Phenyl glycosides from Bacopa monnieri with their antioxidant and anti-inflammatory activities.

Bacopa monnieri (L.) Wettst (Plantaginaceae), is traditionally used in many countries as neural tonic and memory enhancer, or to relieve acute pain and inflammation. This study described the isolation and identification of one new, bacomoside D3 (1), and seven known phenyl glycosides (2 - 8). The structures of isolates were established by analysis of their spectroscopic data or hydrolysis followed by HPLC analysis together with a comparison to those reported in the literature. These compounds were evaluated for antioxidant and anti-inflammatory activities. Among them, compounds 4 and 5 exhibited strong DPPH radical scavenging activity with IC50 values of 9.77 ± 0.08 and 3.50 ± 0.04 µM, respectively. Compounds 2 and 5 significantly inhibited TNF-α production in LPS-stimulated RAW264.7 cells with IC50 values of 40.60 ± 3.05 and 38.19 ± 1.75 µM, respectively. Furthermore, the active compounds could be efficient inhibitors of oxidants by interfering with the DPPH activity in silico study.

Mutation spectrum of retinoblastoma patients in Vietnam.

BACKGROUND: Retinoblastoma (RB), an intraocular malignancy commonly diagnosed in children, is mostly caused by inactivating mutations of both alleles of the RB1 gene. Early genetic screening for RB1 gene mutations would greatly improve treatment outcomes and patient management. METHODS: In this study, both somatic and germline mutations were detected in blood and tumour samples of 42 RB patients using direct sequencing and multiplex ligation-dependent probe amplification. RESULTS: In total, 34 different mutations were found in 36 patients, including 1 SNP, 4 large deletions, 5 splicing sites, 1 missense, 7 frameshifts and 17 nonsense mutations. There were five novel mutations and one unreported which have not been found in large databases such as Leiden Open Variation Database (LOVD) and ClinVar. CONCLUSION: A higher rate of RB patients carrying heterozygous germline mutation and highly prevalent with pathogenic truncated mutation, hence, early detection of RB is essential for vision salvation and genetic counselling.

Repurposing thioridazine for inducing immunogenic cell death in colorectal cancer via eIF2α/ATF4/CHOP and secretory autophagy pathways.

BACKGROUND: Colorectal cancer (CRC) is a highly prevalent cancer type with limited targeted therapies available and 5-year survival rate, particularly for late-stage patients. There have been numerous attempts to repurpose drugs to tackle this problem. It has been reported that autophagy inducers could augment the effect of certain chemotherapeutic agents by enhancing immunogenic cell death (ICD). METHODS: In this study, we employed bioinformatics tools to identify thioridazine (THD), an antipsychotic drug, and found that it could induce autophagy and ICD in CRC. Then in vitro and in vivo experiments were performed to further elucidate the molecular mechanism of THD in CRC. RESULTS: THD was found to induce endoplasmic reticulum (ER) stress in CRC cells by activating the eIF2α/ATF4/CHOP axis and facilitating the accumulation of secretory autophagosomes, leading to ICD. In addition, THD showed a remarkable ICD-activating effect when combined with oxaliplatin (OXA) to prevent tumor progression in the mouse model. CONCLUSIONS: Together, our findings suggest that the repurposed function of THD in inhibiting CRC involves the upregulation of autophagosomes and ER stress signals, promoting the release of ICD markers, and providing a potential candidate to enhance the clinical outcome for CRC treatment. Video Abstract.

Hybrid Electrolyte Design for High-Performance Zinc-Sulfur Battery.

