The Effects of Self-Aromatherapy Massage on Pain and Sleep Quality in Patients with Rheumatoid Arthritis: A Randomized Controlled Trial.

BACKGROUND: Rheumatoid arthritis is the most common form of inflammatory arthritis and can lead to pain, joint deformity, and disability, resulting in poor sleep quality and lower quality of life. The efficacy of aromatherapy massage on pain levels and sleep quality among rheumatoid arthritis patients remains unclear. AIMS: To investigate the effects of aromatherapy on pain and sleep quality among rheumatoid arthritis patients. METHODS: This randomized controlled trial enrolled 102 patients with rheumatoid arthritis from one regional hospital in Taoyuan, Taiwan. Patients were randomly assigned to the intervention (n = 32), placebo (n = 36), or control groups (n = 34). The intervention and placebo groups underwent self-aromatherapy hand massage guided by a self-aromatherapy hand massage manual and video for 10 minutes 3 times a week for 3 weeks. The intervention group used 5% compound essential oils, the placebo group used sweet almond oil, and the control group had no intervention. Pain, sleep quality and sleepiness were measured by using the numerical rating scale for pain, the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale at baseline and at 1, 2, and 3 weeks after the intervention. RESULTS: The intervention and placebo groups had significantly decreased sleep quality and sleepiness scores from baseline to 3 weeks after aromatherapy massage. Compared with the control group, the intervention group showed statistically significant improvement in the sleep quality scores in the first weeks after aromatherapy massage (B = -1.19, 95% confidence interval [CI]: -2.35, -0.02, P =.046), but no statistically significant differences were found in the changes in pain levels from baseline to the three time points. CONCLUSIONS: Aromatherapy massage is effective in improving sleep quality in rheumatoid arthritis patients. More studies are needed to evaluate the effects of aromatherapy hand massage on the pain levels of rheumatoid arthritis patients.

Xinfuli granule alleviates metabolic remodeling through inhibition of endoplasmic reticulum stress and mitochondrial injury in heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: "Qi deficiency-blood stasis-water retention syndrome" was the most frequent syndrome among heart failure(HF) patients according to Traditional Chinese Medicine (TCM) theory. Xinfuli Granule (XG) was constructed on the basis of classical formula "Baoyuan decoction" to enhance the function of nourishing Qi, activating blood and removing water retention. XG treatment has obtained clinical effect on HF patients. AIM OF THE STUDY: The regulation of XG on energy metabolism of HF was investigated with special focus on endoplasmic reticulum stress (ERS) and mitochondrial function. MATERIALS AND METHODS: Components of XG was acquired by UPLC/Q-TOF-MS Analysis, left anterior descending ligation(LAD)-induced HF rats model and hypoxia-ischemia(H-I)-induced H9c2 cells model were constructed to evaluate the effect of XG treatment. Cardiac function was evaluated by echocardiographic parameters, energy metabolism was evaluated by metabolites and ATP/ADP/AMP levels in blood samples, cardiomyocyte morphology and myocardial fibrosis were assessed by HE staining and Masson staining, mitochondrial ultrastructure was observed under Transmission Electron Microscope, viability and apoptosis rate of H9c2 cells was detected by cell counting kit-8 reaction and flow cytometry analysis, respectively. Mitochondrial membrane potential (MMP) of H9c2 cells was observed by JC-1 kit under fluorescent microscope, expression of peroxisome-proliferator-activated receptor (PPAR)-coactivator (PGC1α), ERS-related genes and RHOA/ROCK pathway were analysed by Quantitative Real-time PCR (RT-qPCR) and Western Blot. RESULTS: Here, we showed that XG alleviated cardiac metabolic remodeling and stimulated ATP production through elevated expression of PGC1α in HF rats. XG also helped recover mitochondrial deformation and decrease apoptosis rate accompanied by an increase of the Bcl2/Bax ratio and the mitochondrial membrane potential in hypoxia-ischemia (H-I) H9c2 cells. In addition, we found that XG downregulated ERS-related proteins ATF4, CHOP, Phospho-eIF2α, and Phospho-PERK, and suppressed the RHOA/ROCK pathway, which served as a potential mediator of ERS. CONCLUSIONS: we found that XG improved energy production by alleviating mitochondrial injury and inhibiting ERS in heart failures mediated by the RHOA/ROCK pathway.

