Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Mass spectrometric conditions for cyclobenzaprine, desmethyl cyclobenzaprine and cyclobenzaprine N-oxide. ESI: electrospray ionization, m/z: mass-to-charge ratio, msec: millisecond.

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques:

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: LC-MS/MS chromatogram of desmethyl cyclobenzaprine, cyclobenzaprine, cyclobenzaprine-d3 and cyclobenzaprine N-oxide with the respective structural formula.

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques: Liquid Chromatography with Mass Spectroscopy

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Summary of accuracy and precision results for cyclobenzaprine, desmethyl cyclobenzaprine and cyclobenzaprine N-oxide (accuracy presented as mean relative error and precision as coefficient of variation, n = 5 per run). CV, coefficient of variation; LLOQ, Lower limit of quantification; QC, quality control.

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques: Control

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Impact of excipient addition in preformulation and formulation development of cyclobenzaprine. A : Cumulative amount of permeated drug per cm 2 of the respective sublingual tablet (mean ± SEM; n ≥ 5). B : Cumulative amount of permeated drug per cm 2 of the respective solution (mean ± SEM; n ≥ 5) adapted from , Int. J. Pharm. 2021. C : Dissolution of the respective sublingual tablet (mean ± SEM; n = 3). D : Correlation of obtained cyclobenzaprine permeability with the added amount of dibasic phosphate (mean ± SEM). R 2 : determination coefficient, SEM: standard error of the mean, *: significant value (p < 0.05; unpaired t-test).

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques: Formulation, Dissolution, Permeability

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Disintegration of cyclobenzaprine sublingual tablets after addition of 150 µL freshly collected human saliva in dependence on time.

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques:

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Cytochrome P450 metabolism of cyclobenzaprine. A : Scheme of cyclobenzaprine demethylation by CYP isoenzymes. B : Cumulative amount of permeated desmethyl cyclobenzaprine per cm 2 (mean ± SEM; n = 8). C : Formation of desmethyl cyclobenzaprine by different mucosae and approaches (mean ± SEM; n ≥ 2). D : Formation of desmethyl cyclobenzaprine by human liver microsomes per time (mean ± SEM; n = 3). HLM: human liver microsomes, LLOQ: lower limit of quantification .

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques:

Journal: Pharmaceutics

Article Title: Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies

doi: 10.3390/pharmaceutics13091409

Figure Lengend Snippet: Alteration of cyclobenzaprine sublingual tablets under ambient and stress conditions. ( A ): Cumulative amount of permeated drug per cm 2 of the respective sublingual tablet stored (mean ± SEM; n ≥ 4). ( B ): Dissolution of the respective sublingual tablet stored (mean ± SEM; n = 3). ( C , D ): Visual and microscopic inspection of the primary packaging material and the tablet surface after storage under ambient conditions and stress conditions, respectively. ( E , F ): TOF-MS scan of the rinsed residuals from packaging material after storage under ambient conditions and stress conditions, respectively. m/z: mass-to-charge ratio, SEM: standard error of the mean , *: significant value (p < 0.05; unpaired t-test).

Article Snippet: The simultaneous quantification of cyclobenzaprine hydrochloride (≥98%, Hetero drugs Ltd., Hyderabad, India), its main metabolite desmethyl cyclobenzaprine hydrochloride (99.8%, Toronto Research Chemicals, Toronto, Canada) and cyclobenzaprine N-oxide (96%, Toronto Research Chemicals, Toronto, Canada) as its major degradation product was performed by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Shimadzu Prominence, Shimadzu Europe, Duisburg, Germany; AB Sciex API 2000, Darmstadt, Germany).

Techniques: Dissolution

Journal: Translational Pediatrics

Article Title: Development and external validation of a mitophagy-related diagnostic model for biliary atresia based on cellular infiltration patterns

doi: 10.21037/tp-2025-1-864

Figure Lengend Snippet: Single cell sequencing and immunohistochemistry validate key molecular markers for BA. (A) Representative immunohistochemistry images validating the protein expression of mitophagy-related genes ( IGF2BP3 , NEDD4L , and ALDH2 ) in liver tissues from BA patients and controls (scale bar =100 µm). Ctrl images are from non-tumor liver tissue adjacent to hepatoblastoma specimens. Positive staining appears as brown discoloration and infiltrating immune cells were indicated by red arrows. (B) Differential analysis of single-cell transcription. (a) Single-cell’s cell classification landscape in all samples. (b) The single-cell expression differences of IGF2BP3, NEDD4L, PPIB, and ALDH2 between BA and Ctrl groups. BA, biliary atresia; Ctrl, control; FC, fold change.

