Biosimilar or Not: Physicochemical and Biological Characterization of MabThera and Its Two Biosimilar Candidates.

The development of therapeutic biosimilar antibodies has become an important driving force of the modern biopharmaceutical industry. In this study, physiochemical characteristics (amino acid sequence, intact/subunit molecular weight, isoelectric point, post-translation modification, and disulfide linkage pattern), purity (charge variants, high and low molecular weight variants), antigen binding activity, Fc receptor binding affinity and Fc-effector function (CDC and ADCC) were analyzed by using an extensive set of state-of-the-art and orthogonal analytical technologies to provide a comprehensive characterization of the innovative product rituximab and two biosimilar candidates. The similarity study showed that biosimilar candidate 1 (BC1) and the reference product (RP) MabThera had an identical protein amino acid sequences and highly similar primary structures along with similar purity, heterogeneity profiles, antigen binding activity, Fc receptor binding affinity, and Fc-effector functions.

Flurochloridone induces Sertoli cell apoptosis through ROS-dependent mitochondrial pathway.

Flurochloridone (FLC), a selective herbicide used on a global scale, has been reported to have male reproductive toxicity which underlying mechanism is still largely unknown. The present study was conducted to determine the effects of FLC on Sertoli cell and explore its mechanism by using normal mouse Sertoli (TM4) cell line. Our data indicate that FLC suppressed proliferation of TM4 cells in a dose- and time-dependent manner.

Multiple-fingerprint analysis of Poria cocos polysaccharide by HPLC combined with chemometrics methods.

In this study, the multiple fingerprints, which were integrated with HPGFC-ELSD (high performance gel filtration chromatography - evaporative light scattering detector) fingerprint, PMP-HPLC-DAD (1-phenyl-3-methyl-5-pyrazolone-high performance liquid chromatography - diode array detector) fingerprint of complete acid hydrolysates and HILIC-HPLC-ELSD (hydrophilic interaction - high performance liquid chromatography - evaporative light scattering detector) fingerprint of enzyme hydrolysates, were established to evaluate the quality of polysaccharides from Poria cocos (PCPs). The similarity evaluation showed that 16 batches of PCPs from different origins had high similarity in structural characteristics based on the multiple fingerprints. The chromatographic data of multiple fingerprints of PCPs were fused, processed and analyzed by chemometric methods including HCA (hierarchical cluster analysis), PCA (principal component analysis) and PLS-DA (partial least squares discriminant analysis).

Marker peptide screening and species-specific authentication of Pheretima using proteomics.

Pheretima is a common and valuable animal-derived medication used in traditional Chinese medicine. There are four species of Pheretima specified in the Chinese Pharmacopoeia (2015 edition), i.e.

Glucose-Binding of Periplasmic Protein GltB Activates GtrS-GltR Two-Component System in .

A two-component system GtrS-GltR is required for glucose transport activity in and plays a key role during -host interactions. However, the mechanism of action of GtrS-GltR has not been definitively established. Here, we show that , which encodes a periplasmic glucose binding protein, is essential for the glucose-induced activation of GtrS-GltR in .

Genome-Wide Mapping Reveals Complex Regulatory Activities of BfmR in .

BfmR is a response regulator that modulates diverse pathogenic phenotypes and induces an acute-to-chronic virulence switch in , an important human pathogen causing serious nosocomial infections. However, the mechanisms of action of BfmR remain largely unknown. Here, using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq), we showed that 174 chromosomal regions of MPAO1 genome were highly enriched by coimmunoprecipitation with a C-terminal Flag-tagged BfmR.

Integrative Analysis of Complement System to Prognosis and Immune Infiltrating in Colon Cancer and Gastric Cancer.

Background: The complement system acts as an integral part of the innate immune response, which acts primarily to remove pathogens and injured cells. Emerging evidence has shown the activation of the immune regulatory function of complements in the tumor microenvironment (TME). We revealed the expression levels of various complements in human cancers and their role in tumor prognosis and immune infiltration.

BacteriaAnchoring Hybrid Liposome Capable of Absorbing Multiple Toxins for Antivirulence Therapy of Infection.

Antivirulence therapy by cell membrane coated nanoparticles has shown promise against bacterial infections. However, current approaches remain unsatisfactory when facing () infections, since the secretes multiple bacterial toxins including endotoxins and exotoxins that are challenging to eliminate simultaneously. What is worse, the absorptive scavengers normally rely on random contact of the diffuse toxins, which is not efficient.