Differences in health-related quality of life in children with chronic kidney disease as reported by children and parent proxies.

BACKGROUND: Correlation between reports of children and parent for health-related quality of life (HRQOL) is not well studied. This study aims to assess the degree of agreement between child self- and parent proxy-rated HRQOL and to identify factors associated with discordance at baseline and during follow-up in Taiwanese children with chronic kidney disease (CKD). METHODS: This study includes pediatric patients aged 5-18 years with confirmed CKD. Participants completed the generic version of the Pediatric Quality of Life Inventory (PedsQL) at baseline and every 6 months during follow-up. Child-parent agreement on HRQOL reports was assessed using intraclass correlation coefficient (ICC). Multivariate regression models were used to determine factors associated with child-parent discordance. RESULTS: Of the 112 child-parent dyads included in the analysis, 97 dyads with 640 patient visits were assessed in 4.5 years. Children reported higher total scores on the physical and psychosocial domains as compared to their parent proxies. ICC was low (< 0.5) for the psychosocial domain and moderate for the physical health domain at initial assessment and slightly increased for the physical health (0.62) and for school functioning (0.51) during follow-up. Development of mineral bone disorder/anemia (ß, 11.75 [3.77-19.72]) and proteinuria (ß, 8.48 [1.15-15.81]) in the follow-up were associated with increased discordance in school functioning, and fathers with chronic disease were associated with increased discordance in social functioning (ß, 4.21 [0.68-7.74]). CONCLUSIONS: Parent proxy consistently estimated lower PedsQL score compared to self-reports of children. Child self-rated psychosocial health domains should be evaluated whenever possible to better elucidate treatment outcome over time. A higher resolution version of the Graphical abstract is available as Supplementary information.

Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy.

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.

Complement use of Chinese herbal medicine after percutaneous coronary intervention: a prospective observational study.

BACKGROUND: Chinese herbal medicine is widely used as a complement or alternative treatment in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) in China. We compared the incidence of the major adverse cardiovascular event (MACE) of CAD patients with or without the complement use of Chinese herbal medicine after PCI. METHODS: In this prospective, observational study that was conducted from September 2016 to August 2019 in Fuwai Hospital (China), we followed up consecutive patients who received PCI treatment for two years. MACE was defined as the composite all-cause mortality, revascularization, and myocardial infarction (MI) and was compared between those using (integrative medicine group) or those not using Chinese herbal medicine as an additional treatment to standard Western medicine, with unadjusted (Kaplan-Meier curves) and risk-adjusted (multivariable Cox regression) analyses. RESULTS: A total of 5942 patients after PCI were enrolled in this study, and 5453 patients were included in the final analysis (4189 [76.8%] male; mean age: 61.9 ± 9.9% years). During the follow-ups, 2932 (53.8%) patients used only Western medicine while 2521(46.2%) patients had used Chinese herbal medicine as an additional treatment to standard Western medicine. Patients in the integrative medicine group (IM group) were older than the Western medicine group (WM group), had more females and less previous MI. The incidence of MACE was 15.3% (449/2932) in WM group and 11.54% (291/2521) in IM group. Cox regression analysis showed that cumulative incidence of MACE was 27% lower in patients of the IM group than those in WM group (hazard ratio = 0.73; 95% CI: 0.63-0.85; P < 0.0001). CONCLUSIONS: For CAD patients after PCI treatment, complement use of Chinese herbal medicine is associated with a lower 2-year MACE incidence. Randomized prospective studies are warranted to provide higher levels of benefit evidence in these patients.

Application of Quercus salicina extract in the management of urolithiasis.