Article Snippet: Next, sections were incubated overnight at 4 °C with the following primary antibodies: anti-human ALDH2 (HUABIO, Hangzhou, China; M1509-1, 1:800), NEDD4L (Proteintech, Wuhan, China; 13690-1-AP, 1:800), and IGF2BP3 (Proteintech, Wuhan, China; 14642-1-AP, 1:800).

Techniques: Single Cell, Sequencing, Immunohistochemistry, Expressing, Staining, Control

Journal: Translational Pediatrics

Article Title: Development and external validation of a mitophagy-related diagnostic model for biliary atresia based on cellular infiltration patterns

doi: 10.21037/tp-2025-1-864

Figure Lengend Snippet: The interaction between drugs and IGF2BP3 and NEDD4L proteins. (A-C) The interaction between cyclosporine and IGF2BP3 protein. (D-F) The interaction between cyclosporine and NEDD4L protein. Blue represents drug molecules, with red indicating oxygen atoms within the molecules. Green represents amino acid residues of the protein interacting with the drug molecules. The yellow background indicates the average interaction energy between the protein and drugs (average of 10 simulations).

Article Snippet: Next, sections were incubated overnight at 4 °C with the following primary antibodies: anti-human ALDH2 (HUABIO, Hangzhou, China; M1509-1, 1:800), NEDD4L (Proteintech, Wuhan, China; 13690-1-AP, 1:800), and IGF2BP3 (Proteintech, Wuhan, China; 14642-1-AP, 1:800).

Techniques:

Journal: Translational Pediatrics

Article Title: Development and external validation of a mitophagy-related diagnostic model for biliary atresia based on cellular infiltration patterns

doi: 10.21037/tp-2025-1-864

Figure Lengend Snippet: Potential schematic representation of the BA-CIMDGM genes in the pathogenesis of BA. Upregulated IGF2BP3 in T cells and NEDD4L in macrophages leads to impaired mitophagy and promotes immune activation and cytokines released. And the downregulation of ALDH2 in hepatocytes compromises the mitochondrial antioxidant defense and excessive ROS production, synergistically driving biliary epithelial cell injury and progressive liver fibrosis. BA, biliary atresia; BA-CIMDGM, Biliary Atresia Cell Infiltration Mitophagy Diagnostic Gene Model; ROS, reactive oxygen species.

Article Snippet: Next, sections were incubated overnight at 4 °C with the following primary antibodies: anti-human ALDH2 (HUABIO, Hangzhou, China; M1509-1, 1:800), NEDD4L (Proteintech, Wuhan, China; 13690-1-AP, 1:800), and IGF2BP3 (Proteintech, Wuhan, China; 14642-1-AP, 1:800).

Techniques: Activation Assay, Diagnostic Assay

Journal: Frontiers in Veterinary Science

Article Title: Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration

doi: 10.3389/fvets.2020.580735

Figure Lengend Snippet: Mean plasma pantoprazole concentration (logarithmic scale) vs. time (hr) profiles for neonatal calves ( n = 9) following intravenous (IV) single dose administration of 1.0 mg/kg of pantoprazole.

Article Snippet: Pantoprazole sulfone (Toronto Research Chemicals, Ontario, Canada) became the analyte spiked into blank tissue samples to generate calibration spikes and QC samples.

Techniques: Clinical Proteomics, Concentration Assay

Journal: Frontiers in Veterinary Science

Article Title: Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration

doi: 10.3389/fvets.2020.580735

Figure Lengend Snippet: Pantoprazole pharmacokinetic parameters following a single intravenous (1 mg/kg) administration to neonatal Holstein calves.

Article Snippet: Pantoprazole sulfone (Toronto Research Chemicals, Ontario, Canada) became the analyte spiked into blank tissue samples to generate calibration spikes and QC samples.

Techniques:

Journal: Frontiers in Veterinary Science

Article Title: Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration

doi: 10.3389/fvets.2020.580735

Figure Lengend Snippet: Tissue concentrations of pantoprazole sulfone (μg/g) in collected tissues 1, 3, and 5 days after intravenous administration of pantoprazole (1 mg/kg) from study calves.

Article Snippet: Pantoprazole sulfone (Toronto Research Chemicals, Ontario, Canada) became the analyte spiked into blank tissue samples to generate calibration spikes and QC samples.

Techniques:

Journal: Frontiers in Veterinary Science

Article Title: Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration

doi: 10.3389/fvets.2020.580735

Figure Lengend Snippet: Comparisons of pharmacokinetic parameters of pantoprazole in domestic animal species, after single dose intravenous administration.

Article Snippet: Pantoprazole sulfone (Toronto Research Chemicals, Ontario, Canada) became the analyte spiked into blank tissue samples to generate calibration spikes and QC samples.

