Loss of m6A demethylase ALKBH5 alleviates hypoxia-induced pulmonary arterial hypertension via inhibiting Cyp1a1 mRNA decay.

BACKGROUND: Hypoxia-induced pulmonary artery hypertension (HPH) is a complication of chronic hypoxic lung disease and the third most common type of pulmonary artery hypertension (PAH). Epigenetic mechanisms play essential roles in the pathogenesis of HPH. N6-methyladenosine (m6A) is an important modified RNA nucleotide involved in a variety of biological processes and an important regulator of epigenetic processes. To date, the precise role of m6A and regulatory molecules in HPH remains unclear. METHODS: HPH model and pulmonary artery smooth muscle cells (PASMCs) were constructed from which m6A changes were observed and screened for AlkB homolog 5 (Alkbh5). Alkbh5 knock-in (KI) and knock-out (KO) mice were constructed to observe the effects on m6A and evaluate right ventricular systolic pressure (RVSP), left ventricular and septal weight [RV/(LV + S)], and pulmonary vascular remodeling in the context of HPH. Additionally, the effects of Alkbh5 knockdown using adenovirus were examined in vitro on m6A, specifically in PASMCs with regard to proliferation, migration and cytochrome P450 1A1 (Cyp1a1) mRNA stability. RESULTS: In both HPH mice lung tissues and hypoxic PASMCs, a decrease in m6A was observed, accompanied by a significant up-regulation of Alkbh5 expression. Loss of Alkbh5 attenuated the proliferation and migration of hypoxic PASMCs in vitro, with an associated increase in m6A modification. Furthermore, Alkbh5 KO mice exhibited reduced RVSP, RV/(LV + S), and attenuated vascular remodeling in HPH mice. Mechanistically, loss of Alkbh5 inhibited Cyp1a1 mRNA decay and increased its expression through an m6A-dependent post-transcriptional mechanism, which hindered the proliferation and migration of hypoxic PASMCs. CONCLUSION: The current study highlights the loss of Alkbh5 impedes the proliferation and migration of PASMCs by inhibiting post-transcriptional Cyp1a1 mRNA decay in an m6A-dependent manner.

Association between periprocedural myocardial injury and neointimal characteristics in patients with in-stent restenosis: an optical coherence tomography study.

Background: The relationship between neointimal characteristics of in-stent restenosis (ISR) and periprocedural myocardial injury (PMI) remains unclear. Therefore, this study aimed to investigate the relationship between PMI and neointimal characteristics of ISR by using optical coherence tomography (OCT). Methods: This was a retrospective study. We enrolled 140 patients diagnosed with ISR with normal baseline high-sensitivity troponin T (hs-cTnT) levels who underwent OCT and subsequent revascularization by means of drug-coated balloon (DCB) or drug-eluting stent (DES) between October 2018 and October 2022 in the Affiliated Hospital of Zunyi Medical University. Based on the 4th universal definition of myocardial infarction, patients whose hs-cTnT were increased five times above the upper reference limit (URL) after percutaneous coronary interventions (PCI) were deemed to PMI. The patients were subdivided into PMI (n=53) and non-PMI (n=87) groups. In the univariable analysis, variables in the baselines, angiography characteristics and OCT findings were analyzed with binary logistic regression. A P value of <0.2 was included in the multivariable model. Multivariable logistic regression analysis was used to identify the independent predictors of PMI. Results: The prevalence of intra-intimal microvessels in patients with PMI was higher than in those without PMI (58.5% vs. 32.2%, P=0.003). The ratio of intra-stent plaque rupture (PR) was also higher in patients with PMI (60.4% vs. 40.2%, P=0.021). Multivariable logistic regression analysis showed that intra-intimal microvessels [odds ratio (OR): 3.193, 95% confidence interval (CI): 1.280-7.966; P=0.013] and intra-stent PR (OR: 2.124, 95% CI: 1.153-4.732; P=0.035) were independently associated with PMI. Conclusions: Intra-intimal microvessels and intra-stent PR were independently associated with PMI. Accurate identification and recognition of intra-intimal microvessels and intra-stent PR may be helpful in preventing PMI.

Morphological characteristics of in-stent restenosis with different degrees of area stenosis: an optical coherence tomography study.

