Pyridoxine as a template for the design of antiplatelet agents

The B(6) vitamers have been shown to display beneficial therapeutic effects in cardiovascular related disorders. The design of novel antiplatelet agents using pyridoxine as a template has led to the discovery of a class of novel cardio- and cerebro-protective agents. The present study describes the synthesis of several of these derivatives along with the antiplatelet and antiischemic activity of derivative 16.     

Co-delivery of Vorinostat and Etoposide <Emphasis Type="Italic">Via</Emphasis> Disulfide Cross-Linked Biodegradable Polymeric Nanogels: Synthesis,Characterization, Biodegradation,and Anticancer Activity

Treatment regimens for cancer patients using single chemotherapeutic agents often lead to undesirable toxicity, drug resistance, reduced uptake etc. Combination of two or more drugs is therefore becoming an imperative strategy to overcome these limitations. A step forward can be taken through delivery of the drugs used in combination via nanoparticles. Co-administration of chemotherapeutic drugs encapsulated in nanoparticles has been shown to result in synergistic effects and enhanced therapeutic efficacy. In present study, we explored the combination treatment of histone deacetylase inhibitor vorinostat (VOR) and topoisomerase II inhibitor etoposide (ETOP). The concurrent combination treatment of VOR and ETOP resulted in synergistic effect on human cervical HeLa cancer cells. VOR and ETOP were encapsulated into poly(ethylene glycol) monomethacrylate (POEOMA)-based disulfide cross-linked nanogels. The nanogels were synthesized using atom transfer radical polymerization (ATRP) via cyclohexane/water inverse mini-emulsion and were degradable in presence of intracellular glutathione (GSH) concentration. Both the drugs were loaded into the nanogels by physical encapsulation method and characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD), dynamic light scattering (DLS), and differential scanning calorimetry (DSC). Both VOR- and ETOP-loaded nanogels showed sustained release profile. Furthermore, combination treatment drugs encapsulated of POEOMA nanogel demonstrated enhanced synergistic cytotoxic effect compared with combination of free drugs. Enhanced synergistic cell killing efficiency of drug-loaded POEOMA nanogels was due to increased apoptosis via caspase 3/7 activation. Therefore, combination of VOR- and ETOP-loaded PEG-based biodegradable nanogels may provide a promising therapy with enhanced anticancer effect.     

Aminoacidopathies: Prevalence,Etiology, Screening,and Treatment Options

Inborn errors of metabolism (IEMs) are a group of inherited metabolic disorders which are caused by mutations in the specific genes that lead to impaired proteins or enzymes production. Different metabolic pathways are perturbed due to the deficiency or lack of enzymes. To date, more than 500 IEMs have been reported with most of them being untreatable. However, fortunately 91 such disorders are potentially treatable, if diagnosed at an earlier stage of life. IEMs have been classified into different categories and one class of IEMs, characterized by the physiological disturbances of amino acids is called as aminoacidopathies. Out of 91 treatable IEM, thirteen disorders are amino acid related. Aminoacidopathies can be detected by chromatography and mass spectrometry based analytical techniques (e.g., HPLC, GC–MS, LC–MS/MS) for amino acid level changes, and through genetic assays (e.g., PCR, TaqMan Genotyping, DNA sequencing) at the mutation level in the corresponding genes. Hence, this review is focused to describe thirteen common aminoacidopathies namely: Phenylketonuria (PKU), Maple Syrup Urine Disease (MSUD), Homocystinuria/Methylene Tetrahydrofolate Reductase (MTHFR) deficiency, Tyrosinemia type II, Citrullinemia type I and type II, Argininosuccinic aciduria, Carbamoyl Phosphate Synthetase I (CPS) deficiency, Argininemia (arginase deficiency), Hyperornithinemia–Hyperammonemia–Homocitrullinuria (HHH) syndrome, N-Acetylglutamate Synthase (NAGS) deficiency, Ornithine Transcarbamylase (OTC) deficiency, and Pyruvate Dehydrogenase (PDH) complex deficiency. Furthermore, the etiology, prevalence and commonly used analytical techniques for screening of aminoacidopathies are briefly described. This information would be helpful to researchers and clinicians especially from developing countries to initiate newborn screening programs for aminoacidopathies.     

A method for the synthesis of C-(2-deoxy-β-glycosyl) arenes

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(2) was converted by a Wittig reaction into a mixture of (

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(4,5). Selective deprotection of the 5,6-O-isopropylidene group in compounds 4 and 5 followed by selective silylation at position 6 afforded the separate

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8a–d and the corresponding E-isomers (9a–d). Iodonium-ion-induced cyclization of compounds 8c and 9a-c furnished stereoselectively the

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10a–c. Full deprotection of compounds 10a–c and the O-acetylation led to compounds 11a–c, which on treatment with tributyltin hydride-azobisisobutyromnitrile yielded and the title compounds (12a–c).     

