Etiology and management of urethral calculi:A systematic review of contemporary series

Objective:To conduct a systematic literature review on urethral calculi in a contemporary cohort describing etiology,investigation,and management patterns.Methods:A systematic search of MEDLINE and Cochrane Central Register of Controlled Trials(CENTRAL)databases was performed.Articles,including case reports and case series on urethral calculi published between January 2000 and December 2019,were included.Full-text manuscripts were reviewed for clinical parameters including symptomatology,etiology,medical history,investigations,treatment,and outcomes.Data were collated and analyzed with univariate methods.Results:Seventy-four publications met inclusion criteria,reporting on 95 cases.Voiding symptoms(41.1%),pain(40.0%),and acute urinary retention(32.6%)were common presenting features.Urethral calculi were most often initially investigated using plain X-ray(63.2%),with almost all radio-opaque(98.3%).Urethral calculi were frequently associated with coexistent bladder or upper urinary tract calculi(16.8%)and underlying urethral pathology(53.7%)including diverticulum(33.7%)or stricture(13.7%).Urethral calculi were most commonly managed with external urethrolithotomy(31.6%),retrograde manipulation(22.1%),and endoscopic in situ lithotripsy(17.9%).Conclusion:This unique systematic review of urethral calculi provided a summary of clinical features and treatment trends with a suggested treatment algorithm.Management in contemporary urological practice should be according to calculus size,shape,anatomical location,and presence of urethral pathology.

Biochemistry and transcriptome analysis reveal condensed tannins alleviate liver injury induced by regulating cholesterol metabolism pathway

Free cholesterol has been considered to be a critical risk factor of nonalcoholic fatty liver disease(NAFLD).It remains unknown whether dietary intake of condensed tannins(CTs)have distinguishable effects to alleviate liver damage caused by a high cholesterol diet.Male C57BL/6 mice were fed a high cholesterol diet for 6 weeks,and given CTs treatment at a dosage of 200 mg/(kg·day)at the same time.The results indicated that compared with mice fed a normal diet,a high cholesterol diet group resulted in significant weight loss,dysregulation of lipid metabolism in blood and liver,and oxidative stress in the liver,but CTs treatment dramatically reversed these negative effects.Hematoxylin and eosin(H&E)staining and frozen section observation manifested that CTs treatment could effectively reduce the deposition of liver cholesterol and tissue necrosis caused by high cholesterol intake.CTs alleviated liver injury mainly by regulating the expression of related genes in cholesterol metabolism pathway and AMPK phosphorylation.Our results confirmed that CTs have remarkable cholesterol lowering and anti-liver injury effects in vivo.

Concomitant treatment of ureteral calculi and ipsilateral pelvic sciatic nerve schwannoma with transperitoneal laparoscopic approach: A case report

BACKGROUND Schwannomas are rare peripheral neural myelin sheath tumors that originate from Schwann cells.Of the different types of schwannomas,pelvic sciatic nerve schwannoma is extremely rare.Definite preoperative diagnosis of pelvic schwannomas is difficult,and surgical resection is the gold standard for its definite diagnosis and treatment.CASE SUMMARY We present a case of pelvic schwannoma arising from the sciatic nerve that was detected in a 40-year-old man who underwent computed tomography for intermittent right lower back pain caused exclusively by a right ureteral calculus.Subsequently,successful transperitoneal laparoscopic surgery was performed for the intact removal of the stone and en bloc resection of the schwannoma.The total operative time was 125 min,and the estimated blood loss was inconspicuous.The surgical procedure was uneventful.The patient was discharged on postoperative day 5 with the simultaneous removal of the urinary catheter.However,the patient presented with motor and sensory disorders of the right lower limb,caused by partial damage to the right sciatic nerve.No tumor recurrence was observed at the postoperative appointment.CONCLUSION Histopathological examination of the specimen confirmed the diagnosis of a schwannoma.Thus,laparoscopic surgery is safe and feasible for concomitant extirpation of pelvic schwannomas and other pelvic and abdominal diseases that require surgical treatment.

