irradiation with a wavelength of 455 nm and an intensity of 3000±50 lx, and 12 h of darkness to establish the injury model, and were exposed to light exposure for 14 d. For 14 consecutive durations, a 1 mL dose of the corresponding drug was injected intraperitoneally. The rats were reared for another 5 d with a regular 12 h light-dark cycle and were examined by electroretinography. Specimens were prepared by over anesthesia, HE staining, and the thickness of the outer nuclear layer was observed under a optical microscope; superoxide dismutases(SOD)activity was detected by CheKineTM SOD Activity Assay Kit; and the retinal Caspase-3, quinone oxidoreductase 1(NQO1), glutathione S transferase(GST), Bcl-2, and Bax protein expression in rat retina were detected by Western blot.RESULTS: The amplitude of b-wave in dark-vision ERG 3.0 and 10.0(cd·s)/m2 stimulated light, b-wave in bright-vision ERG 3.0(cd·s)/m2 stimulated light, and the amplitude of the 2nd wave peak of oscillatory potential were significantly lower in blue light injury group than that in the normal control group(all P<0.01), while the amplitude was significantly higher in the N2L medium-dose group than in the blue light injury group(all P<0.05), and was not statistically different from that of the normal control group; the thickness of the retina in the blue light injury group was decreased in the ONL compared with that of the normal control group(P<0.001), while in the N2L medium dose group, it was thicker than that of the blue light injury group(P<0.001), and there was no statistically significant difference from the normal control group; SOD activity was significantly higher in the N2L medium-dose group than in the remaining 5 groups(P<0.05); the expression of Caspase-3, Bax, and NQO1 in the blue light injury group was higher than that of the normal control group(all P<0.01), and expression of Bax and Caspase-3 was significantly lower in the N2L medium-dose group compared with the blue light injury group(all P<0.001), whereas GST, NQO1 and Bcl-2 were significantly increased(all P<0.01).CONCLUSION:A concentration of 2.5 mg/kg N2L can effectively antagonize the damaging effect of blue light on the retina of SD rats, and it is expected to be a preventive and curative drug for it.

Clinical analysis of 14 cases of niacin deficiency / 中华全科医师杂志

The clinical data of 14 patients with niacin deficiency diagnosed and treated in Department of Dermatology, Affiliated Hospital of Jining Medical College from 2012 to 2021 were retrospectively analyzed. There were 11 males and 3 females aged 26-65 years. The etiological factors were alcoholism in 8 cases, gastrointestinal disease in 3 cases, medication history in 1 case, and unknown etiology in 2 cases.Patients had typical skin lesions, 1 case also had both digestive system and nervous system symptoms, and 3 cases had combined digestive system symptoms and 2 cases had neurological symptoms. All patients were systematically treated with oral nicotinamide and vitamin B complex, and also with topical drugs; and they all improved after 14-52 days of treatment. During regular follow-up, 2 cases of alcoholics and 1 case with diarrhea had recurrence. It is suggested that the typical clinical triad of niacin deficiency is uncommon, and the diagnosis is based on the medical history, clinical manifestations and relevant laboratory test, and the treatment with nicotinamide and vitamin B complex is usually effective; alcoholism is the main cause in male patients and is prone to recurrence.

Association of dietary niacin intake with metabolic syndromeamong adults in Zhejiang Province / 预防医学

