PA Treatment Research Articles

Loss Of Cd36 Protects Skeletal Muscle Cells From PA-Induced Apoptosis By Enhancing Autophagy

Studies have shown that skeletal muscle mass was declined with diabetes and obesity. Skeletal muscle mass declines resulting in sarcopenia and metabolic diseases. CD36 is also reported to play a pivotal role in Type 2 Diabetes. Therefore, the apoptosis of skeletal muscle cells plays a vital role in maintaining the functional muscle mass of type 2 diabetes. PURPOSE: To investigate the protective effect of Fatty Acid Translocase (FAT/CD36) against PA-induced apoptosis. METHODS: Cells were differentiated when they reached 80%–90% confluence. Once the long shape occurred in 80%–90% cells, lipofectamine RNAiMAX was used to transfect siCtrl or siCD36.The whole term for knockdown is 72 h. Skeletal muscle cells were harvested after treatment with PA (200 μM) for 16 h. The apoptosis of differentiated skeletal muscle cells induced by PA treatment was monitored by flow cytometry. The gene expression level of endoplasmic reticulum stress-related genes was detected by QPCR. The protein expression level of autophagy-related genes was detected by Western blotting. The t-test was used as the statistical test. RESULTS: Compared with the PA-free culture medium group, skeletal muscle cells treated with PA had increased apoptosis (18.75% ± 1.25% vs. 12.74% ± 0.19%, p < 0.001). Whereas skeletal muscle cells treated with siCD36 transfection can resist apoptosis under PA and PA-free condition (15.86% ± 0.96% vs. 18.75% ± 1.25%, p < 0.05; 9.92% ± 0.37% vs. 12.74% ± 0.19%, p < 0.001) especially in the late stage (10.83% ± 0.49% vs. 13.4% ± 1.52%, p < 0.05; 6.18% ± 0.69% vs. 9.5% ± 0.15%, p < 0.01). The mRNA expression level of Grp78 and Ire1a were increased in CD36 deficiency group (1.23 ± 0.09 vs. 1 ± 0.05, p < 0.05; 1.25 ± 0.07 vs. 1 ± 0.05, p < 0.05). The protein expression level of LC3-II, Beclin1 were significantly increased in CD36 deficiency group (201.71 ± 3.13 vs. 160.40 ± 6.76, p < 0.05, 193.84 ± 2.92 vs. 176.94 ± 1.41, p < 0.05). CONCLUSIONS: CD36, as a signaling molecule, can activate the autophagy pathway through the endoplasmic reticulum, thereby attenuating apoptosis in PA-stimulated skeletal muscle cells, implicating a promising target for metabolic diseases. Supported by the National Natural Science Foundation of China (No. 32071172, 31600966).

Differential non-coding RNAs expression profiles of invasive and non-invasive pituitary adenomas.

BackgroundPituitary adenoma (PA) accounts for 10–15% of all intracranial neoplasms. Despite their benign nature, PA often shows invasive growth. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are a class of non-coding RNAs that play important roles in PA initiation and progression.AimThe aim of this study was to find specific profiles of miR-200a and long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) in PA based on a comparative study using Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses of tumor tissue and plasma.MethodsPlasma and PA tissue samples were obtained from two groups of included patients (15 invasive and 15 non-invasive PA). In addition, plasma samples from patients with invasive PA have collected pre- and post-operation. Plasma and tissue samples subjected to qRT-PCR analyses for the expression levels of miR-200a and lncRNA ANRIL.ResultsThe expression levels of miR-200a and lncRNA ANRIL were increased in tissue samples patients with invasive PA than in the patients with non-invasive PA. In addition, the expression levels of circulating miR-200a and lncRNA ANRIL were increased in patients with invasive PA than in patients with non-invasive PA in the pre-operation period. However, the expression level of plasma circulating miR-200a and lncRNA ANRIL was decreased in patients with invasive PA in the post-operation period. Our results depicted a miR-200a and lncRNA ANRIL expression in tissue and plasma samples in the patients with invasive PA. In addition, Receiver Operating Characteristic (ROC) curve was used to evaluate the diagnostic value of these circulating miR-200a and lncRNA ANRIL.ConclusionThe expression of these tumor-associated ncRNAs has been elevated in the PAs. Therefore, miR-200a and lncRNA ANRIL represents as biomarkers for diagnosis and potential targets for novel invasive PA treatment strategies.

Propionic acid produced by Cutibacterium acnes fermentation ameliorates ultraviolet B-induced melanin synthesis

Ultraviolet irradiation induces melanin accumulation, which can be reduced by the use of chemical whitening products. However, the associated safety concerns of such products have prompted the search for natural and harmless alternatives. This study aimed to identify a natural acidic formulation to reduce skin pigmentation. The metabolite propionic acid (CH3CH2COOH, PA) was the most abundant fatty acid in the filtrate from Pluronic F68 (PF68) fermentation of Cutibacterium acnes (C. acnes) and reduced the DOPA-positive melanocytes by significantly inhibiting cellular tyrosinase activity via binding to the free fatty acid receptor 2 (FFAR2). Moreover, 4 mM PA treatment did not alter melanocyte proliferation, indicating that it is an effective solution for hyperpigmentation, causing no cellular damage. The reduced DOPA-positive melanocytes and tyrosinase activity were also observed in mice ear skin tissue injected with a mixture of C. acnes and PF68, supporting that the inhibition of melanogenesis is likely to be mediated through fermentation metabolites from C. acnes fermentation using PF68 as a carbon source. Additionally, PA did not affect the growth of its parent bacteria C. acnes, hence is a potent fermentation metabolite that does not disrupt the balance of the skin microbiome.

