Functional structural domain synthesis of anti-pancreatic carcinoma pectin-like polysaccharide RN1.

The great structural and functional diversity supports polysaccharides as favorable candidates for new drug development. Previously we reported that a drug candidate pectin-like natural polysaccharide, RN1 might target galectin-3 (Gal-3) to impede pancreatic cancer cell growth in vivo. However, the quality control of polysaccharide-based drug research faces great challenges due to the heterogeneity. A potential solution is to synthesize structurally identified subfragments of this polysaccharide as alternatives. In this work, we took RN1 as an example, and synthesized five subfragments derived from the putative repeating units of RN1. Among them, pentasaccharide 4 showed an approximative binding affinity to Gal-3 in vitro, as well as an antiproliferative activity against pancreatic BxPC-3 cells comparable to that of RN1. Further, we scaled up pentasaccharide 4 to gram-scale in an efficient synthetic route with a 6.9 % yield from D-galactose. Importantly, pentasaccharide 4 significantly suppressed the growth of pancreatic tumor in vivo. Based on the mechanism complementarity of galactin-3 inhibitor and docetaxel, the combination administration of pentasaccharide 4 and docetaxel afforded better result. The result suggested pentasaccharide 4 was one of the functional structural domains of polysaccharide RN1 and might be a leading compound for anti-pancreatic cancer new drug development.

Genome assembly of Erythrophleum Fordii, a special "ironwood" tree in China.

OBJECTIVES: Erythrophleum is a genus in the Fabaceae family. The genus contains only about 10 species, and it is best known for its hardwood and medical properties worldwide. Erythrophleum fordii Oliv. is the only species of this genus distributed in China. It has superior wood and can be used in folk medicine, which leads to its overexploitation in the wild. For its effective conservation and elucidation of the distinctive genetic traits of wood formation and medical components, we present its first genome assembly. DATA DESCRIPTION: This work generated ~ 160.8 Gb raw Nanopore whole genome sequencing (WGS) long reads, ~ 126.0 Gb raw MGI WGS short reads and ~ 29.0 Gb raw RNA-seq reads using E. fordii leaf tissues. The de novo assembly contained 864,825,911 bp in the E. fordii genome, with 59 contigs and a contig N50 of 30,830,834 bp. Benchmarking Universal Single-Copy Orthologs (BUSCO) revealed 98.7% completeness of the assembly. The assembly contained 471,006,885 bp (54.4%) repetitive sequences and 28,761 genes that coded for 33,803 proteins. The protein sequences were functionally annotated against multiple databases, facilitating comparative genomic analysis.

Small-Molecule Analysis Based on DNA Strand Displacement Using a Bacteriorhodopsin Photoelectric Transducer: Taking ATP as an Example.

A uniformly oriented purple membrane (PM) monolayer containing photoactive bacteriorhodopsin has recently been applied as a sensitive photoelectric transducer to assay color proteins and microbes quantitatively. This study extends its application to detecting small molecules, using adenosine triphosphate (ATP) as an example. A reverse detection method is used, which employs AuNPs labeling and specific DNA strand displacement. A PM monolayer-coated electrode is first covalently conjugated with an ATP-specific nucleic acid aptamer and then hybridized with another gold nanoparticle-labeled nucleic acid strand with a sequence that is partially complementary to the ATP aptamer, in order to significantly minimize the photocurrent that is generated by the PM. The resulting ATP-sensing chip restores its photocurrent production in the presence of ATP, and the photocurrent recovers more effectively as the ATP concentration increases. Direct and single-step ATP detection is achieved in 15 min, with detection limits of 5 nM and a dynamic range of 5 nM-0.1 mM. The sensing chip exhibits high selectivity against other ATP analogs and is satisfactorily stable in storage. The ATP-sensing chip is used to assay bacterial populations and achieves a detection limit for Bacillus subtilis and Escherichia coli of 102 and 103 CFU/mL, respectively. The demonstration shows that a variety of small molecules can be simultaneously quantified using PM-based biosensors.

Salidroside suppresses proliferation and migration in prostate cancer via the PI3K/AKT pathway.

