Design and synthesis of novel ß-carboline-bisindole hybrids as potential anticancer agents.

We are reporting a short and convenient pathway for the synthesis of novel ß-carboline-bisindole hybrid compounds from relatively cheap and commercially available chemicals such as tryptamine, dialdehydes and indoles. These newly designed compounds can also be prepared in high yields with the tolerance of many functional groups under mild conditions. Notably, these ß-carboline-bisindole hybrid compounds exhibited some promising applications as anticancer agents against the three common cancer cell lines MCF-7 (breast cancer), SK-LU-1 (lung cancer), and HepG2 (liver cancer). The two best compounds 5b and 5g inhibited the aforementioned cell lines with the same range of the reference Ellipticine at less than 2 µM. A molecular docking study to gain more information about the interactions between the synthesized molecules and the kinase domain of the EGFR was performed. Therefore, this finding can have significant impacts on the development of future research in medicinal chemistry and drug discovery.

Outcome and toxicity of chemoradiation using volumetric modulated arc therapy followed by 3D image-guided brachytherapy for cervical cancer: Vietnam National Cancer Hospital experience.

Background: Volumetric modulated arc therapy (VMAT) and 3D image-guided brachytherapy (3D-IGBT) have recently been introduced in Vietnam for the treatment of locally advanced cervical cancer. This study aims to assess the outcomes and toxicities of chemoradiation using VMAT followed by 3D-IGBT in Vietnamese cervical cancer patients. Materials and methods: A prospective interventional study on 72 patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB3-IIIC2 disease who underwent concurrent chemoradiation using VMAT, followed by 3D-IGBT according to EMBRACE-II protocol. Primary endpoints were locoregional control; secondary endpoints were systemic control and toxicity. Results: Median body volume received 43 Gy was 1589.1 cm3 (range 1214.8-2574.8). Median high-risk clinical target volume (CTV-HR) was 18.8 cm3 (range 8.6-61.2) with a median dose to 90% (D90) of CTV-HR of 90.6 Gy (range 86.8-99.6). Mean doses to 2cc (D2cc) of bladder, rectum, and sigmoid were 75.8, 55.2, and 62.1 Gy, respectively. At median 19-month follow-up (range 12-25), locoregional control and systemic control were 95.8% and 81.9%, respectively. Systemic control was the lowest in N2 disease (54.5%). Grade ≥ 3 acute toxicities were less than 10%, except neutropenia (31.9%). Extended-field radiation increased significantly nausea, fatigue, and thrombocytopenia. No grade ≥ 3 proctitis or cystitis; 8.3% had grade 3 vaginal stenosis. Conclusions: VMAT-based chemoradiation therapy followed by 3D-IGBT achieved high locoregional control with manageable toxicities in locally advanced cervical cancer. Systemic control correlated with disease stage.

Genome-Wide Identification and Analysis of Genes Encoding Putative Heat Shock Protein 70 in Papaya (Carica papaya).

<b>Background and Objective:</b> In high plants, the 70 kDa heat stress proteins (Hsp70-s) have been regarded as one of the vital components of the cellular network of chaperones and folding catalysts that play important roles in numerous biological processes during growth and development. The Hsp70 families have been reported in many plant species, unfortunately, no information on this important protein family in papaya (<i>Carica papaya</i>). The objective of this study was to provide comprehensive information on the CpHsp70 family in papaya. <b>Materials and Methods:</b> The <i>CpHsp70</i> genes in the papaya genome were identified by a basic local alignment search tool against the papaya genome database by using well-known <i>Arabidopsis</i> Hsp70-s. Sequences were then analyzed by various bioinformatics tools to investigate the characteristics of the CpHsp70 family. <b>Results:</b> A total of 12 members of the CpHsp70 family has been identified and characterized in papaya. By using various computational tools, these results revealed that all general characteristics of the CpHsp70 family, like physic-chemical parameters, gene structure, phylogenetic tree and subcellular localization were provided. The transcriptome atlas was applied to re-analyze the expression patterns of genes encoding the CpHsp70 family in major tissues/organs during the growth and development of papaya plants. <b>Conclusion:</b> Results from this work exhibited the characteristics and expression analysis of the <i>CpHsp70</i> genes of this important tropical fruit crop. Taken together, this study could provide a solid foundation of the CpHsp70 family, which will be helpful in the construction of stress tolerance in papaya plants.