LGG-11. BH3-MIMETICS TARGETING BCL-XL SELECTIVELY IMPACT THE SENESCENT COMPARTMENT OF PILOCYTIC ASTROCYTOMA

IntroductionPilocytic astrocytoma (PA) is the most common brain tumor in children. Activation of the mitogen-activated protein kinase (MAPK) pathway is a hallmark of PA. Complete remission in non-resectable tumors is infrequently observed with current therapeutic approaches. Most PA tumors cells are in oncogene-induced senescence (OIS), which may explain the benign growth behavior of PAs but also account for resistance to therapy. Therefore, treatment of PA with senolytic agents such as BH3-mimetics is a promising new approach. MethodsThree patient-derived PA cell lines, DKFZ-BT66, DKFZ-BT308 (both KIAA1549:BRAF-fusion positive) and DKFZ-BT314 (BRAF V600E-mutation positive) were used. Depending on inducible expression or repression of SV40 large T antigen all models can reflect both states of PA, proliferation and OIS. Cells in both states were treated with different BH3-mimetics. Inhibition of metabolic activity was measured after 72 hours. Target expression was assessed by RT-qPCR and Western blot. On-target activity of BH3-mimetics was determined by immunoprecipitation (IP) of Bcl-xL/BAK. ResultsBH3-mimetics with strong binding affinity for Bcl-xL (Navitoclax, A-1131852, A-1155463) showed selectivity for senescent cells in 2/3 models (DKFZ-BT66 and DKFZ-BT314) and acted in nanomolar ranges. IC50s for Navitoclax (Cmax 6600nM in patients) were 40nM (OIS) vs. 200nM (proliferation) and 170nM (OIS) vs. 3700nM (proliferation) in DKFZ-BT66 and DKFZ-BT314, respectively. Target engagement was evident in the Bcl-xL/BAK-IP, and target expression of Bcl-xL was similar in all models studied. The relative resistance of senescent DKFZ-BT308 despite on-target activity is currently being investigated. ConclusionSenolytic treatment of PA with BH3-mimetics targeting Bcl-xL is a promising new strategy directly targeting the major senescent part of the tumor in clinically archivable concentrations. However, our data suggests that not all PAs may respond to treatment. The analysis of comparative gene expression analysis and BH3-profiling is ongoing to define predictive biomarkers.

Effects of n3/n6‐Derived Epoxy‐Fatty Acids on Hepatocyte Cell Death

Background Epoxy-fatty acids (EpFAs) are bioactive lipid mediators that are derived from n3- and n6-polyunsaturated fatty acids (PUFAs) via CYP450 epoxygenation. EpFAs are thought to be beneficial lipids by virtue of their systemic anti-inflammatory, anti-fibrotic, and tissue-regenerative effects. EpFAs are endogenously deactivated by soluble epoxide hydrolase (sEH) to their less biologically active, or in some cases deleterious, dihydroxy-fatty acid (dihydroxy-FAs). Recent work from our group discovered an imbalance in the EpFA/dihydroxy-FA pool in patients with alcohol-associated liver disease (ALD). Importantly, little is known regarding the mechanisms associated with this imbalance or the role of individual EpFAs or dihydroxy-FAs in ALD. Therefore, the objective of this study was to interrogate the effects of EpFAs and dihydroxy-FAs on hepatocyte cell death, a key pathological contributor to liver injury in ALD. Hypothesis EpoxyFAs and dihydroxyFAs will alter hepatocyte survival in vitro following toxic insult in primary or immortalized hepatocytes. Methods Primary mouse hepatocytes, human HepG2, or rat H4IIE cells were treated with 8,9-EET, 8,9-DiHETE, 17,18-EpETE, 19,20-EpDPA, or a vehicle control. Effects on baseline or palmitic acid (PA, 150 µM)-induced cell death were measured by MTT assay and apoptotic cell death was identified by Annexin-V staining (quantified by cellomics analysis). Additionally, primary hepatocytes were isolated from WT and Ephx2-/- mice (global sEH knockout), then exposed to 400 µM PA to determine differences in cell death between genotypes. Cell death was determined by supernatant alanine aminotransferase (ALT) activity and confirmed by MTT assay (n = 3 mice per genotype). Results In both HepG2 cells and primary mouse hepatocytes, n-6-PUFA-derived 8,9-EET had no effect on PA-induced cell death by MTT assay, but its sEH degradation product 8,9-DiHETE significantly decreased cell viability (by 29% in primary cells and 38% in HepG2 cells). By contrast, in H4IIE or HepG2 cells, cellomics analysis showed that n-3-PUFA-derived 19,20-EpDPA reduced PA-induced apoptosis by 21%. Primary mouse hepatocytes derived from Ephx2-/- mice had only a 31% increase in cell death following PA treatment, whereas WT-derived hepatocytes had a 110% increase. These results suggest that with respect to hepatocellular death, n3-derived EpFAs are more beneficial than n6-derived EpFAs. Conclusions PUFA-derived EpFAs and their sEH degradation products have diverse effects in vitro with respect to hepatocyte cell death. In multiple cell lines and in primary mouse hepatocytes, dihydroxy-FAs exacerbated cell death, whereas EpFAs ameliorated it, with n3-derived EpFAs having a more potent effect than those derived from n6-PUFAs. Future studies will further characterize these lipid mediators in liver cell health and determine their mechanisms of action.

