Reduced Serum Cholesterol Levels Research Articles

Cholesterol uptake in the intestine is regulated by the LASP1-AKT-NPC1L1 signaling pathway.

Cholesterol is essential for the stability and architecture of the plasma membrane and a precursor of bile acids and steroid hormones in mammals. Excess dietary cholesterol uptake leads to hypercholesterolaemia, atherosclerosis and plays a role in cancer development. The role of actin-binding scaffolding protein LIM and SH3 protein 1 (LASP1) in cholesterol trafficking has not been investigated previously. Cholesterol levels, its uptake and excretion were studied in mice deficient for low density lipoprotein receptor and Lasp1 (Ldlr-/-Lasp1-/- mice) upon feeding a high fat diet, and in LASP1-knockdown, differentiated human intestinal epithelial Caco-2 cells. Compared to diet-fed Ldlr-/- control mice, Ldlr-/-Lasp1-/- mice displayed a reduction in serum cholesterol levels. Mechanistically, we identified a new role of LASP1 in controlling the translocation of the intestinal cholesterol transporter Niemann-Pick C1-like 1 (NPC1L1) to the apical cell surface, which was limited in LASP1-knockdwon human CaCo-2 enterocytes and in the intestine of Ldlr-/- Lasp1-/- compared to Ldlr-/-mice, linked to LASP1-pAKT signaling but not CDC42 activation. In line, a reduction in cholesterol reabsorption was noted in LASP1-knockdown CaCo-2 cells in vitro, and an enhanced cholesterol excretion via the feces was observed in Ldlr-/- Lasp1-/- mice. These data uncover a novel function of Lasp1 in cholesterol trafficking, promoting cholesterol reabsorption in the intestine. Targeting LASP1 locally could thus represent a novel targeting strategy to ameliorate hypercholesterolemia and associated diseases.

Effects of Simvastatin on Gene Expression and Alkaline Phosphatase Activity in the MG-63 Cell Line Treated With Hyperglycemia for Bone Regeneration.

Background Dental implants have become a widespread treatment option for replacing missing teeth. Adequate bone is required for the placement of dental implants, in the absence of which, augmentation by bone regeneration is done. Antiresorptive drugs are used as treatment procedures for bone regeneration. One such antiresorptive drug is simvastatin (SV), a 3-hydroxy-3-methylglutaryl coenzyme used to manage hyperlipidemia. It reduces serum cholesterol levels and has an advantageous effect on new bone formation. Various studies establish that SV stimulates bone morphogenetic protein (BMP)-2 expression and leads to bone formation. SV prevents the production of isoprenoids and mevalonate, which are essential for osteoclastogenesis and contribute to the bone-sparing effect. Aim The aim of the study was to investigate the osteoregenerative activity of SV in the osteoblast-like cell models, MG-63 cell line, with hyperglycemic conditions. Methodology MG-63 cultures were established under high glucose concentrations during the experimentsand cultured with SV concentrations of 1 µM and 3 µM. The quantification of the expression of the genes, namely, BMP-2 and osteocalcin (OCN) was done by real-time quantitative polymerase chain reaction (RTqPCR). The measurement of alkaline phosphatase activity in the SV-treated cells was also determined. Results According to the results of the study, SV had osteoprotective properties resulting from the inhibition of osteoclast stimulation and osteoinductive properties, facilitated by BMP-2 and OCN. In addition, SV at concentrations of 1 µM and 3 µMincreased the gene expression of BMP-2 and OCN in the MG-63 cell line. Conclusion The results of this study demonstrated that SV had a significant and direct effect on osteogenesis in osteoblasts in vitro.

Cholesterol lowering in diet-induced hypercholesterolemic mice using Lactobacillus bile salt hydrolases with different substrate specificities.