Since 1969, an herbal medicine extracted from Quercus salicina Blume/Quercus stenophylla Makino (QS) has been clinically used for the management of urolithiasis in Japan. Historically, the decoction of leaves and shoots of QS trees was popularly utilized as a folk prescription to remove urinary calculi. This study was designed to perform a brief review of the updated progress of QS extract for urinary stones based on previous studies. A comprehensive literature search was conducted in multiple electronic databases, including Web of Science, PubMed, and EMBASE, and relevant data on QS extract were extracted. As a result, the major mechanism of QS extract for urolithiasis is observed to be closely related to the anti-oxidative activities according to recent studies, leading to inhibition of the accumulation of renal calcium and prevention of stone formation and recurrence of stones. As for the effect of discharging stones, loosening the upper urinary tract has also been noticed recently. More extensive studies are still necessary to systemically evaluate the individual dosage, drug safety, and targeted stone types.

Mitigation effects of high methoxyl pectin on acrylamide formation in the Maillard model system.

Acrylamide (AA) is a potential carcinogen formed during the process of food heating. Pectin is natural food additive widely presented in fruits and vegetables. This study aimed at investigating the influence of the addition of high methoxyl apple pectin (esterification degree: 82.6%) on AA inhibition in the asparagine (Asn)/glucose (Glc) model system. Results showed that temperature (120-180 °C), pH value (6.0-7.2), pectin addition (0.2-1.0%, w/v), substrate concentration (0.01-0.5 M) and molar ratio of Asn/Glc (5:1-1:10) had significant influence on inhibition of pectin on AA formation. With adding 1.0% (w/v) pectin, the pH value, Glc consumption and Schiff base abundance declined in Asn/Glc model system. Moreover, heating treatment decreased the pH value, molecular weight, esterification degree and galacturonic acid content of pectin. Finally, the pectin degradation product was identified, which might compete with Glc for Asn in Maillard reaction, led to AA reduction. This study provided distinct evidence for controlling AA formation.

ACSL4 is a predictive biomarker of sorafenib sensitivity in hepatocellular carcinoma.

Sorafenib is the first-line treatment of advanced hepatocellular carcinoma (HCC). However, there is a lack of validated biomarkers to predict sorafenib sensitivity. In this study we investigated the role of ACSL4, a positive-activating enzyme of ferroptosis, in sorafenib-induced cell death and HCC patient outcome. We showed that ACSL4 protein expression was negatively associated with IC50 values of sorafenib in a panel of HCC cell lines (R = -0.952, P < 0.001). Knockdown of ACSL4 expression by specific siRNA/sgRNA significantly attenuated sorafenib-induced lipid peroxidation and ferroptosis in Huh7 cells, and also rescued sorafenib-induced inhibition of xenograft tumor growth in vivo. We selected 29 HCC patients with surgery as primary treatment and sorafenib as postoperative adjunct therapy from a hospital-based cohort. A high proportion (66.7%) of HCC patients who had complete or partial responses to sorafenib treatment (according to the revised RECIST guideline) had higher ACSL4 expression in the pretreated HCC tissues, compared with those who had stable or progressed tumor growth (23.5%, P = 0.029). Since ACSL4 expression was independent of sorafenib treatment, it could serve as a useful predictive biomarker. Taken together, this study demonstrates that ACSL4 is essential for sorafenib-induced ferroptosis and useful for predicting sorafenib sensitivity in HCC. This study may have important translational impacts in precise treatment of HCC.

Standardized ileal digestible amino acid and metabolizable energy content of wheat from different origins and the effect of exogenous xylanase on their determination in broilers.