Influence of reduced application time on bonding durability of universal adhesives to demineralized enamel.

This study aimed to assess the effect of application time on the microshear bond strength (μSBS) of three universal adhesives in demineralized and sound enamel before and after aging. Bovine teeth (192) were prepared where buccal surfaces were ground and divided into two groups (sound enamel and demineralized enamel). The specimens in each group were divided into 12 subgroups by combining 3 adhesive agents (All-Bond Universal, Scotchbond Universal, and Tokuyama Universal Bond) × 4 adhesion strategy. Each adhesive was applied with either prolonged (PA) or reduced (RA) application time in etch-and-rinse or self-etch mode. Bonded composites were subjected to μSBS testing after 24-h or 2-year water storage. The results were evaluated using four-way ANOVA and Tukey's post-hoc test (α = 0.05). The μSBS of adhesives to sound enamel in both etching modes was mostly similar to demineralized enamel, regardless of application time and aging time. At 24-h, all adhesives with PA in self-etch mode showed higher μSBS when compared with RA, except Tokuyama Universal Bond, but after 2-year aging, no significant difference was found in μSBS between RA and PA. The μSBS of adhesives with PA in etch-and-rinse mode depended on used adhesive and enamel condition compared to RA, regardless of μSBS testing time. PA of adhesives did not reveal a significant difference in μSBS to enamel, regardless of substrate type and etching mode. After 2-year aging, the bond strength of universal adhesives presented no significant difference between PA and RA treatments.

Short-term variations of mycosporine-like amino acids in the carrageenan-producing red macroalga Mazzaella laminarioides (Gigartinales, Rhodophyta) are related to nitrate availability

The effect of solar UV radiation exposure and NO3– supply on mycosporine-like amino acids (MAAs) accumulation in the carrageenan-producing red macroalga Mazzaella laminarioides in a short-term period was studied. Apical segments of M. laminarioides tetrasporophytes were exposed to three treatments of solar radiation (PAR [P], PAR+UV-A [PA], and PAR+UV-A+UV-B [PAB]) under 0.38 mM NO3– or without NO3– supply. Samples were taken at the following local times: 8:00 (initial value), 13:00, and 18:00, and at 8:00 on the following day. Short-term variations in total MAA content were observed, being this variation accounted by the interaction of radiation, time exposure, and NO3– treatments. The highest MAAs content (above 3 mg g−1 DW) was observed at 13:00 under PA (without NO3−) and PAB (with NO3–), and at 18:00 under PA (with NO3–) and PAB (with NO3–) treatments. Four MAAs were identified: asterina-330, shinorine, palythine, and mycosporine-glycine. The content and percentage of each MAA varied during the experimental time. While the accumulation of shinorine and palythine varied according to NO3– supply, mycosporine-glycine did it according to the interaction of time exposure and radiation treatment. The short-term (hours) variations in total MAAs content and the concentration of each MAA as a response to the high solar irradiance received could be a prerequisite in intertidal species to thrive in a highly variable environment.

Effect of 3 autumn pasture management strategies applied to 2 farm system intensities on the productivity of spring-calving, pasture-based dairy systems