The cholesterol-lowering effect of lactic acid bacteria with high activity of bile salt hydrolase (BSH) is unclear. We believe that distinguishing BSH substrate specificity is necessary to study the effect of various BSH enzymes. We engineered a BSH mutant enzyme recombinant strain named F67A, which exclusively hydrolyzes taurocholic acid (TCA) using site-directed mutagenesis, and a previously lab-constructed BSH recombinant strain, YB81 that exclusively hydrolyzes glycocholic acid (GCA). We also constructed the recombinant strain named NB5462, which carries the empty pSIP411 plasmid and was used as a blank control strain. The intestinal flora in pseudo-germ-free (PGF) mice in which intestinal flora were eliminated via antibiotics, and F67A successfully reduced serum cholesterol levels in high-cholesterol diet-fed mice, whereas YB81 did not yield the same results. However, YB81 regained its cholesterol-lowering capacity in specific pathogen-free (SPF) mice with intact intestinal flora. The cholesterol-lowering mechanism of F67A involved modifying the bile acid pool through BSH enzyme activity. This adjustment regulated the expression of intestinal farnesoid X receptor and subsequently elevated hepatic cholesterol 7α-hydroxylase (CYP7A1), effectively reducing cholesterol levels. Conversely, GCA, the substrate of YB81, was found in minimal quantities in mice, preventing it from inducing changes in bile acid pools. In the presence of intestinal flora, the YB81 BSH enzyme induced notable alterations in bile acids by regulating changes in the intestinal flora and BSH within the flora, ultimately resulting in cholesterol reduction. This is the first study investigating the substrate specificity of BSH, demonstrating that different substrate-specific BSH enzymes exhibit cholesterol-lowering properties. Additionally, we elaborate on the mechanism of BSH-mediated enterohepatic axis regulation.

Effects of ethyl acetate extracts of Marsilea crenata Presl. leaves on risks of atherosclerosis in dyslipidemic rats

Background: Dyslipidemia is widely known as a significant contributor to the incidence of cardiovascular diseases (CVD). Over the years, traditional therapeutic strategies, including the use of herbs, have been recognized. Marsilea crenata Presl. (MC), or a plant known for its phytoestrogen content, has shown biological activities similar to oestrogen. These activities comprise the reduction of serum cholesterol levels, thereby having potential roles in managing dyslipidaemia and its associated cardiovascular risks.Objective: This study aims to examine the effects of ethyl acetate extracts of MC leaves on the serum lipid profile of experimental rats with dyslipidaemia induced by high-fat diet (HFD). Methods: This study applied a pretest-post-test study design with control group, involving 30 rats which are divided into 5 treatment groups, namely N (normal), HFD, STA (Simvastatin), MC1, MC2, and MC3. Group N was only treated with standard feed, and the others received HFD on days 1-14. On the 15th – 28th day, the HFD group was treated with standard feed, and the STA group received simvastatin 0.36 mg/200 g BW/day. The groups of MC1, MC2, and MC3 were treated with oral MC extracts at 100, 200, and 400 mg/kgBW, respectively. Their body weight was measured at the beginning of the study, as well as after 2 and 4 weeks. Subsequently, the experimental rats were fasted overnight on the 14th and 28th day. Their blood was collected on the 15th day (pre-test) and 29th day (post-test) to measure serum concentration of total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-c). Low-density lipoprotein cholesterol (LDL-c) concentration was also calculated by using the Friedewald formula. Results: MC3 extracts significantly reduced the TC (-40.95 ± 1.77), TG (-46.12 ± 3.79), and LDL-c levels (-0.017 ± 0.010), and it also increased levels of HDL-c (11.28 ± 2.34) mg/dL in the HFD-induced rats.Conclusion: Ethyl acetate extracts of MC leaves could reduce risk factors for atherosclerosis by returning lipid profile of the dyslipidemic rats to normal conditions with an increased dose.

Confounding Effects of Tamoxifen: Cautionary and Practical Considerations for the Use of Tamoxifen-Inducible Mouse Models in Atherosclerosis Research.