Perioperative and long-term results of ultrasonography-guided single-and multiple-tract percutaneous nephrolithotomy for staghorn calculi

BACKGROUND It is possible that this condition will lead to urosepsis and progressive deterioration of renal function in the absence of surgical intervention.Several recent clinical studies have shown that multi-tract percutaneous nephrolithotomy(MPCNL)has a similar stone free rate(SFR)as standard percutaneous nephrolithotomy(S-PCNL).As a result,M-PCNL was also recommended as a treatment option for staghorn calculi.AIM To examine the perioperative and long-term results of ultrasonography-guided single-and M-PCNL.METHODS This was a retrospective cohort study.Between March 2021 and January 2022,the urology department of our hospital selected patients for the treatment of staghorn calculi using percutaneous nephrolithotomy.The primary outcomes were com plication rate and SFR,and the characteristics of patients,operative parameters,laboratory measurements were also collected.RESULTS In total,345 patients were enrolled in the study(186 in the S-PCNL group and 159 in the M-PCNL group).The SFR in the M-PCNL group was significantly higher than that in the S-PCNL group(P=0.033).Moreover,the incidence rates of hydrothorax(P=0.03)and postoperative infection(P=0.012)were higher in the M-PCNL group than in the S-PCNL group.Logistic regression analysis demonstrated that post-operative white blood cell count(OR=2.57,95%CI:1.90-3.47,P<0.001)and stone size(OR=1.59,95%CI:1.27-2.00,P<0.001)were associated with a higher overall complication rate in the S-PCNL group.Body mass index(OR=1.22,95%CI:1.06-1.40,P=0.004)and stone size(OR=1.70,95%CI:1.35-2.15,P<0.001)were associated with increased overall complications in the M-PCNL group.CONCLUSION Multiple access tracts can facilitate higher SFR while slightly increasing the incidence of acceptable complications.

Associations between remnant cholesterol levels and mortality in patients with diabetes

BACKGROUND Dyslipidemia is frequently present in patients with diabetes.The associations of remnant cholesterol and mortality remains unclear in patients with diabetes.AIM To explore the associations of remnant cholesterol with all-cause and cardiovas-cular mortality in patients with diabetes.METHODS This prospective cohort study included 4740 patients with diabetes who par-ticipated in the National Health and Nutrition Examination Survey from 1999 through 2018.Remnant cholesterol was used as the exposure variable,and all-cause and cardiovascular mortality were considered outcome events.Outcome data were obtained from the National Death Index,and all participants were followed from the interview date until death or December 31,2019.Multivariate proportional Cox regression models were used to explore the associations between exposure and outcomes,in which remnant cholesterol was modeled as both a categorical and a continuous variable.Restricted cubic splines(RCSs)were calculated to assess the nonlinearity of associations.Subgroup(stratified by sex,age,body mass index,and duration of diabetes)and a series of sensitivity analyses were performed to evaluate the robustness of the associations.RESULTS During a median follow-up duration of 83 months,1370 all-cause deaths and 389 cardiovascular deaths were documented.Patients with remnant cholesterol levels in the third quartile had a reduced risk of all-cause mortality[hazard ratio(HR)95%confidence interval(CI):0.66(0.52-0.85)];however,when remnant cholesterol was modeled as a continuous variable,it was associated with increased risks of all-cause[HR(95%CI):1.12(1.02-1.21)per SD]and cardiovascular[HR(95%CI):1.16(1.01-1.32),per SD]mortality.The RCS demonstrated nonlinear associations of remnant cholesterol with all-cause and cardiovascular mortality.Subgroup and sensitivity analyses did not reveal significant differences from the above results.CONCLUSION In patients with diabetes,higher remnant cholesterol was associated with increased risks of all-cause and cardiovascular mortality,and diabetes patients with slightly higher remnant cholesterol(0.68-1.04 mmol/L)had a lower risk of all-cause mortality.