The objective of this study was to investigate the effect of altering autumn pasture availability and farm system intensity on the productivity of spring-calving dairy cows during autumn. A total of 144 Holstein-Friesian and Holstein-Friesian × Jersey crossbred dairy cows were randomly assigned to 2 whole farm system (FS) intensities and 3 autumn pasture availability (PA; measured above 3.5 cm) treatments in a 2 × 3 factorial arrangement. The 2 farm systems consisted of a medium intensity (MI: 2.75 cows/ha, target postgrazing sward height of 4.0-4.5 cm) and high intensity system (HI: 3.25 cows/ha, target postgrazing sward height of 3.5-4.0 cm, + 1.8 kg of concentrate dry matter [(DM)/cow per day]. Within each farm system treatment, cows were further subdivided into 3 different PA management strategies: high PA (HPA), medium PA (MPA), and low PA (LPA). The experimental period lasted for 11 wk from September 1 to housing of all animals on November 20 (±2 d) over 3 yr (2017-2019, inclusive). To establish the different average pasture covers for each PA treatment during autumn and in particular at the end of the grazing season, grazing rotation length was extended by +13 and +7 d for HPA and MPA, respectively, beyond that required by LPA (37 d). There were no significant FS × PA interactions for any of the pasture, dry matter intake, or milk production and composition variables analyzed. There were also no differences in pregrazing sward characteristics or sward nutritive value between FS with the exception of daily herbage allowance, which was reduced for HI system (12.2 vs. 14.2 kg of DM/cow). Milk and milk solid yield were greater for HI groups (15.9 and 1.55 kg/cow per day, respectively) compared with MI (15.4 and 1.50 kg/cow per day, respectively). Mean paddock pregrazing herbage mass was significantly higher with increased PA ranging from a mean of 1,297 kg of DM/ha for LPA to 1,718 and 2,111 kg of DM/ha of available pasture for MPA and HPA, respectively. Despite large differences in pregrazing herbage mass, there was no difference in cumulative pasture production and only modest differences in grazing efficiency and sward nutritive value between PA treatments. On average, closing pasture covers were 420, 650, and 870 kg of DM/ha for LPA, MPA, and HPA, respectively, on December 1. In addition to maintaining similar grazing season lengths and achieving big differences in availability of pasture on farm into late autumn, PA treatment had no significant effect on dry matter intake, milk production, and body condition score during the study period. The results of this study indicate that greater cow performance and pasture utilization can be achieved through a greater daily concentrate allocation along with an increased stocking rate. Moreover, the potential to adapt grazing management practices to increase the average autumn pasture cover in intensive grazing systems is highlighted. In addition, a high dependence on high-quality grazed pasture during late autumn can be ensured without compromising grazing season length while also allowing additional pasture to be available for the subsequent spring.

Effects of abomasal infusions of fatty acids and 1-carbon donors on apparent fatty acid digestibility and incorporation into milk fat in cows

Our primary objective was to determine the effects of the abomasal infusion of 16-carbon (16C) and 22-carbon (22C) fatty acids (FA) on apparent FA digestibility, plasma FA concentrations, and their incorporation into milk fat in cows. Our secondary objective was to study the effects of 1-carbon donors choline and l-serine on these variables. Five rumen-cannulated Holstein cows (214 ± 4.9 d in milk; 3.2 ± 1.1 parity) were enrolled in a 5 × 5 Latin square experiment with experimental periods lasting 6 d. Abomasal infusates consisted of (1) palmitic acid (PA; 98% 16:0 of total fat), (2) PA + choline chloride (PA+CC; 50 g/d of choline chloride), (3) PA + l-serine (PA+S; 170 g/d of l-serine), (4) behenic acid (BA; 92% 22:0 of total fat), and (5) docosahexaenoic acid algal oil (DHA; 47.5% DHA of total fat). Emulsions were formulated to provide 301 g/d of total FA and were balanced to provide a minimum of 40 and 19 g/d of 16:0 and glycerol, respectively, to match the content found in the infused algal oil. Apparent digestibility of FA was highest in DHA, intermediate in PA, and lowest in BA. Digestibility of 16C FA was lowest in BA and highest in PA. The digestibility of 22C FA was highest in DHA relative to BA (99 vs. 58%), whereas 1-carbon donors had no effect on 22C FA digestibility. Plasma 16C FA concentrations were greatest with PA treatment, and 22C FA concentrations were ~3-fold greater in DHA-treated cows relative to all other treatments. Milk fat 16:0 content was highest in PA relative to BA and DHA (e.g., 37 vs. 27% in PA and DHA), whereas the milk yield of 16:0 was higher in PA relative to DHA (i.e., 454 vs. 235 g/d). Similarly, milk 22:0 content and yield were ~10-fold higher in BA relative to all other treatments, whereas DHA treatment resulted in higher content and yield of 22:6 in milk fat relative to all other treatments (41- and 38-fold higher, respectively). Consequently, the content of FA >16C (i.e., preformed) was higher in milk fat from cows infused with BA and DHA relative to PA. De novo FA content in milk did not differ between PA, PA+CC, and PA+S (~16% of milk fat) but was higher in BA and DHA treatments (19 and 21%, respectively). We conclude that FA carbon chain length and degree of saturation affected FA digestibility and availability for absorption as well as their incorporation into milk fat. The abomasal infusion of choline chloride and l-serine did not modify these variables relative to infusing palmitic acid alone.

Autonomous Cortisol Secretion Influences Psychopathological Symptoms in Patients With Primary Aldosteronism

Primary aldosteronism (PA) is associated with impaired quality of life (QoL). Autonomous cortisol cosecretion (ACS) is a relevant phenotype of PA, which could contribute to depression and anxiety disorders. This has not been investigated so far. To evaluate the prevalence of depression and anxiety in PA patients according to ACS. We performed testing for hypercortisolism and evaluated anxiety, depression and QoL by self-rating questionnaires in newly diagnosed PA patients of the German Conn's Registry; 298 patients were reevaluated at follow-up. In the overall cohort, scores for anxiety (P < .001), depression (P < .001), and QoL (mental P = .021; physical P = .015) improved significantly at follow-up. This improvement was seen in both subgroups of patients with and without ACS, with the exception of the mental subscore in no-ACS patients. Analysis for sex differences showed that anxiety decreased significantly in females with ACS and no-ACS, whereas males with no-ACS failed to improve. Depression improved significantly in males and females with ACS (P = .004, P = 0.011 respectively), but not in those with no-ACS. Physical subscore of QoL improved significantly (P = .023) in females with ACS and mental subscore (P = .027) in males with ACS, whereas no differences were seen for the no-ACS groups. Improvement in depression and anxiety scores in response to treatment of PA is more pronounced in patients with ACS in contrast to no-ACS suggesting a role of ACS in the psychopathological symptoms of patients with PA. Furthermore, we observed significant differences in depression and anxiety scores between the sexes.

