Laminin α2 controls mouse and human stem cell behaviour during midbrain dopaminergic neuron development.

Development of the central nervous system requires coordination of the proliferation and differentiation of neural stem cells. Here, we show that laminin alpha 2 (lm-α2) is a component of the midbrain dopaminergic neuron (mDA) progenitor niche in the ventral midbrain (VM) and identify a concentration-dependent role for laminin α2ß1γ1 (lm211) in regulating mDA progenitor proliferation and survival via a distinct set of receptors. At high concentrations, lm211-rich environments maintain mDA progenitors in a proliferative state via integrins α6ß1 and α7ß1, whereas low concentrations of lm211 support mDA lineage survival via dystroglycan receptors. We confirmed our findings in vivo, demonstrating that the VM was smaller in the absence of lm-α2, with increased apoptosis; furthermore, the progenitor pool was depleted through premature differentiation, resulting in fewer mDA neurons. Examination of mDA neuron subtype composition showed a reduction in later-born mDA neurons of the ventral tegmental area, which control a range of cognitive behaviours. Our results identify a novel role for laminin in neural development and provide a possible mechanism for autism-like behaviours and the brainstem hypoplasia seen in some individuals with mutations of LAMA2.

Comparative Assessment of Phytoconstituents, Antioxidant Activity and Chemical Analysis of Different Parts of Milk Thistle Silybum marianum L.

Silybum marianum L. is a therapeutic plant belonging to the family Asteraceae, which has exhibited silymarin, a principal component used to cure various physiochemical disorders. The study appraised the phytochemical analysis, antioxidant activity and chemical analysis of an extract from the seed, stem and leaves. Qualitative and quantitative phytochemical analysis was evaluated by the Folin-Ciocalteu reagent method and aluminum chloride colorimetric method, respectively. While the antioxidant activity was determined by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and acetate buffer in ferric chloride (FRAP) assay, respectively, the chemical profile was evaluated by Gas Chromatography-Mass Spectrometry (GC-MS) assay. The study outcomes identified that alkaloids, glycosides, flavonoids, terpenoids, steroids and catcholic tannins were present in seed, stem and leaves extracts except for saponins and Gallic tannins. Whereas, phenols were absent only in seed extract. Quantitative analysis revealed the presence of phenols and flavonoids in appreciable amounts of 21.79 (GAE/g), 129.66 (QE/g) and 17.29 (GAE/g), 114.29 (QE/g) from the leaves and stem extract, respectively. Similarly, all extracts expressed reasonable DPPH inhibition (IC50) and FRAP reducing power such as 75.98, 72.39 and 63.21% and 46.60, 51.40 and 41.30 mmol/g from the seeds, stem and leaves extract, respectively. Additionally, chemical analysis revealed the existence of 6, 8 and 9 chemical compounds from the seeds, stem and leaves extract, respectively, corresponding to 99.95, 99.96 and 98.89% of the whole extract. The chemical compound, Dibutyl phthalate was reported from all extracts while, Hexadecanoic acid, methyl ester and Silane, (1,1-dimethylethyl), dimethyl (phenylmethoxy) were reported only from the seed and leaves extract. Moreover, Methyl stearate was also a major compound reported from all extracts except for seed extract. It is demonstrable that extracts from different parts of S. marianum possess significant antioxidant activity, as well as valuable chemical compounds accountable for therapeutic effects that might be incorporated as an alternative to synthetic chemical agents.

Comprehensive Phytochemical Profiling, Biological Activities, and Molecular Docking Studies of Pleurospermum candollei: An Insight into Potential for Natural Products Development.

