Linagliptin is a highly specific, long‐acting inhibitor that is used as an orally administrable agent for type‐2 diabetes treatment. Because only the R‐enantiomer is of clinical use, we developed a ...capillary electrophoresis method for the determination of the enantiomeric impurity of this compound. Carboxymethyl‐β‐cyclodextrin was selected as the chiral selector for the separation of linagliptin enantiomers. Design of experiments and desirability functions were used for the analytical optimization, which was focused on understanding and improving the electrophoretic process. The effects of significant parameters (background electrolyte concentration and pH, cyclodextrin concentration, temperature, and voltage) were thoroughly investigated. The complete separation of linagliptin and its enantiomeric impurity with baseline resolution was achieved within 10 min on an uncoated fused‐silica capillary (50 μm inner diameter, 365 μm outer diameter, 64.5/56 cm in total/ effective length) maintained at 25°C, under an applied voltage of 28.0 kV. The background electrolyte contained 70 mM sodium acetate and 4.7 mM carboxymethyl‐β‐cyclodextrin, and the pH was adjusted to 6.10. The method was validated, and a limit of quantitation of 0.05% for the impurity was estimated.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background:Dilated cardiomyopathy (DCM) is an important cause of heart failure and cardiac transplantation. This study determined the prevalence of DCM-associated genes and evaluated the ...genotype-phenotype correlation in Vietnamese patients.Methods and Results:This study analyzed 58 genes from 230 patients. The study cohort consisted of 64.3% men; age at diagnosis 47.9±13.7 years; familial (10.9%) and sporadic DCM (82.2%). The diagnostic yield was 23.5%, 44.0% in familial and 19.6% in sporadic DCM.TTNtruncating variants (TTNtv) were predominant (46.4%), followed byTPM1,DSP,LMNA,MYBPC3,MYH6,MYH7,DES,TNNT2,ACTC1,ACTN2,BAG3,DMD,FKTN,PLN,TBX5,RBM20,TCAP(2–6%). Familial DCM, genotype-positive andTTNtv-positive patients were younger than those with genotype-negative and sporadic DCM. Genotype-positive patients displayed a decreased systolic blood pressure and left ventricular wall thickness compared to genotype-negative patients. Genotype-positive patients, particularly those withTTNtv, had a family history of DCM, higher left atrial volume index and body mass index, and lower right ventricle-fractional area change than genotype-negative patients. Genotype-positive patients reached the combined outcomes more frequently and at a younger age than genotype-negative patients. Major cardiac events occurred more frequently in patients positive with genes other thanTTNtv.Conclusions:The study findings provided an overview of Vietnamese DCM patients’ genetic profile and suggested that management of environmental factors may be beneficial for DCM patients.
Background:Hypertrophic cardiomyopathy (HCM) is associated primarily with pathogenic mutations in sarcomeric genes. The aim of this study was to identify the prevalence and distribution of ...disease-causing mutations in HCM-associated genes and the genotype-phenotype relationship in Vietnamese patients with HCM.Methods and Results:Genetic testing was performed by next-generation sequencing in 104 unrelated probands for 23 HCM-related genes and in 57 family members for the mutation(s) detected. Clinical manifestations were recorded for genotype-phenotype correlation analysis. Mutation detection rate was 43.4%. Mutations inMYBPC3accounted for 38.6%, followed byTPM1(20.5%),MYH7(18.2%),TNNT2(9.1%),TNNI3(4.5%) andMYL2(2.3%). A mutation inGLAassociated with Fabry disease was found in 1 patient. A mutation inTPM1(c.842T>C, p.Met281Thr) was identified in 8 unrelated probands (18.2%) and 8 family members from 5 probands. Genotype-positive status related toMYH7,TPM1, andTNNT2mutations was associated with severe clinical manifestations.MYH7-positive patients displayed worse prognosis compared withMYBPC3-positive patients. Interestingly,TPM1c.842T>C mutation was associated with high penetrance and severe HCM phenotype.Conclusions:We report for the first time the prevalence of HCM-related gene variants in Vietnamese patients with HCM.MYH7,TPM1, andTNNT2mutations were associated with unfavorable prognosis.
Infection with Helicobacter pylori is the strongest known risk factor for gastric cancer, which is one of the leading causes of cancer-related mortality worldwide. H. pylori can contribute to ...carcinogenesis by inducing the genomic instability of infected cells through increasing accumulation of DNA double-stranded breaks (DSBs) and deregulating DSB repair systems. However, the mechanism of this phenomenon is still being elucidated. This study aims to investigate the impact of H. pylori on the efficacy of non-homologous end joining (NHEJ)-mediated repair of DSB. In this study, we used a human fibroblast cell line bearing a single copy of an NHEJ-reporter substrate stably inserted into the genome, which provides a quantitative measurement of NHEJ. Our results indicated the potential abilities of H. pylori strains to alter the NHEJ-mediated repair of proximal DSB in infected cells. In addition, we found an association between the alteration in the NHEJ efficiency, and the inflammation responses of infected cells caused by H. pylori.