ИЗМЕНЕНИЕ ПРОФЕССИОНАЛЬНОЙ МОТИВАЦИИ СРЕДИ СОТРУДНИКОВ СРЕДНЕГО МЕДИЦИНСКОГО ПЕРСОНАЛА В ПАНДЕМИЮ

The pandemic of the new coronavirus infection, which swept the entire world community in 2020, has made strong adjustments in almost all spheres of life, but first of all, in health care. The great majority of the medical staff at the onset of the pandemic had no clinical experience with the COVID-19 patients. In addition to the lack of practical skills in treatment for the period of the onset of mass infections, doctors faced great physical and emotional stress. The article provides a comparative analysis of the questionnaires results from among nursing staff in SRC Burnasyan FMBC in 2018 and 2020. The research results show that in the process of treatment and rehabilitation of pa- tients with COVID-19 in the professional motivation of doctors some changes took place towards personal motivation associated with serving and helping people.

The Ability of Spirulina sp. Microalgae as A Phytoremediation Agents in Liquid Waste of Handling Fish from Cemara Market, Medan

HighlightMicroalgae Spirullina sp. can remediate BOD levels reach on 75.59% with the experiment was 30% liquid waste and 70% water.Microalgae Spirullina sp. can remediate COD levels reach on 79.19% with the experiment was 30% liquid waste and 70% water.Microalgae Spirullina sp. can remediate TSS levels reach on 83.54% with the experiment was 30% liquid waste and 70% water.Microalgae Spirullina sp. can remediate ammonia levels reach on 89.15% with the experiment was 30% liquid waste and 70% water.AbstractContamination material from fish market activities, namely fish handling liquid waste, is a problem facing the city of Medan today. Reduce the level of liquid waste pollutants can be done biologically by using microalgae organisms. One of them is like microalgae Spirulina sp. This study aims to determine the ability of Spirulina sp. for reducing the levels of pollutants in liquid waste of handling fish.There search method was use a Completely Randomized Design (CRD) with five treatments and three replications. Addition of 100 mL of inoculant Spirulina sp. with a density of 1x105 ind/mL of liquid waste mixed with fresh water with to reach a volume of 1000 mL. Each liquid waste concentration of 30%, 60%, 80%, 100%, and control (0%) added 1 mL Walne fertilizer. The results of initial measurements of liquid waste for parameters BOD, COD, TSS, ammonia, and phosphate, respectively are 26.50mg/L, 4400mg/L, 894mg/L, 1.10mg/L, and 16.7 mg/L. Based on the results, the best reduction in BOD level occured in the treatment of 30% (pA) of liquid waste is 17.64 mg/L with phytoremediation efficiency of 75.59%. The best reduction in COD levels occurred in the treatment of 30% (pA) of liquid waste is 1301.12 mg/L with phytoremediation efficiency of 79.19%. The best reduction in TSS levels occurred in the treatment of 60% (pB) of liquid waste is 411 mg/L with phytoremediation efficiency of 83.54%. The best reduction in ammonia levels was at 30% (pA) treatment, which was 0.38 mg/L with phytoremediation efficiency of 89.15%. While the best decrease in phosphate levels occurred in the control treatment (pK), which was 4.45 mg/L with phytoremediation efficiency of 97.35%.

Adrenal (Pro)renin Receptor Expression and Serum Soluble (Pro)renin Receptor Concentration in Primary Aldosteronism

The (pro)renin receptor [(P)RR] is a multifunctioning protein playing roles in various pathological conditions. A soluble form of (P)RR [s(P)RR] has been considered a biomarker for (P)RR expression in tissues. Expression of (P)RR has been described in aldosterone-producing adenoma (APA), but the roles of (P)RR have yet to be fully determined. This study investigated the significance of (P)RR and serum s(P)RR concentrations in patients with APA. We evaluated associations between (P)RR expression and expression of CYP11B2, an aldosterone synthase, and aldosterone production by the adrenal glands and assessed the relationships between serum s(P)RR concentration and background factors. (P)RR colocalized with CYP11B2 and expression levels of (P)RR were positively associated with those of CYP11B2 in APA tissues. (P)RR immunoreactivity in these tissues correlated positively with plasma aldosterone concentrations (PAC) and urinary aldosterone excretion. Also, in APA, (P)RR mRNA abundance was positively correlated with β-catenin mRNA abundance. Significant positive correlations were identified between serum s(P)RR concentration and plasma glucose, hemoglobin A1c, and serum creatinine levels, but not with PAC (in either peripheral vein or adrenal vein) or adrenal (P)RR expression level. This study showed that (P)RR expression level correlates with CYP11B2 expression in APA tissues and PAC and urinary aldosterone excretion, suggesting that (P)RR expression may contribute to aldosterone synthesis via CYP11B2 activation in APAs, although serum s(P)RR concentration failed to show any significant relationship with adrenal (P)RR expression. Adrenal (P)RR activity might offer a therapeutic target in the treatment of PA, although this issue needs to be investigated in future studies.