Objective @#To explore the association of dietary niacin intake and metabolic syndrome ( MS ) and its components among adults in Zhejiang Province, so as to provide the reference for dietary intervention of MS.@*Methods@#Using the multi-stage cluster random sampling method, the permanent residents aged 18 years and above were selected and investigated by a questionnaire developed by China Center for Disease Control and Prevention. Their waist circumference, blood pressure, glucose and lipid were measured. The daily dietary niacin intake of each person were calculated by "24-hour dietary review for 3 consecutive days", and divided into Q1, Q2, Q3 and Q4 groups according to quartiles. The multivariate logistic regression model was used to analyze the association of niacin intake with the risks of MS and its components. @*Results@#Among 2 438 participants, 871 cases with MS were detected, with a detection rate of 35.73%. The multivariate logistic regression analysis showed that compared with niacin intake Q1 group, Q2 ( OR=0.741, 95%CI: 0.561-0.978 ) and Q4 group ( OR=0.679, 95%CI: 0.487-0.947 ) had a lower risk of MS, Q2 ( OR=0.688, 95%CI: 0.516-0.919 ) and Q4 group ( OR=0.678, 95%CI: 0.479-0.960 ) had a lower risk of abdominal obesity, Q4 group ( OR=0.721, 95%CI: 0.536-0.969 ) had a lower risk of hyperglycemia. Further stratificating by gender, compared with niacin intake Q1 group, Q2 ( OR=0.664, 95%CI: 0.453-0.972 ) and Q3 group ( OR=0.646, 95%CI: 0.432-0.965 ) in women had a lower risk of MS, Q2 (OR=0.667, 95%CI: 0.460-0.967) and Q3 group ( OR=0.607, 95%CI: 0.408-0.902 ) had a lower risk of abdominal obesity; Q2 group ( OR=1.836, 95%CI: 1.202-2.805 ) in men had a higher risk of low high-density lipoprotein cholesterol.@*Conclusion@#Niacin intake is associated with an increased risk of MS, abdominal obesity and hyperglycemia.

Nicotinamide riboside regulates inflammation and mitochondrial markers in AML12 hepatocytes

BACKGROUND/OBJECTIVES: The NAD+ precursor nicotinamide riboside (NR) is a type of vitamin B3 found in cow's milk and yeast-containing food products such as beer. Recent studies suggested that NR prevents hearing loss, high-fat diet-induced obesity, Alzheimer's disease, and mitochondrial myopathy. The objective of this study was to investigate the effects of NR on inflammation and mitochondrial biogenesis in AML12 mouse hepatocytes. MATERIALS/METHODS: A subset of hepatocytes was treated with palmitic acid (PA; 250 µM) for 48 h to induce hepatocyte steatosis. The hepatocytes were treated with NR (10 µM and 10 mM) for 24 h with and without PA. The cell viability and the levels of sirtuins, inflammatory markers, and mitochondrial markers were analyzed. RESULTS: Cytotoxicity of NR was examined by PrestoBlue assay. Exposure to NR had no effect on cell viability or morphology. Gene expression of sirtuin 1 (Sirt1) and Sirt3 was significantly upregulated by NR in PA-treated hepatocytes. However, Sirt1 activities were increased in hepatocytes treated with low-dose NR. Hepatic pro-inflammatory markers including tumor necrosis factor-alpha and interleukin-6 were decreased in NR-treated cells. NR upregulated anti-inflammatory molecule adiponectin, and, tended to down-regulate hepatokine fetuin-A in PA-treated hepatocytes, suggesting its inverse regulation on these cytokines. NR increased levels of mitochondrial markers including peroxisome proliferator-activated receptor γ coactivator-1α, carnitine palmitoyltransferase 1, uncoupling protein 2, transcription factor A, mitochondrial and mitochondrial DNA in PA-treated hepatocytes. CONCLUSIONS: These data demonstrated that NR attenuated hepatic inflammation and increased levels of mitochondrial markers in hepatocytes.

Analysis of niacin skin flush in clinical high risk population of psychosis / 上海交通大学学报（医学版）

Objective • To explore and analyze the characteristics of nicotinic acid skin sensitivity in clinical high risk (CHR) population of psychosis. Methods • One hundred and five patients with CHR of psychosis (CHR group) and fifty-one patients with first episode schizophrenia (FES) (FES group) in Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine from Jun. 2016 to Jun. 2018, and fifty-four healthy controls (HC group) were included. The patients of CHR group met the criteria of prodromal syndromes, and the patients of FES group met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). The patients of HC group were matched with CHR group in age and gender. The niacin skin flush of the three groups were detected. The niacin skin flush scores of the three groups were compared by single factor repeated measurement variance analysis (MANOVA). The niacin flush negative rates of the three groups were compared by Chi-square test. Results • Compared with HC group, the niacin skin flush of CHR group and FES group reduced at different concentrations and time points. MANOVA showed a significant main group effect of niacin skin flush (F=1.746, P=0.009). There were no significant group × concentration interaction (F=1.628, P=0.138) and group × time interaction (F=0.851, P=0.531). Compared with HC group, the niacin total flush scores of CHR group were lower (t=-2.697, P=0.008). The significant differences of the proportion of patients with negative niacin reaction among the three groups were found for the concentration of 0.1 mol/L at 5 min (χ2=16.709, P=0.000) and 0.001 mol/L at 20 min (χ2=6.380, P=0.041). Conclusion • The reduction of the niacin skin flush can occur not only in the patients with schizophrenia but also in the CHR of psychosis in the precursor phase. Niacin skin flush may be an early biological marker of schizophrenia.