In recent years, fate-mapping lineage studies in mouse models have led to major advances in vascular biology by allowing investigators to track specific cell populations in vivo. One of the most frequently used lineage tracing approaches involves tamoxifen-inducible CreERT-LoxP systems. However, tamoxifen treatment can also promote effects independent of Cre recombinase activation, many of which have not been fully explored. To elucidate off-target effects of tamoxifen, male and female mice were either unmanipulated or injected with tamoxifen or corn oil. All mice received PCSK9-adeno-associated virus injections and a modified Western diet to induce hypercholesterolemia. After 2 weeks, serum cholesterol and liver morphology were assessed. To determine the duration of any tamoxifen effects in long-term atherosclerosis experiments, mice received either 12 days of tamoxifen at baseline or 12 days plus 2 sets of 5-day tamoxifen boosters; all mice received PCSK9-adeno-associated virus injections and a modified Western diet to induce hypercholesterolemia. After 24 weeks, serum cholesterol and aortic sinus plaque burden were measured. After 2 weeks of atherogenic treatment, mice injected with tamoxifen demonstrated significantly reduced serum cholesterol levels compared with uninjected- or corn oil-treated mice. However, there were no differences in PCSK9-mediated knockdown of LDL (low-density lipoprotein) receptors between the groups. Additionally, tamoxifen-treated mice exhibited significantly increased hepatic lipid accumulation compared with the other groups. Finally, the effects of tamoxifen remained for at least 8 weeks after completion of injections, with mice demonstrating persistent decreased serum cholesterol and impaired atherosclerotic plaque formation. In this study, we establish that tamoxifen administration results in decreased serum cholesterol, decreased plaque formation, and increased hepatic lipid accumulation. These alterations represent significant confounding variables in atherosclerosis research, and we urge future investigators to take these findings into consideration when planning and executing their own atherosclerosis experiments.

Fucogalactan Sulfate (FS) from Laminaria japonica Regulates Lipid Metabolism in Diet-Induced Humanized Dyslipidemia Mice via an Intestinal FXR-FGF19-CYP7A1/CYP8B1 Pathway.

Our previous study found that fucogalactan sulfate (FS) from Laminaria japonica exhibited significant hypolipidemic effects. To further elucidate the mechanism, we first constructed a dyslipidemia mouse model with humanized gut microbiota and proved the main differential metabolic pathway involved bile acid metabolism. Then, we evaluated the beneficial effects of FS on dyslipidemia in this model mice, which revealed that oral FS administration reduced serum cholesterol levels and mitigated liver fat accumulation. Gut microbiota and microbiome analysis showed FS increased the abundance of Ruminococcaceae_NK4A214_group, GCA-900066755, and Eubacterium, which were positively associated with the fecal DCA, β-MCA, and HDCA. Further investigation demonstrated that FS inhibited the hepatic farnesoid X receptor (FXR), while activating the intestinal FXR-FGF19 pathway, leading to suppression of CYP7A1 and CYP8B1, as well as potentially reduced bile acid synthesis and lipid absorption. Overall, FS regulated lipid metabolism in diet-induced humanized dyslipidemia mice via the bile acid-mediated intestinal FXR-FGF19-CYP7A1/CYP8B1 pathway.

Bifidobacterium supplementation attenuates hypercholesterolemia induced gut-brain-testis dysfunction in a rat model

Hypercholesterolemia is the state of high LDL blood cholesterol levels. This may lead to cholesterol accumulation in organs and cause diseases such as male infertility and NAFLD. Recent studies have shown strong correlations between Bifidobacterium strains and plasma cholesterol reduction. Bifidobacterium species are gram positive bacteria known to colonize the human gastrointestinal tract. Studies suggest that Bifidobacterium may reduce serum cholesterol levels by increasing bile salt hydrolase (BSH) activity. BSH increases fecal excretion of bile salt, and to compensate the loss of circulating bile acids, productions of bile acids using cholesterol are promoted. Currently, medications such as statins are commonly used. However, long term consumption could cause adverse effects on male reproductive organs. Bifidobacterium strains are known to regulate the hypothalamus-pituitary-gonadal (HPG) axis by modulating gut microbiota . Gut microbial bacteria such as Bifidobacterium contribute to the host metabolism by enhancing gut barrier integrity, reducing inflammation cytokine expressions, and increasing metabolite productions such as short chain fatty acids (SCFAs). Particularly, SCFAs like butyrate can cross the blood-brain barrier, and consequently affect the HPG axis. This suggests that Bifidobacterium strains may lower serum cholesterol while protecting reproductive organs. Therefore, this study aimed to evaluate and compare the serum cholesterol lowering and HPG axis protecting effects of Bifidobacterium strains with statin in the gut-brain-testis axis of a high cholesterol diet (HCD) induced hypercholesterolemia rat model. 6-week oral gavage of Bifidobacterium strains known to have BSH activity effectively reduced serum total cholesterol and LDL cholesterol levels in rats given HCD for the same period. Moreover, serum inflammatory cytokine IL-1β was reduced by Bifidobacterium treatment. Bifidobacterium also exerted protective effects against intestinal, testicular, and cerebral damage by attenuating disruption of histology and modulating transcript levels of inflammation markers. Notably, Bifidobacterium alleviated the HCD-induced reduction of male sex hormone synthesis markers in the testis, which statin had no effect. Fecal analysis revealed that Bifidobacterium treatment modulates gut microbiota compositions and metabolite levels such as SCFAs. Particularly, 16s rRNA genomic annotation showed that Bifidobacterium strains may have specific functions related to cholesterol reduction. Altogether, Bifidobacterium supplementation may reduce serum cholesterol levels by altering gut microbiota compositions, which affect gut metabolite compositions, inflammatory markers, and sex hormone synthesis markers. In conclusion, Bifidobacterium supplementation is a potential therapeutic approach for hypercholesterolemia-induced intestine, brain, and testis dysfunction. This work was supported by Cellbiotech Co., Ltd. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Statins to Prevent Anthracyclines-Induced Cardiotoxicity