This study was conducted to determine the standardized ileal digestible amino acids (SID AA) and nitrogen-corrected apparent metabolizable energy (AMEn) contents of 6 wheats from different origins in China and incidentally to investigate the effects of exogenous xylanase addition on SID AA and AMEn determination in broiler chicks. A total of 480 chicks were divided into 48 cages of 10 birds each balanced for body weight and fed 8 types of diets in a completely randomized design (6 replicated cages per diet) from 21 to 26 d of age. The individual wheat constituted the only source of crude protein in a semi-purified experimental diet. A nitrogen-free diet was designed to estimate basal endogenous AA loss and determine the SID AA. Titanium oxide (0.3%) was used as an indigestibility marker, and nutrient digestibility and retention were determined by the substitution method. From day 24 to 26, excreta samples were collected for AMEn determination. On day 26, the birds were euthanized, and ileum contents were obtained for AA digestibility determination. Wheat from Gansu had greater (P < 0.05) SID AA contents except Lys, Thr, Phe, and Cys, with a higher (P < 0.001) AMEn (11.83 MJ/kg) than the other wheats. The SID content of mean indispensable amino acids and dispensable amino acids were 87.35% and 88.17%, respectively, and the average AMEn value of 6 wheats was 11.14 MJ/kg. Compared with the diet without xylanase, the added xylanase resulted in higher (P < 0.05) SID contents of Met, Lys, Trp, Arg, Ile, Leu, Val, Gly, Asp, Glu, Pro, and Ala; the SID AA values were raised by 1.96% (mean of all AA); and the AMEn content was significantly increased (+0.87 MJ/kg) (P < 0.05). In conclusion, origins of wheats have significant effects on SID AA and AMEn values which were positively correlated with crude protein content of wheat; exogenous xylanase addition to a wheat-based poultry diet could significantly improve SID AA and AMEn contents for broilers.

Qishen capsule safely boosts cardiac function and angiogenesis via the MEK/ERK pathway in a rat myocardial infarction model.

BACKGROUND: Qishen (QS) capsules, a Traditional Chinese Medicine, has been widely used to treat coronary heart disease in China. However, evidence of its effectiveness remains unclear. METHODS: To explore whether QS has cardioprotective efficacy and/or promotes angiogenesis after myocardial infarction (MI), we performed experiments in a preclinical rat MI model. One month after left anterior descending coronary artery ligation, the rats received either QS solution (0.4 g/kg/day) or the same volume of saline by intragastric injection for four weeks. RESULTS: Echocardiographic and hemodynamic analyses demonstrated relatively preserved cardiac function in MI rats administered QS. Indeed, QS treatment was associated with reduced infarct scar size and heart weight index, and these beneficial effects were responsible for enhancing angiogenesis. Mechanistically, QS treatment increased phosphorylation of protein kinase B (Akt) and downregulated phosphorylation of mitogen-activated protein kinase/extracellular-regulated kinase (MEK/ERK). CONCLUSIONS: QS therapy can improve the cardiac function of rats after MI by an underlying mechanism involving increased angiogenesis, at least partially via activation of the Akt signaling pathway and inhibition of MEK/ERK phosphorylation.

Utilization trends in traditional Chinese medicine for acute myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: Among heart diseases, acute myocardial infarction (AMI) is the most serious and life-threatening emergency. In Taiwan, heart disease has consistently ranked second among the top 10 leading causes of death since 2007, second only to malignant tumors; however, population-based studies on the use of traditional Chinese medicine (TCM) in AMI cases are limited. AIM OF THE STUDY: This study investigated the characteristics of TCM users and prescriptions of TCM, and their differences between two cohorts of patients with AMI, identified 10 years apart. MATERIALS AND METHODS: A cross-sectional study was conducted using the Taiwan National Health Insurance claims database. From among two random sample of 1 million beneficiaries selected from the claims database, we identified two cohorts of patients with first hospitalization for AMI in between 2000-2001 and 2010-2011. Patients who had received TCM therapy within one year after hospital discharge were defined as TCM users, whereas, all the other patients with AMI were considered non-users of TCM. We compared the characteristics of TCM use and the patterns of prescriptions between the two cohorts. RESULTS: The proportion of patients receiving TCM care was similar between the two AMI cohorts; 20% (85/418) of the patients were diagnosed in 2000-2001 and 21% (169/817) in 2010-2011. In the 2010-2011 AMI cohort, the proportion of men was smaller among TCM users than non-users, and TCM users were less likely to have hyperlipidemia. Among TCM users, the most frequently prescribed herb was Dan-shen (Salvia miltiorrhiza Bunge, Salvia root) in both cohorts. The most commonly used Chinese herbal formulations were Xue-Fu-Zhu-Yu-Tang (Blood Mansion Dispel Stasis) for the 2000-2001 cohort and Zhi-Gan-Cao-Tang (Honey-Fried Licorice Decoction) for the 2010-2011 cohort. CONCLUSIONS: This study revealed the differences in the prescription frequency of Chinese herbal formulation among the two cohort of patients with AMI, suggesting that the practice of prescribing TCM has evolved from post-antique formula to classical remedies during the 10 years evaluated. Further investigations are needed to evaluate if the change in the utilization of Chinese herbal formulations impacts the effectiveness of the treatment.