Plant metabolomics for studying the effect of two insecticides on comprehensive constituents of Lonicerae Japonicae Flos.

Pesticides' overuse and misuse have been reported to induce ingredient variations in herbal medicine, which is now gaining attention in the medicinal field as a form of alternative medicine. To date, available studies on pesticide-induced ingredient variations of herbal medicine are limited only on a few compounds and remain most others unexamined. In this study, a plant metabolomics-based strategy was performed to systematically explore the effects of two frequently used insecticides on the comprehensive constituents of Lonicerae Japonicae Flos (LJF), the flower buds of Lonicera japonica Thunb.

Helix Matrix Transformation Combined With Convolutional Neural Network Algorithm for Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry-Based Bacterial Identification.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis is a rapid and reliable method for bacterial identification. Classification algorithms, as a critical part of the MALDI-TOF MS analysis approach, have been developed using both traditional algorithms and machine learning algorithms. In this study, a method that combined helix matrix transformation with a convolutional neural network (CNN) algorithm was presented for bacterial identification.

Calibration transfer between modelled and commercial pharmaceutical tablet for API quantification using backscattering NIR, Raman and transmission Raman spectroscopy (TRS).

Backscattering NIR, Raman (BSR) and transmission Raman spectroscopy (TRS) coupled with chemometrics have shown to be rapid and non-invasive tools for the quantification of active pharmaceutical ingredient (API) content in tablets. However, the developed models are generally specifically related to the measurement conditions and sample characteristics. In this study, a number of calibration transfer methods, including DS, PDS, DWPDS, GLSW and SST, were evaluated for the spectra correction between modelled tablets produced in the laboratory and commercial samples.

Ursodeoxycholic Acid Protects Against Arsenic Induced Hepatotoxicity by the Nrf2 Signaling Pathway.

Arsenic is ubiquitous toxic metalloid responsible for many human diseases all over the world. Contrastingly, Ursodeoxycholic acid (UDCA) has been suggested as efficient antioxidant in various liver diseases. However, there are no reports of the effects of UDCA on arsenious acid [As(III)]-induced hepatotoxicity.

Untargeted multi-residue method for the simultaneous determination of 141 veterinary drugs and their metabolites in pork by high-performance liquid chromatography time-of-flight mass spectrometry.

A rapid, simple and generic analytical method has been developed for the analysis of veterinary drugs in pork by a quadrupole time-of-flight mass spectrometry (Q-TOF MS). This method allows for the simultaneous identification, screening and quantitation of 141 veterinary drug residues and metabolites from eighteen different classes. After extraction with acetonitrile/water and clean-up with C cartridges, the samples were analyzed by HPLC-Q-TOF MS.

Mutation-induced remodeling of the BfmRS two-component system in clinical isolates.

Genetic mutations are a primary driving force behind the adaptive evolution of bacterial pathogens. Multiple clinical isolates of , an important human pathogen, have naturally evolved one or more missense mutations in , which encodes the sensor histidine kinase of the BfmRS two-component system (TCS). A mutant BfmS protein containing both the L181P and E376Q substitutions increased the phosphorylation and thus the transcriptional regulatory activity of its cognate downstream response regulator, BfmR.

Screening for illegal addition of glucocorticoids in adulterated cosmetic products using ultra-performance liquid chromatography/tandem mass spectrometry with precursor ion scanning.

Rationale: The screening for illegal adulteration of glucocorticoids (GCs) in cosmetics is challenging due to the vast variety of potential GCs that are present to improve the declared effects. An effective analytical method to screen illegally added GCs in cosmetics is vital to protect consumers.

Methods: An ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method using precursor ion scanning (PIS) acquisition mode was developed to screen GCs in cosmetics.

Endoplasmic reticulum stress-related neuroinflammation and neural stem cells decrease in mice exposure to paraquat.

Paraquat (PQ), a widely used herbicide, could cause neurodegenerative diseases, yet the mechanism remains incompletely understood. This study aimed to investigate the direct effect of PQ on NSC in vivo and its possible mechanism. Adult C57BL/6 mice were subcutaneously injected with 2 mg/kg PQ, 20 mg/kg PQ or vehicle control once a week for 2 weeks, and sacrificed 1 week after the last PQ injection.

[Contamination of zearalenone and its dietary exposure assessment in coix seed in Shanghai].