Exogenous niacin treatment increases NADPH oxidase in kiwifruit / O tratamento com niacina exógena NADPH oxidase em kiwis

Abstract Kiwifruit are a popular fruit worldwide; however, plant growth is threatened by abiotic stresses such as drought and high temperatures. Niacin treatment in plants has been shown to increase NADPH levels, thus enhancing abiotic stresses tolerance. Here, we evaluate the effect of niacin solution spray treatment on NADPH levels in the kiwifruit cultivars Hayward and Xuxiang. We found that spray treatment with niacin solution promoted NADPH and NADP+ levels and decreased both O2·- production and H2O2 contents in leaves during a short period. In fruit, NADPH contents increased during early development, but decreased later. However, no effect on NADP+ levels has been observed throughout fruit development. In summary, this report suggests that niacin may be used to increase NADPH oxidases, thus increasing stress-tolerance in kiwifruit during encounter of short-term stressful conditions.

Resumo Kiwis são uma fruta popular em todo o mundo; No entanto, o crescimento das plantas é ameaçado por estresses abióticos como a seca e as altas temperaturas. O tratamento com niacina em plantas mostrou aumentar os níveis de NADPH, aumentando assim a tolerância a stress abiótico. Aqui, avaliamos o efeito do tratamento com spray de solução de niacina sobre os níveis de NADPH nos cultivares de kiwis Hayward e Xuxiang. Descobrimos que o tratamento por spray com solução de niacina promoveu níveis de NADPH e NADP + e diminuiu a produção de O2·- e os teores de H2O2 nas folhas durante um curto período. Nos frutos, os teores de NADPH aumentaram durante o desenvolvimento precoce, mas diminuíram mais tarde. No entanto, não se observou qualquer efeito nos níveis de NADP + ao longo do desenvolvimento do fruto. Em resumo, este relatório sugere que a niacina pode ser utilizada para aumentar NADPH oxidases, aumentando assim a tolerância ao estresse em kiwis durante o encontro de condições estressantes de curto prazo.

Assessment of Intake of Nicotinic Acid and Nicotinamide in Relation to Tolerable Upper Intake Levels