SWEET Gene Family in Sugar Beet (Beta vulgaris): Genome-Wide Survey, Phylogeny and Expression Analysis.

<b>Background and Objective:</b> The SWEET (Sugars Will Eventually be Exported Transporter) proteins play important roles in modulating the growth and development processes in plants. However, little information is available on the SWEET family in sugar beet (<i>Beta vulgaris</i>). The objectives of this present study were to genome-wide identify and characterize the BvSWEET family in sugar beet. <b>Materials and Methods:</b> Based on the available genome, proteome and transcriptome databases of sugar beet, various computational tools have been used to analyze the nucleotide and full-length protein sequences of members of the BvSWEET family. <b>Results:</b> A total of 16 members of the BvSWEET family has been identified in sugar beet at the genome-wide scale. Structural analysis indicated that the BvSWEET family exhibited variable characteristics. Furthermore, the BvSWEET family in sugar beet could be categorized into four distinct groups like in other plant species. Of our interest, we found that some <i>BvSWEET</i> genes exhibited strongly preferential expression in major organs/tissues under adverse environmental stimuli. <b>Conclusion:</b> The results provided a comprehensive foundation for further functional characterization of the <i>BvSWEET </i>gene family.

Effect of NPK-SRFS on the Growth, Yield and Essential Oil Composition of Basil (Ocimum basilicum L.).

<b>Background and Objective:</b> Basil (<i>Ocimum basilicum</i> L.), an aromatic herb, is considered one of the most important crops with essential oils as well as other bioactive compounds. Basil leaves have tremendous pharmaceutical benefits and are used for foods. Slow-release fertilizers have been developed to optimize the fertilization of crops. This work aims to discover the effect of NPK Slow-Release Fertilizer Coated by Starch (NPK-SRFS) at different rates on growth, yield and essential oil components of basil grown on the field in Northern Vietnam. <b>Materials and Methods:</b> Basil seedlings, sown from seeds, were used as plant materials. NPK-SRFS was stocked in the Faculty of Chemistry, Hanoi Pedagogical University 2. The experiments were designed in a fully randomized block model, consisting of four treatments with different rates of NPK-SRFS. Each treatment had three replicates with an area of 8 m². Duncan's Multiple Range Test was being used for statistical analysis (p = 0.05). <b>Results:</b> All 3 NPK-SRFS treatments significantly increased the number of buds and leaves per plant compared to the control. However, NPK-SRFS at different rates affected diversely plant height and leaf area of the basil. F5.0 and F10 treatments accelerated chlorophyll content as well as Fv/Fm value in comparison with none NPK-SRFS treatment. The application of NPK-SRFS at different rates caused slightly different changes in basil essential oil composition, especially the content of Methyl Chavicol, the most abundant oxygenated monoterpene and α-trans-Bergamotene, the most abundant sesquiterpene hydrocarbon. <b>Conclusion:</b> The present study provides further insight into the influence of NPK-SRFS on the growth, yield and essential oil components of basil.

Molecular surveillance and temporal monitoring of malaria parasites in focal Vietnamese provinces.