The purpose of this study was to find the biological propensities of the vegetable plant Pleurospermum candollei by investigating its phytochemical profile and biological activities. Phytochemical analysis was done by spectroscopic methods to investigate the amount of total polyphenols, and biological evaluation was done by the different antioxidant, enzyme inhibitory (tyrosinase, α-amylase, and α-glucosidase), thrombolytic, and antibacterial activities. The highest amount of total phenolic and flavonoid contents was observed in methanolic extract (240.69 ± 2.94 mg GAE/g and 167.59 ± 3.47 mg QE/g); the fractions showed comparatively less quantity (57.02 ± 1.31 to 144.02 ± 2.11 mg GAE/g, and 48.21 ± 0.75 to 96.58 ± 2.30 mg QE/g). The effect of these bioactive contents was also related to biological activities. GCMS analysis led to the identification of bioactive compounds with different biological effects from methanolic extract (antioxidant; 55.07%, antimicrobial; 56.41%), while the identified compounds from the n-hexane fraction with antioxidant properties constituted 67.86%, and those with antimicrobial effects constituted 82.95%; however, the synergetic effect of polyphenols may also have contributed to the highest value of biological activities of methanolic extract. Molecular docking was also performed to understand the relationship of identified secondary metabolites with enzyme-inhibitory activities. The thrombolytic activity was also significant (40.18 ± 1.80 to 57.15 ± 1.10 % clot lysis) in comparison with streptokinase (78.5 ± 1.53 to 82.34 ± 1.25% clot lysis). Methanolic extract also showed good activity against Gram-positive strains of bacteria, and the highest activity was observed against Bacillus subtilis. The findings of this study will improve our knowledge of phytochemistry, and biological activities of P. candollei, which seems to be a ray of hope to design formulations of natural products for the improvement of health and prevention of chronic diseases; however, further research may address the development of novel drugs for use in pharmaceuticals.

Compritol-Based Alprazolam Solid Lipid Nanoparticles for Sustained Release of Alprazolam: Preparation by Hot Melt Encapsulation.

The current study was designed to investigate the feasibility of incorporating the water-insoluble lipophilic drug Alprazolam (Alp) into solid lipid nanoparticles (SLNs) to offer the combined benefits of the quick onset of action along with the sustained release of the drug. Therefore, compritol-based alprazolam-loaded SLNs (Alp-SLNs) would provide early relief from anxiety and sleep disturbances and long-lasting control of symptoms in patients with depression, thereby enhancing patient compliance. The optimized Alp-SLNs analyzed by DLS and SEM showed consistent particle size of 92.9 nm with PI values and standard deviation of the measurements calculated at <0.3 and negative surface charge. These characteristic values demonstrate the desired level of homogeneity and good physical stability of Alp-SLNs. The SLNs had a good entrapment efficiency (89.4%) and high drug-loading capacity (77.9%). SEM analysis revealed the smooth spherical morphology of the SLNs. The physical condition of alprazolam and absence of interaction among formulation components in Alp-SLNs was confirmed by FTIR and DSC analyses. XRD analysis demonstrated the molecular dispersion of crystalline alprazolam in Alp-SLNs. The in vitro release study implied that the release of Alp from the optimized Alp-SLN formulation was sustained as compared to the Alp drug solution because Alp-SLNs exhibited sustained release of alprazolam over 24 h. Alp-SLNs are a promising candidate to achieve sustained release of the short-acting drug Alp, thereby reducing its dosing frequency and enhancing patient compliance.

Identification of NSAIDs as lipoxygenase inhibitors through highly sensitive chemiluminescence method, expression analysis in mononuclear cells and computational studies.

Here we report the inhibitory effects of nine non-steroidal anti-inflammatory drugs (NSAIDs) on soybean 15-lipoxygenase (15-LOX) enzyme (EC 1.13.11.12) by three different methods; UV-absorbance, colorimetric and chemiluminescence methods. Only two drugs, Ibuprofen and Ketoprofen, exhibited enzyme inhibition by UV-absorbance method but none of the drug showed inhibition through colorimetric method. Chemiluminescence method was found highly sensitive for the identification of 15-LOX inhibitors and it was more sensitive and several fold faster than the other methods. All tested drugs showed 15-LOX-inhibition with IC50 values ranging from 3.52 ± 0.08 to 62.6 ± 2.15 µM by chemiluminescence method. Naproxen was the most active inhibitor (IC50 3.52 ± 0.08 µM) followed by Aspirin (IC50 4.62 ± 0.11 µM) and Acetaminophen (IC50 6.52 ± 0.14 µM). Ketoprofen, Diclofenac and Mefenamic acid showed moderate inhibitory profiles (IC50 24.8 ± 0.24 to 39.62 ± 0.27 µM). Piroxicam and Tenoxicam were the least active inhibitors with IC50 values of 62.6 ± 2.15 µM and 49.5 ± 1.13 µM, respectively. These findings are supported by expression analysis, molecular docking studies and density functional theory calculations. The expression analysis and flow cytometry apoptosis analysis were carried out using mononuclear cells (MNCs) which express both human 15-LOX and 5-LOX. Selected NSAIDs did not affect the cytotoxic activity of MNCs at IC50 concentrations and the cell death showed dose dependent effect. However, MNCs apoptosis increased only at the higher concentrations, demonstrating that these drugs may not induce loss of immunity in septic and other inflammatory conditions at the acceptable inhibitory concentrations. The data collectively suggests that NSAIDs not only inhibit COX enzymes as reported in the literature but soybean 15-LOX and MNCs LOXs are also inhibited at differential values. A comparison of the metabolomics studies of arachidonic acid pathway after inhibition of either COX or LOX enzymes may reconfirm these findings.