The morphological characteristics of in-stent restenosis (ISR) in relation to varying degrees of area stenosis have not been comprehensively examined. This study aimed to explore the tissue characteristics of patients experiencing ISR with different degrees of area stenosis through the utilization of optical coherence tomography (OCT). In total, 230 patients with ISR who underwent OCT were divided into the following three groups: area stenosis (AS) < 70% (n = 26); 70-80% (n = 119) and AS ≥ 80% (n = 85). Among the 230 patients, the clinical presentation as stable angina was 61.5% in AS < 70%, followed by 47.2% in 70% < AS ≤ 80%, and 31.8% in AS ≥ 80% (P = 0.010). The OCT findings showed that heterogeneous neointima, ISNA, LRP, neointima rupture, TCFA-like pattern, macrophage infiltration, red and white thrombus was more common with AS increased. Ordinal logistic regression analysis showed that higher AS was associated with previous dyslipidemia (odds ratio [OR], 4.754; 95% confidence interval [CI], 1.419-15.927, P = 0.011), neointimal rupture (OR: 3.640; 95% CI, 1.169-11.325, P = 0.026), red thrombus (OR: 4.482; 95% CI, 1.269-15.816, P = 0.020) and white thrombus (OR: 5.259; 95% CI, 1.660-16.659, P = 0.005). Patients with higher degrees of area stenosis in the context of ISR exhibited a greater number of discernible morphological characteristics as identified through OCT analysis. Furthermore, previous dyslipidemia, neointimal rupture, white thrombus and red thrombus were highly associated with and the progression of ISR lesions.

Association of the monocytes to high-density lipoprotein cholesterol ratio with in-stent neoatherosclerosis and plaque vulnerability: An optical coherence tomography study.

BACKGROUND: Monocyte-to-high-density lipoprotein cholesterol ratio (MHR) is an independent predictor of atherosclerosis and in-stent restenosis (ISR). However, the association between MHR and the incidence of in-stent neoatherosclerosis (ISNA) remains to be validated. METHODS: This study included 216 patients with acute coronary syndrome who had 220 ISR lesions and had undergone optical coherence tomography (OCT). All eligible patients were divided into three groups according to their MHR tertile level. OCT characteristics were comparatively analyzed between groups of different MHR levels, and univariate and multivariate logistic regression analyses were constructed to assess correlations between MHR level and ISNA as well as in-stent thin-cap fibroatheroma (TCFA). A receiver operating characteristic curve was used to determine the optimal MHR thresholds for predicting ISNA and in-stent TCFA. RESULTS: The incidence of ISNA (70.3% vs. 61.1% vs. 20.3%, P < 0.001) and in-stent TCFA (40.5% vs. 31.9% vs. 6.8%, P < 0.001) was the highest in the third tertile, followed by the second and first tertiles, respectively. Multivariate analysis revealed that MHR was independently associated with ISNA (odds ratio [OR], 7.212; 95% confidence interval [CI], 1.287-40.416; P = 0.025) and in-stent TCFA (OR, 5.610; 95% CI, 1.743-18.051; P = 0.004) after adjusting for other clinical factors. The area under the curve was 0.745 (95% CI, 0.678-0.811; P < 0.001) for the prediction of ISNA and 0.718 (95% CI, 0.637-0.778; P < 0.001) for the prediction of in-stent TCFA. CONCLUSION: MHR levels are an independent risk factor for ISNA.

Methyltransferase like 3-mediated N6-methylatidin methylation inhibits vascular smooth muscle cells phenotype switching via promoting phosphatidylinositol 3-kinase mRNA decay.