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the intake of niacin in the Norwegian population. NFSA has also requested that VKM conduct scenario calculations to illustrate the consequences of establishing separate maximum limits for nicotinic acid (1, 4, 8 or 10 mg/day) and nicotinamide (100, 500, 700 or 900 mg/day) in food supplements, by assessing these scenarios against existing tolerable upper intake levels (ULs). The current maximum limit for niacin added to food supplements is 32 mg/day, including nicotinic acid, nicotinamide and inositol hexanicotinate. The term niacin (vitamin B3) comprises the two main water-soluble forms nicotinic acid and nicotinamide (niacinamide). The human body can get niacin from the diet or synthesise it from the essential amino acid tryptophan. Dietary intakes are expressed as milligram niacin equivalents (NEs), which correspond to 1 mg of pure niacin or 60 mg of tryptophan. In the body, niacin primarily functions as a component of the coenzymes NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate) which are present in all cells. These coenzymes play essential roles for the functioning of a wide range of enzymes involved in the metabolism of carbohydrates, amino acids and fat. In addition to its function in coenzymes, niacin is involved in DNA repair and gene stability. Niacin has a half-life of 20-40 minutes in the human body. Late symptoms of severe niacin deficiency (pellagra) include fatigue, headache, apathy, depression, memory loss, dementia, pigmented skin rash after sun exposure, bright red tongue, vomiting, diarrhoea, and constipation. Flushing (burning and itching of the face, arms and chest) and stomach irritation are the main side effects of moderately high supplemental intake of nicotinic acid (>35 mg/day). Long-term use of high doses (≥3000 mg/day) of nicotinic acid as a cholesterol-lowering drug can also be toxic to the liver. Nicotinamide, however, does not have these effects. In general, the risk of nicotinamide toxicity appears to be quite low. VKM proposes to adopt the ULs of nicotinic acid and nicotinamide set by the Scientific Committee for Food Safety (SCF) in 2002, which are based on one human dose-response study (nicotinic acid) and several human dose-response studies (nicotinamide), respectively. Hence, the UL for supplemental nicotinic acid is suggested to 10 mg/day for adults and the UL for supplemental nicotinamide to 900 mg/day for adults. The ULs for children and adolescents have been derived on the basis of their body weights. The ULs set for nicotinic acid and nicotinamide concern only intake from supplements since intake of nicotinic acid and nicotinamide from regular foods is considered to be without risk of negative health effects. Therefore, VKM has not conducted or evaluated scenarios with intake from both diet and the separated new maximum limits for nicotinic acid and nicotinamide in food supplements suggested by NFSA. Dietary calculations, however, have been performed for niacin intakes (includes both nicotinic acid and nicotinamide) in various percentiles (P5, P25, mean, P50, P75 and P95) in children (2-, 4- and 9-year-olds), adolescents (13-year-olds) and adults as background information. Mean and median intakes of niacin from the diet alone are above or at the recommended intakes for all age groups. Because UL for supplemental nicotinic acid is 10 mg/day for adults, none of the suggested maximum limits in food supplements (1, 4, 8, or 10 mg/day) will lead to exceedance of this UL in adults. In 13-year-olds and 9-year-olds, supplements with 8 mg nicotinic acid per day will lead to exceedance of UL, and in 4-year-olds and 2-year-olds supplementation of 4 mg nicotinic acid per day will lead to exceedance of the UL for nicotinic acid. Because UL for supplemental nicotinamide is 900 mg/day for adults, none of the suggested maximum limits in food supplements (100, 500, 700 or 900 mg/day) will lead to exceedance of UL in adults. In 13-year-olds, supplements with 700 mg nicotinamide per day will lead to exceedance of UL. In 9-year-olds, 4-year-olds and 2-year-olds, supplementation of 500 mg nicotinamide per day will lead to exceedance of the UL for nicotinic acid.

Sustained-release niacin induced acute liver failure: an autopsy report

Niacin, either alone or in combination with other anti-hyperlipidemic agents, safely and effectively addresses most lipid abnormalities in patients with mixed dyslipidemias. Niacin is the only available agent that significantly lowers lipoprotein (a) and has the greatest high density lipoprotein cholesterol-raising effects of all available agents. Despite niacin’s numerous beneficial lipid effects, patient compliance to long-term therapy is challenged by its common side effects which include nausea, pruritus, and vasodilatory flushing. The incidence of these unpleasant side effects in patients taking the Immediate Release (IR) form of the drug is close to 100 %. To avoid these side effects, Sustained Release (SR) formulations of the drug were created which lower the rate of nausea, flushing and pruritus markedly. Unfortunately, the SR form is associated with a high incidence of chemical hepatitis and rarely fulminant hepatic failure, which is not seen in patients taking the IR form. We report the autopsy findings of a 68 years old man who died of fulminant liver failure three weeks after switching from IR to SR form of niacin. All other toxic, infectious and autoimmune causes of liver failure were ruled out clinically. His liver biopsy one-week antemortem was consistent with chemical hepatitis, such as has been described for slow-release niacin. At autopsy the liver showed diffuse massive hepatic necrosis with no background fibrosis. SR Niacin is widely available over the counter; however, there is substantial scientific evidence that the drug is associated with potentially fatal hepatotoxicity.