Low-temperature co-purification of NOx and Hg0 from simulated flue gas by CexZryMnzO2/r-Al2O3: the performance and its mechanism.

In this study, series of CexZryMnzO2/r-Al2O3 catalysts were prepared by impregnation method and explored to co-purification of NOx and Hg0 at low temperature. The physical and chemical properties of the catalysts were investigated by XRD, BET, FTIR, NH3-TPD, H2-TPR, and XPS. The experimental results showed that 10% Ce0.2Zr0.3Mn0.5O2/r-Al2O3 yielded higher conversion on co-purification of NOx and Hg0 than the other prepared catalysts at low temperature, especially at 200-300 °C. 91% and 97% convert rate of NOx and Hg0 were obtained, respectively, when 10% Ce0.2Zr0.3Mn0.5O2/r-Al2O3 catalyst was used at 250 °C. Moreover, the presence of H2O slightly decreased the removal of NOx and Hg0 owing to the competitive adsorption of H2O and Hg0. When SO2 was added, the removal of Hg0 first increased slightly and then presented a decrease due to the generation of SO3 and (NH4)2SO4. The results of NH3-TPD indicated that the strong acid of 10% Ce0.2Zr0.3Mn0.5O2/r-Al2O3 improved its high-temperature activity. XPS and H2-TPR results showed there were high-valence Mn and Ce species in 10% Ce0.2Zr0.3Mn0.5O2/r-Al2O3, which could effectively promote the removal of NOx and Hg0. Therefore, the mechanisms of Hg0 and NOx removal were proposed as Hg (ad) + [O] → HgO (ad), and 2NH3/NH4+ (ad) + NO2 (ad) + NO (g) → 2 N2 + 3H2O/2H+, respectively. Graphical abstract ᅟ.

[Effect of Acupuncture on Inflammatory Cytokines in Patients with Acute Pelvic Inflammatory Disease].

OBJECTIVE: To observe the effect of acupuncture on inflammatory indices and symptoms in patients with acute pelvic inflammatory disease, and investigate its mechanism. METHODS: Seventy-nine patients with acute pelvic inflammatory disease were randomly assigned to a control group (n＝37) given conventional treatment and an observation group (n＝42) given conventional treatment and acupuncture therapy. In the observation group, acupionts of Zhongji(CV 3), Guanyuan(CV 4), Zigong(EX-CA 1), Zusanli(ST 36), Sanyinjiao(SP 6), etc. were selected. Each group received treatment once daily, for a total of 7 days. Tumor necrosis factor (TNF)-α， interleukin (IL)-10 and C-reactive protein (CRP) in the serum, white blood cell (WBC) and neutrophil counts, size of pelvic mass and depth of pelvic effusion, and clinical symptoms were assayed pretreatment and on days 3 and 7. RESULTS: WBC and neutrophils were significantly decreased after treatment in both groups (P<0.05), and more in the observation group than in the control group (P<0.05). After treatment, the size of pelvic mass and depth of effusion were less in both groups (P<0.05), and the efficacy in the observation group was superior to that in the control group (P<0.05). In the observation group, serum TNF-α， and CRP on day 3 and day 7 were significantly lower than those before treatment (P<0.05). Se-rum TNF-α and CRP were significantly down-regulated in the observation group compared with those in the control group on both day 3 and day 7 (P<0.05). In the observation group, serum IL-10 was higher on both day 3 and day 7 than that before treatment (P<0.05), and was statistically different from that in the control group on both days (P<0.05). The clinical efficacy in the observation group was superior to that in the control group (95.24% vs 81.08%, P<0.05). CONCLUSION: Acupuncture can regulate the levels of inflammatory markers in patients with acute pelvic inflammatory disease, and improve clinical symptoms.