Objective: To analyze the zearalenone(ZEN) level in coix seed, and assess the risk of dietary exposure of ZEN in coix seed in Shanghai.

Methods: The ZEN contents of 147 coix seed samples collected in Shanghai were determined. The consumption data of 730 adults in Shanghai was collected by questionnaire survey with random sampling method.

Combined application of extended depth of field imaging, image stitching and polarized microscopy techniques in identification of .

Objective: As traditional techniques for microscopic identification of Chinese medicines currently lack objective and high-quality reference images, here we developed a systemic procedure to be used in microscopic identification of Chinese medicines, which would lead to more objective, effective and accurate identification process.

Methods: (Jixueteng in Chinese) was used as the specimen in the development of such procedure. Jixueteng samples were microscopically examined in bright- and dark-field microscopy.

Comparative anti-inflammatory effect of curcumin at air-liquid interface and submerged conditions using lipopolysaccharide stimulated human lung epithelial A549 cells.

Background: Inhalation of aerosolized drugs is a promising entry route for rapid and non-invasive therapeutics delivery to the lung. Curcumin exhibits potent anti-inflammatory properties, which are effective for use in lung diseases. The anti-inflammatory properties of curcumin have been widely studied in vitro with cells cultured in submerged conditions, however, the effectiveness using air-liquid interface (ALI) exposure is currently unknown.

A new strategy of studying protein-protein interactions: Integrated strong anion exchange/reversed-phase chromatography/immunoprecipitation coupled with mass spectrometry for large-scale identification of proteins interact with immunoglobulin G in HeLa cells.

Recently, significant research efforts have been devoted to the development of technology for large-scale analysis of protein-protein interactions. Herein, a comprehensive method by coupling the first-dimension strong anion exchange chromatography with the second-dimension reversed-phase liquid chromatography via immunoprecipitation technique and high-resolution mass spectrometry analysis was developed for analyzing protein-protein interactions. After two-dimensional liquid chromatography separation, 108 fractions were obtained in one experiment.

A gold foil covered fused silica capillary tip as a sheathless interface for coupling capillary electrophoresis-mass spectrometry.

A method for the preparation of an on-column ESI emitter used as the sheathless interface for coupling capillary electrophoresis (CE) with mass spectrometry (MS) was developed. The emitter was directly fabricated at the outlet end of the separation capillary which was etched with HF solution to a symmetrical tip. The tip was covered with a small piece of gold foil which was fixed by epoxy resin glue for electrical contact.

Alteration of protein homeostasis mediates the interaction of Pseudomonas aeruginosa with Staphylococcus aureus.

Intracellular protein degradation is essential for the survival of all organisms, but its role in interspecies interaction is unknown. Here, we show that the ClpXP protease of Pseudomonas aeruginosa suppresses its antimicrobial activity against Staphylococcus aureus, a common pathogen co-isolated with P. aeruginosa from polymicrobial human infections.

High performance liquid chromatography-tandem mass spectrometry method for residue determination of 39 plant growth regulators in root and rhizome Chinese herbs.

A simple, rapid, and effective method based on salting-out extraction and LC-MS/MS techniques was developed for the determination of 39 plant growth regulator (PGR) residues in two of the most common root and rhizome Chinese herbs, Codonopsis Radix (Dangshen) and Notoginseng Radix et Rhizoma (Sanqi). The extraction process was performed with acetonitrile-water (5:1) and citrate buffer extraction salt. The performance of the method was validated in accordance with the analytical quality control criteria of SANTE/11813/2017 guidelines.

Isolation and identification of a new sildenafil analogue, hydroxycarbodenafil, found as an adulterant in a health supplement.

During routine screening of illegal adulterants in health supplements, a novel sildenafil analogue was discovered, and subsequently isolated by recrystallization. Its structure was elucidated by extensive analyses of high resolution mass spectrometry (HRMS), one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) data. The analogue was finally determined as hydroxycarbodenafil, featuring a hydroxyethyl group instead of an ethyl group on piperazine ring in comparison with carbodenafil.

Metabolite Profiling and Distribution of Militarine in Rats Using UPLC-Q-TOF-MS/MS.

Militarine, a natural glucosyloxybenzyl 2-isobutylmalate, isolated from , was reported with a prominent neuroprotective effect recently. The limited information on the metabolism of militarine impedes comprehension of its biological actions and pharmacology. This study aimed to investigate the metabolite profile and the distribution of militarine in vivo, which help to clarify the action mechanism further.