BACKGROUND: Prostate cancer (PCa) is one of the most common malignancies in men. PCa is difficult to detect in its early stages, and most patients are diagnosed in the middle to late stages. At present, drug therapy for advanced PCa is still insufficient. Some patients develop drug resistance in the later stage of therapy, which leads to tumor recurrence, metastasis and even treatment failure. Therefore, it is crucial to find new and effective drugs to treat prostate cancer. OBJECTIVE: The aim of this study was to investigate the anti-cancer effect of salidroside, an active ingredient in a traditional Chinese herbal medicine, on PCa. METHODS: Two human PCa cell lines, PC3 and DU145, were cultured and treated with salidroside. Cell viability and proliferation ability were analyzed through CCK-8 and colony assays, and cell migration ability was detected by Transwell and Scratch assays. RT-PCR and WB were used to detected the expression levels of moleculars related to cell proliferation, apoptosis, migration, and AKT signaling pathway. Forthmore, we performed rescue experiments with agonist to verify the affected signaling pathway. RESULTS: Salidroside inhibited the proliferation, colony formation, and migration of PCa cells. Meanwhile, apoptosis of PCa cells was enhanced. Moreover, salidroside inhibited PI3K/AKT pathway in PCa cells. The treatment of AKT agonist 740Y-P abrogated the inhibitory effect of salidroside on the PI3K/AKT signaling pathway. CONCLUSIONS: Our study demonstrated that in PCa cells, salidroside inhibites proliferation and migration and promots apoptosis via inhibiting PI3K/AKT pathway.

A pectic polysaccharide isolated from Achyranthes bidentata is metabolized by human gut Bacteroides spp.

Achyranthes bidentata (A. bidentata) is a famous traditional Chinese medicine (TGM) for treatment osteoporosis. Polysaccharides, a major factor for shaping the gut microbiota, are the primary ingredients of A. bidentata. However, bioactivity of A. bidentata polysaccharide on human gut microbiota (HGM) remains unknown. Here, a homogeneous pectic polysaccharide A23-1 with average molecular weight of 93.085 kDa was extracted and purified from A. bidentata. And A23-1 was compsed of rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose in a molar ratio of 7.26: 0.76: 5.12: 2.54: 23.51: 60.81. GC-MS, partial acid hydrolysis and NMR results indicated the backbone of A23-1 was composed of 1, 2, 4-Rhap and 1, 4-GlapA, while the branches were composed of galactose, arabinose, glucose and glucuronic acid. Further, A23-1 was found to be degraded into monosaccharides and fragments. Taking Bacteroides thetaiotaomicron (BT) as a model, we suggested three polysaccharide utilization loci (PULs) might be involved in the A23-1 degradation. Degraded products generated by BO might not support the growth of probiotics. Besides, acetate and propionate as the main end products were generated by Bacteroides spp. and probiotics utilizing A23-1. These findings suggested A23-1 was possible one of food sources of human gut Bacteroides spp.

[Application of "major scientific issues and engineering technology difficulties in traditional Chinese medicine(2019-2021)" in national science and t echnology layout].

In order to judge the future development trend of science and technology, plan ahead and lay out the frontier technology fields and directions, China Association of Chinese Medicine(CACM) has launched consultation projects for collecting "major scienti-fic issues and engineering technology difficulties in traditional Chinese medicine(TCM)" for the industry for three consecutive years since 2019. Up to now, 18 projects have been selected as major issues for research, and some experience and achievements have been made. These projects have been applied in important scientific and technological work such as scientific and technological planning and deployment at all levels of national, local, and scientific research institutions, the selection and cultivation of major national scientific and technological projects, and the construction of innovation bases, giving full play to the role of the think tank advisory committee of CACM. This study reviewed the selection of major issues for the first time, systematically combed its application in the national layout of science and technology, and put forward the existing problems and improvement suggestions, aiming to provide new ideas for further improving the selection of major issues and research direction, providing a theoretical basis and decision support for the national scientific and technological layout in the field of TCM, and promoting scientific and technological innovation to facilitate the high quality development of TCM.

A structure defined pectin SA02B from Semiaquilegia adoxoides is metabolized by human gut microbes.