Evaluation of Adrenal Vein Sampling Use and Outcomes in Patients With Primary Aldosteronism

BackgroundPrimary aldosteronism (PA) occurs in 10%-20% of patients with resistant hypertension. Guidelines recommend adrenal vein sampling (AVS) to identify patients for surgical management. We evaluate the use of AVS in managing PA to better understand the selection and outcomes of medical versus surgical treatment. MethodsA retrospective review was performed, and patients were divided into those who did (AVS) and did not have AVS (non-AVS). Demographics, aldosterone and renin levels, blood pressure, comorbidities, and antihypertensive medications were recorded. Reasons to defer AVS and medical versus surgical decision-making were examined and groups were compared. ResultsWe included 113 patients; 39.8% (45/113) had AVS, whereas 60.2% (68/113) did not. Groups were similar in age, body mass index, and initial systolic blood pressure (SBP).In patients who underwent AVS, 31 of 45 (68.9%) had unilateral secretion and were referred for surgery, whereas 13 of 45 (28.9%) had bilateral secretion. Of the 31 referred for surgery, 26 underwent laparoscopic adrenalectomy, all cured; four refused surgery; and one counseled toward medical management by their physician.In 68 non-AVS patients, 6 (8.8%) underwent adrenalectomy without sampling and 2 with no clinical improvement. The remaining deferrals were because of normal or bilateral adrenal nodules on imaging (8/68, 11.8%); medical management due to poor surgical candidacy (12/68, 17.6%); patient refusal of intervention (13/68, 19.1%); or reasons not stated (28/68, 41.1%). At the follow-up, patients who underwent AVS had lower median SBP (135.4 mmHg versus 144.7 mmHg, P = 0.0241) and shorter follow-up (17.7 mo versus 54.0 mo, P < 0.0001). Surgically managed patients had biochemical resolution of PA with normalization of potassium levels (3.6 to 4.7mEq/L, P < 0.00001). ConclusionsAVS correctly selects patients for surgical management avoiding unnecessary surgery. However, despite guidelines, AVS is not always pursued as part of PA treatment, potentially excluding surgical candidates.

Effect of feeding a palmitic acid–enriched supplement on production responses and nitrogen metabolism of mid-lactating Holstein and Jersey cows

This study evaluated the effect of feeding a palmitic acid-enriched supplement on production responses and nitrogen metabolism of mid-lactating Holstein and Jersey cows. Eighty mid-lactating dairy cows, 40 Holstein and 40 Jersey, were used in a randomized complete block design with a split-plot arrangement; the main plot was breed and the subplot was fatty acid treatment. Cows within each breed were assigned to 1 of 2 treatments: (1) control diet with no fat supplement or (2) control diet plus a palmitic acid-enriched supplement dosed at 1.5% of diet dry matter (PA treatment). The treatment period was 6 wk with the final 3 wk used for data and sample collection. There were no treatment × breed interactions for the variables analyzed. Compared with control, PA treatment increased milk fat yield (1.36 vs. 1.26 kg/d) and tended to increase 3.5% fat-corrected milk (35.6 vs. 34.0 kg/d) and energy-corrected milk (35.7 vs. 34.1 kg/d). There was no effect of PA treatment on dry matter intake, milk yield, milk protein yield, milk lactose yield, body condition score, body weight (BW) change, nitrogen intake, and variables related to nitrogen metabolism and excretion. Compared with Holstein cows, Jersey cows had greater dry matter intake as a percent of BW (4.90 vs. 3.37% of BW) and lower milk production (29.6 vs. 32.7 kg/d) and milk lactose yield (1.58 vs. 1.42 kg/d), but tended to have greater milk fat yield (1.36 vs. 1.26 kg/d). There was a breed effect on BW change; Holstein cows gained 0.385 kg/d during the experiment, and Jersey cows gained 0.145 kg/d. Jersey cows had lower nitrogen intake (636 vs. 694 g/d), blood urea nitrogen (12.6 vs. 13.8 mg/dL), urine total nitrogen (125 vs. 145 g/d), and urine total nitrogen as a percent of nitrogen intake (19.5 vs. 21.1%). Overall, feeding a palmitic acid-enriched supplement increased milk fat yield as well as dry matter and fiber digestibility in both Holstein and Jersey cows. The PA treatment did not have any major effects on nitrogen metabolism in both Holstein and Jersey cows. In addition, our results indicated that Jersey cows had lower urinary nitrogen excretion (g/d) than Holstein cows.