Molecular basis of cross-resistance to acetohydroxy acid synthase-inhibiting herbicides in Sagittaria trifolia L.

Acetohydroxy acid synthase (AHAS)-inhibiting herbicides are one of the most commonly used herbicides for controlling the growth of Sagittaria trifolia L. in paddy fields in Northeastern China. In this study, we collected five suspected resistant populations of S. trifolia (R1-R5) from three different provinces of Northeastern China. The results of whole-plant bioassays revealed that those populations showed high level of resistance to bensulfuron-methyl with resistance index (GR50 R/S) ranging from 39.90 to 88.50. The results of AHAS-activity assays were consistent with the results of the whole-plant bioassays. The AHAS gene analysis showed that R2 and R3 populations contained Pro-197-Leu mutations that were highly resistant to penoxsulam; R1 and R4 populations contained Pro-197-Ser mutations that were highly resistant to bispyribac­sodium; R5 population contained Trp-574-Leu mutation that showed high resistance to IMI, PT, PTB and SU herbicides. The AHAS with resistance mutations showed less sensitivity to feedback inhibition by BCAAs and R genotypes had increased free BCAAs.

New drugs and new concerns: Gaining insight through Pharmacovigilance of direct acting Anti-Viral's in chronic HCV patients.

OBJECTIVE: The study aimed to assess the safety profile of Direct Acting Anti-Viral's (DAAs) among patients with chronic Hepatitis C Virus (HCV). METHODS: This multicenter, analytical cross-sectional study was conducted in six gastroenterology and Hepatology centers including Liver Center Faisalabad, Allama Iqbal Medical Institute and Liver Center DHQ Hospital Sialkot, Isra Hospital Hyderabad, Allied Hospital Faisalabad and Rehman Medical Institute Peshawar, between May 2018 and May 2019. The data regarding patient demographics, treatment plan and the frequency of Adverse Events (AEs), and their severity was collected using a pre-designed questionnaire and analyzed through SPSS version 20.0. RESULTS: A total of 511 HCV patients were enrolled, with an overall male majority. Around 66.3% patients experienced a total of 419 AEs, out of which 61 events were suspected from DAAs while remaining 317 events were associated with Ribavirin. Pyrexia (24.6%) and fatigue (14.8%) were the most commonly reported AEs among patients receiving DAAs. Factors such as Ribavirin-based treatments and the presence of Cirrhosis were more likely to promote AEs occurrence OR [95%CI] i.e. 5.2(2.3-9.1) and 1.9(1.1-3.1) respectively (p < 0.05). CONCLUSION: It is concluded from the study results that DAAs have displayed promising outcomes due to the minimal and minor AEs reported.

Spinasterol, 22,23-Dihydrospinasterol and Fernenol from Citrullus Colocynthis L. with Aphicidal Activity against Cabbage Aphid Brevicoryne Brassicae L.

Brevicoryne brassicae is a problematic pest in cabbage and other field crops. Synthetic pesticides are used to control this pest, but they are injurious for human health and the environment. The present study aimed to purify and identify the active compounds from Citrullus colocynthis leaves with an appraisal of their efficacy against B. brassicae. Separation and purification were performed via different chromatographic techniques. Molecular analysis and chemical structures were recognized by mass spectrum (MS) and nuclear magnetic resonance (NMR), respectively. Moreover, in vitro and in vivo aphicidal activity was assessed using various concentrations, i.e., 6.25, 12.5, 25 and 50 µg/mL at 12, 24, 48 and 72 h exposure. The outcome shows that mass spectrum analyses of the purified compounds suggested the molecular formulae are C30H50O and C29H50O, C29H48O. The compounds were characterized as fernenol and a mixture of spinasterol, 22,23-dihydrospinasterol by 1H-NMR and 13C-NMR spectrum analysis. The toxicity results showed that the mixture of spinasterol and 22,23-dihydrospinasterol showed LC50 values of 32.36, 44.49 and 37.50 µg/mL by contact, residual and greenhouse assay at 72 h exposure, respectively. In contrast, fernenol recorded LC50 values as 47.99, 57.46 and 58.67 µg/mL, respectively. On the other hand, spinasterol, 22,23-dihydrospinasterol showed the highest mortality, i.e., 66.67%, 53.33% and 60% while, 30%, 23.33% and 25% mortality was recorded by fernenol after 72 h at 50 µg/mL by contact, residual and greenhouse assay, respectively. This study suggests that spinasterol, 22,23-dihydrospinasterol are more effective against B. brassicae which may be introduced as an effective and suitable substitute of synthetic chemical pesticides.