Polysaccharide is one of the major factors for shaping the gut microbiota. However, bioactivity of polysaccharide isolated from Semiaquilegia adoxoides on human gut microbiota remains unclear. Thus, we hypothesize gut microbes may act on it. Herein, pectin SA02B from the roots of Semiaquilegia adoxoides with molecular weight 69.26 kDa was elucidated. The backbone of SA02B was composed of alternate 1, 2-linked α-Rhap and 1, 4-linked α-GalpA, with branches of terminal (T) -, 1, 4-, 1, 3- and 1, 3, 6-linked ß-Galp, T-, 1, 5- and 1, 3, 5-linked α-Araf and T-, 1, 4-linked-ß-Xylp substituted at C-4 of 1, 2, 4-linked α-Rhap. Bioactivity screening showed SA02B promoted the growth of Bacteroides spp. which deconstructed it into monosaccharide. Simultaneously, we observed competition might exist between Bacteroides spp. and probiotics. Besides, we found that both Bacteroides spp. and probiotics could generate SCFAs grown on SA02B. Our findings highlight SA02B may deserve as a prebiotic to be explored to benefit the health gut microbiota.

Antiglycation Effects of Adlay Seed and Its Active Polyphenol Compounds: An In Vitro Study.

This study aimed to evaluate the antiglycation effects of adlay on protein glycation using in vitro glycation assays. Adlay seed was divided into the following four parts: the hull (AH), testa (AT), bran (AB), and polished adlay (PA). A solvent extraction technique and column chromatography were utilized to investigate the active fractions and components of adlay. Based on a BSA-glucose assay, the ethanolic extracts of AT (ATE) and AB (ABE) revealed a greater capacity to inhibit protein glycation. ATE was further consecutively partitioned into four solvent fractions with n-hexane, ethyl acetate (ATE-Ea), 1-butanol (ATE-BuOH), and water. ATE-BuOH and -Ea show marked inhibition of glucose-mediated glycation. Medium-high polarity subfractions eluted from ATE-BuOH below 50% methanol with Diaion HP-20, ATE-BuOH-c to -f, exhibited superior antiglycation activity, with a maximum inhibitory percentage of 88%. Two phenolic compounds, chlorogenic acid and ferulic acid, identified in ATE-BuOH with HPLC, exhibited potent inhibition of the individual stage of protein glycation and its subsequent crosslinking, as evaluated by the BSA-glucose assay, BS-methylglyoxal (MGO) assay, and G.K. peptide-ribose assay. In conclusion, this study demonstrated the antiglycation properties of ATE in vitro that suggest a beneficial effect in targeting hyperglycemia-mediated protein modification.

Xuebijing Injection Regulates Mitochondrial N-formyl Peptides/NLRP3 Inflammatory Pathway to Treat Severe Acute Pancreatitis in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Xuebijing injection （XBJ） on sodium taurocholate （Na-Tc）-induced severe acute pancreatitis （SAP） in rats. MethodForty rats were randomly assigned into 5 groups： sham operation group， SAP model group， and low-， medium-， and high-dose （4， 8， 12 mL·kg·d-1， respectively） XBJ groups. SAP model was established by retrograde injection of Na-Tc （1 mL·kg-1） into the biliary and pancreatic ducts. XBJ was injected intraperitoneally 3 days before and 0.5 h after modeling. The ascitic fluid volume and the pancreas weight-to-body weight ratio were measured. The pathological changes of pancreatic tissue were observed via hematoxylin-eosin （HE） staining. The protein levels of formyl peptide receptor 1 （FPR1） and nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） in pancreatic tissue were detected by immunohistochemistry. Western blot was employed to determine the expression levels of NADH-ubiquinone oxidoreductase chains 1-6 （MT-ND1， MT-ND2， MT-ND3， MT-ND4， MT-ND5， and MT-ND6） in rat plasma. ResultCompared with sham operation group， the SAP model group showcased increased ascitic fluid volume and pancreas weight-to-body weight ratio （P<0.05）， serious lesions in pancreatic tissue， increased total pathological score （P<0.05）， and up-regulated protein levels of FPR1 and NLRP3 in pancreatic tissue （P<0.05）. The model group had lower MT-ND2 level （P<0.05） and higher MT-ND1， MT-ND3， and MT-ND6 levels in plasma （P<0.05） than the sham operation group， while MT-ND4 and MT-ND5 had no significant differences between the two groups. Compared with SAP model group， the XBJ treatment decreased ascitic fluid volume and pancreas weight-to-body weight ratio （P<0.01）， ameliorated pancreatic lesions， and down-regulated the protein levels of FPR1 and NLRP3 in pancreatic tissue （P<0.01）. The treatments， especially high-dose XBJ （P<0.01）， down-regulated the expression of MT-ND1 （P<0.01）， MT-ND3 （P<0.01）， MT-ND6 （P<0.01）， and MT-ND4 and did not change that of MT-ND5. ConclusionXBJ may antagonize partial mitochondrial N-formyl peptides and excessive inflammatory response mediated by FPR1/NLRP3 to treat SAP in rats.