N6-methylatidine (m6A) is involved in post-transcriptional metabolism and a variety of pathological processes. However, little is known about the role of m6A in vascular proliferative diseases, particularly in vascular smooth muscle cells (VSMCs) phenotype switching-induced neointimal hyperplasia. In the current study, we discovered that methyltransferase like 3 (METTL3) is a critical candidate for catalyzing a global increase in m6A in response to carotid artery injury and various VSMCs phenotype switching. The inhibited neointimal hyperplasia was obtained after in vivo gene transfer to knock-down Mettl3. In vitro overexpression of Mettl3 resulted in increased VSMC proliferation, migration, and reduced contractile gene expression with a global elevation of m6A modification. In contrast, Mettl3 knockdown reversed this facilitated phenotypic switch in VSMCs, as demonstrated by downregulated m6A, decreased proliferation, migration, and increased expression of contractile genes. Mechanistically, Mettl3 knock-down was found to promote higher phosphatidylinositol 3-kinase (Pi3k) mRNA decay thus inactivating the PI3K/AKT signal to inhibit VSMCs phenotype switching. Overall, our findings highlight the importance of METTL3-mediated m6A in VSMCs phenotype switching and offer a novel perspective on targeting METTL3 as a therapeutic option for VSMCs phenotype switching modulated pathogenesis, including atherosclerosis and restenosis.

Improvement on blood pressure and skin using roselle drink: A clinical trial.

Roselle (Hibiscus sabdariffa L.) is an increasingly attractive plant for its health and pharmaceutical, beverage, and cosmetic applications. The purpose of this study was to investigate the clinical effects of roselle drink on antioxidant activity, blood pressure, and skin condition. Roselle drink used in this study contained rich phenolics (1.96 g of gallic acid equivalent/100 ml) and anthocyanins (1.65 g of cyanidin-3-glucoside equivalent/100 ml). In a randomized, cross-over, double-blind, placebo-controlled clinical study, 39 healthy adults received drank 200 ml of roselle drink or placebo-control drink for 6 months. A significant reduction in the blood pressure was observed in the roselle drink treated group when compared with preintervention values. After 6 months of treatment with roselle drink, serum phenolics contents, the levels of Trolox equivalent antioxidant capacity (TEAC), glutathione, superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G-6-PDH), glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-Rd) were significantly increased in healthy subjects. However, a significant increment in skin redness and skin moisture was observed in the facial skin of roselle drink-treated participants. Oral administration of roselle drink for 6 months significantly lowered the blood pressure, improved antioxidation level, and positively regulated skin redness as well as moisture. Phenolics and anthocyanins in roselle could be the major potential contributors to such health effects. PRACTICAL APPLICATIONS: Roselle is a typical plant. Continuous administration of roselle drink clearly improved antioxidation levels, reduced blood pressure and positively regulated skin redness and moisture. Phenloics and anthocyanins in roselle could be the major potentila contributors of such health benefits.

Efficacy of Probiotic Milk Formula on Blood Lipid and Intestinal Function in Mild Hypercholesterolemic Volunteers: A Placebo-control, Randomized Clinical Trial.

Several studies have reported that probiotics could modulate host lipid metabolism via altering the intestinal microbiota. Hence, the current study was aimed to assess the efficacy of a mixture of probiotic-contained milk formula (PMF) with three different bacterial strains [Lactobacillus acidophilus (La5), Lactobacillus casei (TMC), Bifidobacterium lactis (Bb12)] on lipid profile and intestinal function in healthy mild hypercholesterolemic volunteers. Totally, 40 healthy mild hypercholesterolemic subjects (180-220 mg/dL) were randomly assigned into two groups as placebo or experimental group. All the subjects were requested to drink either PMF (experimental) or skimmed milk drink formula-placebo (30 g mixed with 200 mL of water) for 10 weeks and continued by 2 weeks of the follow-up period. Supplementation of PMF for 10 weeks significantly improved (p < 0.05) the fecal weight, fecal movement (decreased fecal gastrointestinal passing time) by improving intestinal microbiota (increasing beneficial bacterial species like Lactobacillus, Bifidobacterium spp.), and lag time of low-density lipoprotein (LDL) oxidation. Also, intake of PMF substantially reduced (p < 0.05) the levels of total cholesterol (TC; 8.1%) and low-density lipoprotein cholesterol (LDL-c; 10.4%) and thus showcasing its cardioprotective efficacy. PMF considerably improves gastrointestinal function by modulating fecal movement, intestinal microbiota, and decrease cholesterol and might be helpful in the management of hypercholesterolemia.

Chemopreventive and Chemotherapeutic Effect of Propolis and Its Constituents: A Mini-review.