BACKGROUND: While the World Health Organization (WHO) Southeast Asia region has the second highest incidence of malaria worldwide, malaria in Vietnam is focal to few provinces, where delayed parasite clearance to anti-malarial drugs is documented. This study aims to understand Plasmodium species distribution and the genetic diversity of msp1 and msp2 of parasite populations using molecular tools. METHODS: A total of 222 clinical isolates from individuals with uncomplicated malaria were subjected to Plasmodium species identification by nested real-time PCR. 166 isolates positive for Plasmodium falciparum mono infections were further genotyped for msp1 (MAD20, K1, and RO33), and msp2 allelic families (3D7 and FC27). Amplicons were resolved through capillary electrophoresis in the QIAxcel Advanced system. RESULTS: Mono-infections were high and with 75% P. falciparum, 14% Plasmodium vivax and 9% P. falciparum/P. vivax co-infections, with less than 1% Plasmodium malariae identified. For msp1, MAD20 was the most prevalent (99%), followed by K1 (46%) allelic family, with no sample testing positive for RO33 (0%). For msp2, 3D7 allelic family was predominant (97%), followed by FC27 (10%). The multiplicity of infection of msp1 and msp2 was 2.6 and 1.1, respectively, and the mean overall multiplicity of infection was 3.7, with the total number of alleles ranging from 1 to 7. CONCLUSIONS: Given the increasing importance of antimalarial drugs in the region, the genetic diversity of P. falciparum msp1 and msp2 should be regularly monitored with respect to treatment outcomes and/or efficacy studies in regions, where there are ongoing changes in the malaria epidemiology.

Diagnostic Function of 3-Tesla Magnetic Resonance Imaging for the Assessment of Brachial Plexus Injury.

BACKGROUND: This study aimed to evaluate the diagnostic function of 3-Tesla (T) magnetic resonance imaging (MRI) during the assessment of brachial plexus injury (BPI), in comparison with intraoperative findings. METHODS: A retrospective study was performed on 60 patients (47 men and 13 women), who had clinical manifestations of BPI, underwent 3T MRI of the brachial plexus, and were surgically treated at the Viet Duc and Vinmec Times City hospitals, in Hanoi, Vietnam, from March 2016 to December 2019. Preganglionic and postganglionic lesion features were identified on MRI. The diagnostic function of MRI features for the determination of BPI was evaluated and correlated with intraoperative findings. RESULTS: The root avulsion and pseudomeningocele preganglionic injuries were observed in 57% and 43% of MRIs, respectively, and were commonly observed at the C7 and C8 roots. Nerve disruption and never edema were observed in 47.56% and 33.53% of MRIs, respectively, and were commonly observed at the C5 and C6 roots. The sensitivity, specificity, accuracy, positive prognostic value, and negative prognostic value of 3T MRI were 64.12%, 92.90%, 80.33%, 87.50%, and 76.96%, respectively, for the diagnosis of total avulsion, and 68.52%, 83.33%, 80.67%, 47.44%, and 92.34%, respectively, for the diagnosis of nerve disruption. CONCLUSION: MRI offers valuable details regarding the location, morphology, and severity of both preganglionic and postganglionic injuries during the preoperative diagnosis of BPI. However, this modality played a moderate diagnostic role. Therefore, 3T MRI should be used as a supplemental evaluation, coupled with clinical tests and electromyography, to determine the most appropriate treatment strategies for BPI patients.

Enhanced Photocatalytic Activity of {110}-Faceted TiO2 Rutile Nanorods in the Photodegradation of Hazardous Pharmaceuticals.

Rutile TiO2 with highly active facets has attracted much attention owing to its enhanced activity during the photocatalytic degradation of pollutants such as pharmaceuticals in wastewater. However, it is difficult to obtain by controlling the synthetic conditions. This paper reports a simple hydrothermal synthesis of rutile TiO2 nanorods with highly exposed {110} facets. The obtained rutile was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM), and Raman spectroscopy. The main contribution to the photocatalytic activity comes from rutile nanorods with highly dominant active {110} facets, which were studied in the photodegradation of reactive cinnamic acid and more recalcitrant ibuprofen. The contribution of active species was also investigated. The present work further confirmed the hydrothermal synthesis route for controlling the preparation of highly crystalline and active rutile nanocrystals.

Clinical utility of an optimised multiplex real-time PCR assay for the identification of pathogens causing sepsis in Vietnamese patients.