Hepatic steatosis is associated with dysregulated cholesterol metabolism and altered protein acetylation dynamics in chickens

Background Hepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed to systematically investigate the genetic regulatory mechanisms of hepatic steatosis in laying hens.Methods Ninety individuals with the most prominent characteristics were selected from 686 laying hens according to the accumulation of lipid droplets in the liver, and were graded into three groups, including the control, mild hepatic steatosis and severe hepatic steatosis groups. A combination of transcriptome, proteome, acetylome and lipidome analyses, along with bioinformatics analysis were used to screen the key biological processes, modifications and lipids associated with hepatic steatosis.Results The rationality of the hepatic steatosis grouping was verified through liver biochemical assays and RNA-seq. Hepatic steatosis was characterized by increased lipid deposition and multiple metabolic abnormalities. Integration of proteome and acetylome revealed that differentially expressed proteins(DEPs) interacted with differentially acetylated proteins(DAPs) and were involved in maintaining the metabolic balance in the liver. Acetylation alterations mainly occurred in the progression from mild to severe hepatic steatosis, i.e., the enzymes in the fatty acid oxidation and bile acid synthesis pathways were significantly less acetylated in severe hepatic steatosis group than that in mild group(P < 0.05). Lipidomics detected a variety of sphingolipids(SPs) and glycerophospholipids(GPs) were negatively correlated with hepatic steatosis(r ≤-0.5, P < 0.05). Furthermore, the severity of hepatic steatosis was associated with a decrease in cholesterol and bile acid synthesis and an increase in exogenous cholesterol transport.Conclusions In addition to acquiring a global and thorough picture of hepatic steatosis in laying hens, we were able to reveal the role of acetylation in hepatic steatosis and depict the changes in hepatic cholesterol metabolism. The findings provides a wealth of information to facilitate a deeper understanding of the pathophysiology of fatty liver and contributes to the development of therapeutic strategies.

Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

Inhibitory effect of procyanidin B2 and tannin acid on cholesterol esterase and their synergistic effect with orlistat

This study was aimed to analyze the effect of procyanidin B2(PC)and tannin acid(TA)on the activities of cholesterol esterase(CEase)and the inhibitory mechanisms of enzymatic activity.The interaction mechanisms were investigated by enzymatic kinetics,multi-spectroscopy methods,thermodynamics analysis,molecular docking,and dynamic simulations.PC and TA could bind with CEase and inhibit the activity of enzyme in a mixed-competitive manner and non-competitive manner,which was verified by molecular docking simulations and dynamics simulations.Also,PC and TA showed the synergistic inhibition with orlistat.Fluorescence,UVvis and the thermodynamic analysis revealed that the complexes were formed from CEase and inhibitors by noncovalent interaction.As revealed by the circular dichroism results,both PC and TA decreased enzymatic activities by altering the conformations of CEase.The inhibition of PC and TA on CEase might be one mechanism for its cholesterol-lowering effect.

Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

Wrist-ankle acupuncture combined with pain nursing for the treatment of urinary calculi with acute pain