Adlay Testa (Coix lachryma-jobi L. var. Ma-yuen Stapf.) Ethanolic Extract and Its Active Components Exert Anti-Proliferative Effects on Endometrial Cancer Cells via Cell Cycle Arrest.

Endometrial cancer is the most common malignant tumors of gynecologic neoplasms in Western society. In recent years, the incidence of endometrial cancer has increased, and it has become the third most common female gynecological cancer (after ovarian and cervical cancer) in Taiwan. Adlay (Coix lachryma-jobi L. var. Ma-yuen Stapf.) has been demonstrated to have bioactive polyphenols, flavonoids, phytosterols, and essential nutrients for health benefits, including anticancer effects in humans. However, little is known about the effect of adlay seeds on endometrial cancer. Our study aimed to investigate the potential growth inhibitory effects of several adlay seed fractions, including ethyl acetate (ATE-EA) and its bioactive constituents, separately on endometrial cancer cells-HEC-1A (phosphatase and tensin homolog-positive) and RL95-2 (phosphatase and tensin homolog-negative)-and identify related active ingredients. In addition, the potential active fractions and the phytochemical compounds were elucidated. The results demonstrate superior activity of ATE-EA with significant in vitro cell proliferation inhibitory capacity, particularly its C.D.E.F-subfraction. Moreover, HPLC- and GC/FID-based quantification of ATE-EA subfractions showed that phenolic compounds (caffeic acid, protocatechuic acid, and p-hydroxybenzaldehyde), flavonoids, steroids, and fatty acid compounds exert anti-proliferative effects in the cell model. Finally, it was shown that cell growth and cell cycle arrest most significantly occurred in the in G1 or G2/M phase under ATE-EA treatment. Collectively, our results demonstrate an antiproliferative effect of ATE-EA on endometrial cancer cells that suggest a positive health outcome for women from consumption of these compounds.

Integrated analysis of source-specific risks for PM2.5-bound metals in urban, suburban, rural, and industrial areas.

The levels and characteristics of atmospheric metals vary in time and location, can result in various health impacts, which increases the challenge of air quality management. We aimed to investigate PM2.5-bound metals in multiple locations and propose a methodology for comparing metal elements across study regions and prioritizing source contributions through integrated health risk assessments. PM2.5-bound metals were collected in the urban, suburban, rural, and industrial regions of Taiwan between 2016 and 2018. We incorporated the positive matrix factorization (PMF) with health risk assessments (considering estimates of the margin of exposure (MOE) and excess cancer risk (ECR)) to prioritize sources for control. We found that the concentrations of Fe, Zn, V, Cu, and Mn (industry-related metals) were higher at the industrial site (Kaohsiung) and Ba, Cr, Ni, Mo, and Co (traffic-related metals) were higher at the urban site (Taipei). The rural site (Hualian) had good air quality, with low PM2.5 and metal concentrations. Most metal concentrations were higher during the cold season for all study sites, except for the rural. Ambient concentrations of Mn, Cr, and Pb obtained from all study sites presents a higher health risk of concern. In Kaohsiung, south Taiwan, PM2.5-bound metals from the iron ore and steel factory is suggested as the first target for control based on the calculated health risks (MOE < 1 and ECR > 10-6). Overall, we proposed an integrated strategy for initiating the source management prioritization of PM2.5-bound metals, which can aid an effort for policymaking.

Identification of Bioactive Components from Ruellia tuberosa L. on Improving Glucose Uptake in TNF-α-Induced Insulin-Resistant Mouse FL83B Hepatocytes.