Study of niacin skin flushing response for the diagnosis of major depressive disorder / 中国神经精神疾病杂志

Objective To investigate the difference of niacin skin flush response between patients with major depressive disorder (MDD) and healthy controls (HCs), and its sensitivity and specificity for the diagnosis of MDD. Methods Twenty-one untreated patients with MDD and 28 age- and gender-matched HCs were enrolled in this study. The severity of depressive symptoms was assessed mainly by using the 17-item Hamilton Depression Rating Scale (HDRS-17). Methyl Nicotinate (MN) solution at 8 different concentrations (10-5 mol/L, 10-4 mol/L, 10-3.5 mol/L, 10-3 mol/L, 10-2.5 mol/L, 10-2 mol/L, 10-1.5 mol/L, 10-1 mol/L) were applied on subjects' forearms. Signals of blood flow were collected using the Doppler Laser Flowmetry to detect the skin flushing of the test. Results Under the concentrations of 10-2.5 mol/L, 10-2 mol/L, 10-1.5 mol/L and 10-1 mol/L MN solution, the blood flow was significantly higher in depressive patients than in HCs (P<0.01). The MN sensitivity (logEC50) was inversely correlated to the severity of depressive symptoms (r=-0.57, P<0.05). ROC curve analysis implied that the maximum blood flow (MBF) caused by the niacin skin flush response, could efficiently discriminate MDD from HCs (AUC=0.90, P<0.01). Conclusion The presence of enhanced niacin skin flush response may be helpful in the diagnosis of MDD.

Pellagra affecting a patient with Crohn's disease

Abstract: Pellagra is a nutritional disease caused by a deficiency of niacin. It may lead to death if not identified and treated timely. We review the literature and report a female patient presented with clinical features of pellagra as a complication of Crohn's disease.

Relationship between Dietary Intake and Depression in Metabolic Syndroem among Korean Adults: Korea National Health and Nutrition Examination Survey 2014 / 農村醫學 地域保健

OBJECTIVES: Metabolic syndrome and depression are interconnected disorders. Although many studies have assessed the association between dietary intake and each disorder independently, few studies have examined the association between depression and dietary intake in patients with metabolic syndrome. Our study examined the association between depression and dietary intake in adults with metabolic syndrome. METHODS: We analyzed the second data set (2014) from the sixth KNHNES. Of the patients with metabolic syndrome, the final study population comprised 1,334 patients, aged 20 to 60 years, with metabolic syndrome as defined by KNHNES and depression diagnosed by a physician. We examined the patients??dietary intake obtained using the 24-h recollection method in KNHNES. RESULTS: Depression group had a lower niacin dietary intake than those without depression in both male and female (male P=0.047, female P=0.025). None of the other components had any association between depression group and those without depression group in both male and female. CONCLUSIONS: This study demonstrates that a low dietary intake of niacin may be related to the depression in patients with metabolic syndrome. The results indicate that it is worthwhile to evaluate the nutritional status in patients who have been diagnosed with both metabolic syndrome and depression.

Niacin accelerates LDL-C uptake in HepG2 cells via downregulation of PCSK9 / 中国药理学通报

Aim To explore the effects of niacin on LDL-C uptake and metabolism in HepG2 cells,and to clarify the functions of niacin in lipid-lowering and slo-wing the atherosclerosis process,thus to provide a sci-entific basis for niacin as a lipid-lowering drug in clini-cal development.Methods Oil red O staining was used to observe HepG2 cells after lipid uptake.Enzy-matic method was used to determine the content of in-tracellular free cholesterol (FC)and total cholesterol (TC).The LDLR levels on the surface of cell mem-brane were detected by immunofluorescence flow cy-tometer.The mRNA and protein expressions of LDLR, SREBP2 and PCSK9 were analyzed by qPCR and Western blot.Results The results of oil red O staining showed that the rate of oil red O-positive cells and the number of red lipid droplets were significantly in-creased in niacin group than control group.Niacin sig-nificantly increased the levels of TC and FC in HepG2 cells(P <0.05 ).What’s more,niacin significantly upregulated the expression of LDLR and significantly downregulated the protein expression of PCSK9,while it had no effect on the expression of SREBP2.Conclu-sion Niacin accelerates LDL-C uptake probably via downregulating the expression of PCSK9 and reducing the degradation of LDLR protein in HepG2 cells.

Exogenous niacin treatment increases NADPH oxidase in kiwifruit

Abstract Kiwifruit are a popular fruit worldwide; however, plant growth is threatened by abiotic stresses such as drought and high temperatures. Niacin treatment in plants has been shown to increase NADPH levels, thus enhancing abiotic stresses tolerance. Here, we evaluate the effect of niacin solution spray treatment on NADPH levels in the kiwifruit cultivars Hayward and Xuxiang. We found that spray treatment with niacin solution promoted NADPH and NADP+ levels and decreased both O2·- production and H2O2 contents in leaves during a short period. In fruit, NADPH contents increased during early development, but decreased later. However, no effect on NADP+ levels has been observed throughout fruit development. In summary, this report suggests that niacin may be used to increase NADPH oxidases, thus increasing stress-tolerance in kiwifruit during encounter of short-term stressful conditions.