INTRODUCTION: For the identification of bacterial pathogens, blood culture is still the gold standard diagnostic method. However, several disadvantages apply to blood cultures, such as time and rather large volumes of blood sample required. We have previously established an optimised multiplex real-time PCR method in order to diagnose bloodstream infections. MATERIAL AND METHODS: In the present study, we evaluated the diagnostic performance of this optimised multiplex RT-PCR in blood samples collected from 110 septicaemia patients enrolled at the 108 Military Central Hospital, Hanoi, Vietnam. RESULTS: Positive results were obtained by blood culture, the Light Cylcler-based SeptiFast® assay and our multiplex RT-PCR in 35 (32%), 31 (28%), and 31 (28%) samples, respectively. Combined use of the three methods confirmed 50 (45.5%) positive cases of bloodstream infection, a rate significantly higher compared to the exclusive use of one of the three methods (P=0.052, 0.012 and 0.012, respectively). The sensitivity, specificity and area under the curve (AUC) of our assay were higher compared to that of the SeptiFast® assay (77.4%, 86.1% and 0.8 vs. 67.7%, 82.3% and 0.73, respectively). Combined use of blood culture and multiplex RT-PCR assay showed a superior diagnostic performance, as the sensitivity, specificity, and AUC reached 83.3%, 100%, and 0.95, respectively. The concordance between blood culture and the multiplex RT-PCR assay was highest for Klebsiella pneumonia (100%), followed by Streptococcus spp. (77.8%), Escherichia coli (66.7%), Staphylococcus spp. (50%) and Salmonella spp. (50%). In addition, the use of the newly established multiplex RT-PCR assay increased the spectrum of identifiable agents (Acintobacter baumannii, 1/32; Proteus mirabilis, 1/32). CONCLUSION: The combination of culture and the multiplex RT-PCR assay provided an excellent diagnostic accomplishment and significantly supported the identification of causative pathogens in clinical samples obtained from septic patients.

Enrichment of bacterial DNA for the diagnosis of blood stream infections.

BACKGROUND: Blood cultures are commonly employed to identify bacterial pathogens causing sepsis. PCR assays to diagnose septicemia require extraction of bacterial DNA from blood samples and thus, delay the initiation of appropriate antimicrobial treatment. The presence of abundant human DNA may hamper the sensitivity of PCR in the detection of bacteria. METHODS: We used serial dilutions of E. Coli spiked pseudo-blood-sepsis samples to develop a simple method that combines the use of a polar detergent solvent and adjustment of the basic pH to remove human DNA. A 16S rRNA gene-based screening algorithm was established to differentiate Gram-positive and Gram-negative groups of bacteria and the family of Enterobacteriaceae. A stringent validation with appropriate controls was implemented. The method of human DNA removal was then applied on 194 sepsis blood samples and 44 cerebrospinal fluid (CSF) samples by real-time PCR. RESULTS: This uncomplicated and straightforward approach allows to remove up to 98 % of human DNA from peripheral blood of septic patients. The inhibitory effect of human DNA is efficiently prevented and the detection limit of real-time PCR is increased to 10 E. Coli CFUs/ml. This sensitivity is 10 times higher compared to conventional real-time PCR assays. The classical blood culture detected 58/194 (30 %) of sepsis and 9/44 (21 %) of CSF samples. Out of the 194 blood samples tested, the conventional real-time PCR targeting 13 common sepsis causing pathogens correctly detected the bacterial DNA in 16/194 (8 %) only and 14/44 (32 %) in cerebrospinal fluid samples. Our newly established approach was able to provide correct diagnoses in 78 (40 %) of the 194 blood samples and in 14 (32 %) of the CSF samples. The combination of both blood cultures and our technique raised the rate of sepsis diagnoses to 112/194 (58 %). Of the total group tested positive, 46 (24 %) cases showed overlap with the classical methodology. CONCLUSION: We report a simple optimized in-house protocol for removal of human DNA from blood sepsis samples as a pre-analytical tool to prepare DNA for subsequent PCR assays. With the detection increase of our in-house DNA removal approach, subsequent PCR assays can reach detection limits of 10 E. coli CFUs/ml and significantly improve the diagnostic rate in blood sepsis cases.

Simple multiplex PCR assays to detect common pathogens and associated genes encoding for acquired extended spectrum betalactamases (ESBL) or carbapenemases from surgical site specimens in Vietnam.