BACKGROUND Urological calculi often cause renal colic,which is characterized by paroxysmal or persistent severe pain in the upper abdomen or lumbar region.Development of methods to quickly relieve these pain symptoms has garnered clinical attention.Wrist-ankle acupuncture is a type of floating acupuncture therapy administered at selected points in the carpal and ankle areas,and it has good pain-relieving effects.We used wrist-ankle acupuncture combined with pain nursing for pain intervention in patients with renal calculi to confirm its application and safety.AIM To study the effect of wrist-ankle acupuncture combined with pain nursing in the treatment of urinary calculi with acute pain.METHODS Eighty-two patients with urinary calculi with acute pain as the first symptom followed at our hospital from November 2019 to June 2021 were enrolled in the study and classified into two groups according to the odd and even numbers of the visit sequences,each with 41 cases.The control group received a routine nursing intervention and intramuscular injection of nonsteroidal anti-inflammatory drugs,whereas the observation group received pain management nursing and wrist-ankle acupuncture.Subsequently,the pain-relieving effect was compared between the two groups.RESULTS The score on the visual analog scale(VAS)at 24,48,and 72 h postintervention was decreased in both groups compared with the baseline data;moreover,the observation group scored significantly lower than the control group on the VAS at each time point after the intervention(P<0.05).The clinical efficacy at 24 h postintervention was not significantly different between the two groups(P>0.05).In turn,the pain recurrence rate at 72 h postintervention was lower in the observation group compared with the control group(P<0.05).Finally,the nursing satisfaction rate in the observation group was significantly higher than that observed in the control group(P<0.05).No serious adverse reactions occurred during the treatment and the safety of treatment was high in both groups.CONCLUSION Wrist-ankle acupuncture combined with pain nursing for treating urolithiasis with acute pain effectively alleviated the degree of pain and reduced the recurrence rate,which was worthy of clinical application.

Lower Baseline LDL Cholesterol Affects All-cause Mortality in Patients with First Percutaneous Coronary Intervention

Objective Foreign studies have reported that coronary artery disease(CAD) patients with high baseline low-density lipoprotein cholesterol(LDL-C) may have a good prognosis, which is called the “cholesterol paradox”. This study aimed to examine whether the “cholesterol paradox” also exists in the Chinese population.Methods A total of 2,056 patients who underwent the first percutaneous coronary intervention(PCI)between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L(100 mg/d L). The outcomes of interest included major adverse cardiovascular events(MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke.Results All-cause mortality occurred in 8 patients(0.7%) from the low-LDL-C group and 12 patients(2.4%) in the high-LDL-C group, with a significant difference between the two groups(adjusted hazard ratio: 4.030, 95% confidence interval: 1.088–14.934;P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups.Conclusion In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the “cholesterol paradox” may be inapplicable to Chinese populations.

An Analysis of Health Factors Affecting Employees’ Absenteeism: Influences of HDL Cholesterol and Blood Sugar Levels

Background: Workers’ health condition is an important issue. It affects not only the well-being of workers but also the firms and society as a whole through medical costs and productivity losses due to absenteeism and presenteeism. Data and Methods: Data were obtained from 1136 employees at an operational site of a large corporation. The dataset contained both medical checkups and working record information. Health factors affecting long-term absence (over three days in three months) were analyzed. Logistic regression models and the procedure for selecting proper covariates based on likelihood test statistics and the Akaike information criterion were used. Results: Among health factors, high-density lipoprotein cholesterol (HDL-C) and blood sugar levels were important in the selected model. For HDL-C, the odds ratio (OR) based on one standard deviation difference was 0.75 with a 95% confidence interval (CI) of 0.59 - 0.95. For blood sugar, the OR was 1.20 with a 95% CI of 1.01 - 1.42. Improving HDL-C and blood sugar levels would reduce long-term absence by 25% and 20%, respectively. Conclusion: Controlling HDL-C and blood sugar levels is important to reduce long-term absenteeism. These factors can be improved by modifying eating habits. Since the operational site has its own company cafeterias, which most employees use, nutritional intervention is relatively easy with little or no cost. It may be worthwhile to implement nutritional intervention, especially for patients with low HDL-C or high blood sugar levels. Limitations: The results of this study were based on one operational site of a corporation. The employees were mainly operators working inside the building. The results may be different from other types of jobs and working conditions, such as fieldwork. Analyses of different types of jobs and working conditions are necessary.