Synthesis, fungicidal activity and SAR of 3,4-dichloroisothiazole-based cycloalkylsulfonamides.

To develop more valuable and effective fungicide candidates, a novel series of 3,4-dichloroisothioxazole-based cycloalkylsulfonamides were synthesized and their structures were identified by 1H NMR, 13C NMR, MS and elemental analysis. Compound 3k was further confirmed by X-ray single crystal diffraction. The in vitro bioassay results demonstrated that the target compounds showed significant fungicidal activity on mycelial growth and spore germination of Botrytis cinerea. Especially, compound 3j, with prominent inhibition effect on mycelial with EC50 and EC80 values of 1.4 and 23.7 µg/mL respectively, was comparable to the selected commercial fungicide. Moreover, at 50 µg/mL, the inhibition rate of compound 3j on spore germination was recorded up to 89.7%. The further in vivo bioassay results indicated compound 3j continued to show high control effect on tomato leaves, flowers and fruit at 200 µg/mL, with control efficiencies of 94.3%, 89.3% and 91.9%, respectively. The structure-activity relationship showed that the compound with a five-membered ring possessed the best activity after the introduction of the active fragment of the 3,4-dichloroisothioxazole, provided a valuable idea for further creation of new fungicides.

Phytochemical Analysis, Biochemical and Mineral Composition and GC-MS Profiling of Methanolic Extract of Chinese Arrowhead Sagittaria trifolia L. from Northeast China.

Sagittaria trifolia is a medicinal foodstuff of China and East Asia belonging to the family Alismataceae. Samples of S. trifolia tubers were collected from Meihekow, Siping, Jilin, Harbin and Wuchang from Northeast China. The current study was aimed to evaluate the qualitative and quantitative analysis, antioxidant activity, biochemical analysis and chemical composition of different populations of S. trifolia. By using Folin-Ciocalteu, aluminium chloride colourimetric and 1,1-diphenyl-1-picrylhydrazyl (DPPH), total phenol and flavonoids content and antioxidant activity was analysed. Furthermore, chemical composition, biochemical analysis and mineral substances were also determined. The results showed the presence of flavonoids, phenols, saponins, tannins, glycosides and steroids except for alkaloids and terpenoids by qualitative analysis. Quantitative analysis revealed that highest total phenol, flavonoids content and antioxidant potential identified from Meihekow, i.e., 2.307 mg GAE/g, 12.263 mg QE/g and 77.373%, respectively. Gas chromatography-mass spectrometry results showed the presence of 40 chemical compounds corresponding to 99.44% of total extract that might be responsible for antioxidant properties. Mineral and biochemical analysis revealed the presence of calcium, magnesium, potassium, sodium, iron, copper, zinc and, carbohydrate, protein, fibre and fat contents, respectively. Interestingly, all S. trifolia populations collected from different locations possess similar composition. The dietary values, phytoconstituents, antioxidant activities and nutritional and curative chemical compounds of S. trifolia are beneficial for the nutritherapy of human beings.

Cholesterol oxidase: ultrahigh-resolution crystal structure and multipolar atom model-based analysis.

Examination of protein structure at the subatomic level is required to improve the understanding of enzymatic function. For this purpose, X-ray diffraction data have been collected at 100 K from cholesterol oxidase crystals using synchrotron radiation to an optical resolution of 0.94 Å. After refinement using the spherical atom model, nonmodelled bonding peaks were detected in the Fourier residual electron density on some of the individual bonds. Well defined bond density was observed in the peptide plane after averaging maps on the residues with the lowest thermal motion. The multipolar electron density of the protein-cofactor complex was modelled by transfer of the ELMAM2 charge-density database, and the topology of the intermolecular interactions between the protein and the flavin adenine dinucleotide (FAD) cofactor was subsequently investigated. Taking advantage of the high resolution of the structure, the stereochemistry of main-chain bond lengths and of C=O···H-N hydrogen bonds was analyzed with respect to the different secondary-structure elements.