•Apply an NHEJ-reporter substrate-bearing cell line to quantitatively measure of NHEJ efficiency in H. pylori-infected cells.•H. pylori infection alters the NHEJ-mediated repair of proximal DSB in infected cells.•There is an association between the alteration in the NHEJ efficiency and the inflammation responses of infected cells.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A new geranylated coumarin, (E)-4-(1-hydroxypropyl)-5,7-dihydroxy-6-(3,7-dimethyl-2,6-octadienyl)-8-(3-methyl-1-oxobutyl)coumarin (named surangin D), was isolated from the bark of Mammea siamensis ...collected in Vietnam, along with four known coumarins, surangins B and C, and theraphins B and C, and seven xanthones, 1,7-dihydroxyxanthone, 7-hydroxy-1-methoxyxanthone, 1,7-dimethoxyxanthone, 1,7-dimethoxy-6-hydroxyxanthone, 1,6,7-trihydroxyxanthone, 1,3,7-trihydroxyxanthone, and 1,7-dihydroxy-3-methoxyxanthone. Their structures were determined by spectroscopic methods (mainly 1D- and 2D-NMR) and preparation of methylated derivatives. The four coumarins, surangins C and D and theraphins B and C, were tested for inhibition of cell proliferation in DLD-1 (colon cancer), MCF-7 (breast adenocarcinoma), HeLa (human cervical cancer) and NCI-H460 (human lung cancer) cell lines using the sulforhodamine B (SRB) assay. In all four cell lines, theraphin C showed the strongest activity (IC50 in the range of 1.6—5.7 μM). Testing the anti-proliferative effect of the methylated derivatives showed reduced cellular effects of all derivatives, indicating that the number and position of free hydroxyl groups were very important for the anti-proliferative effect.
Background The burden of Helicobacter pylori-induced gastric cancer varies based on predominant H. pylori population in various geographical regions. Vietnam is a high H. pylori burden country with ...the highest age-standardized incidence rate of gastric cancer (16.3 cases/100,000 for both sexes) in Southeast Asia, despite this data on the H. pylori population is scanty. We examined the global context of the endemic H. pylori population in Vietnam and present a contextual and comparative genomics analysis of 83 H. pylori isolates from patients in Vietnam. Results There are at least two major H. pylori populations are circulating in symptomatic Vietnamese patients. The majority of the isolates (~ 80%, 66/83) belong to the hspEastAsia and the remaining belong to hpEurope population (~ 20%, 17/83). In total, 66 isolates (66/83) were cagA positive, 64 were hspEastAsia isolates and two were hpEurope isolates. Examination of the second repeat region revealed that most of the cagA genes were ABD type (63/66; 61 were hspEastAsia isolates and two were hpEurope isolates). The remaining three isolates (all from hspEastAsia isolates) were ABC or ABCC types. We also detected that 4.5% (3/66) cagA gene from hspEastAsia isolates contained EPIYA-like sequences, ESIYA at EPIYA-B segments. Analysis of the vacA allelic type revealed 98.8% (82/83) and 41% (34/83) of the strains harboured the s1 and m1 allelic variant, respectively; 34/83 carried both s1m1 alleles. The most frequent genotypes among the cagA positive isolates were vacA s1m1/cagA + and vacA s1m2/cagA + , accounting for 51.5% (34/66) and 48.5% (32/66) of the isolates, respectively. Conclusions There are two predominant lineages of H. pylori circulating in Vietnam; most of the isolates belong to the hspEastAsia population. The hpEurope population is further divided into two smaller clusters. Keywords: H. pylori, Vietnam, Molecular epidemiology
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This study deployed ultrasonic-assisted extraction (UAE), combined with natural deep eutectic solvents (NADES), to extract phenolics and flavonoids from the black mulberry fruit, and the antioxidant ...activity was examined. The extraction yields of NADES-based UAE were assessed based on the yields of phenolics and flavonoids extracted from the black mulberry fruit. This study selected the molar ratios of hydrogen bond acceptors (HBA) and hydrogen bond donors HBD at 1:2 from previous studies. Choline chloride-lactic acid showed the highest solubility with phenolics and flavonoids among NADES systems. One-factor experiments evaluated the effect of UAE conditions (liquid-to-solid ratio (LSR), water content in NADES, temperature, and time) on TPC, TFC, and antioxidant activity. The suitable NADES-based UAE conditions for extracting phenolics and flavonoids from the black mulberry fruit were 60 ml/g of LSR, 40% water content, 70 °C, and 15 min. Response surface methodology with the Box-Behnken design model optimized the NADES-based UAE process based on response (TPC, TFC, ABTS, OH, and DPPH). The optimal conditions for the NADES-based UAE process were 70 ml/g of LSR, 38.9% water content in NADES, 67.9 °C, and 24.2 min of extraction time. The predicted values of the Box-Behnken design were compatible with the experimental results. Moreover, scanning electron microscopy (SEM) was used to survey the surface of black mulberry fruit with and without sonication. SEM can assist in demonstrating the destructive effect of NADES and ultrasonic waves on material surfaces. SEM findings indicated the high surface destruction capacity of NADES, which partially contributed to a superior extraction yield of NADES than conventional organic solvents. The study proposes an efficient and green method for extracting bioactive compounds from black mulberry fruits. The black mulberry fruit extracts can be applied to meat preservation and beverages with high antioxidants.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Amoxicillin-resistant Helicobacter pylori (H. pylori) strains seem to have increased over time in Vietnam. This threatens the effectiveness of H. pylori eradication therapies with this antibiotic. ...This study aimed to investigate the prevalence of primary resistance of H. pylori to amoxicillin and to assess its association with pbp1A point mutations in Vietnamese patients.
