cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5876655.v2
title: Lipid-based nanocarrier efficiently delivers highly water soluble drug across the blood–brain barrier into brain

description: Delivering highly water soluble drugs across blood–brain barrier (BBB) is a crucial challenge for the formulation scientists. A successful therapeutic intervention by developing a suitable drug delivery system may revolutionize treatment across BBB. Efforts were given here to unravel the capability of a newly developed fatty acid combination (stearic acid:oleic acid:palmitic acid = 8.08:4.13:1) (ML) as fundamental component of nanocarrier to deliver highly water soluble zidovudine (AZT) as a model drug into brain across BBB. A comparison was made with an experimentally developed standard phospholipid-based nanocarrier containing AZT. Both the formulations had nanosize spherical unilamellar vesicular structure with highly negative zeta potential along with sustained drug release profiles. Gamma scintigraphic images showed both the radiolabeled formulations successfully crossed BBB, but longer retention in brain was observed for ML-based formulation (MGF) as compared to soya lecithin (SL)-based drug carrier (SYF). Plasma and brain pharmacokinetic data showed less clearance, prolonged residence time, more bioavailability and sustained release of AZT from MGF in rats compared to those data of the rats treated with SYF/AZT suspension. Thus, ML may be utilized to successfully develop drug nanocarrier to deliver drug into brain across BBB, in a sustained manner for a prolong period of time and may provide an effective therapeutic strategy for many diseases of brain. Further, many anti-HIV drugs cannot cross BBB sufficiently. Hence, the developed formulation may be a suitable option to carry those drugs into brain for better therapeutic management of HIV.
DOI: 10.6084/m9.figshare.5876655.v1
title: Lipid-based nanocarrier efficiently delivers highly water soluble drug across the blood–brain barrier into brain

description: Delivering highly water soluble drugs across blood–brain barrier (BBB) is a crucial challenge for the formulation scientists. A successful therapeutic intervention by developing a suitable drug delivery system may revolutionize treatment across BBB. Efforts were given here to unravel the capability of a newly developed fatty acid combination (stearic acid:oleic acid:palmitic acid = 8.08:4.13:1) (ML) as fundamental component of nanocarrier to deliver highly water soluble zidovudine (AZT) as a model drug into brain across BBB. A comparison was made with an experimentally developed standard phospholipid-based nanocarrier containing AZT. Both the formulations had nanosize spherical unilamellar vesicular structure with highly negative zeta potential along with sustained drug release profiles. Gamma scintigraphic images showed both the radiolabeled formulations successfully crossed BBB, but longer retention in brain was observed for ML-based formulation (MGF) as compared to soya lecithin (SL)-based drug carrier (SYF). Plasma and brain pharmacokinetic data showed less clearance, prolonged residence time, more bioavailability and sustained release of AZT from MGF in rats compared to those data of the rats treated with SYF/AZT suspension. Thus, ML may be utilized to successfully develop drug nanocarrier to deliver drug into brain across BBB, in a sustained manner for a prolong period of time and may provide an effective therapeutic strategy for many diseases of brain. Further, many anti-HIV drugs cannot cross BBB sufficiently. Hence, the developed formulation may be a suitable option to carry those drugs into brain for better therapeutic management of HIV.
DOI: 10.6084/m9.figshare.5903767.v3
title: New model of proliferative vitreoretinopathy in rabbit for drug delivery and pharmacodynamic studies

description: Blinding retinal diseases become more epidemic as the population ages. These diseases, such as diabetic retinopathy and macular edema, are of chronic nature and require protracted drug presence at the disease site. A sustained intravitreal porous silicon delivery system with dexamethasone (pSiO<sub>2</sub>-COO-DEX) was evaluated in a new rabbit model of proliferative vitreoretinopathy (PVR) in a real treatment design. In contrast to the pretreatment design model, pSiO<sub>2</sub>-COO-DEX was intravitreally injected into the eyes with active inflammation. Subretinal injection of vascular endothelial growth factor (VEGF) and Matrigel induced a late-onset vitreoretinal inflammation that gradually developed into PVR. This method mimics the human disease better than PVR induced by either intravitreal cell injection or trauma. The pSiO<sub>2</sub>-COO-DEX intervened eyes had minimal PVR, while balanced saline solution or free dexamethasone intervened eyes had significantly more PVR formation. In addition, adding VEGF to the Matrigel for subretinal injection induced greater inflammation and retinal neovascularization in comparison to only Matrigel injected under the medullary ray. Clinical and pathological examinations, including fundus fluorescein angiography and optical coherence tomography, confirmed these changes. In the current study, neither subretinal injection of Matrigel or subretinal injection of VEGF and Matrigel induced choroidal neovascularization. However, the current PVR model demonstrates a chronic course with moderate severity, which may be useful for drug screening studies.
DOI: 10.6084/m9.figshare.5903767.v2
title: New model of proliferative vitreoretinopathy in rabbit for drug delivery and pharmacodynamic studies