Resumo Kiwis são uma fruta popular em todo o mundo; No entanto, o crescimento das plantas é ameaçado por estresses abióticos como a seca e as altas temperaturas. O tratamento com niacina em plantas mostrou aumentar os níveis de NADPH, aumentando assim a tolerância a stress abiótico. Aqui, avaliamos o efeito do tratamento com spray de solução de niacina sobre os níveis de NADPH nos cultivares de kiwis Hayward e Xuxiang. Descobrimos que o tratamento por spray com solução de niacina promoveu níveis de NADPH e NADP + e diminuiu a produção de O2·- e os teores de H2O2 nas folhas durante um curto período. Nos frutos, os teores de NADPH aumentaram durante o desenvolvimento precoce, mas diminuíram mais tarde. No entanto, não se observou qualquer efeito nos níveis de NADP + ao longo do desenvolvimento do fruto. Em resumo, este relatório sugere que a niacina pode ser utilizada para aumentar NADPH oxidases, aumentando assim a tolerância ao estresse em kiwis durante o encontro de condições estressantes de curto prazo.

Nicotinamide Reduces Amyloid Precursor Protein and Presenilin 1 in Brain Tissues of Amyloid Beta-Tail Vein Injected Mice

The purpose of this study is to investigate whether nicotinic acid (NA) and nicotinamide (NAM) reduce the Alzheimer disease (AD)-related gene expression in brain tissues of amyloid beta (Aβ)-injected mice. Male Crj:CD1 (ICR) mice were divided into 6 treatment groups; 1) control, 2) Aβ control, 3) Aβ + NA 20 mg/kg/day (NA20), 4) Aβ + NA40, 5) Aβ + NAM 200 mg/kg/day (NAM200), and 6) Aβ + NAM400. After 1-week acclimation period, the mice orally received NA or NAM once a day for a total of 7 successive days. On day 7, biotinylated Aβ42 was injected into mouse tail vein. At 5 hours after the injection, blood and tissues were collected. Aβ42 injection was confirmed by Western blot analysis of Aβ42 protein in brain tissue. NAM400 pre-treatment significantly reduced the gene expression of amyloid precursor protein and presenilin 1 in brain tissues. And, NAM200 and NAM400 pre-treatments significantly increased sirtuin 1 expression in brain tissues, which is accompanied by the decreased brain expression of nuclear factor kappa B by 2 doses of NAM. Increased expression of AD-related genes was attenuated by the NAM treatment, which suggests that NAM supplementation may be a potential preventive strategy against AD-related deleterious changes.

Effects of CurTn on proliferation of VSMC / 中国药理学通报

Aim To explore the anti-proliferation effects of curcumin trinicotinate ( CurTn ) on vascular smooth muscle cell ( VSMC ) and its mechanism. Methods The cells were cultured in DMEM supple-mented with 10% fetal bovine serum. MTT assay was used to examine cell proliferation. FCM was used to observe cell cycle. The expressions of PCNA, Cy-clinD1 and p-ERK1/2 were analyzed using Western blot. Results CurTn could inhibit the proliferation of VSMC and showed a certain amount-time relationship. What’ s more, CurTn could increase the G1 phase pro-portion of cell, decrease the S phase proportion and the expression level of PCNA protein. It was also found that CurTn significantly inhibit the protein expression of p-ERK1/2 and Cyclin D1 . Conclusion CurTn may inhibit the proliferation of VSMC via downregulating the expression of CyclinD1 and p-ERK1/2 .