Propolis is a bee wax rich in various phytocomponents and traditionally used to treat various ailments. Propolis is reported to possess an array of biological properties including anti-inflammatory, antioxidant, anti-cancer, and anti-diabetic as well as cardioprotective, hepatoprotective, renoprotective, and derma protective activities. A plethora of studies confirmed that propolis is effective against various types of cancer including head and neck, lung, liver, brain (glioma), pancreas, kidney, prostate, skin (melanoma), breast, oral, esophagus, gastric, colorectal, and bladder cancers. However, many researchers have demonstrated that propolis displays potent chemoprotective/chemopreventive or anti-cancer activity against only a few types of cancers like oral, gastrointestinal, dermal (melanoma), breast, and prostate cancers. Therefore, this mini-review only summarizes the chemopreventive/chemotherapeutic activities of propolis and its updated underlying mechanisms. Taken together, propolis displays potent chemoprotective or anti-cancer effect due to the presence of various phytocomponents which contribute to pro-apoptotic, cytotoxic, anti-proliferative (cell cycle arrest), anti-metastatic, anti-invasive, anti-angiogenic and anti-genotoxic or anti-mutagenic properties along with antioxidant, immunomodulatory, and anti-inflammatory functions. Hence, propolis could be used as an adjuvant for treating various cancers along with standard chemotherapeutic drugs. However, many large-scale clinical studies are needed to justify such applications.

Exploring Consumers' Purchase Intention of An Innovation of the Agri-Food Industry: A Case of Artificial Meat.

Green consumption is an emerging environmental topic receiving global attention. Because livestock production is a primary source of greenhouse gas emission, the "low-carbon diet" has become a new trend in the catering industry. Fast food companies have been launching vegetarian products because artificial meat requires less water and land resources than traditional livestock and has lower carbon emissions. This study explores the influence of consumers' attitude, subjective norms (SNs), and perceived behavioral control (PBC) on their purchase intention for vegetarian burgers from the product knowledge (PK) and environmental concern (EC) perspectives. Based on the theory of planned behavior, the purchase intention of people from different food cultures to pay for fast food burgers is discussed. Five hundred questionnaires were distributed, of which 436 were valid. The results revealed that: (1) consumers' SNs , PBC, and EC significantly affect purchase intention (PI), and SNs and PK have no significant relationship with PI; and (2) vegetarians are willing to pay higher prices than nonvegetarians. This study recommends that industry personnel should attempt to increase consumers' knowledge regarding artificial meat and expand marketing channels to improve the convenience of purchasing artificial meat foods by conducting lectures and media promotion, respectively.

The ergogenic activity of cider vinegar: A randomized cross-over, double-blind, clinical trial.

This randomized, double-blind, clinical trial was designed to compare the endurance capacity (ergogenic property) in healthy athletes after consumption of apple cider vinegar (ACV) and a commercial sports drink (CSD) before and during endurance exercise. Fourteen healthy participants were enrolled in this trial and were divided into two groups as ACV and CSD with seven participants in each. Participants were requested to consume 500 mL of either commercial ACV or CSD 1 h before endurance exercise (bicycle ergometer). Blood samples were collected at baseline, 0, 20, 40, 60 min until exhaustion to assess glucose, lactate, ammonia and non-esterified fatty acids (NEFA). Respiratory exchange rate (RER) score was measured every 15 min and the heart rate (HR) was measured every 5 min. The outcome of the present trial clearly showed that no significant differences were observed between ACV and CSD except in the blood level of ammonia (only at exhaustion time). Thus, these results show that ACV and the CSD both possessing the ergogenic property, enhanced blood glucose, NEFA, and suppress the production of lactate as well as maintains normal RER score, and HR throughout the endurance exercise. Overall this trial showcases that ACV did not significantly improve the ergogenic activity over the CSD.

Anti-inflammatory properties of fermented pine (Pinus morrisonicola Hay.) needle on lipopolysaccharide-induced inflammation in RAW 264.7 macrophage cells.