While anthracyclines are a class of chemotherapeutic agents that have improved the treatment of a broad spectrum of malignancies, it is one of the most cardiotoxic agents used to treat the tumor. Despite their dose-dependent cardiotoxicity, anthracyclines-based chemotherapy has become the main stay of tumor therapy due to its efficacy. Meanwhile, Statins, widely used in the clinical setting to reduce serum cholesterol levels and to reduce cardiac morbidity and mortality, have pleiotropic biological effects independent of their lipid-lowering effects. Many studies at home and abroad believe that statins can prevent the cardiotoxicity caused by anthracyclines and propose that statins can play beneficial pleiotropic cardiovascular effects through anti-inflammatory and antioxidant mechanisms, thus playing a cardioprotective effect. Illuminating the mechanisms of Anthracyclines-induced cardiotoxicity and Statins associated therapeutic continue to be the main focus in the field of anti-tumor. Therefore, we summarized the current research surrounding the mechanisms of anthracyclines-induced cardiotoxicity and the protective effect of statins on anthracyclines-induced cardiotoxicity and its possible mechanism.

Reduced Cholesterol Levels during Acute Human Babesiosis.

Babesiosis, an intra-erythrocytic protozoan disease, is an emerging zoonotic parasitic disease worldwide. Cholesterol levels are correlated with severe infections, such as sepsis and COVID-19, and anecdotal reports suggest that high-density lipoprotein (HDL) cholesterol declines during acute babesiosis. Our aim was to describe the cholesterol levels in patients with acute babesiosis diagnosed in an endemic area in New York, hypothesizing that HDL levels correlate with the severity of infection. We reviewed the medical records of adult patients with babesiosis diagnosed by identification of Babesia parasites on a thin blood smear and confirmed by polymerase chain reaction from 2013 to 2018, who also had available a lipid profile drawn at the time of clinical presentation. Additional lipid profile levels were considered as "baseline" if they were drawn within 2 months before or after the infection as part of routine care. A total of 39 patients with babesiosis had a lipid profile drawn on presentation. The patients were divided into two groups for comparison based on the treating physician's clinical decision: 33 patients who were admitted to the hospital and 8 patients who were evaluated as outpatients. A history of hypertension was more common in admitted patients (37% vs. 17%, p = 0.02). The median levels of low-density lipoprotein (LDL) and HDL were significantly reduced in admitted patients compared to non-admitted patients (46 vs. 76 mg/dL, p = 0.04; and 9 vs. 28.5 mg/dL, p = 0.03, respectively). In addition, LDL and HDL levels returned to baseline values following resolution of acute babesiosis. LDL and HDL levels are significantly reduced during acute babesiosis, suggesting that cholesterol depletion may predict disease severity. Pathogen and host factors may contribute to a reduction in serum cholesterol levels during acute babesiosis.