Diarylsulfonamides and their bioisosteres as dual inhibitors of alkaline phosphatase and carbonic anhydrase: Structure activity relationship and molecular modelling studies.

The effect of bioisosteric replacement of carboxamide linking group with sulfonamide linking group, on alkaline phosphatase (AP) and carbonic anhydrase (CA) inhibition activity of aromatic benzenesulfonamides was investigated. A series of carboxamide linked aromatic benzenesulfonamides 1a-1c, 2a-2d and their sulfonamide linked bioisosteres 3a-3d, 4a-4d was synthesized and evaluated for inhibitory activity against bovine tissue non-specific alkaline phosphatase (TNAP), intestinal alkaline phosphatase (IAP) and bCA II. A significant increase in CA inhibition activity was observed upon bioisosteric replacement of carboxamide linking group with a sulfonamide group. Some of these compounds were identified as highly potent and selective AP inhibitors. Compounds 1b, 2b, 3d, 4d 5b and 5c were found to be selective bTNAP inhibitors, whereas compounds 1a, 1c, 2a, 2c, 2d, 3a, 3c, 4a, 4b, 4c, 5a were found to be selective bIAP inhibitors. For most active AP inhibitor 3b, detailed kinetic studies indicated a competitive mode of inhibition against tissue non-specific alkaline phosphatase (TNAP) and non-competitive mode of inhibition against intestinal alkaline phosphatase (IAP). Molecular docking studies were carried out to rationalize important binding site interactions.

A polyhedral oligomeric silsesquioxane-based bilayered dermal scaffold seeded with adipose tissue-derived stem cells: in vitro assessment of biomechanical properties.

BACKGROUND: Although commercial skin substitutes are widely available, its use remains challenging at surgery and postoperatively. The high cost is also prohibitive. We designed and characterized a scaffold for dermal replacement, using advanced nanocomposite materials, which are known to have unique nanoscale features that enhance cellular behavior. METHODS: A bilayered scaffold was developed using the nanocomposite, polyhedral oligomeric silsesquioxane, incorporated into poly(caprolactone-urea)urethane, resulting in a mechanically robust bioabsorbable polymer; forming the inner layer, which was designed with a range of porosities. The removable outer layer contained nanosilver. Tensile testing, surface tension, permeability, and scanning electron microscopy were performed. Optimal pore morphology for cellular proliferation was elucidated through adipose tissue-derived stem cell culture and a cell viability assay. All tests were repeated on Integra Dermal Regeneration Template. RESULTS: The physical construct was easy to handle and clinically applicable. Macroporosity and permeability of scaffolds was demonstrated, confirmed by scanning electron microscopy. Both tensile strength and surface tension were comparable with skin; outer layer demonstrated hydrophobicity and inner layer showed hydrophilicity. Cell assay confirmed cellular proliferation onto the scaffold, comparable with Integra. CONCLUSIONS: We demonstrate that a porous bilayered dermal scaffold could form the basis of a new generation of skin substitute that is both mechanically robust and harbors the ability for enhancing cell regeneration.

Novel synthesis of dihydropyrimidines for α-glucosidase inhibition to treat type 2 diabetes: in vitro biological evaluation and in silico docking.

A convenient and efficient new method has been established for the synthesis of dihydropyrimidines by inexpensive and non-toxic N-acetyl glycine (NAG) catalysed reaction of aromatic aldehydes with ethyl acetoacetate and urea/thiourea. This method is applicable for various substituted aldehydes as well as urea and thiourea. It has also been used to synthesize bicyclic oxygen-bridged pyrimidine derivatives (4d, 4j). The biological assay revealed that the majority of compounds synthesized displayed modest inhibitory activity against α-glucosidase at low micro-molar concentrations. Molecular docking studies were also performed on the most active compound, 4f (with IC50 value 112.21±0.97 µM), to show the enzyme - inhibitor interactions.

Antioxidant, insecticidal activity and chemical profiling of flower's extract of Parthenium weed (Parthenium hysterophorus L.).

