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Ruminant animals rely on the activities of β-glucosidases from residential microbes to convert feed fibers into glucose for further metabolic uses. In this report, we determined the structures of Br2, which is a glycoside hydrolase family 1 β-glucosidase from the bovine rumen metagenome. Br2 folds into a classical (β/α)8-TIM barrel domain but displays unique structural features at loop β5→α5 and α-helix 5, resulting in different positive subsites from those of other GH1 enzymes. Br2 exhibited the highest specificity toward laminaritriose, suggesting its involvement in β-glucan hydrolysis in digested feed. We then substituted the residues at subsites +1 and + 2 of Br2 with those of Halothermothrix orenii β-glucosidase. The C170E and C221T mutations provided favorable interactions with glucooligosaccharide substrates at subsite +2, while the A219N mutation probably improved the substrate preference for cellobiose and gentiobiose relative to laminaribiose at subsite +1. The N407Y mutation increased the affinity toward cellooligosaccharides. These results give further insights into the molecular determinants responsible for substrate specificity in GH1 β-glucosidases and may provide a basis for future enzyme engineering applications.

Background: N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiopulmonary exercise testing (CPET) are useful for severity assessment in patients with pulmonary hypertension (PH). Correlations between these tests in pre-capillary PH patients is less well studied. Methods: We studied 23 patients with pre-capillary PH: 8 with idiopathic pulmonary arterial hypertension (IPAH), 6 with systemic sclerosis-associated PAH (SSc-PAH), and 9 with chronic thromboembolic pulmonary hypertension (CTEPH). Clinical evaluation, NT-proBNP levels, six-minute walking test (6MWT), spirometry, and CPET were evaluated on the same day. Correlation between NT-proBNP levels and CPET parameters were investigated. Results: In all patients, NT-proBNP levels were significantly correlated with peak oxygen uptake (VO 2 ) ( r = −0.47), peak oxygen pulse ( r = −0.43), peak cardiac output (CO) ( r = −0.57), peak end-tidal partial pressure of carbon dioxide (P ET CO 2 ) ( r = −0.74), ventilatory equivalent to carbon dioxide (VE/VCO 2 ) at anaerobic threshold (AT) ( r = 0.73), and VE/VCO 2 slope ( r = 0.64). Significant correlations between NT-proBNP levels and peak P ET CO 2 and VE/VCO 2 were found in IPAH and CTEPH subgroups, and a significant correlation between NT-proBNP levels and VO 2 at AT was found in the CTEPH subgroup. No significant correlation was found in the SSc-PAH subgroup. Conclusion: NT-proBNP levels were significantly correlated with CPET parameters in patients with IPAH and CTEPH subgroups, but not in SSc-PAH subgroup. A further study with larger population is required to confirm these preliminary findings.

A novel endophytic actinomycete strain GKU 173T isolated from the roots of Acacia mangium Willd. showed potential plant growth promoting (PGP) activity. Phylogenetic analysis, based on 16S rRNA gene, indicated that strain GKU 173T was the most closely related to Fodinicola feengrottensis HKI 0501T—the only species in the genus Fodinicola. Morphology and chemotaxonomy of strain GKU 173T indicated that it belongs to the genus Fodinicola by having meso-diaminopimelic acid in the cell wall and xylose as the characteristic cell-wall sugars. The cellular fatty acid profile mainly comprised iso-C16:0, anteiso-C17:0, iso-C18:0, and iso-C17:0. The major menaquinones were MK-9(H4), MK-9(H6), and MK-9(H8). The main polar phospholipids contained diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Genome analysis signified DNA G+C content of 67.81 mol%. The level of digital DNA-DNA relatedness between strain GKU 173T and the type strain was 21.30%. On the basis of polyphasic characteristics, strain GKU 173T clearly represents a novel species of the genus Fodinicola, for which the name Fodinicola acaciae sp. nov. (= TBRC 10620T = NBRC 114213T) is proposed. Furthermore, genome analysis of both strains suggested that members of the genus Fodinicola are promising sources of beneficial PGP-actinomycetes and novel secondary metabolites.

Asiatic acid is a triterpenoid isolated from Centella asiatica. The present study aimed to investigate whether asiatic acid could lessen the metabolic, cardiovascular complications in rats with metabolic syndrome (MS) induced by a high-carbohydrate, high-fat (HCHF) diet. Male Sprague-Dawley rats were fed with HCHF diet with 15% fructose in drinking water for 12 weeks to induce MS. MS rats were treated with asiatic acid (10 or 20 mg/kg/day) or vehicle for a further three weeks. MS rats had an impairment of oral glucose tolerance, increases in fasting blood glucose, serum insulin, total cholesterol, triglycerides, mean arterial blood pressure, heart rate, and hindlimb vascular resistance; these were related to the augmentation of vascular superoxide anion production, plasma malondialdehyde and tumor necrosis factor-alpha (TNF-α) levels (p < 0.05). Plasma nitrate and nitrite (NOx) were markedly high with upregulation of inducible nitric oxide synthase (iNOS) expression, but dowregulation of endothelial nitric oxide synthase (eNOS) expression (p < 0.05). Asiatic acid significantly improved insulin sensitivity, lipid profiles, hemodynamic parameters, oxidative stress markers, plasma TNF-α, NOx, and recovered abnormality of eNOS/iNOS expressions in MS rats (p < 0.05). In conclusion, asiatic acid improved metabolic, hemodynamic abnormalities in MS rats that could be associated with its antioxidant, anti-inflammatory effects and recovering regulation of eNOS/iNOS expression.