Early Supplementation of d-Cysteine or l-Cysteine Prevents Hypertension and Kidney Damage in Spontaneously Hypertensive Rats Exposed to High-Salt Intake.

SCOPE: We investigate whether early supplementation of precursors of hydrogen sulfide (H2 S), d- or l-cysteine can prevent hypertension and kidney damage in spontaneously hypertensive rats (SHR) treated with high-salt. METHODS AND RESULTS: We examine 12-week-old male SHRs from four groups: SHR, high salt SHR (SHRs received 1% NaCl in drinking water for 8 weeks), high salt SHR+d (SHRs received high salt and d-cysteine), and high salt SHR+l (SHRs received high salt and l-cysteine). d- or l-cysteine was supplemented at 8 mmol kg-1 body weight/day between 4 and 6 weeks of ages. High salt intake exacerbate hypertension and kidney damage in SHRs, which is prevented by d- or l-cysteine supplementation. d- or l-Cysteine supplementation reduce the degree of high salt-induced oxidative stress damage. Renal 3-mercaptopyruvate sulphurtransferase (3MST) protein levels and activity are reduced by d- or l-cysteine supplementation. Additionally, d- or l-Cysteine supplementation reduce renal angiotensin I and angiotensin II concentrations, decrease mRNA expression of Ren, and increase protein levels of type 2 angiotensin II receptor. CONCLUSION: Early supplementation of d- or l-cysteine before hypertension becomes evident and may protect against hypertension and kidney damage in adult SHRs exposed to high salt consumption via regulation of oxidative stress, renin-angiotensin system, and H2 S-generating pathways.

Determination of oral bioavailability of curcuminoid dispersions and nanoemulsions prepared from Curcuma longa Linnaeus.

BACKGROUND: Curcuminoid from Curcuma longa Linnaeus has been demonstrated to be effective in anti-cancer and anti-inflammation. The objectives of the present study were to prepare curcuminoid dispersion and nanoemulsion from C. longa and determine their oral bioavailabilities in rats. RESULTS: After curcuminoid extraction using 99.5% ethanol, bisdemethoxycurcumin (BDMC), demethoxycurcumin (DMC) and curcumin were separated within 10 min by high-performance liquid chromatography using an Eclipse XDB-C18 column (Agilent, Palo Alto, CA, USA) and a gradient mobile phase of 0.1% aqueous formic acid and acetonitrile, with a flow rate of 1 mL min-1 , column temperature of 35 °C and detection wavelength of 425 nm. Curcuminoid nanoemulsion at a particle size of 12.1 nm and encapsulation efficiency 98.8% was prepared using lecithin, Tween 80 and water. A pharmacokinetic study in rats revealed that the parameters including Tmax , Cmax , t1/2 and the area under the curve were higher for curcuminoid nanoemulsions than for curcuminoid dispersion at the same dose employed for gavage administration, whereas, for intravenous injection, an opposite trend was shown. The oral bioavailabilities of BDMC, DMC, curcumin and total curcuminoids in nanoemulsion and dispersion were 34.39 and 4.65%, 39.93 and 5.49%, 47.82 and 9.38%, and 46 and 8.7%, respectively. CONCLUSION: The results of the present study demonstrate a higher oral bioavailability after incorporation of curcuminoid into nanoemulsion, facilitating its application as a botanic drug. © 2017 Society of Chemical Industry.

Borneol Dehydrogenase from Pseudomonas sp. Strain TCU-HL1 Catalyzes the Oxidation of (+)-Borneol and Its Isomers to Camphor.