description: Blinding retinal diseases become more epidemic as the population ages. These diseases, such as diabetic retinopathy and macular edema, are of chronic nature and require protracted drug presence at the disease site. A sustained intravitreal porous silicon delivery system with dexamethasone (pSiO<sub>2</sub>-COO-DEX) was evaluated in a new rabbit model of proliferative vitreoretinopathy (PVR) in a real treatment design. In contrast to the pretreatment design model, pSiO<sub>2</sub>-COO-DEX was intravitreally injected into the eyes with active inflammation. Subretinal injection of vascular endothelial growth factor (VEGF) and Matrigel induced a late-onset vitreoretinal inflammation that gradually developed into PVR. This method mimics the human disease better than PVR induced by either intravitreal cell injection or trauma. The pSiO<sub>2</sub>-COO-DEX intervened eyes had minimal PVR, while balanced saline solution or free dexamethasone intervened eyes had significantly more PVR formation. In addition, adding VEGF to the Matrigel for subretinal injection induced greater inflammation and retinal neovascularization in comparison to only Matrigel injected under the medullary ray. Clinical and pathological examinations, including fundus fluorescein angiography and optical coherence tomography, confirmed these changes. In the current study, neither subretinal injection of Matrigel or subretinal injection of VEGF and Matrigel induced choroidal neovascularization. However, the current PVR model demonstrates a chronic course with moderate severity, which may be useful for drug screening studies.
DOI: 10.6084/m9.figshare.16698592
title: Supplementary Material for: Serum biomarker status with a distinctive pattern in prognosis of gastroenteropancreatic neuroendocrine carcinoma

description: Medicine
DOI: 10.6084/m9.figshare.16698592.v1
title: Supplementary Material for: Serum biomarker status with a distinctive pattern in prognosis of gastroenteropancreatic neuroendocrine carcinoma

description: Medicine
DOI: 10.5517/ccvsmjr
title: CCDC 798235: Experimental Crystal Structure Determination

description: Related Article: Li Yuan, Wen-Guan Lu|2011|Wuji Huaxue Xuebao|27|1324|
DOI: 10.17632/k6g9h8g288.1
title: Transition zone escape induced by India-Eurasia collision explains Cenozoic intracontinental basalts in Central Asia

description: Table S1. Major-element data of minerals, including olivine, clinopyroxene and Fe-Ti oxides from the Piqiang basalts (analyzed by EPMA).
Table S2. Trace-element data of olivine phenocrysts from the Piqiang basalts (analyzed by LA-ICP-MS).
Table S3. U-Pb age data of zircons from the Piqiang basalts.
Table S4. Trace-element data of zircons from the Piqiang basalts and estimated oxygen states.
Table S5. Hf-isotope data of zircons from the Piqiang basalts.
Table S6. Whole-rock major- and trace-element data for the Piqiang basalts.
Table S7. Whole-rock Sr-Nd-Pb-Hf isotope data for the Piqiang basalts.
Table S8. Estimation of water content, redox condition, and crystallization temperature of the Piqiang magmas based on olivine-liquid equilibrium.
Table S9. Trace-element and isotope data for end-members used in geochemical modelling.
DOI: 10.17632/pz7kkhk2bv.1
title: R-group replacement resource

description: A database with R-groups frequently used in medicinal chemistry and their preferred replacements is provided. For frequently used R-groups, replacements are organized in hierarches as specified in the readme.txt file.
DOI: 10.17632/dgtvds3xn5.1
title: ANUVUD, calculation of unit geometry and NBO analysis

description: Gaussian 16 calculations for species ANUVUD

An earlier post investigated large anomeric effects involving two oxygen atoms attached to a common carbon atom. Another entry is ANUVUD[3] with a crystal structure (data DOI: 10.5517/ccdc.csd.cc24zxdg) shown below and CN and CO lengths of 1.391 and 1.559Å, which in this case ARE reasonably replicated by calculation (1.402, 1.499). This effect is promoted by the good leaving group ability of the carboxylate anion and the antiperiplanar orientation of the nitrogen lone pair with respect to the C-O bond, E(2)=35.2 kcal/mol (DOI: 10.14469/hpc/8807)
DOI: 10.17632/h7bxnynd7s.1
title: Raw data - "SUMO orchestrates multiple alternative DNA-protein crosslink repair pathways" (Serbyn et al, Cell Reports 2021)