Rechargeable aqueous Zn/S batteries exhibit high capacity and energy density. However, the long-term battery performance is bottlenecked by the sulfur side reactions and serious Zn anode dendritic growth in the aqueous electrolyte medium. This work addresses the problem of sulfur side reactions and zinc dendrite growth simultaneously by developing a unique hybrid aqueous electrolyte using ethylene glycol as a co-solvent. The designed hybrid electrolyte enables the fabricated Zn/S battery to deliver an unprecedented capacity of 1435 mAh g-1 and an excellent energy density of 730 Wh kg-1 at 0.1 Ag-1 . In addition, the battery exhibits capacity retention of 70% after 250 cycles even at 3 Ag-1 . Moreover, the cathode charge-discharge mechanism studies demonstrate a multi-step conversion reaction. During discharge, the elemental sulfur is sequentially reduced by Zn to S2- ( S 8 → S x 2 - → S 2 2 - + S 2 - ) ${{\rm{S}}_8}{\bm{ \to }}{\rm{S}}_{\rm{x}}^{2{\bm{ - }}}{\bm{ \to }}{\rm{S}}_2^{2{\bm{ - }}}{\bm{ + }}{{\rm{S}}^{2{\bm{ - }}}})$ , forming ZnS. On charging, the ZnS and short-chain polysulfides will oxidize back to elemental sulfur. This electrolyte design strategy and unique multi-step electrochemistry of the Zn/S system provide a new pathway in tackling both key issues of Zn dendritic growth and sulfur side reactions, and also in designing better Zn/S batteries in the future.

BMX, a specific HDAC8 inhibitor, with TMZ for advanced CRC therapy: a novel synergic effect to elicit p53-, ß-catenin- and MGMT-dependent apoptotic cell death.

BACKGROUND: Despite advances in treatment, patients with refractory colorectal cancer (CRC) still have poor long-term survival, so there is a need for more effective therapeutic options. METHODS: To evaluate the HDAC8 inhibition efficacy as a CRC treatment, we examined the effects of various HDAC8 inhibitors (HDAC8i), including BMX (NBM-T-L-BMX-OS01) in combination with temozolomide (TMZ) or other standard CRC drugs on p53 mutated HT29 cells, as well as wild-type p53 HCT116 and RKO cells. RESULTS: We showed that HDAC8i with TMZ cotreatment resulted in HT29 arrest in the S and G2/M phase, whereas HCT116 and RKO arrest in the G0/G1 phase was accompanied by high sub-G1. Subsequently, this combination approach upregulated p53-mediated MGMT inhibition, leading to apoptosis. Furthermore, we observed the cotreatment also enabled triggering of cell senescence and decreased expression of stem cell biomarkers. Mechanistically, we found down-expression levels of ß-catenin, cyclin D1 and c-Myc via GSK3ß/ß-catenin signaling. Intriguingly, autophagy also contributes to cell death under the opposite status of ß-catenin/p62 axis, suggesting that there exists a negative feedback regulation between Wnt/ß-catenin and autophagy. Consistently, the Gene Set Enrichment Analysis (GSEA) indicated both apoptotic and autophagy biomarkers in HT29 and RKO were upregulated after treating with BMX. CONCLUSIONS: BMX may act as a HDAC8 eraser and in combination with reframed-TMZ generates a remarkable synergic effect, providing a novel therapeutic target for various CRCs. Video Abstract.

Agallochin P, a new diterpene from Vietnamese mangrove Excoecaria agallocha L.

A new diterpene (1) along with eight known compounds (2-9) were isolated from Excoecaria agallocha leaves. The structure and relative configuration of new compound were established on the basis of spectroscopic data analysis and confirmed by NMR chemical shifts calculation with DP4+ probability. Cytotoxicity of the isolated compounds were also evaluated.[Formula: see text].

Graptopetalum paraguayense Extract Ameliorates Proteotoxicity in Aging and Age-Related Diseases in Model Systems.

Declines in physiological functions are the predominant risk factors for age-related diseases, such as cancers and neurodegenerative diseases. Therefore, delaying the aging process is believed to be beneficial in preventing the onset of age-related diseases. Previous studies have demonstrated that Graptopetalum paraguayense (GP) extract inhibits liver cancer cell growth and reduces the pathological phenotypes of Alzheimer's disease (AD) in patient IPS-derived neurons. Here, we show that GP extract suppresses ß-amyloid pathology in SH-SYS5Y-APP695 cells and APP/PS1 mice. Moreover, AMP-activated protein kinase (AMPK) activity is enhanced by GP extract in U87 cells and APP/PS1 mice. Intriguingly, GP extract enhances autophagy in SH-SYS5Y-APP695 cells, U87 cells, and the nematode Caenorhabditis elegans, suggesting a conserved molecular mechanism by which GP extract might regulate autophagy. In agreement with its role as an autophagy activator, GP extract markedly diminishes mobility decline in polyglutamine Q35 mutants and aged wild-type N2 animals in C. elegans. Furthermore, GP extract significantly extends lifespan in C. elegans.