Most plant-produced monoterpenes can be degraded by soil microorganisms. Borneol is a plant terpene that is widely used in traditional Chinese medicine. Neither microbial borneol dehydrogenase (BDH) nor a microbial borneol degradation pathway has been reported previously. One borneol-degrading strain, Pseudomonas sp. strain TCU-HL1, was isolated by our group. Its genome was sequenced and annotated. The genome of TCU-HL1 consists of a 6.2-Mbp circular chromosome and one circular plasmid, pTHL1 (12.6 kbp). Our results suggest that borneol is first converted into camphor by BDH in TCU-HL1 and is further decomposed through a camphor degradation pathway. The recombinant BDH was produced in the form of inclusion bodies. The apparent Km values of refolded recombinant BDH for (+)-borneol and (-)-borneol were 0.20 ± 0.01 and 0.16 ± 0.01 mM, respectively, and the kcat values for (+)-borneol and (-)-borneol were 0.75 ± 0.01 and 0.53 ± 0.01 s-1, respectively. Two plant BDH genes have been reported previously. The kcat and kcat/Km values of lavender BDH are about 1,800-fold and 500-fold lower, respectively, than those of TCU-HL1 BDH. IMPORTANCE: The degradation of borneol in a soil microorganism through a camphor degradation pathway is reported in this study. We also report a microbial borneol dehydrogenase. The kcat and kcat/Km values of lavender BDH are about 1,800-fold and 500-fold lower, respectively, than those of TCU-HL1 BDH. The indigenous borneol- and camphor-degrading strain isolated, Pseudomonas sp. strain TCU-HL1, reminds us of the time 100 years ago when Taiwan was the major producer of natural camphor in the world.

Aqueous Oldenlandia diffusa extracts inhibits colorectal cancer cells via activating AMP-activated protein kinase signalings.

Here we evaluated the anti-cancer activity of aqueous Oldenlandia diffusa (OD) extracts (ODE) in colorectal cancer (CRC) cells. We showed that ODE exerted potent anti-proliferative, cytotoxic and pro-apoptotic activities against a panel of established CRC lines (HCT-116, DLD-1, HT-29 and Lovo) and primary (patient-derived) human CRC cells. ODE activated AMP-activated protein kinase (AMPK) signaling, which led to subsequent mTORC1 inhibition and Bcl-2/HIF-1α downregulation in CRC cells. In ODE-treated CRC cells, AMPKα1 formed a complex with p53. This might be important for p53 activation and subsequent cancer cell apoptosis. Inhibition of AMPK signaling, though dominant negative (dn) mutation or shRNA/siRNA knockdown of AMPKα1 attenuated ODE-exerted CRC cytotoxicity. In vivo, i.p. administration of ODE inhibited HCT-116 xenograft tumor growth in SCID mice. In addition, AMPK activation, mTORC1 inhibition and p53 activation were observed in ODE-treated HCT-116 xenograft tumors. These results suggest that ODE inhibits CRC cells in vitro and in vivo, possibly via activation of AMPK-dependent signalings.

Paricalcitol Attenuates Cardiac Fibrosis and Expression of Endothelial Cell Transition Markers in Isoproterenol-Induced Cardiomyopathic Rats.

OBJECTIVES: Acute cardiomyopathy is a health problem worldwide. Few studies have shown an association between acute cardiomyopathy and low vitamin D status. Paricalcitol, a vitamin D receptor activator, clinically benefits patients with advanced kidney disease. The effect of paricalcitol supplement on cardiac remodeling in cardiomyopathic rats is unknown. This experimental study investigated the effect of paricalcitol in rats with cardiomyopathy induced by isoproterenol. DESIGN: Prospective, randomized, controlled experimental study. SETTING: Hospital-affiliated animal research institution. SUBJECTS: Eight-week-old male Wistar-Kyoto rats. INTERVENTIONS: Male Wistar-Kyoto rats were first injected intraperitoneally with isoproterenol to create a rat model of acute cardiomyopathy. Then paricalcitol was administered intraperitoneally to isoproterenol-injected rats at a dosage of 200 ng three times a week for 3 weeks. Relevant cardiomyopathy-related variables were measured regularly in three groups of rats, controls, isoproterenol, and isoproterenol plus paricalcitol. Rat hearts were obtained for evaluation of cardiac fibrosis using Masson trichrome staining and commercially available software, and evaluation of cell transition using immunofluorescence staining analysis. MEASUREMENTS AND MAIN RESULTS: Isoproterenol infusions generated significant cardiac fibrosis (p < 0.001). Subsequent paricalcitol treatment attenuated the isoproterenol-induced cardiac fibrosis (p = 0.006). Fluorescence showed colocalization of endothelial and fibroblast cell markers (cluster differentiation 31 and α-smooth muscle actin, respectively) in the isoproterenol-treated hearts. Paricalcitol injections attenuated the isoproterenol-induced fluorescence intensity of two cell markers (p < 0.01). CONCLUSIONS: Paricalcitol injections may ameliorate isoproterenol-induced cardiac fibrosis possibly through regulating cell transition.