Ruellia tuberosa L. (RTL) has been used as a folk medicine to cure diabetes in Asia. RTL was previously reported to alleviate hyperglycemia, insulin resistance (IR), abnormal hepatic detoxification, and liver steatosis. However, the potential bioactive compounds of RTL have still not been identified. The aim of this study was to investigate the bioactive compounds in RTL ethyl acetate (EA) fractions by using a glucose uptake assay in TNF-α-treated mouse FL83B hepatocytes to discover a mechanism by which to improve IR. The bioactive compounds were identified by the high-performance liquid chromatography (HPLC) assay. Using the Sephadex LH20 gel packing chromatography column, the EAF5 fraction was isolated from RTL and significantly increased glucose uptake in TNF-α-treated FL83B cells. Moreover, the MCI gel packing chromatography column separated EAF5 into five subfractions and had no significant cytotoxic effect in FL83B cells when treated at the concentration of 25 µg/ml. Among the subfractions, EAF5-5 markedly enhanced glucose uptake in TNF-α-treated FL83B cells. The possible bioactive compounds of the EAF5-5 fraction that were identified by the HPLC assay include syringic acid, p-coumaric acid, and cirsimaritin. The bioactive compound with the best effect of increasing glucose uptake was p-coumaric acid, but its effect alone was not as good as the combined effect of all three compounds of the EAF5-5 fraction. Thus, we speculate that the antidiabetic effect of RTL may be the result of multiple active ingredients.

Alleviative effect of Ruellia tuberosa L. on NAFLD and hepatic lipid accumulation via modulating hepatic de novo lipogenesis in high-fat diet plus streptozotocin-induced diabetic rats.

Ruellia tuberosa L. (RTL) exhibits phytochemical activities and has been used as a folk medicine for curing diabetes mellitus in East Asia for decades. This study investigated the effect of RTL aqueous and ethanolic extracts on nonalcoholic fatty liver disease (NAFLD) and hepatic lipid accumulation in high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats. Administration of RTL aqueous extract (RTLW) or ethanolic extract (RTLE) at dosage of 100 or 400 mg/kg body weight for 4 weeks was carried out in HFD/STZ-induced T2DM rats. Liver weight, adipose (epididymal and perirenal adipose tissues) weight, hepatic triglyceride level, and de novo lipogenesis (DNL)-associated protein expression were monitored after scarification. The results revealed that RTLW and RTLE reduced relative liver weight and relative fat weights in HFD/STZ-induced T2DM rats. RTLW and RTLE also ameliorated NAFLD and hepatic triglyceride (TG) accumulation in diabetic rats. Moreover, hepatic DNL-regulated enzymes such as sterol regulatory element-binding protein-1 (SREBP1) and fatty acid synthase (FAS) expression were significantly suppressed by RTLE (100 and 400 mg/kg body weight) in diabetic rats. The evidences of this study suggest that RTL possesses potential on alleviating NAFLD and lipid accumulation via regulating DNL in the liver of HFD/STZ-induced T2DM rats.

Combination-Responsive MoO3- x-Hybridized Hyaluronic Acid Hollow Nanospheres for Cancer Phototheranostics.

It is of extreme importance to reduce side effects resulting from the nonspecific uptake of phototherapeutic agents by normal tissues. Currently, the single responsive strategy still cannot entirely satisfy the requirements of practical applications. In this study, we developed one kind of combination-responsive phototherapeutic nanoplatforms, where oxygen-deficient molybdenum oxide (MoO3- x) hybridized hyaluronic acid (HA) hollow nanospheres, namely, MoO3- x@HA HNSs, were constructed via a facile one-step method. In MoO3- x@HA HNSs, the reasonable combination of actively targeted specificity endowed by the HA component and tumor microenvironment-responsive phototherapy activity induced by the MoO3- x component can effectively improve the precision of phototherapy. The in vitro and in vivo experimental results confirm that MoO3- x@HA HNSs can selectively kill CD44-overexpressing cancer cells and inhibit tumor growth under an 808 nm laser irradiation, revealing their remarkable synergistic photothermal therapy/photodynamic therapy effect with CD44 receptor-targeted specificity and pH responsiveness in treating cancer. We also prove that MoO3- x@HA HNSs can serve as one kind of contrast agent to achieve the computed tomography/photoacoustic imaging. Encouraged by these results, it is anticipated that the reasonable combination of active targeting and tumor microenvironment responsiveness can be a promising strategy to develop phototherapeutic nanoplatforms for precise multimodality cancer theranostics.

Protective effect of Ruellia tuberosa L. extracts against abnormal expression of hepatic detoxification enzymes in diabetic rats.