Risk factors of concurrent urinary sepsis in patients with diabetes mellitus comorbid with upper urinary tract calculi

BACKGROUND Urinary sepsis is frequently seen in patients with diabetes mellitus(DM)complicated with upper urinary tract calculi(UUTCs).Currently,the known risk factors of urinary sepsis are not uniform.AIM To analyze the risk factors of concurrent urinary sepsis in patients with DM complicated with UUTCs by logistic regression.METHODS We retrospectively analyzed 384 patients with DM complicated with UUTCs treated in People’s Hospital of Jincheng between February 2018 and May 2022.The patients were screened according to the inclusion and exclusion criteria,and 204 patients were enrolled.The patients were assigned to an occurrence group(n=78)and a nonoccurrence group(n=126).Logistic regression was adopted to analyze the risk factors for urinary sepsis,and a risk prediction model was established.RESULTS Gender,age,history of lumbago and abdominal pain,operation time,urine leukocytes(U-LEU)and urine glucose(U-GLU)were independent risk factors for patients with concurrent urinary sepsis(P<0.05).Risk score=0.794×gender+0.941×age+0.901×history of lumbago and abdominal pain-1.071×operation time+1.972×U-LEU+1.541×U-GLU.The occurrence group had notably higher risk scores than the nonoccurrence group(P<0.0001).The area under the curve of risk score for forecasting concurrent urinary sepsis in patients was 0.801,with specificity of 73.07%,sensitivity of 79.36%and Youden index of 52.44%.CONCLUSION Sex,age,history of lumbar and abdominal pain,operation time,ULEU and UGLU are independent risk factors for urogenic sepsis in diabetic patients with UUTC.

Diagnostic and prognostic implications of non-high-density lipoprotein cholesterol and homocysteine levels for cognitive impairment in thalamic infarction

BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which seriously affects their safety.Therefore,it is essential to analyze the independent risk factors that influence the prognosis of patients with thalamic infarction and develop corresponding preventive measures.AIM To explore the effect of non-high-density lipoprotein cholesterol(non-HDL-C)and Homocysteine(Hcy)levels in cognitive impairment in thalamic infarction.METHODS From March 2019 to March 2022,80 patients with thalamic infarction were divided into a group with cognitive impairment[Montreal Cognitive Assessment(MoCA)score<26;35 patients]and a group with normal cognitive function(MoCA score of 26-30;45 patients)according to the MoCA score.In addition,50 healthy people in the same period were selected as the control group.A correlation between the non-HDL-C and Hcy levels and the MoCA score and receiver operating characteristic curve was observed,and the serum non-HDL-C and Hcy levels were analyzed for the diagnosis of cognitive impairment in patients with thalamic infarction.According to the Modified Rankin Scale(MRS)score,80 patients with thalamic infarction were divided into a good prognosis group(MRS score≤2)and a poor prognosis group(MRS score>2).RESULTS The non-HDL-C and Hcy levels were significantly higher in the group with cognitive impairment than in the group with normal cognitive function(P<0.05).There was no significant difference in the non-HDL-C level between the control group and the group with normal cognitive function(P>0.05).The MoCA scores of the group with cognitive impairment were significantly lower than those of the group with normal cognitive function and the control group(P<0.05).There was a significant difference between the control group and the group with normal cognitive function(P<0.05).The non-HDL-C and Hcy levels were correlated with the MoCA score(P<0.05),cognitive impairment[areas under the curve(AUC)=0.709,95%confidence interval(95%CI):0.599-0.816],the non-HDL-C level,and could predict cognitive impairment in patients with thalamic infarction(AUC=0.738,95%CI:0.618-0.859).Hcy combined with non-HDL-C levels can predict cognitive impairment in patients with thalamic infarction(AUC=0.769,95%CI:0.721-0.895).RESULTS There were 50 patients in the good prognosis group and 30 patients in the poor prognosis group.Compared with the good prognosis group,in the poor prognosis group,the National Institutes of Health Stroke Scale(NIHSS)score,non-HDL-C level,Hcy level,large-area cerebral infarction,atrial fibrillation,and activated partial prothrombin time were statistically significant(P<0.05).The non-HDL-C level,the Hcy level,the NIHSS score,extensive cerebral serum,and atrial fibrillation may all be independent risk factors for poor prognosis in patients with thalamic infarction(P<0.05).CONCLUSION Non-HDL-C and Hcy levels are positively correlated with cognitive impairment in patients with thalamic infarction.Non-HDL-C and Hcy levels can be used in the diagnosis of cognitive impairment in patients with thalamic infarction,and the combined detection effect is better.The main factors affecting the prognosis of patients with thalamic infarction are the non-HDL-C level,the Hcy level,the NIHSS score,large-area cerebral infarction,and atrial fibrillation.Clinically,corresponding preventive measures can be formulated based on the above factors to prevent poor prognosis and reduce mortality.