The roles of Niacin in the treatment of diabetic retinopathy and its mechanism / 中华眼底病杂志

Objective To investigate the protective effect of Niacin on blood-retina barrier (BRB) in diabetic rats and related mechanism.Methods The male Wistar rats (60) were divided into control (CON) group,diabetes (DM) group and Niacin-treated (NA) group,20 rats in each group.Rats diabetes models were induced with streptozotocin injection.Niacin (40 mg/kg · d) was administrated orally everyday in Niacin-treated group until sacrificed after 3 months.Pathological outcomes,total cholesterol (TC) and highdensity lipoprotein (HDL) were evaluated at month 3.Optical microscopy was used to observe the retinal structure.The integrity of BRB and the vascular permeability was quantified by analyzing albumin leakage using Evans blue (EB) method.The relative expressions of Claudin-5,Occludin,zonula occluden (ZO)-1 and GPR109A mRNA in rat retinas were detected by reverse transcription PCR (RT-PCR) and relative expression of GPR109A,tumor necrosis factor (TNF)-α and interleukin (IL)-6 by Western blot.Results Compared to CON group,the TC content was increased and HDL content was decreased in DM group (t=4.034,5.831;P＜0.05).Compared to DM group,the TC content was decreased and HDL content was increased in NA group (t=6.868,3.369;P＜0.05).The retinal structure of CON group was normal.Pathological changes were found in the DM group,such as tumescent nuclei and disorganized structures.The retinal structure of NA group was similar to the control group.Evans blue dye that the microvascular leakage in DM group was increased compared with CON group (t=24.712,P＜0.05),while in NA group was decreased compared with DM group (t =16.414,P＜ 0.05).The mRNA expression of Occludin,Claudin-5,ZO-1 in DM group were decreased compared with CON group (t=11.422,12.638,12.060;P＜ 0.05),while in NA group were increased compared with DM group (t=5.278,3.952,8.030;P＜0.05).The mRNA expression of GPR109A in NA group were increased compared with DM group (t=5.053,P＜ 0.05).The protein expression of GPR109A,IL-6,TNF-αin DM group were increased compared with CON group (t=4.915,11.106,6.582;P＜0.05).Compared to DM group,the protein expression of GPR109A was increased (t=5.806,P＜0.05),while the protein expression of IL-6 and TNF-α were decreased (t=10.131,5.017;P＜0.05).Conclusion Niacin has the protective effect for BRB by up-regulating GPR109A expression which may suppress inflammation.

Combination of Loperamide and Niacin modify DENA induced altered Liver enzymes .

Hepatocellular Carcinoma (HCC) is among the most lethal cancers which makes it the third most frequent cause of cancer related deaths. Diethylnitrosamine (DENA) is a potent initiator and hepatocarcinogen in rats. DENA induced Hepatocellular damage clearly demonstrates by the elevated levels of liver enzymes serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (ALP), and α-feto protein (AFP). This work is an attempt to test the hypothesis that Loperamide (5mg/kg) and Niacin in combination restores the DENA (160mg/kg) induced altered enzymes after single i.p administration in Wistar rats. The ability to alter the enzymes was measured by comparing biochemical serum markers and AFP. The results have confirmed the significant elevation of these parameters in DENA control group compared to normal control and the therapeutic groups. Therapeutic group significantly reveals that Loperamide and Niacin restores the altered hepatic enzymes towards the Normal. Key messages: Our data reveals and confirms that this remarkable combination possess the potential for the treatment of hepatocellular carcinomas in rats exposed to DENA. Administration of Loperamide + Niacin relatively improved the biochemical parameters to values approximating those of the normal controls

Dislipidemias: ¿qué hay de nuevo? / Dyslipidemia: what's new?

En los últimos años han surgido algunas investigaciones y guías de práctica clínica relacionadas con el diagnóstico y tratamiento de las dislipidemias, que aportaron nuevos conocimientos (y controversias) sobre dicha problemática. En este resumen se describen, en primer lugar, las características de las "nuevas guías" norteamericanas para el manejo del colesterol publicadas a fines de 2013 y se comparan con las recomendaciones tradicionales. En segundo lugar, se analizan los últimos estudios que evaluaron el impacto cardiovascular de otros fármacos hipolipemiantes (ezetimibe y ácido nicotínico) en pacientes en prevención secundaria tratados con estatinas. Finalmente, se mencionan las nuevas drogas hipolipemiantes desarrolladas en los últimos años, como el lomitapide, el mipomersen y los inhibidores de la PCSK9, y se comentan el mecanismo de acción, su eficacia, sus efectos colaterales y los escenarios clínicos en donde podrían utilizarse. (AU)