Effect of Bone Resorption Inhibitors on Serum Cholesterol Level and Fracture Risk in Osteoporosis: Randomized Comparative Study Between Minodronic Acid and Raloxifene

The positive link between osteoporosis and hypercholesterolemia has been documented, and bone resorption inhibitors, such as nitrogen-containing bisphosphonates (N-BP) and selective estrogen receptor modulators (SERMs), are known to reduce serum cholesterol levels. However, the relationship between the baseline cholesterol level and incident fracture rate under the treatment using the bone resorption inhibitors has not been documented. We investigated the relation between vertebral fracture incident and the baseline cholesterol levels and cholesterol-lowering effect of N-BP and SERM in osteoporosis through a prospective randomized open-label study design. Patients with osteoporosis (n = 3986) were allocated into two groups based on the drug used for treatment: minodronic acid (MIN) (n = 1624) as an N-BP and raloxifene (RLX) as an SERM (n = 1623). Serum levels of cholesterol and incidence of vertebral fracture were monitored for 2 years. The vertebral fracture rates between the two groups were compared using the pre-specified stratification factors. The patients receiving MIN with baseline low-density lipoprotein (LDL)-cholesterol level of ≥ 140 mg/dL, high-density lipoprotein cholesterol level < 40 mg/dL, age group of ≥ 75 years, and T score of BMD ≥ -3 SD had significantly lower vertebral fracture rates than those receiving RLX (incidence rate ratios (IRR) 0.45 [95% confidence interval (CI) 0.30 0.75, p = 0.001], 0.25 [95% CI 0.09 0.65, p = 0.005], 0.71 [95% CI 0.56 0.91, p = 0.006], 0.47 [95% CI 0.30 0.75, p = 0.0012], respectively). The cholesterol-lowering effect was stronger in the RLX group than in the MIN group, regardless of prior statin use. These results indicated that MIN treatment was more effective in reducing fracture risk in patients with higher LDL cholesterol levels, although its cholesterol-lowering ability was lesser than the RLX treatment.Trial registration University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR), No. UMIN000005433; date: April 13, 2011.

Effect of Linoleic Acid on Cholesterol Levels in a High-Fat Diet-Induced Hypercholesterolemia Rat Model.

Cardiovascular disease is the leading cause of morbidity and mortality worldwide, accounting for almost one-third of all deaths. The risk factors for developing this disease include high levels of serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL), alongside low levels of high-density lipoprotein (HDL). Dietary linoleic acid has been suggested to reduce these risk factors. This study aims to determine the effects of linoleic acid on cholesterol levels, liver function tests, and structural changes in liver tissue in comparison with fenofibrate in a hypercholesterolemic rat model. Thirty-six male Sprague Dawley rats (150-180 g) were divided into non-hypercholesterolemic and hypercholesterolemic groups. Hypercholesterolemia was induced in the rats by feeding them with a high-fat diet for two weeks. After two weeks, the non-hypercholesterolemic and hypercholesterolemic rats were equally divided into six groups (n = 6): control non-hypercholesterolemic rats, non-hypercholesterolemic rats treated with fenofibrate (60 mg/kg), non-hypercholesterolemic rats treated with linoleic acid (5 mg/kg), control hypercholesterolemic rats, hypercholesterolemic rats treated with fenofibrate (60 mg/kg), and hypercholesterolemic rats treated with linoleic acid (5 mg/kg). The changes in the rats' body weight, serum lipid profiles, atherogenic indices, and liver function test results were obtained. The rats' liver tissues were stained for histopathological analysis. The linoleic acid-treated hypercholesterolemic rats exhibited significantly reduced serum TC, TG, LDL, aspartate aminotransferase, and alanine aminotransferase levels, as well as increased HDL levels compared with the control hypercholesterolemic rats. These linoleic acid effects were comparable to those in the fenofibrate-treated hypercholesterolemic rats. In conclusion, linoleic acid possesses early anti-hypercholesterolemic properties, which may be due to the reductions in serum cholesterol levels and mild early structural changes in the liver tissues of hypercholesterolemic rats. Therefore, continued studies on linoleic acid in atherosclerotic and/or obese animal models are suggested.

Effects of Different Concentration of Copper on Performance, Immunity and Carcass Traits in Broiler Japanese Quails.