This study was aimed to explore the antioxidant and anti-inflammatory activity of various pine needle products (non-fermented, fermented, and commercial) extracted with different solvents (hexane, ethyl acetate, and water) in lipopolysaccharide (LPS) induced RAW 264.7 cells. The phenolic/flavonoid contents of ethyl acetate extract of fermented pine needle (EAE-FPN) is higher than other pine product extracts (hexane/water). The levels of antioxidant indices (TEAC, DPPH) as well as free radical scavenging activity (H2 O2 ) were significantly improved in EAE-FPN than other pine needle product extracts. The levels of ROS and various inflammatory markers (NO, PGE2, TNF-α, and IL-1ß/6) were considerably abolished by EAE-FPN in a dose-dependent manner (50-200 µg/ml). Moreover, the protein expressions of inducible NO synthase (iNOS), cyclooxygenase 2 (COX-2), and nuclear factor Kappa B (NF-κB) p65 subunit were also markedly downregulated by EAE-FPN. Collectively, EAE-FPN with phenolic/flavonoid content showed excellent antioxidant and anti-inflammatory properties via modulating NF-κB signaling pathway. PRACTICAL APPLICATIONS: Pine needle drink (Pinus morrisonicola Hay) has been used as a functional beverage for many years due to its various biological properties in Asia especially in Taiwan, China, and Korea. Many researchers hinted various biological activity of fermented pine needle product but none of them explored the in-depth mechanism underpinning its antioxidant and anti-inflammatory properties in LPS-induced RAW 264.7 cell model. Hence, the current cell line study was designed to assess the underlying mechanism behind the antioxidant and anti-inflammatory activity of Pine needles extract (both non-fermented and fermented) in LPS-induced RAW 264.7 cells (macrophage). The outcome of this study distinctly showed that EAE-FPN displayed potent antioxidant and anti-inflammatory activities by regulating NF-κB signaling pathway. Therefore, pine needle could be developed into functional drink to abolish the progression of inflammatory responses in various disease condition.

Effect of a balanced nutrition meal replacement diet with altered macromolecular composition along with caloric restriction on body weight control.

The prevalence of obesity and its related metabolic syndrome (MetS) has shown an upsurge in recent years due to modified lifestyle patterns. The present study was designed to investigate the impact of a nutritionally balanced conventional meal replacement diet with modified macromolecular composition (rich in soy/pea protein and soluble fibers) and caloric restriction on Taiwanese obese subjects. Obese subjects (BMI > 27; n = 50, male 23, female 27) were recruited and requested to replace two meals per day (breakfast and lunch or dinner) with the balanced nutritional meal replacement diet (equal to 240 kcal) for 8 weeks with one regular meal and make sure that the daily target calorie limit (caloric restriction) was less than 1500 kcal day-1 for men and 1200 kcal day-1 for women. After eight weeks of intervention with a calorie-restricted balanced partial meal replacement diet, the levels of body weight, body fat, and waist circumference were significantly reduced by 4.1 kg, 2.38%, and 5.06 cm, respectively. The levels of serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-c) were significantly decreased (p < 0.05) with a significant increase (p < 0.05) in high-density lipoprotein cholesterol (HDL-c) levels after 8 weeks of intervention with the meal replacement diet. Moreover, the levels of insulin, homeostatic model assessment-insulin resistance (HOMA-IR), leptin, thiobarbituric acid reactive substances (TBARS) and cardiovascular risk factors were significantly attenuated (p < 0.05). To conclude, the present intervention with meal replacement and caloric restriction on obese subjects could concomitantly decrease the body weight and glycemic and cardiovascular risk factors and thereby lower the risk of various metabolic disorders.

Down-regulation of partial substitution for staple food by oat noodles on blood lipid levels: A randomized, double-blind, clinical trial.

This clinical trial was conducted to assess the lipid-lowering activity of oat noodles by replacing partial staple food (wheat or rice noodle) in normal and mildly hypercholesterolemic subjects. Totally 84 healthy and mild hypercholesterolemic subjects were recruited and divided into 2 groups as experimental (oat noodles) and placebo (wheat noodles) and instructed to consume 100 g of oat noodles or wheat noodles (replacing one or two meals/day) for 10 weeks and followed by 2 weeks of follow up (without noodle consumption). Various anthropometric measurements and biochemical analysis were carried out during initial (baseline), 2nd, 6th, 10th and 12th week (follow-up). Consumption of oat noodles by replacing staple food for 10 weeks significantly reduced (**p < 0.01) the levels of total cholesterol (TC; 17.46%) and low-density lipoprotein LDL-c (19.03%) in both healthy and mildly hypercholesterolemic subjects. However, the hypocholesterolemic effect is significantly higher in mildly hypercholesterolemic subjects as compared with normal subjects. A pronounced decline (*p < 0.05) in the levels of various cardiovascular diseases (CVDs) markers including TC/HDL and LDL/HDL ratios and blood pressure (SBP; 11.09% and DBP; 7.48%) were observed in oat noodles supplemented subjects as equivalence with the placebo group. The partial replacement of staple food with oat noodle could considerably improve the health status of all subjects especially in hypercholesterolemic subjects and thus lower the risk of CVDs.