description: Raw data for the Serbyn et al, 2021 manuscript "SUMO orchestrates multiple alternative DNA-protein crosslink repair pathways". Includes raw FACS analysis data and images of immunoblot, spot assay, tetrad analyses.
DOI: 10.6084/m9.figshare.13213911.v1
title: Direct nose to brain delivery of small molecules: critical analysis of data from a standardized <i>in vivo</i> screening model in rats

description: The blood–brain barrier (BBB) is often a limiting factor for getting drugs in the brain. Bypassing the BBB by intranasal (IN), or also called nose to brain (NTB), route is an interesting and frequently investigated concept for brain drug delivery. However, despite the body of evidence for IN drug delivery in literature over the last decades, reproducibility and interpretation of animal data remain challenging. The objective of this project was to assess the feasibility and value of a standardized IN screening model in rats for the evaluation of direct brain delivery. A chemically diverse set of commercial and internal small molecules were tested in the <i>in vivo</i> model with different doses and/or formulations. Data were analyzed using different ways of ratio calculations: blood concentration at time of sacrifice, total exposure in blood (area under the curve, AUC) and the brain or olfactory bulb concentrations. The IN route was compared to another parenteral route to decide if there is potential direct brain transport. The results show that blood and tissue concentrations and ratios are highly variable and not always reproducible. Potential direct brain delivery was concluded for some compounds, however, sometimes depending on the analysis: using blood levels at sacrifice or AUC could lead to different conclusions. We conclude that a screening model for the evaluation of direct brain transport of small molecules is very difficult to achieve and a conclusion based on a limited number of animals with this variability is questionable.
DOI: 10.17632/4x2w5f63zx.1
title: Seasonal climate variations in the Baltic Sea during the Last Interglacial based on foraminiferal geochemistry

description: We present trace element and stable isotopes data from study sites in the Baltic Sea based on benthic foraminiferal calcite. The data was used for reconstruction of seawater conditions during the last interglacial period (LIG). Our reconstructions reflect the evolution of seasonal temperature and salinity, rather than annual mean conditions.
DOI: 10.6084/m9.figshare.16698595
title: Data_PlosOne.zip

description: Raw Data used for the study of unintentional and intentional interpersonal coordination between human subjects and a robot
DOI: 10.5281/zenodo.5226515
title: Lipidomic dataset on PBMCS and plasma of obese patient with or without dysglycemia

description: Lipidomic dataset on PBMCS and plasma of obese patient with or without dysglycemia.
DOI: 10.5281/zenodo.5226514
title: Lipidomic dataset on PBMCS and plasma of obese patient with or without dysglycemia

description: Lipidomic dataset on PBMCS and plasma of obese patient with or without dysglycemia.
DOI: 10.6084/m9.figshare.12601195.v4
title: Mechanistic and biological characterisation of novel <i>N</i><sup>5</sup>-substituted paullones targeting the biosynthesis of trypanothione in <i>Leishmania</i>

description: Trypanothione synthetase (TryS) produces <i>N</i><sup>1</sup><i>,N<sup>8</sup></i>-bis(glutathionyl)spermidine (or trypanothione) at the expense of ATP. Trypanothione is a metabolite unique and essential for survival and drug-resistance of trypanosomatid parasites. In this study, we report the mechanistic and biological characterisation of optimised <i>N</i><sup>5</sup>-substituted paullone analogues with anti-TryS activity. Several of the new derivatives retained submicromolar IC<sub>50</sub> against leishmanial TryS. The binding mode to TryS of the most potent paullones has been revealed by means of kinetic, biophysical and molecular modelling approaches. A subset of analogues showed an improved potency (EC<sub>50</sub> 0.5–10 µM) and selectivity (20–35) against the clinically relevant stage of <i>Leishmania braziliensis</i> (mucocutaneous leishmaniasis) and <i>L. infantum</i> (visceral leishmaniasis). For a selected derivative, the mode of action involved intracellular depletion of trypanothione. Our findings shed light on the molecular interaction of TryS with rationally designed inhibitors and disclose a new set of compounds with on-target activity against different <i>Leishmania</i> species.
DOI: 10.6084/m9.figshare.12601195.v5
title: Mechanistic and biological characterisation of novel <i>N</i> <sup>5</sup>-substituted paullones targeting the biosynthesis of trypanothione in <i>Leishmania</i>