In recent years, some research and clinical practice guidelines related to the diagnosis and treatment of dyslipidemia, which provided new knowledge (and controversy) about this problem have emerged. In this review, the characteristics of the American "new guidelines" for cholesterol management published by the end of 2013 are described, and they are compared with the traditional recommendations. In addition, recent studies assessing the cardiovascular impact of other lipid-lowering drugs (ezetimibe and nicotinic acid) in patients in secondary prevention treated with statins are analyzed. Finally, new hypolipidemic drugs developed in recent years are mentioned (lomitapide, mipomersen and PCSK9 inhibitors), discussing the mechanism of action, efficacy, side effects and clinical settings where they could be used. (AU)

El ácido nicotínico aumenta el transporte celular de colesterol de las lipoproteínas de alta densidad en pacientes con hipoalfalipoproteinemia / Nicotinic acid increases cellular transport of high density lipoprotein cholesterol in patients with hypoalphalipoproteinemia

Background: Plasma high density lipoproteins (HDL) are involved in reverse cholesterol transport mediated by the scavenger receptor class B type I (SR-BI). Nicotinic acid increases HDL cholesterol levels, even though its specific impact on SR-BI dependent-cellular cholesterol transport remains unknown. Aim: To determine the effect of nicotinic acid on HDL particle functionality in cholesterol efflux and uptake mediated by SR-BI in cultured cells in hypoalphalipoproteinemic patients. Material and Methods: In a pilot study, eight patients with low HDL (≤ 40 mg/dL) were treated with extended release nicotinic acid. HDL cholesterol and phospholipid levels, HDL2 and HDL3 fractions and HDL particle sizes were measured at baseline and post-therapy. Before and after nicotinic acid treatment, HDL particles were used for cholesterol transport studies in cells transfected with SR-BI. Results: Nicotinic acid treatment raised total HDL cholesterol and phospholipids, HDL2 levels as well as HDL particle size. Nicotinic acid significantly increased HDL cholesterol efflux and uptake capacity mediated by SR-BI in cultured cells. Conclusions: Nicotinic acid therapy increases SR-BI-dependent HDL cholesterol transport in cultured cells, establishing a new cellular mechanism by which this lipid-lowering drug appears to modulate HDL metabolism in patients with hypoalphalipoproteinemia.

Effects of niacin on lipid metabolism in rat model of non-alcoholic fatty liver disease / 临床肝胆病杂志

ObjectiveTo investigate the effects of niacin on the lipid metabolism in rat model of non-alcoholic fatty liver disease (NAFLD). MethodsForty Sprague-Dawley rats were randomly divided into control group, model group, intervention group 1 (0.5% niacin), and intervention group 2 (1% niacin). Rats were fed with high-fat diet for 8 weeks to induce an NAFLD model. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase, levels of total cholesterol (TC), triglyceride, and free fatty acid in serum and liver tissue, and level of malondialdehyde (MDA) in liver tissue were measured using assay kits. The morphological and histopathological changes in the liver were observed under a microscope. Comparison of data between groups was made by univariate analysis of variance using SPSS software; moreover, least significant difference test (equal variance assumed) and Tamhane's T2 test (equal variance not assumed) were used for pairwise comparison. ResultsCompared with the model group, every intervention group had significantly lower levels of ALT, TC, AST, TG, and FFA (all P＜0.05) in serum and level of MDA in liver tissue (P＜0.05), and had significantly increased expression of PPARα mRNA (P＜0.05), DGAT2 mRNA (P＜0.05), and SREBP1c mRNA (P＜0.05). Intervention group 2 had significantly reduced expression of DGAT2 mRNA and SREBP1c mRNA compared with intervention group 1 (P＜0.05). Compared with the model group, the intervention groups had relieved fatty degeneration of hepatocytes and alleviated inflammatory cell infiltration in the centrilobular portion of the liver. ConclusionNiacin regulates lipid metabolism in NAFLD animal models, reduces lipid oxidative stress, and significantly reduces liver steatosis and fibrosis by regulating the expression of PPARα mRNA, DGAT2 mRNA, and SREBP1c mRNA, so as to realize the protective effect against NAFLD.