Metastable 1T'-phase group VIB transition metal dichalcogenide crystals.

Metastable 1T'-phase transition metal dichalcogenides (1T'-TMDs) with semi-metallic natures have attracted increasing interest owing to their uniquely distorted structures and fascinating phase-dependent physicochemical properties. However, the synthesis of high-quality metastable 1T'-TMD crystals, especially for the group VIB TMDs, remains a challenge. Here, we report a general synthetic method for the large-scale preparation of metastable 1T'-phase group VIB TMDs, including WS2, WSe2, MoS2, MoSe2, WS2xSe2(1-x) and MoS2xSe2(1-x). We solve the crystal structures of 1T'-WS2, -WSe2, -MoS2 and -MoSe2 with single-crystal X-ray diffraction. The as-prepared 1T'-WS2 exhibits thickness-dependent intrinsic superconductivity, showing critical transition temperatures of 8.6 K for the thickness of 90.1 nm and 5.7 K for the single layer, which we attribute to the high intrinsic carrier concentration and the semi-metallic nature of 1T'-WS2. This synthesis method will allow a more systematic investigation of the intrinsic properties of metastable TMDs.

A novel nested allele-specific PCR protocol for the detection of the HLA-A*33:03, a SCAR-associated allele, in Vietnamese people.

BACKGROUND: Severe cutaneous adverse drug reactions (SCARs) are rare but deadly drug reactions with severe damages to patients. One of the most well-known SCARs risk factors is the human leukocyte antigen (HLA) genes polymorphism. Among the HLA polymorphic alleles, the HLA-A*33:03 allele has been found in association with SCARs induced by various drugs, especially in Asian people. There has not been any report on the specific detection protocol of the HLA-A*33:03 allele. OBJECTIVE: This study aimed to design a nested AS-PCR protocol for detecting and distinguishing diplotype genotype of the HLA-A*33:03 allele. METHODS: A nested allele-specific (AS)-PCR protocol with four primer sets was designed. The method was compared with the Sanger sequencing method on 100 samples of unknown genotypes of unrelated Vietnamese people. RESULTS: The nested AS-PCR method could identify the HLA-A*33:03 allele and the HLA-A*33:03 diplotype genotypes. Comparison with the Sanger sequencing method showed an absolute agreement (κ = 1.00, p < 0.001). The nested ASPCR protocol had a sensitivity of 100% (95%CI: 92.13-100%) and a specificity of 100% (95%CI: 93.51-100%). The protocol was used for the determination of HLA-A*33:03 allele distribution in 810 unrelated Vietnamese Kinh people, showing a frequency of HLA-A*33:03 carriers of 19.6% and an allele frequency of 10.55%. CONCLUSIONS: A novel nested AS-PCR method with a hundred-percent sensitivity and a specificity for the HLA-A*33:03 allele detection was reported. The protocol can be applied for the stratification of patients at SCAR risks with various drugs.

High-Yield Exfoliation of Ultrathin 2D Ni3 Cr2 P2 S9 and Ni3 Cr2 P2 Se9 Nanosheets.

Multinary layered 2D nanomaterials can exhibit distinct physicochemical properties and innovative applications as compared to binary 2D nanomaterials due to their unique crystal structures. However, it still remains a challenge for the high-yield preparation of high-quality multinary 2D nanosheets. Here, the high-yield and large-scale production of two quaternary metal thiophosphate nanosheets are reported, i.e., Ni3 Cr2 P2 S9 and Ni3 Cr2 P2 Se9 , via the liquid exfoliation of their layered bulk crystals. The exfoliated single-crystalline Ni3 Cr2 P2 S9 nanosheets, with a lateral size ranging from a few hundred nanometers to a few micrometers and thickness of 1.4 ± 0.2 nm, can be easily used to prepare flexible thin films via a simple vacuum filtration process. As a proof-of-concept application, the fabricated thin film is used as a supercapacitor electrode with good specific capacitance. These high-yield, large-scale, solution-processable quaternary metal thiophosphate nanosheets could also be promising in other applications like biosensors, cancer therapies, and flexible electronics.

Garcinoxanthones SV, new xanthone derivatives from the pericarps of Garcinia mangostana together with their cytotoxic and antioxidant activities.