Pediococcus acidilactici intake decreases the clinical severity of atopic dermatitis along with increasing mucin production and improving the gut microbiome in Nc/Nga mice

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with intestinal microflora. Since specific probiotics may have better efficacy for AD, we determined the efficacy of Pediococcus acidilactici SRCM102024 (PA) for treating AD in HaCaT cells and NC/Nga mice and explored the mechanism of action. AD-like pathology was induced in HaCaT cells and the dorsal skin of Nc/Nga mice by local exposure to 2,4-dinitrochlorobenzene (DNCB). In AD-lesion induced mice, PA in low-, medium- and high-dosages (5 × 10E6, 5 × 10E7 and 5 × 10E8 CFU/kg bw, respectively) and dexamethasone (3 mg/kg bw, positive-control) were orally administered for 5 weeks. The clinical AD severity, serum immunoglobulin E (IgE) and TNF-α, gene expressions of interleukin (IL)-4, IL-13, and TNF-α and gut microflora were measured. PA treatment (100–300 CFU/mL) dose-dependently increased cell survival in DNCB-induced HACAT cells. PA reduced the relative mRNA expression of PAR-2, TNF-α, IL-4 and IL-13 in the cells. In dorsal skin of Nc/Nga mice applied with DNCB, PA dose-dependently attenuated erythema, hemorrhage, edema, excoriation, dryness and scratching behavior and PA-H improved the clinical symptoms similar to the positive-control. PA-M and PA-H treatment significantly prevented the disturbance of the dorsal skin tissues and decreased the inflammatory cellular infiltrate of mast cells, compared to the control. PA dose-dependently reduced serum IgE and TNF-α concentrations and the mRNA expression of TNF-α, IL-4, and IL-13 in dorsal skin. In gut microflora, relative counts of Lactobacillales, Butyricicoccus and Ruminococcus were decreased in the AD-control compared to the positive-control and the PA-M and PA-H prevented their decrease. However, the positive-control increased serum AST and ALT activities, indicating liver damage as an adverse effect. In conclusion, oral treatment of PA (human equivalent 1 × 10E9-1 × 10E10) relieved the AD symptoms by dose-dependently preventing over-activation of the immune response. Oral PA intake may be a safe and effective alternative therapy for AD.

Control of the hydrophobicity of rare earth oxide coatings deposited by solution precursor plasma spray by hydrocarbon adsorption

The basis of the hydrophobicity of lanthanide rare earth oxides (REOs) has been the subject of considerable debate. To explore this question, the wetting behaviors and surface compositions of hierarchically-structured Yb2O3 (one of the REOs) coatings and non-REO Al2O3 coatings deposited via solution precursor plasma spray process were investigated in this work. The Yb2O3 coatings were subjected to a number of post-deposition treatments including vacuum (1−15 Pa) treatment, Ar-plasma treatment, heat treatment (400 °C), long-time air exposure and ultra-high vacuum (1 × 10−7 Pa) treatment. Subsequent characterization showed that different post-deposition treatments resulted in different wetting behavior for the Yb2O3 coatings which correlated with the content of hydrocarbon on the surface. Yb2O3 coatings exhibited reversible transitions between superhydrophobicity after vacuum treatment and superhydrophilicity after Ar-plasma or heat treatment, linked to hydrocarbon adsorption onto and desorption from the surface. Yb2O3 coatings after long-time air exposure and ultra-high vacuum treatment both remained hydrophilic and showed a smaller hydrocarbon content than coatings after vacuum treatment. Al2O3 coatings with hierarchical surface structures similar to the Yb2O3 coatings showed an increase in WCA to only ∼17° after the same vacuum treatment, indicating the REO has a much higher affinity for hydrocarbon adsorption than Al2O3, and that the content of hydrocarbon adsorbed on the surface of the REO determined the wetting behavior.

MON-213 Cardiac Damage and Related Risk Factors in Patients with Primary Aldosteronism

Primary aldosteronism (PA) is the most common cause of secondary hypertension. Overseas flow surveys show that compared with essential hypertension (EH), the risk of cardiovascular and cerebrovascular diseases and kidney damages in PA patients is increased, and the mortality rate of cardiovascular events is higher than that in EH patients, in addition,this effect is independent of elevated blood pressure. The difference of cardiac damage between PA and EH patients was analyzed by echocardiography. Methods From April 28, 2017 to April 28, 2019, patients with primary aldosteronism diagnosed by ICD in Department of Endocrinology and Metabolism, Department of Cardiology and Urology were extracted from the adrenal group database of the Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, and ICD diagnosis in Department of Endocrinology and Metabolism during the same period was also extracted. In patients with essential hypertension, the differences of clinical indicators and echocardiography between the two groups were compared, and the differences of cardiac damage and related risk factors between the two groups were explored. Results 295 patients were included in this study, including 148 patients in PA group (50.17%) and 147 patients in EH group (49.83%). There was no significant difference in gender, age, BMI, course of disease and average blood pressure between the two groups (P > 0.05). The levels of serum aldosterone and BNP in PA group were significantly higher than those in EH group, and the levels of serum renin and minimum blood potassium were significantly lower than those in EH group (P < 0.05). Left ventricular diameter (LV), left atrial diameter (LA), interventricular septal thickness (IVS), left ventricular posterior wall thickness (LVPW), ascending aorta diameter (AAO), end-diastolic diameter (EDD), end-diastolic volume (EDV) and stroke volume (SV) in PA group were significantly higher than those in EH group (P < 0.05). It was significantly higher than that in EH group (P < 0.05). The correlation analysis of variables with statistical significance between the two groups showed that serum renin activity level was negatively correlated with LV, AAO, EDD and SV, and the lowest serum potassium level was negatively correlated with LVPW and AAO. CONCLUSION Compared with EH of the same age, course of disease and blood pressure level, PA patients are more likely to suffer from cardiac damage, which is manifested by heart growth, ventricular septal thickening and cardiac function decline, and is closely related to the inhibition of serum renin activity and serum potassium level. Clinical attention should be paid to early screening and treatment of PA and its complications in order to reduce the risk of cardiac death.Key words: primary aldosteronism; echocardiography; cardiovascular risk factors