Ruellia tuberosa L. (RTL) has been used as a folk medicine for curing diabetes mellitus in East Asia decades. This study investigated the effect of RTL on hepatic detoxification enzyme expression in diabetic rats. Male Wistar rats were fed a high fat diet (HFD) and intraperitoneally injected with streptozotocin (STZ) to induce diabetes. Subsequently, rats received oral administrations of 100 or 400 mg kg-1 body weight RTL extract, in either water (RTLW) or ethanol (RTLE), once a day for 4 weeks. The real-time PCR analyses showed that abnormality of hepatic phase I and II detoxification enzyme expression was observed in diabetic rats. However, both RTLW and RTLE significantly normalized the expression of hepatic phase I detoxification enzymes such as CYP 2E1, and expression of phase II detoxification enzymes such as UGT 1A7 and GST M1 in diabetic rats. Furthermore, we found that fasting serum glucose, hemoglobin A1C (HbA1C) and the area under the curve of oral glucose tolerance test (AUCOGTT) levels were significantly reduced in both RTLW and RTLE treated diabetic rats. Moreover, both RTLW and RTLE significantly increased the activity of hepatic anti-oxidative enzymes such as superoxide dismutase (SOD) in diabetic rats. The present study suggests that RTL may ameliorate abnormal hepatic detoxification function via alleviating hyperglycemia and enhancing hepatic antioxidant capacity in HFD/STZ-induced diabetic rats.

p-Hydroxyacetophenone suppresses nuclear factor-κB-related inflammation in nociceptive and inflammatory animal models.

p-Hydroxyacetophenone (HAP) is a crucial chemical compound present in plants of the genus Artemisia, which are used in traditional therapies for treating jaundice, hepatitis, and inflammatory diseases. Nevertheless, the bioactivity of HAP remains to be identified in order to prove its importance in the plants of genus Artemisia. This study investigated the antioxidative, antinociceptive, and anti-inflammatory effects of HAP, and probed its possible molecular mechanisms. Our results revealed that HAP (80 mg/kg, intraperitoneally) in vivo reduced the acetic acid-induced writhing response and formalin-induced licking time. Moreover, in the λ-carrageenan-induced acute-inflammatory paw edema model in mice, HAP significantly improved hind paw swelling and neutrophil infiltration. In a homogenized paw tissue examination, HAP attenuated pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-1ß, and interleukin-6. Simultaneously, HAP also inhibited the production of nuclear factor kappa B, cyclooxygenase-2, and nitric oxide (NO). Another examination revealed that HAP exerted anti-inflammatory activity by decreasing malondialdehyde levels in the edematous paw through increasing the activities of superoxide dismutase, glutathione peroxidase, and glutathione reductase in the liver. These findings may be beneficial in understanding the therapeutic effects of some plants of the genus Artemisia in the pretreatment of inflammation-associated diseases.

A Practical Guide to Ordering and Interpreting Coagulation Tests for Patients on Direct Oral Anticoagulants in Singapore.

INTRODUCTION: Direct oral anticoagulants (DOACs) are establishing themselves as principle choices for the treatment of a variety of thrombotic disorders. DOACs are also known to affect common coagulation tests which are routinely performed for patients in clinical practice. An understanding of their varied effects is crucial for the appropriate ordering of coagulation tests and their interpretation. MATERIALS AND METHODS: Laboratories in public and private healthcare institutions and commercial sectors were surveyed on coagulation tests offered and their methods. A Medline and bibliography search, including a search on search engines, was performed for publications reporting the effects of dabigatran, apixaban and rivaroxaban on these coagulation tests. These papers were reviewed and summarised for consensus recommendations. RESULTS: Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are variably affected by the DOACs and dependent of the coagulation assays used. Clinicians must know which laboratory has performed these tests to logically interpret test results. A normal PT or aPTT does not exclude the presence of residual DOACs effect. The thrombin time is sensitive to dabigatran but not apixaban or rivaroxaban. Specialised coagulation tests such as thrombophilia tests are also variably affected by the DOACs. All laboratories in Singapore however, employ similar test methods permitting a common set of recommendations for specialised coagulation testing. CONCLUSION: Knowledge of the effects of DOACs on coagulation testing is essential to determine the appropriateness of performing such tests and interpreting them coherently. Practical recommendations which are tests and location-specific are set out in this paper.

Determination and Pharmacokinetic Comparisons of Atractylodin after Oral Administration of Crude and Processed Atractylodis rhizoma.