Beneficial effect of Burdock complex on asymptomatic Helicobacter pylori-infected subjects: A randomized, double-blind placebo-controlled clinical trial.

BACKGROUND: Burdock complex (BC) constitutes of burdock (Arctium lappa), angelica (Angelica sinensis), gromwell (Lithospermum erythrorhizon), and sesame (Sesamum indicum) oil, which are commonly used in traditional Chinese medicine (TCM) for treating various disorders. This study intended to examine the anti-H. pylori activity of BC on AGS cell model as well as in asymptomatic H. pylori-infected subjects. MATERIALS AND METHODS: AGS cell incubated with H. pylori and treated with BC to evaluate the minimum inhibition concentration (MIC), cell viability (MTT) anti-adhesion activity, and inflammatory markers. In case of clinical trial, H. pylori-positive subjects (urea breath test [UBT] >10%, n = 36) were enrolled and requested to intake BC (n = 19) or placebo (n = 17) for 8 weeks. Antioxidant capacity, total phenol, UBT, inflammatory markers were analyzed at the initial, 4th, 8th, and 10th weeks. Moreover, the endoscopic examination was carried out on baseline and 10th week. RESULTS: In vitro studies showed that BC treatment significantly inhibited (P < .05) the inflammatory markers and adhesion of H. pylori to AGS cell. However, H. pylori-infected subject ingested with BC for 8 weeks significantly decreased (P < .05) the UBT value, inflammatory markers with improved antioxidant activity, and phenolic levels as compared to placebo. Also, consumption of BC considerably healed the ulcer wound. CONCLUSION: Overall, the BC could attenuate H. pylori infection by inhibiting H. pylori adhesion and subsequent inflammatory response on the gastric epithelial cell (AGS) as well as clinically ameliorated UBT, antioxidant capacity, and alleviated inflammation to display its anti-H. pylori activity.

Comparative studies on the hypolipidemic, antioxidant and hepatoprotective activities of catechin-enriched green and oolong tea in a double-blind clinical trial.

This study aimed to compare the beneficial effect of catechin-enriched green tea and oolong tea on mildly hypercholesterolemic subjects. Sixty mildly hypercholesterolemic subjects (180-220 mg dL-1) were enrolled and divided into three groups as catechin-enriched green tea (CEGT), catechin-enriched oolong tea (CEOT) or placebo. The subjects were instructed to drink 2 × 300 mL of CEGT (780.6 mg of catechin), CEOT (640.4 mg of catechin) or placebo beverage for 12 weeks. Drinking CEGT and CEOT significantly decreased (p < 0.05) the body weight, fat, and BMI, lipid peroxidation as well as lipid profile (TC, LDL-c, HDL-c, and TG). Also, intervention with CEGT and CEOT significantly improved (p < 0.05) the oxidative indices (TEAC and GSH) and antioxidant enzymes (SOD, CAT, GPx, and GR). Moreover, ultrasound examination endorsed the hepatoprotective activity of CEGT and CEOT by reverting mild fatty liver to the normal hepatic condition because of antioxidant and hypolipidemic activities. To summarize, both CEGT and CEOT showed similar antioxidant and hepatoprotective activities. However, CEOT displayed superior lipid-lowering activity compared to CEGT or placebo, and hence it could be used to amend the wellness condition of mildly hypercholesterolemic subjects.

Efficacy of protein rich pearl powder on antioxidant status in a randomized placebo-controlled trial.