Pantothenic acid promotes dermal papilla cell proliferation in hair follicles of American minks via inhibitor of DNA Binding 3/Notch signaling pathway

AimsPantothenic acid (PA) has been applied to treat alopecia, but the underlying mechanism is still unclear. Our study aims to explore the underlying mechanism of PA in regulating hair follicle (HF) growth. Main methodsMink HFs and dermal papilla (DP) cells were isolated and cultured in vitro. HFs and DP cells were treated with 0, 10, 20, 40 μg/ml PA. The effect of PA on HF growth, DP cell proliferation, cell cycle distribution, cell migration, and insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) expressions in DP cells was measured. Moreover, the effect of PA on inhibitor of DNA binding 3 (ID3)/Notch signaling pathway was analyzed. Subsequently, ID3 was silenced to validate whether ID3/Notch signaling pathway was involved in regulating DP cell proliferation by PA. Key findingsBoth 20 μg/ml and 40 μg/ml PA promoted HF growth, G1/S transition of DP cells and IGF-1 and VEGF expressions in DP cells, while only 20 μg/ml PA promoted cell viability and the migration of DP cells. Thus 20 μg/ml PA was chosen for the following experiments. PA treatment was found to up-regulate ID3 expression but down-regulate Notch receptor 1 (Notch1) and Notch signaling targets expressions. Furthermore, ID3 knockdown reversed PA-induced cell proliferation and inhibition of Notch1 and Notch signaling targets expressions, indicating that PA-induced DP cell proliferation and inhibition of Notch signaling were mediated via up-regulation of ID3. SignificanceThis study provides an underlying mechanism related to the effect of PA on stimulating DP cell proliferation.

Evaluation of anticancer activities of Poria cocos ethanol extract in breast cancer: In vivo and in vitro, identification and mechanism

Ethnopharmacological relevancePoria cocos Wolf (P. cocos), a well-known traditional East-Asian medicinal and edible fungus, is one of the most important components in Chinese medicine formulas like “Guizhi fuling wan” to treat hyperplasia of mammary glands and breast cancer. Aiming of studyIn this study, we attempted to verify the anticancer efficacy of the ethanol extract of P. cocos (PC) on the breast cancer as well as to investigate its most active compound and its underlying molecular mechanism in vivo and in vitro. Materials and methodsThe key anti-cancer components were separated and purified through chromatography and identified by spectral analyses. The in vivo anti-breast cancer efficacy and side effects of PC were evaluated in BALB/c nude mice that have been subcutaneously injected with breast cancer cells MDA-MB-231. Cytotoxicity, apoptosis and cell cycle arrest of PC were evaluated in vitro by cell viability assays and flow cytometry. The protein levels were examined via western blotting. ResultsPachymic acid (PA), separated and identified as the most active compound, induced the significant cytotoxicity on breast cancer cells MDA-MB-231(IC50 value, 2.13 ± 0.24 μg/mL) and was not active against the normal breast epithelium cells MCF-10A. The in vivo experiment revealed that PC could significantly inhibit the tumor development and the final mean tumor weight of the mice in the PC group (0.51 ± 0.12g) was significantly lower than that in the model group (1.22 ± 0.45g). Notably, compared to the first-line anticancer drug cisplatin, PC showed less side effects on the function of the vital organs and the muscle strength of the mice. Among in vitro study, PC significantly inhibited the cell growth of MDA-MB-231 by inducing cell apoptosis and cell cycle arrested at G0/G1 phase in a dose-dependent manner. The expression of cell cycle-associated cyclin D1, cyclin E, CDK2, and CDK4 were downregulated, while p53 and p21 expression were upregulated following the PA treatment. In addition, PA downregulated the apoptotic regulator Bcl-2, increased the expression of pro-apoptotic protein Bax, and promoted the release of cytochrome c and the activation of cleaved caspase-3, -9 and caspase -8 via mitochondria-mediated and death receptor-mediated signaling pathways. ConclusionThis study verified the anticancer efficacy of PC on breast cancer in vivo and in vitro through induction of cell apoptosis and G0/G1 cell cycle arrest. The data also suggested that PA could be developed as an efficacious agent for breast cancer treatment with less side effects.