description: Trypanothione synthetase (TryS) produces <i>N</i> <sup>1</sup> <i>,N<sup>8</sup> </i>-bis(glutathionyl)spermidine (or trypanothione) at the expense of ATP. Trypanothione is a metabolite unique and essential for survival and drug-resistance of trypanosomatid parasites. In this study, we report the mechanistic and biological characterisation of optimised <i>N</i> <sup>5</sup>-substituted paullone analogues with anti-TryS activity. Several of the new derivatives retained submicromolar IC<sub>50</sub> against leishmanial TryS. The binding mode to TryS of the most potent paullones has been revealed by means of kinetic, biophysical and molecular modelling approaches. A subset of analogues showed an improved potency (EC<sub>50</sub> 0.5–10 µM) and selectivity (20–35) against the clinically relevant stage of <i>Leishmania braziliensis</i> (mucocutaneous leishmaniasis) and <i>L. infantum</i> (visceral leishmaniasis). For a selected derivative, the mode of action involved intracellular depletion of trypanothione. Our findings shed light on the molecular interaction of TryS with rationally designed inhibitors and disclose a new set of compounds with on-target activity against different <i>Leishmania</i> species.
DOI: 10.6084/m9.figshare.10303787
title: Inhibition of SARS-CoV 3CL protease by flavonoids

description: There were severe panics caused by Severe Acute Respiratory Syndrome (SARS) and Middle-East Respiratory Syndrome-Coronavirus. Therefore, researches targeting these viruses have been required. Coronaviruses (CoVs) have been rising targets of some flavonoids. The antiviral activity of some flavonoids against CoVs is presumed directly caused by inhibiting 3C-like protease (3CLpro). Here, we applied a flavonoid library to systematically probe inhibitory compounds against SARS-CoV 3CLpro. Herbacetin, rhoifolin and pectolinarin were found to efficiently block the enzymatic activity of SARS-CoV 3CLpro. The interaction of the three flavonoids was confirmed using a tryptophan-based fluorescence method, too. An induced-fit docking analysis indicated that S1, S2 and S3′ sites are involved in binding with flavonoids. The comparison with previous studies showed that Triton X-100 played a critical role in objecting false positive or overestimated inhibitory activity of flavonoids. With the systematic analysis, the three flavonoids are suggested to be templates to design functionally improved inhibitors.
DOI: 10.6084/m9.figshare.10303787.v2
title: Inhibition of SARS-CoV 3CL protease by flavonoids

description: There were severe panics caused by Severe Acute Respiratory Syndrome (SARS) and Middle-East Respiratory Syndrome-Coronavirus. Therefore, researches targeting these viruses have been required. Coronaviruses (CoVs) have been rising targets of some flavonoids. The antiviral activity of some flavonoids against CoVs is presumed directly caused by inhibiting 3C-like protease (3CLpro). Here, we applied a flavonoid library to systematically probe inhibitory compounds against SARS-CoV 3CLpro. Herbacetin, rhoifolin and pectolinarin were found to efficiently block the enzymatic activity of SARS-CoV 3CLpro. The interaction of the three flavonoids was confirmed using a tryptophan-based fluorescence method, too. An induced-fit docking analysis indicated that S1, S2 and S3′ sites are involved in binding with flavonoids. The comparison with previous studies showed that Triton X-100 played a critical role in objecting false positive or overestimated inhibitory activity of flavonoids. With the systematic analysis, the three flavonoids are suggested to be templates to design functionally improved inhibitors.
DOI: 10.6084/m9.figshare.10303787.v1
title: Inhibition of SARS-CoV 3CL protease by flavonoids

description: There were severe panics caused by Severe Acute Respiratory Syndrome (SARS) and Middle-East Respiratory Syndrome-Coronavirus. Therefore, researches targeting these viruses have been required. Coronaviruses (CoVs) have been rising targets of some flavonoids. The antiviral activity of some flavonoids against CoVs is presumed directly caused by inhibiting 3C-like protease (3CLpro). Here, we applied a flavonoid library to systematically probe inhibitory compounds against SARS-CoV 3CLpro. Herbacetin, rhoifolin and pectolinarin were found to efficiently block the enzymatic activity of SARS-CoV 3CLpro. The interaction of the three flavonoids was confirmed using a tryptophan-based fluorescence method, too. An induced-fit docking analysis indicated that S1, S2 and S3′ sites are involved in binding with flavonoids. The comparison with previous studies showed that Triton X-100 played a critical role in objecting false positive or overestimated inhibitory activity of flavonoids. With the systematic analysis, the three flavonoids are suggested to be templates to design functionally improved inhibitors.
DOI: 10.6084/m9.figshare.12601195
title: Mechanistic and biological characterisation of novel <i>N</i> <sup>5</sup>-substituted paullones targeting the biosynthesis of trypanothione in <i>Leishmania</i>