Xinfuli improves cardiac function, histopathological changes and attenuate cardiomyocyte apoptosis in rats with doxorubicin-induced cardiotoxicity.

BACKGROUND: Xinfuli Granule (XG), a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and the underlying mechanisms of Xinfuli in rats with doxorubicin-induced cardiotoxicity. METHODS: Sprague-Dawley rats were treated with intraperitoneal injection of Doxorubicin (DOX, 2.5 mg/kg per week) for six weeks, and then randomly divided into four groups which received intragastrically administration of normal saline (control group) or different dosage of XG (0.675 g/kg per day, 1.35 g/kg per day, and 2.7g/kg per day, respectively) for six weeks. Transthoracic echocardiography was performed to evaluate the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) before and after the XG treatment and histopathologic changes were also examined. Myocardial cell apoptosis was detected by TUNEL staining. The expression of related genes and proteins were analyzed using immunohistochemical staining. RESULTS: Compared to those in the control group, rats in XG treated groups showed significantly improved cardiac function and milder cardiac histopathological changes, lower cardiomyocyte apoptosis index, higher expression of Bcl-2 and lower expression of Bax. CONCLUSIONS: Administration of XG improves cardiac function and histopathological changes in rats with doxorubicin-induced cardiotoxicity. These effects are associated with inhibition of cardiomyocyte apoptosis, perhaps via regulation of Bcl-2 and Bax protein expression.

Loss of Egr-1 sensitizes pancreatic ß-cells to palmitate-induced ER stress and apoptosis.

UNLABELLED: Pancreatic ß-cells are particularly susceptible to fatty-acid-induced endoplasmic reticulum (ER) stress and apoptosis. To understand how ß-cells sense fatty acid stimuli and translate into a long-term adaptive response, we investigated whether palmitic acid (PA) regulates early growth response-1 (Egr-1), an immediate-early transcription factor, which is induced by many environmental stimuli and implicated in cell proliferation, differentiation, and apoptosis. We found that Egr-1 was rapidly and transiently induced by PA in MIN6 insulinoma cells, which was accompanied by calcium influx and ERK1/2 phosphorylation. Calcium chelation and MEK1/2 inhibition blocked PA-induced Egr-1 upregulation, suggesting that PA induces Egr-1 expression through a calcium influx-MEK1/2-ERK1/2 cascade. Knockdown of Egr-1 increased PA-induced caspase-3 activation and ER stress markers and decreased PA-induced Akt phosphorylation and insulin secretion and signaling. Akt replenishment and insulin supplementation rescued PA-induced apoptosis in Egr-1 knockdown cells. These results suggest that the absence of Egr-1 loses its ability to couple the short-term insulin/Akt pathway to long-term survival adaptation. Finally, Egr-1-deficient mouse islets are more susceptible to ex vivo stimuli of apoptosis. In human pancreatic tissues, EGR1 expression correlated with expression of ER stress markers and anti-apoptotic gene. In conclusion, Egr-1 is induced by PA and further attempts to rescue ß-cells from ER stress and apoptosis through improving insulin/Akt signaling. Our study underscores Egr-1 as a critical early sensor in pancreatic ß-cells to translate fatty acid stimuli into a cellular adaptation mechanism. KEY MESSAGE: PA stimulates Egr-1 expression via a calcium influx-MEK1/2-ERK1/2-Elk-1 cascade. Egr-1 attenuates PA-induced ER stress and apoptosis. Egr-1 maintains Akt survival pathway to protect ß-cells from PA-induced apoptosis. Egr-1-deficient islets are prone to ex vivo stimuli of apoptosis. Human EGR1 expression correlates with genes for ER stress and anti-apoptosis.