Xanthones (9H-xanthene-9-ones) are considered to be very promising compounds due to a variety of interesting biological and pharmacological activities. In this study, column chromatography of the methanol extract of the Garcinia mangostana L. pericarps resulted in the isolation of four new xanthones (garcinoxanthones SV, 1-4) and five known analogs including garcinone E (5), 11-hydroxy-1-isomangostin (6) mangostenone E (7), 1,3,6,7-tetrahydroxyxanthone (8), and α-mangostin (9). The structures of the new compounds were elucidated by NMR, HRESIMS, and ECD spectra. Compound 8 (1,3,6,7-tetrahydroxyxanthone) was found from the G. mangostana pericarps for the first time. All the isolated compounds (1-8) were evaluated for their 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and cytotoxicity in vitro against three human cancer cell lines including SK-LU-1, MCF7, and HT-29 cell lines. Compounds 3, 5, and 8 exhibited significant DPPH scavenging capacity with IC50 values of 68.55, 63.05, and 28.45 µM, respectively, in comparison with ascorbic acid (IC50 = 48.03 µM). Compounds 5 and 8 showed moderate cytotoxic effects against the three human cancer cell lines with IC50 value ranges of 19.86-27.38 µM.

A Novel Allele-Specific PCR Protocol for the Detection of the HLA-C*03:02 Allele, a Pharmacogenetic Marker, in Vietnamese Kinh People.

BACKGROUND: Allopurinol, a common anti-hyperuricemia drug, is well known as an inducer of severe cutaneous adverse drug reactions (SCARs). One of the most well-defined risk factors of allopurinol-induced SCARs is the presence of polymorphic alleles of human leukocyte antigen (HLA) genes, such as HLA-B*58:01 and HLA-C*03:02 alleles. There is no commercial test or published in-house protocol for the specific detection of the HLA-C*03:02 allele. In this article, we established for the first time a simple allele-specific (AS) PCR method to identify HLA-C*03:02 allele carriers, and at the same time, determine their zygosities. METHODS: A two-step AS-PCR protocol, using four primer sets, was designed to specifically amplify and differentiate the HLA-C*03:02 allele from 17 other HLA-C alleles found in Vietnamese people. The protocol was validated with PCR-sequencing-based typing (SBT) of 100 samples of unknown genotypes. RESULTS: The PCR protocol can detect the HLA-C*03:02 allele and determine the zygosity. The results of this protocol were highly consistent with those of the SBT (ĸ = 0.98, p < 0.001). Regarding the specific detection of the HLA-C*03:02 allele, the PCR protocol had a sensitivity of 100% (95% CI: 91.61-100%) and specificity of 98.3% (95% CI: 90.9-99.7%). The protocol was used to determine the distribution of the HLA-C*03:02 allele in 810 unrelated Vietnamese Kinh people, 14.2% of which were HLA-C*03:02 carriers, the allele frequency was 7.5%. CONCLUSION: A novel AS-PCR protocol with a sensitivity of 100% for the detection of the HLA-C*03:02 allele was established. The protocol can be used for personalized treatment with allopurinol in order to minimize the risk of SCARs in Vietnamese people as well as in other Asian populations with similar genetic characteristics.

Controllable growth of Au nanostructures onto MoS2 nanosheets for dual-modal imaging and photothermal-radiation combined therapy.

Multifunctional theranostic nanoagents are attractive to realize comprehensive imaging and effective treatment of tumours. Herein, a novel strategy is developed to controllably guide the epitaxial growth of gold nanostructures onto MoS2 nanosheets. The as-prepared MoS2-Au nanostructures (MA) manifest an enhanced near-infrared (NIR) absorbance with strong photostability. After modification, the obtained MA-PEG shows strong X-ray attenuation and photothermal conversion ability, promising for CT and photoacoustic imaging with an enhanced intensity in tumours. Moreover, in vivo photothermal and radiation therapy with MA-PEG achieves synergistic tumour treatment efficiency through hyperthermia elevated oxygenation level and sensitized radiation therapy. This work illustrates the development of a unique MA nanostructure with enhanced NIR absorbance and strong photoelectric absorbance as a multifunctional theranostic agent with great potential for dual-modal imaging-guided photothermal-radiation therapy of cancer.