In this study, the effects of dietary copper supplements on broiler Japanese quail growth performance, immune response, blood biochemistry, and carcass quality were examined. Two copper sources (copper sulphate-CuS, and copper methionine-CuM), each at five distinct dietary dosages of 5, 10, 15, 100, and 150mg/kg, were used. A total of 280 (10 × 4 × 7) day-old quail chicks of uniform body weight were randomly distributed into 10 treatments with 4 replicates each and having 7 chicks in each replicate. In comparison to CuS-supplemented diets, CuM-supplemented diets (100mg Cu/kg diet) considerably (P ≤ 0.01) increased body weight gain and improved feed conversion ratio (FCR). In the 150-mg CuM/kg diet, the cell-mediated immune response (foot web index to PHAP) was considerably (P ≤ 0.01) greater. The humoral immune response (HA titre to SRBC) was substantially (P ≤ 0.01) lower with CuS-supplemented meals than with CuM-supplemented diets. When compared to CuS source, the weight of the bursa and spleen from CuM source was considerably (P ≤ 0.01) higher. The 100- and 150-mg CuM/kg diets considerably (P ≤ 0.01) reduced serum cholesterol levels. Thus, it may be concluded that dietary supplementation of copper methionine as a source of Cu @ 100mg Cu/kg diet to broiler Japanese quails was more effective in improving growth performance, immunological response, carcass quality features, and serum cholesterol reduction.

Engineering of efficiency-enhanced Cas9 and base editors with improved gene therapy efficacies

Editing efficiency is pivotal for the efficacies of CRISPR-based gene therapies. We found that fusing an HMG-D domain to the N terminus of SpCas9 (named efficiency-enhanced Cas9 [eeCas9]) significantly increased editing efficiency by 1.4-fold on average. The HMG-D domain also enhanced the activities of non-NGG PAM Cas9 variants, high-fidelity Cas9 variants, smaller Cas9 orthologs, Cas9-based epigenetic regulators, and base editors in cell lines. Furthermore, we discovered that eeCas9 exhibits comparable off-targeting effects with Cas9, and its specificity could be increased through ribonucleoprotein delivery or using hairpin single-guide RNAs and high-fidelity Cas9s. The entire eeCas9 could be packaged into an adeno-associated virus vector and exhibited a 1.7- to 2.6-fold increase in editing efficiency targeting the Pcsk9 gene in mice, leading to a greater reduction of serum cholesterol levels. Moreover, the efficiency of eeA3A-BE3 also surpasses that of A3A-BE3 in targeting the promoter region of γ-globin genes or BCL11A enhancer in human hematopoietic stem cells to reactivate γ-globin expression for the treatment of β-hemoglobinopathy. Together, eeCas9 and its derivatives are promising editing tools that exhibit higher activity and therapeutic efficacy for both invivo and exvivo therapeutics.

Atorvastatin ameliorates lipid overload-induced mitochondrial dysfunction and myocardial hypertrophy by decreasing fatty acid oxidation through inactivation of the p-STAT3/CPT1 pathway

Although statins are shown to have cardiac pleiotropic effects independent of lowering cholesterol, the underlying mechanism remains unclear. Mitochondrial dysfunction induced by increased fatty acid oxidation (FAO) is the culprit in the development of cardiac hypertrophy and dysfunction. This study was to explore whether the cardiac pleiotropic effects of atorvastatin were associated with FAO regulation, with a specific focus on carnitine palmitoyltransferase 1 (CPT1). High-fat diet (HFD)-fed mice and palmitic acid (PA)-stimulated neonatal rat primary cardiomyocytes (NRCMs) were treated with atorvastatin, with or without FAO modulators, signal transducer and activator of transcription 3 (STAT3) agonist, and inhibitor. Atorvastatin (3 mg/kg) did not reduce serum cholesterol levels in HFD-fed mice but ameliorated mitochondrial dysfunction and cardiac hypertrophy. In vitro, atorvastatin and the FAO inhibitor alleviated PA-induced mitochondrial dysfunction and cardiomyocyte hypertrophy. However, the FAO enhancer eliminated atorvastatin’s protective effects. Furthermore, atorvastatin decreased CPT1 and FAO levels and prevented STAT3 phosphorylation and nuclear translocation. STAT3 inhibitor had the same inhibitory effects as atorvastatin on CPT1, FAO levels, and cardiomyocyte hypertrophy, whereas STAT3 agonist disrupted these effects of atorvastatin. Our results demonstrate that atorvastatin decreases myocardial FAO by inactivating the p-STAT3/CPT1 signaling pathway, which improves lipid overload-induced mitochondrial dysfunction and cardiac hypertrophy in a cholesterol-independent manner. This is the first study to explore the cardiac pleiotropic effects of atorvastatin with respect to FAO. However, whether atorvastatin regulates FAO in the cardiac hypertrophy model induced by other variables has not been investigated in this work, and this is expected to be performed in the future.