Naive patients who presented with dyspepsia undergoing upper gastrointestinal endoscopy were recruited. Rapid urease tests and PCR assays were used to diagnose H. pylori infection. Amoxicillin susceptibility was examined by E-tests. Molecular detection of the mutant pbp1A gene conferring amoxicillin resistance was carried out by real-time PCR followed by direct sequencing of the PCR products. Phylogenetic analyses were performed using the Tamura-Nei genetic distance model and the neighbor-joining tree building method.
There were 308 patients (46.1% men and 53.9% women, p = 0.190) with H. pylori infection. The mean age of the patients was 40.5 ± 11.4 years, ranging from 18 to 74 years old. The E-test was used to determine the susceptibility to amoxicillin (minimum inhibitory concentration (MIC) ≤ 0.125 μg/ml) in 101 isolates, among which the rate of primarily resistant strains to amoxicillin was 25.7%. Then, 270 sequences of pbp1A gene fragments were analysed. There were 77 amino acid substitution positions investigated, spanning amino acids 310-596, with the proportion varying from 0.4 to 100%. Seven amino acid changes were significantly different between amoxicillin-sensitive (Amox
) and amoxicillin-resistant (Amox
) samples, including Phe
to Leu (p < 0.001), Ser
to Arg (p < 0.001), Glu/Asn
(p = 0.009), Val
to Met (p = 0.021), Phe
to Val (p < 0.001), Asp
to Glu (p = 0.044), and Ser/Ala/Gly
(p = 0.001). Phylogenetic analyses suggested that other molecular mechanisms might contribute to amoxicillin resistance in H. pylori in addition to the alterations in PBP1A.
We reported the emergence of amoxicillin-resistant Helicobacter pylori strains in Vietnam and new mutations statistically associated with this antimicrobial resistance. Additional studies are necessary to identify the mechanisms contributing to this resistance in Vietnam.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Obesity and associated liver disease are a growing public health concern. Pharmacological agents to treat non-alcoholic fatty liver disease are limited. FGF21, a hormone secreted by the liver and ...potent metabolic modulator, is a promising therapeutic target for this indication with several analogs currently in clinical development. However, concerns about a negative effect of FGF21 on female fertility have not been fully addressed.
After induction of obesity, female C57BL/6N mice received a 7-day course of subcutaneously administered FGF21. Control groups received either high-fat diet (HFD) or a normal diet (ND). The mothers were then mated with lean males for 12 weeks. The estrous cycle was recorded for two weeks after breeding. The metabolic phenotype, liver steatosis and reproductive organs were assessed at sacrifice 14 weeks after treatment.
A short-course treatment of FGF21 leads to weight reduction during treatment but has no long-term impact on liver steatosis. A treatment with FGF21 leads to a reduction in the number of pregnancies (0 vs 1, p = 0.019) and no viable pup was born to a mother previously treated with FGF21. The FGF21 treatment affected the number of cycles (1 vs 3, p = 0.048) and amount in diestrus (54 vs 75%, p = 0.008) 12 weeks after the treatment. Additionally, the number of corpora lutea (0.8 vs 3.0, p = 0.016), and mature follicles (0 vs 1, p = 0.037) was reduced compared to the ND group while uterine histology remained unaffected.
A short-term treatment with FGF21 has a long-term effect on female fertility in mice. This represents a potential safety concern for FGF21 analogs currently in clinical development. Reproductive health outcomes should be included in upcoming clinical trials.
FGF21; Fertility; Non-alcoholic fatty liver disease; High-fat diet.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This research combined ultrasonic-assisted extraction (UAE) and natural deep eutectic solvent (NADES) to recover phenolic and flavonoid components from mangosteen rind. The antioxidant activities ...were determined using DPPH, ABTS+, and hydroxyl assays. NADES prepared from lactic and 1,2–propanediol had the highest extraction efficiency based on the total flavonoid content (TFC) and phenolic contents (TPC). Single-factor experiments were employed to assess the influence of UAE conditions (liquid-to-solid ratio, temperature, water content in NADES, and time) on TFC, TPC, and antioxidant activities. NADES-based UAE conditions were optimized using response surface methodology with the Box-Behnken design model on five dependent responses (TPC, TFC, DPPH, ABTS, and OH). The optimal conditions for the lactic-1,2–Propanediol-based UAE process were 76.7 ml liquid/g solid with 30.3% of water content at 57.5 °C for 9.1 min. Scanning electron microscopy (SEM) was applied to examine the surface morphology of mangosteen rind before and after sonication. This study proposes an efficient, green, and practical approach for recovering phenolics and flavonoids from mangosteen rinds.
Display omitted
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