Comparative Observation on Nursing Effect of Nursing Intervention and Routine Nursing in Patients with Renal Calculi and Gastric Ulcer and the Impacts on Epidermal Growth Factor

Objective: To explore the comparative observation on nursing effect of nursing intervention and routine nursing in patients with renal calculi and gastric ulcer and the impacts on epidermal growth factor. Methods: A total of 72 patients with renal calculi and gastric ulcer were selected and treated in our hospital from January 2018 to December 2018. They were divided into the observation group and the control group, 36 for each. Comprehensive nursing intervention was implemented in the observation group, whereas routine nursing was implemented in the control group. The level of epidermal growth factor, nursing satisfaction, renal calculi recurrence rate, average hospital stay and postoperative blood loss were compared between the two groups after nursing. Results: There was no significant difference in the level of epidermal growth factor between the two groups before nursing (P > 0.05), while after nursing, the level in the observation group was higher compared with the control group, and the difference between the two groups was significant (P Conclusion: With regard to patients with renal calculi and gastric ulcer, comprehensive nursing intervention can improve nursing satisfaction and quality of patients’ lives, reduce calculi recurrence rate, and increase the level of epidermal growth factor, which has clinical application value.

Chronic Supplementation with L-Isoleucine Alone or in Combination with Exercise Reduces Hepatic Cholesterol Levels with No Effect on Serum Glucose, Insulin, or Lipids in Rats Fed a High Fructose Diet

The thought of using branched-chain amino acids (BCAA) in the prevention and treatment of certain disorders is becoming increasingly popular. Individual BCAA use has been associated with improving glucose tolerance and liver disease. Previous studies have cited improvements in glucose metabolism with a single dose of L-isoleucine (ILE). However, it is still unclear whether chronic consumption of ILE has any direct benefit. The objective of this study was to examine the influence of chronic ILE supplementation alone or in combination with exercise on fasting serum glucose, insulin, lipids, and lipoprotein cholesterol levels;glucose tolerance;and hepatic lipids in rats. Male Sprague-Dawley rats (n = 40) were divided into Control (low fructose diet);High Fructose diet (HF);HF plus 1.5% ILE (HF + ILE);HF plus exercise (HF + EX);and HF plus 1.5% ILE and exercise (HF + ILE + EX). The HF diets consisted of 70% kcalories from fructose. After 6 weeks of treatment, no significant differences were observed between groups for changes in fasting serum glucose, insulin, lipids, or lipoprotein cholesterol levels. However, hepatic total cholesterol was significantly lower in the HF + ILE + EX compared to the Control and HF, while, the HF + ILE had significantly lower hepatic free cholesterol compared to the HF. We also found no differences between groups for serum glucose response following an oral glucose tolerance test. In conclusion, our study shows that ILE supplementation in rats does not influence serum glucose and lipid biomarkers but may have an influence on lipid metabolic pathways within the liver.