Health care personnel at a community hospital have used cinnamon stomachic mixture for treatment of patients with functional dyspepsia for many years and they claimed that cinnamon stomachic mixture was effective without any supportive evidence. Objective: To determine the efficacy, safety, patients’ compliance and satisfaction with the treatment of cinnamon stomachic mixture. Methods: This was a randomized controlled study in 318 adults with functional dyspepsia presenting to 6 community hospitals. The patients were randomized to receive 105 mg of simethicone three times a day or 30 ml of cinnamon stomachic mixture three times a day for 7 to 14 days. The patients were evaluated for improvement of symptoms, compliance to medication and patients’ satisfaction with the treatment. The data were analysed by descriptive statistics, chi-square statistics, student t test, analysis of variance and non-parametric tests where appropriate. Results: One hundred and fifty patients received simethicone and 168 patients received cinnamon stomachic mixture. The baseline characteristics of the patients in both groups were not significantly different. The patients’ compliance to simethicone and cinnamon stomachic mixture was 82% and 89.3% respectively (p=0.09). The severity of the symptoms after treatment and the response rates were not significantly different between both groups. Side effects were observed in 9.3% and 9.5% in the simethicone group and the cinnamon stomachic mixture group respectively. Most of the patients in both groups were satisfied with the treatments they received. The cost of a 14-day course of cinnamon stomachic mixture was 36 baht compared with 84 baht for that of simethicone. Conclusion: Cinnamon stomachic mixture is effective and safe for the treatment of the patients with functional dyspepsia similar to simethicone.

Background: Nefopam is a non-opioid, non-nonsteroidal anti-imflammatory drug, analgesic drug that inhibits the reuptake of serotonin, norepinephrine, and dopamine. It is widely used as an adjuvant for pain. This study investigated whether the intraoperative, intravenous infusion of nefopam (20 mg) reduces postoperative morphine consumption, pain scores, and alleviates neuropathic pain in patients undergoing cervical spine surgery., Methods: A prospective, paralleled design, randomized study was conducted on 50 patients (aged 18-75 years) in a university-based hospital. The patients were assigned to an intervention or a control group (25 patients in each). The intervention group received a 1-hour infusion of nefopam (20 mg) before the end of surgery. The control group received normal saline (NSS). The outcome measures were morphine consumption during the first 24 postoperative hours, numerical rating scale (NRS) pain scores, and scores for the Thai version of the Neuropathic Pain Symptom Inventory (NPSI-T) in patients with neuropathic pain and adverse drug reactions. The NPSI-T scores were assessed on the preoperative day, postoperative day 1, 3, 15, and 30. The outcome assessors were blinded to group allocation., Results: Fifty patients were analyzed. During the first 24 postoperative hours, morphine consumption was 8 mg (nefopam) and 12 mg (NSS; P = .130). The intervention and control groups demonstrated no significant differences in the median NRS scores or total NPSI-T scores or adverse drug reactions., Conclusions: A single, intraoperative infusion of 20 mg of nefopam did not significantly reduce postoperative (24 hours) morphine consumption in patients undergoing anterior cervical spine surgery., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background. Airway inflammation and oxidative stress may be linked in obstructive sleep apnea (OSA) patients. We determined the effectiveness of continuous positive airway pressure (CPAP) therapy in reducing fractional exhaled nitric oxide (FeNO) and malondialdehyde (MDA) levels in OSA patients. Methods. Thirteen patients with OSA and 13 normal controls were recruited. FeNO and MDA levels were measured in the controls and in OSA patients before and after three months of CPAP therapy. Results. FeNO and MDA levels were higher in the patients compared to the age and gender matched controls (FeNO: 25.9 ± 5.0 versus 17.5 ± 5.9 ppb, P < 0.001; MDA: 14.6 ± 7.8 versus 2.1 ± 0.3 μmol/L, P < 0.001). FeNO and MDA levels were lower post-CPAP compared to pre-CPAP (FeNO: 25.9 ± 5.0 versus 17.0 ± 2.3 ppb, P < 0.001; MDA: 14.6 ± 7.8 versus 10.0 ± 6.4 μmol/L, P < 0.01). Apnea-hypopnea index (15.9 ± 6.6 versus 4.1 ± 2.1/h, P < 0.001) and mean arterial pressure (P < 0.01) decreased following CPAP treatment. Daytime mean SpO2 (P < 0.05) increased. Conclusion. Our study demonstrates that CPAP therapy yields clinical benefits by reducing upper airway inflammation and oxidative stress in OSA patients.

Objective: Prenatal exposure to organophosphate pesticides can lead to developmental neurotoxicity. A longitudinal birth cohort was established to investigate pesticide exposures from different agricultural activities. Maternal urinary organophosphate metabolites were measured at 28 weeks of pregnancy (n=86), delivery (n=67) and 2 months postpartum (n=51)., Method: Subjects were interviewed with questionnaires about work, home and behavioral factors potentially associated with pesticide exposures, and spot urine samples were also collected. The urine samples were analyzed for dimethyl phosphate (DMP), diethyl phosphate (DEP), diethyl thiophosphate (DETP) and diethyl dithiophosphate (DEDTP), using gas chromatography-mass spectrometry., Results: The urinary DMP and dialkyl phosphate (DAP) concentrations at 28 weeks of pregnancy and delivery were not significantly different, but the DMP and DAP concentrations at 28 weeks of pregnancy and DAP concentrations at delivery were significantly different (p<0.05) from those at 2 months postpartum. The factors influencing the urinary DAP concentrations at 28 weeks of pregnancy included insecticide used in the home, living close to agricultural farmland, frequency of agricultural field visits during the first and second trimesters of pregnancies, occupation of subjects, pesticide used and other agricultural activities., Conclusions: The urinary organophosphate metabolites, DMP, DEP, DETP, DEDTP, total DEP and DAPs, at 28 weeks of pregnancy, delivery and 2 months postpartum fluctuated depending on their pesticide exposures both at home and in agricultural fields.