Pearl is one of the well-known traditional Chinese medicine (TCM) prescribed for treating various skin and bone related disorders due to its abundant proteins and mineral contents. The present investigation focused on antioxidation and life span prolonging effects from different extracts of pearl powder. During in vitro studies, various oxidative indices were evaluated, along with lifespan-prolonging effect were checked using wild-type Caenorhabditis elegans. For the clinical trial, 20 healthy middle-aged subjects were recruited and separated into 2 groups as experimental and placebo group, who received 3 g of pearl powder/d (n = 10) and 3 g of placebo/d (n = 10) for 8 weeks, respectively. During the initial, 2nd, 4th, 6th, 8th and 10th weeks the blood samples were collected for biochemical analysis. The protein extract of pearl powder recorded maximum (p < 0.05) antioxidant activity (20-68%) as well as efficiently prolonged the life span of C. elegans by 18.87%. Pearl powder supplemented subjects showed a substantial increase (p < 0.05) in total antioxidant capacity from 0.45 to 0.69 mM, total thiols from 0.23 to 0.29 mM, Glutathione content from 5.89 to 9.19 µM, enzymic antioxidant activity (SOD-1248 to 1308; Gpx-30 to 32; GR-2.4 to 2.9) as well as considerably suppressed the lipid peroxidation products from 4.95 to 3.27 µM. The outcome of both in-vitro and in-vivo antioxidant activity inferred that protein extract of pearl powder was a potent antioxidant and thereby prolonged the lifespan of C. elegans. Hence, pearl powder could be recommended for treating various age-related degenerative disorders.

A randomized, double-blind clinical study of the effects of Ankascin 568 plus on blood lipid regulation.

Hyperlipidemia and inflammation play important roles in the development and progression of atherosclerosis. Atherosclerosis is regarded as an inflammatory response of blood vessels to injury at the start of atherosclerotic plaque formation, which then leads to cardiovascular events. Edible fungi of the Monascus species have been used as traditional Chinese medicines in East Asia for several centuries. The fermented products of Monascus purpureus NTU 568 possess a number of functional secondary metabolites including the anti-inflammatory pigments monascin and ankaflavin. Compounds derived from M. purpureus have been shown to have hypolipidemic effects. We aimed to evaluate the effects of M. purpureus NTU 568 fermentation product an extract (Ankascin 568 plus) containing monascin and ankaflavin on blood lipids in volunteers with borderline high levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) by conducting a 12-week randomized, double-blind, placebo-controlled, adaptive-design study. This study enrolled 40 subjects aged 18-65 years from a population of patients with TC and LDL-C levels of ≥180 mg/dL and 130-190 mg/dL, respectively. Measured endpoints included lipid profile, liver, kidney and thyroid function, electrolyte balance, creatinine phosphokinase, and fasting blood glucose. After 4 weeks of treatment (500 mg Ankascin 568 plus/day), the changes in the lipid levels showed that the active products had a more favorable effect than the placebo. Compared to the baseline, statistically significant decreases of 11.9% and 19.0% were observed in TC and LDL-C levels, respectively (p < 0.05 for all pairs). This study demonstrated that subjects administered one 500 mg capsule of Ankascin 568 plus for more than 4 weeks exhibited a significant reduction in serum TC and LDL-C levels. Therefore, Ankascin 568 plus may be a potentially useful agent for the regulation of blood lipids and the treatment of coronary artery diseases.

Regulatory efficacy of fermented plant extract on the intestinal microflora and lipid profile in mildly hypercholesterolemic individuals.