BACKGROUND: In traditional Chinese medicine, Atractylodis rhizoma is the dried rhizome of Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz. After being processed, the dryness of A. rhizoma decreased, and the function of tonifying spleen increased. Therefore, the processed A. rhizoma is the best choice of clinical application. As the main active components, polyethylene alkynes exhibits various desirable pharmacological effects including anti-inflammatory, anti-bacterial and anti-arrhythmia activity. However, there is no report on the pharmacokinetic comparisons of atractylodin, one of polyethylene alkynes, in bio-samples after oral administration of crude and processed A. rhizoma until now. The in vivo study of active components of A. rhizoma would be necessary and helpful for clinical application and clarification of processing principle. OBJECTIVE: To compare the pharmacokinetic parameters of atractylodin after oral administration of crude and processed A. rhizoma, and clarify the processing principle of A. rhizoma. MATERIALS AND METHODS: Plasma concentrations of atractylodin in rats were determined by reversed-phase high-performance liquid chromatogram and the main pharmacokinetic parameters were estimated with Drug and Statistics 2.0 Software Package (Chinese Pharmacological Society, Shanghai, China). RESULTS: The AUC0-t, AUC0→∞, Tmax, and Cmax of processed A. rhizoma were increased significantly (P < 0.05) compared with that in crude A. rhizoma after using Student's t-test. CONCLUSIONS: Processing A. rhizoma with wheat bran by stir-frying can promote and accelerate the absorption of atractylodin. SUMMARY: In this paper, a RP-HPLC method with UV detection for quantification of atractylodin (a main active component in Atractylodis Rhizoma) in rat plasma has been developed and applied to a preliminary pharmacokinetic study of atractylodin after oral administration of crude and processed Atractylodis Rhizoma respectively. The result indicates that processing Atractylodis Rhizoma with wheat-bran can promote and accelerate the absorption of atractylodin.

Vescalagin from Pink Wax Apple [Syzygium samarangense (Blume) Merrill and Perry] Alleviates Hepatic Insulin Resistance and Ameliorates Glycemic Metabolism Abnormality in Rats Fed a High-Fructose Diet.

This study investigates the ameliorative effect of vescalagin (VES) isolated from Pink wax apple fruit on hepatic insulin resistance and abnormal carbohydrate metabolism in high-fructose diet (HFD)-induced hyperglycemic rats. The results show that in HFD rats, VES significantly reduced the values of the area under the curve for glucose in an oral glucose tolerance test and the homeostasis model assessment of insulin resistance index. VES significantly enhanced the activity of hepatic antioxidant enzymes while reducing thiobarbituric acid-reactive substances in HFD rats. Western blot assay revealed that VES reduced hepatic protein expression involved in inflammation pathways while up-regulating expression of hepatic insulin signaling-related proteins. Moreover, VES up-regulated the expression of hepatic glycogen synthase and hepatic glycolysis-related proteins while down-regulating hepatic gluconeogenesis-related proteins in HFD rats. This study suggests some therapeutic potential of VES in preventing the progression of diabetes mellitus.

Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet.

Herein, we investigated the hypoglycemic effect of plant gallic acid (GA) on glucose uptake in an insulin-resistant cell culture model and on hepatic carbohydrate metabolism in rats with a high-fructose diet (HFD)-induced diabetes. Our hypothesis is that GA ameliorates hyperglycemia via alleviating hepatic insulin resistance by suppressing hepatic inflammation and improves abnormal hepatic carbohydrate metabolism by suppressing hepatic gluconeogenesis and enhancing the hepatic glycogenesis and glycolysis pathways in HFD-induced diabetic rats. Gallic acid increased glucose uptake activity by 19.2% at a concentration of 6.25 µg/mL in insulin-resistant FL83B mouse hepatocytes. In HFD-induced diabetic rats, GA significantly alleviated hyperglycemia, reduced the values of the area under the curve for glucose in an oral glucose tolerance test, and reduced the scores of the homeostasis model assessment of insulin resistance index. The levels of serum C-peptide and fructosamine and cardiovascular risk index scores were also significantly decreased in HFD rats treated with GA. Moreover, GA up-regulated the expression of hepatic insulin signal transduction-related proteins, including insulin receptor, insulin receptor substrate 1, phosphatidylinositol-3 kinase, Akt/protein kinase B, and glucose transporter 2, in HFD rats. Gallic acid also down-regulated the expression of hepatic gluconeogenesis-related proteins, such as fructose-1,6-bisphosphatase, and up-regulated expression of hepatic glycogen synthase and glycolysis-related proteins, including hexokinase, phosphofructokinase, and aldolase, in HFD rats. Our findings indicate that GA has potential as a health food ingredient to prevent diabetes mellitus.