Transcranial Direct-Current Stimulation Regulates MCT1-PPA-PTEN-LONP1 Signaling to Confer Neuroprotection After Rat Cerebral Ischemia–Reperfusion Injury

Propionic acid (PPA) is a critical metabolite involved in microbial fermentation, which functions to reduce fat production, inhibit inflammation, and reduce serum cholesterol levels. The role of PPA in the context of cerebral ischemia–reperfusion (I/R) injury has yet to be clarified. Increasing evidence indicate that transcranial direct-current stimulation (tDCS) is a safe approach that confers neuroprotection in cerebral ischemia injury. Here, we show that the levels of PPA were reduced in the ischemic brain following a rat cerebral I/R injury and in the cultured rat cortical neurons after oxygen–glucose deprivation (OGD), an in vitro model of ischemic injury. We found that the decreased levels of transporter protein monocarboxylate transporter-1 (MCT1) were responsible for the OGD-induced reduction of PPA. Supplementing PPA reduced ischemia-induced neuronal death after I/R. Moreover, our results revealed that the neuroprotective effect of PPA is mediated through downregulation of phosphatase PTEN and subsequent upregulation of Lon protease 1 (LONP1). We demonstrated that direct-current stimulation (DCS) increased MCT1 expression and PPA level in OGD-insulted neurons, while tDCS decreased the brain infarct volume in the MCAO rats via increasing the levels of MCT1 expression and PPA. This study supports a potential application of tDCS in ischemic stroke.

Screening bile salt hydrolase activity of Lactobacillus isolated from Vietnamese human origins

Hypercholesterolemia is a major cause of cholesterol build-up in the coronary arteries, which can subsequently lead to heart disease or atherosclerosis. Cholesterol levels can be lowered by cholesterol-lowering drugs but some of these drugs may have harmful side effects, while supplementation of Lactobacillus has shown the potential to reduce serum cholesterol levels by virtue of bile salt hydrolase (bsh) activity. In this study, Lactobacillus plantarum VFE-04, L. rhamnosus VFE-08, and L. plantarum VFE-14, had been isolated from Vietnamese healthy adults, were able to deconjugate glycodeoxycholate (GDC) on MRS plates and MRS broth supplemented with GDC. In addition, deconjugating activity of L. plantarum VFE-04, L. rhamnosus VFE-08, and L. plantarum VFE-14 were also found in cell-free extract as expressed by amount of glycine that released in the supernatant. Four bsh genes including bsh1, bsh2, bsh3, and bsh4 have been identified by PCR in these strains. In addition, L. plantarum VFE-04, L. rhamnosus VFE-08, and L. plantarum VFE-14 also showed high ability to resist bile salts and low pH. The results of 16S rRNA gene analyses showed that L. plantarum VFE-04, L. rhamnosus VFE-08, and L. plantarum VFE-14 and had high similarity scores with L. plantarum ZZU 23 (100%), L. rhamnosus JCM 1136 (99%) and L. plantarum S7 (98.65%), respectively. This study suggests that L. plantarum VFE-04, L. rhamnosus VFE-08, and L. plantarum VFE-14 have the potential to be explored as probiotics in the management of hypercholesterolaemia in near future.

Hydrophilic phytosterol derivatives: A short review on structural modifications, cholesterol-lowering activity and safety

Phytosterols have received extensive attention owing to their excellent cholesterol-lowering activity and the role in cardiovascular diseases prevention. However, poor solubility in both oil and water limited the application of free phytosterols in the food industry. Chemical or enzymatic modifications were effective to improve the physicochemical properties as well as the bioavailability and cholesterol-lowering activity of phytosterols. Higher oil solubility and lower melting point of phytosterols have been achieved by esterification and transesterification with fatty acids and triacylglycerols so as to enhance the bioavailability, reduce formation of precipitates, and improve the sensory quality of products. While the researches on the improvement on its water solubility is a hot topic. Hydrophilic phytosterol derivatives have promising applications in the food industry because most of foods belong to aqueous matrix. Hydrophilic modification is useful and meaningful for phytosterols in both industrial and commercial applications. This review mainly highlights the hydrophilic phytosterol derivatives in the following aspects: (i) hydrophilic modifications of phytosterols by coupling with various polar components; (ii) cholesterol-lowering activity and possible molecular mechanisms of hydrophilic phytosterol derivatives on reducing serum cholesterol level; and (iii) safety evaluation of hydrophilic phytosterol derivatives in cell-culture studies, animal models and clinical trials.