Parthenium hysterophorus L., an invasive alien species and notorious weed, offers various benefits to the medical and agrochemical industries. This study aimed to evaluate the antioxidant and insecticidal activities of P. hysterophorus flower extract and conduct chemical profiling to identify the phytoconstituents responsible for these biological effects. The antioxidant activity was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, while gas chromatography mass spectrometry (GCMS) analysis was employed for chemical configuration evaluation. Our findings demonstrate that the dichloromethane (DCM) extract of P. hysterophorus exhibits potent radical scavenging activity (95.03%). Additionally, phytochemical analysis revealed significant amounts of phenols and flavonoids in the distilled water and ethyl acetate extracts (103.30 GAEg-1 and 138.67 QEg-1, respectively). In terms of insecticidal activity, the flower extract displayed maximum mortality rates of 63.33% and 46.67% after 96 hours of exposure at concentrations of 1000 µgmL-1 and 800 µgmL-1, respectively, with similar trends observed at 72 hours. Furthermore, the P. hysterophorus extracts exhibited LC50 values of 1446 µgmL-1 at 72 hours and 750 µgmL-1 at 96 hours. Imidacloprid, the positive control, demonstrated higher mortality rates at 96 hours (97.67%) and 72 hours (91.82%). Moreover, the antioxidant activity of P. hysterophorus extracts exhibited a strong correlation with phenols, flavonoids, and extract yield. GCMS analysis identified 13 chemical compounds, accounting for 99.99% of the whole extract. Ethanol extraction yielded the highest percentage of extract (4.34%), followed by distilled water (3.22%), ethyl acetate (3.17%), and dichloromethane (2.39%). The flower extract of P. hysterophorus demonstrated significant antioxidant and insecticidal activities, accompanied by the presence of valuable chemical compounds responsible for these biological effects, making it a promising alternative to synthetic agents. These findings provide a novel and fundamental basis for further exploration in purifying the chemical compounds for their biological activities.

Secondary metabolic profiling, antioxidant potential, enzyme inhibitory activities and in silico and ADME studies: a multifunctional approach to reveal medicinal and industrial potential of Tanacetum falconeri.

Tanacetum falconeri is a significant flowering plant that possesses cytotoxic, insecticidal, antibacterial, and phytotoxic properties. Its chemodiversity and bioactivities, however, have not been thoroughly investigated. In this work, several extracts from various parts of T. falconeri were assessed for their chemical profile, antioxidant activity, and potential for enzyme inhibition. The total phenolic contents of T. falconeri varied from 40.28 ± 0.47 mg GAE/g to 11.92 ± 0.22 mg GAE/g in various extracts, while flavonoid contents were found highest in TFFM (36.79 ± 0.36 mg QE/g extract) and lowest (11.08 ± 0.22 mg QE/g extract) in TFSC (chloroform extract of stem) in similar pattern as found in total phenolic contents. Highest DPPH inhibition was observed for TFFC (49.58 ± 0.11 mg TE/g extract) and TFSM (46.33 ± 0.10 mg TE/g extract), whereas, TFSM was also potentially active against (98.95 ± 0.57 mg TE/g) ABTS radical. In addition, TFSM was also most active in metal reducing assays: CUPRAC (151.76 ± 1.59 mg TE/g extract) and FRAP (101.30 ± 0.32 mg TE/g extract). In phosphomolybdenum assay, the highest activity was found for TFFE (1.71 ± 0.03 mg TE/g extract), TFSM (1.64 ± 0.035 mg TE/g extract), TFSH (1.60 ± 0.033 mg TE/g extract) and TFFH (1.58 ± 0.08 mg TE/g extract), while highest metal chelating activity was recorded for TFSH (25.93 ± 0.79 mg EDTAE/g extract), TFSE (22.90 ± 1.12 mg EDTAE/g extract) and TFSC (19.31 ± 0.50 mg EDTAE/g extract). In biological screening, all extracts had stronger inhibitory capacity against AChE while in case of BChE the chloroform extract of flower (TFFC) and stem (TFSC) showed the highest activities with inhibitory values of 2.57 ± 0.24 and 2.10 ± 0.18 respectively. Similarly, TFFC and TFSC had stronger inhibitory capacity (1.09 ± 0.015 and 1.08 ± 0.002 mmol ACAE/g extract) against α-Amylase and (0.50 ± 0.02 and 0.55 ± 0.02 mmol ACAE/g extract) α-Glucosidase. UHPLC-MS study of methanolic extract revealed the presence of 133 components including sterols, triterpenes, flavonoids, alkaloids, and coumarins. The total phenolic contents were substantially linked with all antioxidant assays in multivariate analysis. These findings were validated by docking investigations, which revealed that the selected compounds exhibited high binding free energy with the enzymes tested. Finally, it was found that T. falconeri is a viable industrial crop with potential use in the production of functional goods and nutraceuticals.