description: Trypanothione synthetase (TryS) produces <i>N</i> <sup>1</sup> <i>,N<sup>8</sup> </i>-bis(glutathionyl)spermidine (or trypanothione) at the expense of ATP. Trypanothione is a metabolite unique and essential for survival and drug-resistance of trypanosomatid parasites. In this study, we report the mechanistic and biological characterisation of optimised <i>N</i> <sup>5</sup>-substituted paullone analogues with anti-TryS activity. Several of the new derivatives retained submicromolar IC<sub>50</sub> against leishmanial TryS. The binding mode to TryS of the most potent paullones has been revealed by means of kinetic, biophysical and molecular modelling approaches. A subset of analogues showed an improved potency (EC<sub>50</sub> 0.5–10 µM) and selectivity (20–35) against the clinically relevant stage of <i>Leishmania braziliensis</i> (mucocutaneous leishmaniasis) and <i>L. infantum</i> (visceral leishmaniasis). For a selected derivative, the mode of action involved intracellular depletion of trypanothione. Our findings shed light on the molecular interaction of TryS with rationally designed inhibitors and disclose a new set of compounds with on-target activity against different <i>Leishmania</i> species.
DOI: 10.6084/m9.figshare.12850343.v3
title: Design, synthesis and biological evaluation of a new thieno[2,3-<i>d</i>]pyrimidine-based urea derivative with potential antitumor activity against tamoxifen sensitive and resistant breast cancer cell lines

description: Breast cancer (BC) and endocrine resistance to chemotherapy are challenging problems where angiogenesis plays fundamental roles. Thus, targeting of VEGFR-2 signalling pathway has been an attractive approach. In this study, we synthesised a new sorafenib analogue, thieno[2,3-<i>d</i>]pyrimidine based urea derivative, <b>KM6</b>. It showed 65% inhibition of VEGF2 tyrosine kinase activity and demonstrated a potential antitumor activity in TAM-resistant, LCC2, and its parental MCF7 BC cells. <b>KM6</b> retained the sensitivity of LCC2 through upregulation of key enzymes of apoptosis and proteins of cell death including caspases 3, 8, 9, P53, BAX/BCL-2 ratio and LDH in media. It downregulated mRNA expression of Ki-67, survivin, Akt, and reduced levels of ROS and glucose uptake. Moreover, <b>KM6</b> reduced the levels of inflammation markers PGE2, COX2, IL-1β and IL6 and metastasis markers MMP-2 and MMP-9. In conclusion, <b>KM6</b> is a promising compound for ER + and TAM-resistant BC with many potential antitumor and polypharmacological mechanisms.
DOI: 10.6084/m9.figshare.12850343
title: Design, synthesis and biological evaluation of a new thieno[2,3-<i>d</i>]pyrimidine-based urea derivative with potential antitumor activity against tamoxifen sensitive and resistant breast cancer cell lines

description: Breast cancer (BC) and endocrine resistance to chemotherapy are challenging problems where angiogenesis plays fundamental roles. Thus, targeting of VEGFR-2 signalling pathway has been an attractive approach. In this study, we synthesised a new sorafenib analogue, thieno[2,3-<i>d</i>]pyrimidine based urea derivative, <b>KM6</b>. It showed 65% inhibition of VEGF2 tyrosine kinase activity and demonstrated a potential antitumor activity in TAM-resistant, LCC2, and its parental MCF7 BC cells. <b>KM6</b> retained the sensitivity of LCC2 through upregulation of key enzymes of apoptosis and proteins of cell death including caspases 3, 8, 9, P53, BAX/BCL-2 ratio and LDH in media. It downregulated mRNA expression of Ki-67, survivin, Akt, and reduced levels of ROS and glucose uptake. Moreover, <b>KM6</b> reduced the levels of inflammation markers PGE2, COX2, IL-1β and IL6 and metastasis markers MMP-2 and MMP-9. In conclusion, <b>KM6</b> is a promising compound for ER + and TAM-resistant BC with many potential antitumor and polypharmacological mechanisms.