Therapeutic effects of statins on osteoarthritis: A review.

Osteoarthritis (OA) is a progressive joint disease. The etiology of OA is considered to be multifactorial. Currently, there is no definitive treatment for OA, and the existing treatments are not very effective. Hypercholesterolemia is considered a novel risk factor for the development of OA. Statins act as a competitive inhibitor of the β-hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase and are widely used to manage hypercholesterolemia. Inhibition of HMG-CoA reductase results in reduced synthesis of a metabolite named mevalonate, thereby reducing cholesterol biosynthesis in subsequent steps. By this mechanism, statins such as atorvastatin and simvastatin could potentially have a preventive impact on joint cartilage experiencing osteoarthritic deterioration by reducing serum cholesterol levels. Atorvastatin can protect cartilage degradation following interleukin-1β-stimulation. Atorvastatin stimulates the STAT1-caspase-3 signaling pathway that was shown to be responsible for its anti-inflammatory effects on the knee joint. Simvastatin had chondroprotective effects on OA in vitro by reducing matrix metalloproteinases expression patterns. In this study, we tried to review the therapeutic effects of statins on OA.

Gut Commensal Parabacteroides goldsteinii MTS01 Alters Gut Microbiota Composition and Reduces Cholesterol to Mitigate Helicobacter pylori-Induced Pathogenesis.

Helicobacter pylori infection is closely associated with various gastrointestinal diseases and poses a serious threat to human health owing to its increasing antimicrobial resistance. H. pylori possesses two major virulence factors, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), which are involved in its pathogenesis. Probiotics have recently been used to eradicate H. pylori infection and reduce the adverse effects of antibiotic-based therapies. Parabacteroides goldsteinii MTS01 is a novel next-generation probiotic (NGP) with activities that can alleviate specific diseases by altering the gut microbiota. However, the mechanism by which P. goldsteinii MTS01 exerts its probiotic effects against H. pylori infection remains unclear. Our results showed that administration of P. goldsteinii MTS01 to H. pylori-infected model mice altered the composition of the gut microbiota and significantly reduced serum cholesterol levels, which mitigated H. pylori-induced gastric inflammation. In addition, the pathogenic effects of H. pylori VacA and CagA on gastric epithelial cells were markedly abrogated by treatment with P. goldsteinii MTS01. These results indicate that P. goldsteinii MTS01 can modulate gut microbiota composition and has anti-virulence factor functions, and thus could be developed as a novel functional probiotic for reducing H. pylori-induced pathogenesis.

The Role of Phytosterols in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease is now recognized as the most common cause of chronic liver disease with an increasing prevalence in both adults and children. Although the symptoms are absent or poorly expressed in most cases, some patients may progress to end-stage liver disease. The pathogenesis of NAFLD is known to be multifactorial. Current therapeutic recommendations focus on lifestyle changes in order to reduce the incidence of risk factors and drugs targeting major molecular pathways potentially involved in the development of this disease. Given that a pharmacological treatment, completely safe and effective, is not currently known in recent years more research has been done on the effects that some bio-active natural compounds, derived from plants, have in preventing the onset and progression of NAFLD. Numerous studies, in animals and humans, have shown that phytosterols (PSs) play an important role in this pathology. Phytosterols are natural products that are found naturally in plant. More than 250 phytosterols have been identified, but the most common in the diet are stigmasterol, β-sitosterol, and campesterol. Consumption of dietary PSs can reduce serum cholesterol levels. Due to these properties, most studies have focused on their action on lipid metabolism and the evolution of NAFLD. PSs may reduce steatosis, cytotoxicity oxidative stress, inflammation, and apoptosis. The purpose of this review is to provide an overview of the importance of dietary phytosterols, which are a window of opportunity in the therapeutic management of NAFLD.