In recent years, the use of fermented plant products to protect against various metabolic syndromes has been increasing enormously. The objective of this study was to check the regulatory efficacy of fermented plant extract (FPE) on intestinal microflora, lipid profile, and antioxidant status in mildly hypercholesterolemic volunteers. Forty-four mildly hypercholesterolemic individuals (cholesterol 180-220 mg/dL) were recruited and assigned to two groups: experimental or placebo. Volunteers were requested to drink either 60 mL of FPE or placebo for 8 weeks. Anthropometric measurements were done in the initial, 4th, 8th, and 10th weeks. The anthropometric parameters such as body weight, body fat, and body mass index were markedly lowered (p<0.05) on FPE intervention participants. Moreover, the total antioxidant capacity and total phenolics in plasma were considerably increased along with a reduction (p<0.05) in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) after FPE supplementation. Participants who drank FPE showed a pronounced increase (p<0.05) in the number of beneficial bacteria such as Bifidobacterium spp. and Lactobacillus spp., whereas the number of harmful bacteria such as Escherichia coli and Clostridium perfringens (p<0.05) were concomitantly reduced. Furthermore, the lag time of LDL oxidation was substantially ameliorated in FPE-administered group, thus indicating its antioxidative and cardioprotective properties. Treatment with FPE substantially improved the intestinal microflora and thereby positively regulated various physiological functions by lowering the anthropometric parameters, TC, and LDL-c, and remarkably elevated the antioxidant capacity and lag time of LDL oxidation. Therefore, we recommended FPE beverage for combating hypercholesterolemia.

A randomized, double-blind clinical study to determine the effect of ANKASCIN 568 plus on blood glucose regulation.

Diabetes is the fourth major cause of death in Taiwan. High blood glucose can lead to macrovascular diseases, small vessel diseases (retinopathy, kidney disease), and neuropathy. This study aimed to investigate whether Monascus-fermented products (ANKASCIN 568 plus) can regulate blood glucose and blood lipids. This study enrolled 39 patients with a fasting blood glucose level between 100 mg/dL and 180 mg/dL, and a glycated hemoglobin (HbA1c) level of <9%. All patients were randomly divided into placebo (n=20) and experimental (n=19) groups. Each patient received two placebo capsules (maltodextrin) or ANKASCIN 568 plus capsules daily for 12 weeks. The patients were screened during follow-up 4 weeks after the administration of sample or placebo had been discontinued. Blood and urine samples were collected at the initial, 6th week, 12th week, and 16th week. The anthropometric indicators of blood pressure, fasting plasma glucose level, postprandial plasma glucose level, insulin level, insulin resistance, blood lipid changes, and liver, kidney, and thyroid function indices were measured. After 6 weeks, changes in fasting blood glucose, low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) levels showed that ANKASCIN 568 plus had a more favorable effect than the placebo. Compared to baseline, a statistically significant decrease of 8.5%, 10.3%, and 7.5% was observed in fasting blood glucose, LDL-C and, TC levels, respectively (p<0.05 for all pairs). Therefore, ANKASCIN 568 plus produced by Monascus purpureus NTU 568 fermentation may be a potentially useful agent for the regulation of blood glucose and blood lipids and for treatment of coronary artery diseases.

Docosahexaenoic acid increases the expression of oxidative stress-induced growth inhibitor 1 through the PI3K/Akt/Nrf2 signaling pathway in breast cancer cells.

Oxidative stress-induced growth inhibitor 1 (OSGIN1), a tumor suppressor, inhibits cell proliferation and induces cell death. N-6 and n-3 PUFAs protect against breast cancer, but the molecular mechanisms of this effect are not clear. We investigated the effect of n-6 and n-3 PUFAs on OSGIN1 expression and whether OSGIN1 is involved in PUFA-induced apoptosis in breast cancer cells. We used 100 µM of n-6 PUFAs including arachidonic acid, linoleic acid, and gamma-linolenic acid and n-3 PUFAs including alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid (DHA). Only DHA significantly induced OSGIN1 protein and mRNA expression. DHA triggered reactive oxygen species (ROS) generation and nuclear translocation of Nrf2. LY294002, a PI3K inhibitor, suppressed DHA-induced OSGIN1 protein expression and nuclear accumulation of Nrf2. Nrf2 knockdown attenuated DHA-induced OSGIN1 expression. N-Acetyl-l-cysteine, a ROS scavenger, abrogated the DHA-induced increases in Akt phosphorylation, Nrf2 nuclear accumulation, and OSGIN1 expression. DHA induced the Bax/Bcl-2 ratio, mitochondrial accumulation of OSGIN1 and p53, and cytochrome c release; knockdown of OSGIN1 diminished these effects. In conclusion, induction of OSGIN1 by DHA is at least partially associated with increased ROS production, which activates PI3K/Akt/Nrf2 signaling. Induction of OSGIN1 may be involved in DHA-induced apoptosis in breast cancer cells.