Radio-protective and antioxidative activities of astaxanthin from newly isolated radio-resistant bacterium <Emphasis Type="Italic">Deinococcus</Emphasis> sp. strain WMA-LM9

A radio-resistant bacterium, designated as strain WMA-LM9, was isolated from desert soil. 16S rRNA gene sequencing indicated that the bacterium belongs to genus Deinococcus with maximum similarity to Deinococcus radiopugnans. Deinococcus sp. strain WMA-LM9 was found to be resistant to a ultraviolet (UV) dose of 5 × 10³ J/m², hydrogen peroxide (50 mM) and mitomycin C (10 μg/ml). A carotenoid pigment was extracted using chloroform/methanol/acetone (7:5:3) and purified by high-performance liquid chromatography on a C₁₈ analytical column. The compound was characterised as mono-esterified astaxanthin by ¹H, ¹³C nuclear magnetic resonance and mass spectrometry. It was tested for antioxidant activity, total flavonoids and phenolic content, radioprotective potential in correlation to the prevention of protein oxidation and DNA strand breaks in vitro. The carotenoid pigment showed a very potent antioxidant activity and significantly stronger scavenging ability against superoxides, with an IC₅₀ (concentration causing 50% inhibition of the desired activity) of 41.6 μg/ml. The total phenolic and flavonoid contents were 12.1 and 7.4 μg in terms of gallic acid and quercetin equivalents per milligram of dried mass, respectively. astaxanthin also showed a higher inhibitory action against oxidative damage to collagen, elastin and bovine serum albumin than did β-carotene. The carotenoid also inhibited breaks to DNA strands, as indicated by the results of the DNA damage prevention assay. We conclude that astaxanthin from Deinococcus sp. strain WMA-LM9 has protective effects against radiation-mediated cell damage, and it also protects cellular protein and DNA against oxidative stress and other anti-oxidant activities.     

Ellis–van Creveld syndrome and profound deafness resulted by sequence variants in the <Emphasis Type="Italic">EVC</Emphasis> / <Emphasis Type="Italic">EVC2</Emphasis> and <Emphasis Type="BoldItalic">TMC1</Emphasis> genes

Ellis–van Creveld syndrome is an autosomal recessive skeletal dysplasia primarily characterized by the features such as disproportionate dwarfism, short ribs, short limbs, dysplastic nails, cardiovascular malformations, post-axial polydactyly (PAP) (bilateral) of hands and feet. EVC/EVC2 located in head-to-head arrangement on chromosome 4p16 are the causative genes for EvC syndrome. In the study, we present two families, A and B, with Pakistani and Republic of Kosovo origin, respectively. They showed features of EvC syndrome and were clinically and genetically characterized. In family A, the affected members showed an additional feature of profound deafness. The whole exome sequencing (WES) in this family revealed two homozygous variants in EVC2 (c.30dupC; p.Thr11Hisfs*45) and TMC1 (\(\hbox {c}.1696\hbox {-}1\hbox {G}{>}\hbox {A}\)) genes. In family B, WES revealed novel compound heterozygous variants (p.Ser307Pro, \(\hbox {c}.2894{+}3\hbox {A}{>}\hbox {G}\)) in the EVC gene. This study reports first case of variants in the genes causing EvC syndrome and profound deafness in the same family.     

Differences in physiological and biochemical characteristics in response to single and combined drought and salinity stresses between wheat genotypes differing in salt tolerance

The combined drought and salinity stresses pose a serious challenge for crop production, but the physiological mechanisms behind the stresses responses in wheat remains poorly understood. Greenhouse pot experiment was performed to study differences in genotype response to the single and combined (D + S) stresses of drought (4% soil moisture, D) and salinity (100 mM NaCl, S) using two wheat genotypes: Jimai22 (salt tolerant) and Yangmai20 (salt‐sensitive). Results showed that salinity, drought and/or D + S severely reduces plant growth, biomass and net photosynthetic rate, with a greater effect observed in Yangmai20 than Jimai22. A notable improvement in water use efficiency (WUE) by 239, 77 and 103% under drought, salinity and D + S, respectively, was observed in Jimai22. Moreover, Jimai22 recorded higher root K⁺ concentration in drought and salinity stressed condition and shoot K⁺ under salinity alone than that of Yangmai20. Jimai22 showed lower increase in malondialdehyde (MDA) accumulation, but higher activities of superoxide dismutase (SOD, EC 1.15.1.1) and guaicol peroxidase (POD, EC 1.11.1.7), under single and combined stresses, and catalase (CAT, EC 1.11.1.6) and ascorbate peroxidase (APX, EC 1.11.1.11) under single stress. Our results suggest that high tolerance of Jimai22 in both drought and D + S stresses is closely associated with larger root length, higher Fv/Fm and less MDA contents and improved capacity of SOD and POD. Moreover, under drought Jimai22 tolerance is firmly related to higher root K⁺ concentration level and low level of Na⁺, high‐net photosynthetic rate and WUE as well as increased CAT and APX activities to scavenge reactive oxygen species.