Techniques:

Journal: Breast Cancer Research : BCR

Article Title: Effects of lovastatin on breast cancer cells: a proteo-metabonomic study

doi: 10.1186/bcr2485

Figure Lengend Snippet: Cell proliferation of human breast cancer cell lines . (a) MDAMB231 and (b) MDAMB468. Cells were treated with increasing concentrations of lovastatin lactone or lovastatin acid (μg/mL) for 48 hours. Data are presented as mean ± standard deviation (n = 5) * P < 0.05;** P < 0.05; *** P < 0.001.

Article Snippet: Lovastatin (in its lactone and hydroxy acid form) was purchased from Toronto Research Chemicals (North York, Ontario, Canada).

Techniques: Standard Deviation

Journal: Breast Cancer Research : BCR

Article Title: Effects of lovastatin on breast cancer cells: a proteo-metabonomic study

doi: 10.1186/bcr2485

Figure Lengend Snippet: Changes in expression of proteins involved in (a) regulation of cell cycle and cell death and (b) oxidative and metabolic processes of human MDAMB231 and MDAMB468 cells . Both cell lines were treated with 8 μg/mL lovastatin lactone (Lova Lac) or lovastatin acid (Lova Ac) for 48 hours. Data represent relative spot volumes (as calculated from two-dimensional gel images of whole cell extracts; data are presented as mean ± standard deviation (n = 5) * P < 0.05;** P < 0.05; *** P < 0.001). Gel spots which showed significant differences in their volume between the control and lovastatin-treated cells were cut-out, proteins were digested and analyzed using liquid chromatography (LC) mass spectrometry (MS)/MS analysis. In MDAMB231 cells they were identified as GTPase-activating protein SH3-domain-binding protein 1 (G3BP1), TNF type 1 receptor-associated protein (TRAP1) and glutathione S-transferase (GST) omega proteins (Table 1a), whereas the spot belonging to citrate lyase beta and sterol carrier protein 2 (SCP-2) originated from MDAMB468 cells (Table 1b). Cofilin1/2 was identified as upregulated in both cell lines. The image and changes as observed in MDAMB231 cells is shown.

Article Snippet: Lovastatin (in its lactone and hydroxy acid form) was purchased from Toronto Research Chemicals (North York, Ontario, Canada).

Techniques: Expressing, Two-Dimensional Gel Electrophoresis, Standard Deviation, Control, Liquid Chromatography, Mass Spectrometry, Tandem Mass Spectroscopy, Binding Assay

Journal: Breast Cancer Research : BCR

Article Title: Effects of lovastatin on breast cancer cells: a proteo-metabonomic study

doi: 10.1186/bcr2485

Figure Lengend Snippet: Western blot analysis of proteins involved in small GTPase-mediated cell signaling . Breast cancer cell lines MDAMB231 and MDAMB468 were treated with 8 μg/mL lovastatin lactone (Lova Lac) or lovastatin acid (Lova Ac) for 48 hours. For key proteins, western blot analysis was performed based on MDAMB231 cell extracts (for Ras homolog gene family member A (RhoA), cell division cycle 42 (CDC42) and GTPase-activating protein SH3-domain-binding protein 1 - phospho form (pG3BP1)), otherwise both cell lines are shown. Densitometry data were normalized based on the amount of β-actin. Data are presented as means ± standard deviations (n = 3) * P < 0.05;** P < 0.05; *** P < 0.001). Gel images were cropped to improve the clarity and conciseness of the presentation. GDI-2, Rho GDP dissociation inhibitor 2.

Article Snippet: Lovastatin (in its lactone and hydroxy acid form) was purchased from Toronto Research Chemicals (North York, Ontario, Canada).

Techniques: Western Blot, Binding Assay

Journal: Breast Cancer Research : BCR

Article Title: Effects of lovastatin on breast cancer cells: a proteo-metabonomic study

doi: 10.1186/bcr2485

Figure Lengend Snippet: Western blot analysis of proteins involved in regulation of the cell cycle including the modulation of the E2F1-Rb activity . Breast cancer cell lines MDAMB231 and MDAMB468 were treated with 8 μg/mL lovastatin lactone (Lova Lac) or lovastatin acid (Lova Ac) for 48 hours. Western blot analysis of prohibitin was performed based on MDAMB231 cell extracts, otherwise both cell lines are shown. Densitometry data were normalized based on the amount of β-actin. Data are presented as means ± standard deviations (n = 3) * P < 0.05;** P < 0.05; *** P < 0.001. Gel images were cropped to improve the clarity and conciseness of the presentation. HMGB1, high-mobility group box 1; MCM7, minichromosome maintenance protein 7; MSH2, MutS homolog 2.

Article Snippet: Lovastatin (in its lactone and hydroxy acid form) was purchased from Toronto Research Chemicals (North York, Ontario, Canada).