UNLABELLED: Surgical site infection (SSI) is common in Vietnamese post-operative patients. It contributes to increased morbidity, mortality, hospitalization time and health care expenditure. Bacterial culture is considered the gold standard procedure to identify SSI pathogens and antibiotic resistant properties; however, it can detect microbes that can readily grow and is time-consuming. We propose optimized multiplex PCR assays to diagnose the most relevant microbes and associated genes encoding for acquired extended spectrum betalactamases (ESBL) or carbapenemases from Vietnamese patients with SSI in a hospital setting in Hanoi. METHODS: Ninety-one patients (n = 91) were collected in order to identify microbial pathogens and associated genes encoding for acquired extended spectrum betalactamases (ESBL) or carbapenemases by both conventional bacterial culture and in-house multiplex PCR assays. RESULT AND CONCLUSION: The novel in-house multiplex PCR assays are comparable to the bacterial culture approach in screening for common pathogens causing SSI and for relevant genotypes conferring betalactam/carbapenem resistance for bacteria. This is the first report of Turkey-specific ESBL gene (PER-1) and two Oxacilinase families (Oxa23 and Oxa 58) in Vietnam.

S-bacillithiolation protects conserved and essential proteins against hypochlorite stress in firmicutes bacteria.

AIMS: Protein S-bacillithiolations are mixed disulfides between protein thiols and the bacillithiol (BSH) redox buffer that occur in response to NaOCl in Bacillus subtilis. We used BSH-specific immunoblots, shotgun liquid chromatography (LC)-tandem mass spectrometry (MS/MS) analysis and redox proteomics to characterize the S-bacillithiolomes of B. subtilis, B. megaterium, B. pumilus, B. amyloliquefaciens, and Staphylococcus carnosus and also measured the BSH/oxidized bacillithiol disulfide (BSSB) redox ratio after NaOCl stress. RESULTS: In total, 54 proteins with characteristic S-bacillithiolation (SSB) sites were identified, including 29 unique proteins and eight proteins conserved in two or more of these bacteria. The methionine synthase MetE is the most abundant S-bacillithiolated protein in Bacillus species after NaOCl exposure. Further, S-bacillithiolated proteins include the translation elongation factor EF-Tu and aminoacyl-tRNA synthetases (ThrS), the DnaK and GrpE chaperones, the two-Cys peroxiredoxin YkuU, the ferredoxin-NADP(+) oxidoreductase YumC, the inorganic pyrophosphatase PpaC, the inosine-5'-monophosphate dehydrogenase GuaB, proteins involved in thiamine biosynthesis (ThiG and ThiM), queuosine biosynthesis (QueF), biosynthesis of aromatic amino acids (AroA and AroE), serine (SerA), branched-chain amino acids (YwaA), and homocysteine (LuxS and MetI). The thioredoxin-like proteins, YphP and YtxJ, are S-bacillithiolated at their active sites, suggesting a function in the de-bacillithiolation process. S-bacillithiolation is accompanied by a two-fold increase in the BSSB level and a decrease in the BSH/BSSB redox ratio in B. subtilis. INNOVATION: Many essential and conserved proteins, including the dominant MetE, were identified in the S-bacillithiolome of different Bacillus species and S. carnosus using shotgun-LC-MS/MS analyses. CONCLUSION: S-bacillithiolation is a widespread redox control mechanism among Firmicutes bacteria that protects conserved metabolic enzymes and essential proteins against overoxidation.

Inhibition of acetyl phosphate-dependent transcription by an acetylatable lysine on RNA polymerase.

The ability of bacteria to adapt to environmental changes has allowed these organisms to thrive in all parts of the globe. By monitoring their extracellular and intracellular environments, bacteria assure their most appropriate response for each environment. Post-translational modification of proteins is one mechanism by which cells respond to their changing environments. Here, we report that two post-translational modifications regulate transcription of the extracytoplasmic stress-responsive promoter cpxP: (i) acetyl phosphate-dependent phosphorylation of the response regulator CpxR and (ii) acetyl coenzyme A-dependent acetylation of the α subunit of RNA polymerase. Together, these two post-translational modifications fine-tune cpxP transcription in response to changes in the intracellular environment.