Linearly Polarized Luminescence of Atomically Thin MoS2 Semiconductor Nanocrystals.

Atomically thin layers of transition-metal dichalcogenides semiconductors, such as MoS2, exhibit strong and circularly polarized light emission due to inherent crystal symmetries, pronounced spin-orbit coupling, and out-of-plane dielectric and spatial confinement. While the layer-by-layer confinement is well-understood, the understanding of the impact of in-plane quantization in their optical spectrum is far behind. Here, we report the optical properties of atomically thin MoS2 colloidal semiconductor nanocrystals. In addition to the spatial-confinement effect leading to their blue wavelength emission, the high quality of our MoS2 nanocrystals is revealed by narrow photoluminescence, which allows us to resolve multiple optically active transitions, originating from quantum-confined excitons (coupled electron-hole pairs). Surprisingly, in stark contrast to monolayer MoS2, the luminescence of the lowest-energy levels is linearly polarized and persists up to room temperature, meaning that it could be exploited in a variety of light-emitting applications.

Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer.

Low response rate and recurrence are common issues in lung cancer; thus, identifying a potential compound for these patients is essential. Utilizing an in silico screening method, we identified withaferin A (WA), a cell-permeable steroidal lactone initially extracted from Withania somnifera, as a potential anti-lung cancer and anti-lung cancer stem-like cell (CSC) agent. First, we demonstrated that WA exhibited potent cytotoxicity in several lung cancer cells, as evidenced by low IC50 values. WA concurrently induced autophagy and apoptosis and the activation of reactive oxygen species (ROS), which plays an upstream role in mediating WA-elicited effects. The increase in p62 indicated that WA may modulate the autophagy flux followed by apoptosis. In vivo research also demonstrated the anti-tumor effect of WA treatment. We subsequently demonstrated that WA could inhibit the growth of lung CSCs, decrease side population cells, and inhibit lung cancer spheroid-forming capacity, at least through downregulation of mTOR/STAT3 signaling. Furthermore, the combination of WA and chemotherapeutic drugs, including cisplatin and pemetrexed, exerted synergistic effects on the inhibition of epidermal growth factor receptor (EGFR) wild-type lung cancer cell viability. In addition, WA can further enhance the cytotoxic effect of cisplatin in lung CSCs. Therefore, WA alone or in combination with standard chemotherapy is a potential treatment option for EGFR wild-type lung cancer and may decrease the occurrence of cisplatin resistance by inhibiting lung CSCs.

Preparation of 1T'-Phase ReS2 xSe2(1- x) ( x = 0-1) Nanodots for Highly Efficient Electrocatalytic Hydrogen Evolution Reaction.

As a source of clean energy, a reliable hydrogen evolution reaction (HER) requires robust and highly efficient catalysts. Here, by combining chemical vapor transport and Li-intercalation, we have prepared a series of 1T'-phase ReS2 xSe2(1- x) ( x = 0-1) nanodots to achieve high-performance HER in acid medium. Among them, the 1T'-phase ReSSe nanodot exhibits the highest hydrogen evolution activity, with a Tafel slope of 50.1 mV dec-1 and a low overpotential of 84 mV at current density of 10 mA cm-2. The excellent hydrogen evolution activity is attributed to the optimal hydrogen absorption energy of the active site induced by the asymmetric S vacancy in the highly asymmetric 1T' crystal structure.

C29 sterols with a cyclopropane ring at C-25 and 26 from the Vietnamese marine sponge Ianthella sp. and their anticancer properties.

Two new C(29) sterols with a cyclopropane ring at C-25 and C-26, petrosterol-3,6-dione (1) and 5alpha,6alpha-epoxy-petrosterol (2), along with petrosterol (3), were isolated from the Vietnamese marine sponge Ianthella sp. The structures of the new compounds were elucidated by comprehensive spectroscopic analyses. Compounds 1-3 showed cytotoxic activities on A549, HL-60, MCF-7, SK-OV-3, and U937 cancer cell lines with IC(50) in the range of 8.4-22.6 microM, whereas compounds 1-3 exhibited only weak cytotoxic activities on HT-29 cell. After HL-60 cells were treated with the compounds, several apoptosis events like chromatin condensation and the increase of the population of sub-G1 hypodiploid cells were observed. These data supported that the compounds might have potential for leukemia treatment.