Techniques: Western Blot, Activity Assay

Journal: Breast Cancer Research : BCR

Article Title: Effects of lovastatin on breast cancer cells: a proteo-metabonomic study

doi: 10.1186/bcr2485

Figure Lengend Snippet: Western blot analysis of proteins involved in regulation of apoptosis and AKT-signaling . Breast cancer cell lines MDAMB231 and MDAMB468 were treated with 8 μg/mL lovastatin lactone (Lova Lac) or lovastatin acid (Lova Ac) for 48 hours. For key proteins, western blot analysis of phosphatase and tensin homolog (PTEN), pAkt and N-myc downstream regulated gene 1 (NDRG1) was performed based on MDAMB231 cell extracts, otherwise both cell lines are shown. Densitometry data were normalized based on the amount of β-actin. Data are presented as means ± standard deviations (n = 3) * P < 0.05;** P < 0.05; *** P < 0.001). Gel images were cropped to improve the clarity and conciseness of the presentation. PCNA, proliferating cell nuclear antigen.

Article Snippet: Lovastatin (in its lactone and hydroxy acid form) was purchased from Toronto Research Chemicals (North York, Ontario, Canada).

Techniques: Western Blot

Journal: Breast Cancer Research : BCR

Article Title: Effects of lovastatin on breast cancer cells: a proteo-metabonomic study

doi: 10.1186/bcr2485

Figure Lengend Snippet: Intracellular concentrations (nmol/g cell weight) of 13 C-labeled endogenous metabolites (glycolysis and TCA cycle intermediates, glucose) and lipid metabolites (choline-containing phospholipids, cholesterol)

Article Snippet: Lovastatin (in its lactone and hydroxy acid form) was purchased from Toronto Research Chemicals (North York, Ontario, Canada).

Techniques:

Journal: Breast Cancer Research : BCR

Article Title: Effects of lovastatin on breast cancer cells: a proteo-metabonomic study

doi: 10.1186/bcr2485

Figure Lengend Snippet: Changes in intracellular 13 C-labeled -alanine, -lactate, -glucose and -glutamine signals in MDAMB468 cells treated with 8 μg/mL lovastatin acid for 48 hours . 13 C-NMR spectra with embedded, corresponding 1 H-NMR spectra are shown (including citrate at 2.52 + 2.69 ppm). Arrows indicate the direction of signal changes (increase or decrease). Ala, alanine; Gln, glutamine; Glu, glutamine; GSH, total glutathione; Lac, lactate.

Article Snippet: Lovastatin (in its lactone and hydroxy acid form) was purchased from Toronto Research Chemicals (North York, Ontario, Canada).

Techniques: Labeling

Journal: Breast Cancer Research : BCR

Article Title: Effects of lovastatin on breast cancer cells: a proteo-metabonomic study

doi: 10.1186/bcr2485

Figure Lengend Snippet: Representative 1 H-NMR spectra of MDAMB468 lipid extracts . Cells were treated with 8 μg/mL lovastatin acid for 48 hours. Arrows indicate the direction of signal changes (decrease). Chol, cholesterol (C18 and C19, CH 3 ); Δ (δ), double bond; F, fatty acid side chain; F α , F β , protons in the fatty acid chain; Fmix: -(CH 2 )n-, tCho, total choline-containing phospholipids.

Article Snippet: Lovastatin (in its lactone and hydroxy acid form) was purchased from Toronto Research Chemicals (North York, Ontario, Canada).

Techniques:

Journal: Breast Cancer Research : BCR

Article Title: Effects of lovastatin on breast cancer cells: a proteo-metabonomic study

doi: 10.1186/bcr2485

Figure Lengend Snippet: Schematic diagram summarizing the effects of lovastatin lactone and acid on signaling pathways as found in the present study . The solid arrows mark the directional change of proteins (up- or down-regulation). Doted arrows mark hypothesized change in protein expression/activity. CDC42, cell division cycle 42; G3BP1, GTPase-activating protein SH3-domain-binding protein 1; GDI-2, Rho GDP dissociation inhibitor 2; LIMK, LIM domain kinase; MAPK, mitogen-activated protein kinase; MCM7, minichromosome maintenance protein 7; MSH2, MutS homolog 2; NDRG1, N-myc downstream regulated gene 1; p21, cyclin-dependent kinase inhibitor 1A; PCNA, proliferating cell nuclear antigen; PI3K, phosphoinositide 3-kinase; PTEN, phosphatase and tensin homolog; Rb, retinoblastoma protein; RhoA, Ras homolog gene family member A.

Article Snippet: Lovastatin (in its lactone and hydroxy acid form) was purchased from Toronto Research Chemicals (North York, Ontario, Canada).

Techniques: Protein-Protein interactions, Expressing, Activity Assay, Binding Assay