Thrombin increases the expression of cholesterol 25-hydroxylase in rat astrocytes after spinal cord injury

Astrocytes are important cellular centers of cholesterol synthesis and metabolism that help maintain normal physiological function at the organism level.Spinal cord injury results in aberrant cholesterol metabolism by astrocytes and excessive production of oxysterols,which have profound effects on neuropathology.25-Hydroxycholesterol(25-HC),the main product of the membrane-associated enzyme cholesterol-25-hydroxylase(CH25H),plays important roles in mediating neuroinflammation.However,whether the abnormal astrocyte cholesterol metabolism induced by spinal cord injury contributes to the production of 25-HC,as well as the resulting pathological effects,remain unclear.In the present study,spinal cord injury-induced activation of thrombin was found to increase astrocyte CH25H expression.A protease-activated receptor 1 inhibitor was able to attenuate this effect in vitro and in vivo.In cultured primary astrocytes,thrombin interacted with protease-activated receptor 1,mainly through activation of the mitogen-activated protein kinase/nuclear factor-kappa B signaling pathway.Conditioned culture medium from astrocytes in which ch25h expression had been knocked down by siRNA reduced macrophage migration.Finally,injection of the protease activated receptor 1 inhibitor SCH79797 into rat neural sheaths following spinal cord injury reduced migration of microglia/macrophages to the injured site and largely restored motor function.Our results demonstrate a novel regulatory mechanism for thrombin-regulated cholesterol metabolism in astrocytes that could be used to develop anti-inflammatory drugs to treat patients with spinal cord injury.

The role of cholesterol in modifying the lipid-lowering effects of Fuzhuan brick-tea in Caenorhabditis elegans via SBP-1/SREBP

Fuzhuan brick-tea(FZT)has long been consumed for its supposed weight loss and lipid-lowering benefi ts.In this study,we show that the regulation of fat storage in Caenorhabditis elegans from a water extract of FZT was affected by cholesterol levels.We found that FZT signifi cantly decreased fat storage under normal cholesterol levels or in a cholesterol-free diet,while lipid accumulation was increased for a high cholesterol diet.Moreover,this mechanism may involve the conserved sterol regulatory element-binding protein(SREBP)/mediator-15(MDT-15)signaling pathway and the nuclear hormone receptor NHR-80.In addition,lipid synthesis-related genes inhibited by FZT were partially affected by a cholesterol-free diet.Thus,our fi ndings suggested that the potential lipid-lowering effects of FZT may depend on the cholesterol level,which may help to improve the consumption of FZT.

Mechanism of Niacin Induced Hot Flushes and Suppression of Cholesterol

Niacin or nicotinic acid is a form of B3 vitamin prescribed at higher concentrations for the suppression of cholesterol levels. Supplemental doses may cause very little or no side effects. However, higher concentrations of niacin cause hot flushes for most people. Here we propose a biochemical mechanism of niacin induced hot flushes. Orally taken prescription doses of niacin are converted to NAD with the liberation of excess pyrophosphate which in turn releases energy in the form of heat (hot flushes through capsaicin receptor) by the action of pyrophosphatases. The excess pyrophosphate may suppress cholesterol biosynthesis through feedback mechanism. The pathways of NAD and cholesterol biosynthesis were discussed with refence to the production and function of pyrophosphate.

Cytotoxicity of Cholesterol Oxides and the Consequences of Relative Molecular Similarity to cGMP Nucleotide

Cholesterol and cholesterol oxides impact on the functional properties of cells, in respect of the intracellular and extracellular distribution of compounds across cell membranes, carcinogenesis and drug resistance. Abnormal levels of cholesterol oxides and steroids in cancerous tissues promote interest in steroid receptor cross-talk during cell-signalling and the steroid metabolome of cancer patients. The research literature links the cytotoxic properties of oxysterols to interference with the NO/cGMP pathway. cGMP participates in cell-signalling and has a molecular structure that relates to cancer-inducing and cancer-preventing agents. This study uses a molecular modelling approach to compare the structures of cholesterol oxides to cGMP. Cholesterol and cholesterol oxide structures fit to a cGMP structural template in several ways, some of which are replicated by corticosteroids and gonadal steroid hormones. The results of this study support the concept that cholesterol oxides modulate cell apoptosis and autophagy via the NO/cGMP pathway and in conjunction with steroid hormones participate in modulating regulation of cell function by cGMP.