A fast process for imprinting micro and nano patterns on electrospun fiber meshes at physiological temperatures.

Electrospun fiber meshes are patterned at length scales comparable to or lower than their fiber diameter. Simple nano- and microgrooves and closed geometric shapes are imprinted in different tones using a fast imprint process at physiological temperatures. Human mesenchymal stromal cells cultured on patterned scaffolds show differences in cellular morphology and cytoskeleton organization. Microgrooved electrospun fibers support upregulation of alkaline phosphatase and bone morphogenetic protein-2 gene expression when cells are cultured in osteogenic medium.

Experimental and theoretical charge density analysis of a bromoethyl sulfonium salt.

Bromoethyl sulfonium trifluoromethanesulfonate is a salt complex in which a sulfur atom makes three covalent bonds. This molecule has been proved to act as an efficient annulation reagent which results in formation of synthetically challenging and pharmaceutically important 4-, 5-, 6-, and 7-membered heterocycles in excellent yields. The charge density of the molecule was determined from both experimentally and theoretically derived diffraction data. The stereochemistry and electron density topology of the sulfonium group was analyzed. To understand the chemical reactivity of the molecule, the electrostatic potential difference between the two carbon atoms of the bromoethyl group was investigated. It has been considered that the hydrogen atoms on the carbon atom bound to sulfur are more acidic in character due to their vicinity with the triply covalently bonded positively charged sulfur atom. The electropositivity of the S-attached and Br-attached methylene groups are compared in the experimental and theoretical charge densities using topological atomic charges and electrostatic potential at the molecular surface.

Delivering enhanced cardiovascular (hypertension) disease care through private health facilities in Pakistan.

BACKGROUND: Cardiovascular diseases (CVDs) are one of the leading causes of death and disability in the world. Over 80% of CVD deaths take place in low-and middle-income countries. One-third of the population aged above 40 years suffers from Hypertension (HTN) and this is largely unreported as there is no registry for CVDs. No guidelines are available for use in health care facilities, especially private health facilities where practice among GPs varies considerably. We aim to conduct a Cluster Randomized Controlled trial delivering a quality HTN-CVD care package at strengthened private health facilities as compared to current practice at private health facilities. METHODS/DESIGN: A pragmatic cluster randomized trial, with qualitative and economic studies, will be conducted in Sargodha district of Punjab, Pakistan, from January 2012 to December 2016. At least 912 hypertensives will be registered in the two arms, six clusters per arm. The proposed cluster randomized controlled trial will evaluate the effects of delivering quality HTN-CVD care, through enabled private health care facilities, to achieve better case registration, adherence and hypertension control also blood glucose and serum cholesterol control. The trial will be conducted through the doctors and paramedics at private health facilities. Main outcomes are mean difference in Systolic blood pressure among the two arms. Secondary outcomes are mean change in total serum cholesterol levels and mean change in glycaemic control achieved in the adult hypertensive patients. Individual and Cluster level analysis will be done according to intention-to-treat. DISCUSSION: Due to the high burden of disease where 1 in 3 individuals aged above 45 suffers from hypertension, topped with the fact that there is a dearth of a set of available, standardised guidelines for management, the disease is constantly on a hike in Pakistan. The government has made no effort to issue a set of guidelines adapted specifically for our population and this becomes more of a problem when managing CVD in urban population through private practitioners whose practices vary widely.If our set of context sensitive guidelines show an effectiveness in the proposed intervention districts it will be replicated in other such settings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN34381594.

N,N,N',N'-Tetra-methyl-ethylene-diammonium tetra-chlorido-zincate.

The asymmetric unit of the title compound, (C6H18N2)[ZnCl4], consists of one tetra-chlorido-zincate anion and two half-N,N,N'N'-tetra-methyl-ethylenedi-ammonium cations. Each of the two di-ammonium cations is located about an inversion center and one of them is disordered over two sets of sites in a 0.780 (17):0.220 (17) ratio. The Zn(II) atom has a slightly distorted tetra-hedral coordination environment. The cations and anions are connected via N-H⋯Cl hydrogen bonds into chains extending along [0-11].