Inhibition of Staphylococcus epidermidis and Pseudomonas aeruginosa biofilms by grape and rice agroindustrial residues.

Agroindustrial wastes are generated daily and seem to be rich in bioactive molecules. Thus, they can potentially be used as source of compounds able to control bacterial biofilms. We investigated the potential of extracts from the residues of rice and grape to combat clinically important bacterial biofilms.

Branched-chain amino acids: physico-chemical properties, industrial synthesis and role in signaling, metabolism and energy production.

Branched-chain amino acids (BCAAs)-leucine (Leu), isoleucine (Ile), and valine (Val)-are essential nutrients with significant roles in protein synthesis, metabolic regulation, and energy production. This review paper offers a detailed examination of the physico-chemical properties of BCAAs, their industrial synthesis, and their critical functions in various biological processes. The unique isomerism of BCAAs is presented, focusing on analytical challenges in their separation and quantification as well as their solubility characteristics, which are crucial for formulation and purification applications.

Mechanistic insights into the biological activity of S-Sulfocysteine in CHO cells using a multi-omics approach.

S-Sulfocysteine (SSC), a bioavailable L-cysteine derivative (Cys), is known to be taken up and metabolized in Chinese hamster ovary (CHO) cells used to produce novel therapeutic biological entities. To gain a deeper mechanistic insight into the SSC biological activity and metabolization, a multi-omics study was performed on industrially relevant CHO-K1 GS cells throughout a fed-batch process, including metabolomic and proteomic profiling combined with multivariate data and pathway analyses. Multi-layered data and enzymatical assays revealed an intracellular SSC/glutathione mixed disulfide formation and glutaredoxin-mediated reduction, releasing Cys and sulfur species.

Sodium chloride impacts glycosylation and N- and O-glycan site occupancy of an Fc-fusion protein.

Fc-fusion proteins are highly complex molecules, difficult to manufacture at scale. In this work, undesired proteoforms were detected during the manufacture of a therapeutic fusion protein produced in CHO cells. These species were characterized using gel electrophoresis, size exclusion chromatography and liquid chromatography-mass spectrometry leading to the identification of low molecular weight proteoforms presenting low N- and O-glycan site occupancy, as well as a low sialylation content.

A reflection on the improvement of Chinese hamster ovary cell-based bioprocesses through advances in proteomic techniques.

Chinese hamster ovary (CHO) cells are the preferred mammalian host for the large-scale production of recombinant proteins in the biopharmaceutical industry. Research endeavors have been directed to the optimization of CHO-based bioprocesses to increase protein quantity and quality, often in an empirical manner. To provide a rationale for those achievements, a myriad of CHO proteomic studies has arisen in recent decades.

Red Pepper Prevents Cardiometabolic Risk in Rats Fed with an Ultra-Processed Diet.

Metabolic syndrome is a serious health condition reaching epidemic proportions worldwide and is closely linked to an increased risk of cardiovascular problems. The lack of appropriate treatment paves the way for developing new therapeutic agents as a high priority in the current research. In this study, we evaluated the protective effects of red pepper on metabolic syndrome scenarios induced by an ultra-processed diet in rats.

Nanoemulsion Containing Kojic Dipalmitate and Rosehip Oil: A Promising Formulation to Treat Melasma.

Melasma is a hard-to-treat hyperpigmentation disorder. Combined incorporation of kojic dipalmitate (KDP), the esterified form of kojic acid, and rosehip oil, an oil with antioxidant and skin-regenerating properties, into nanocarrier systems appears to be a suitable strategy to develop high-performance formulations. A high-energy method (Ultra-Turrax) was used to develop nanoemulsions containing up to 2 mg/mL KDP, 5% rosehip oil, and 7.

Stability and Requirement for Thiamin in a Cell Culture Feed Used to Produce New Biological Entities.

Thiamin is susceptible to heat and oxidation, which is a concern for the development of concentrated and room temperature stable feeds used to produce recombinant proteins. Hence, it is critical to understand the reactivity and necessity of the vitamin in liquid feeds to be able to either develop mitigation strategies to stabilize the vitamin or to remove thiamin from formulations if it is unnecessary. LC-MS/MS was used to investigate thiamin stability in different liquid feed formulations and to identify thiamin degradation products.

Copper impurity of iron raw material contributes to improved cell culture performance.

Cell culture medium (CCM) formulations are chemically defined to reduce lot-to-lot variability and complexity of the medium while still providing all essential nutrients supporting cell growth and productivity of various cell lines. However, raw material impurities may still introduce variations and inconsistencies to final CCM formulations. In one of our previous studies (Weiss et al.

Degradation Products of Tryptophan in Cell Culture Media: Contribution to Color and Toxicity.

Biomanufacturing processes may be optimized by storing cell culture media at room temperature, but this is currently limited by their instability and change in color upon long-term storage. This study demonstrates that one of the critical contributing factors toward media browning is tryptophan. LC-MS technology was utilized to identify tryptophan degradation products, which are likely formed primarily from oxidation reactions.

S-Sulfocysteine - Investigation of cellular uptake in CHO cells.

For the generation of therapeutic proteins in cell culture, high producing clones are used. These clones have a high demand in amino acids to support cell growth and productivity. l-cysteine (Cys) is critical in highly concentrated feeds due to low stability of Cys and low solubility of the oxidation product cystine at neutral pH.

Adherent and suspension baby hamster kidney cells have a different cytoskeleton and surface receptor repertoire.

Animal cell culture, with single cells growing in suspension, ideally in a chemically defined environment, is a mainstay of biopharmaceutical production. The synthetic environment lacks exogenous growth factors and usually requires a time-consuming adaptation process to select cell clones that proliferate in suspension to high cell numbers. The molecular mechanisms that facilitate the adaptation and that take place inside the cell are largely unknown.

Synthesis and antileukemic activity of an ursolic acid derivative: A potential co-drug in combination with imatinib.

Imatinib, a specific Bcr-Abl tyrosine kinase inhibitor, is the most commonly used drug in the treatment of chronic myeloid leukemia. However, optimal response is not achieved in up to 33% of patients. Therefore, development of novel therapeutic strategies for chronic myeloid leukemia is critical.

Rapid size-exclusion high performance liquid chromatography method for the quality control of amyloid-β oligomers.

Amyloid-β (Aβ) dysmetabolism is thought to be the main trigger for neurodegenerative events in Alzheimer's disease (AD). In particular, soluble Aβ oligomers (AβOs) are proposed as key mediators of synaptic and cognitive dysfunction in AD. Over the past few decades, AβOs prepared from synthetic Aβ have been widely applied in vitro and in vivo, the so-called chemical models of AD, uncovering their multiple neurotoxic mechanisms.

Impact of iron raw materials and their impurities on CHO metabolism and recombinant protein product quality.

Cell culture medium (CCM) composition affects cell growth and critical quality attributes (CQAs) of monoclonal antibodies (mAbs) and recombinant proteins. One essential compound needed within the medium is iron because of its central role in many cellular processes. However, iron is also participating in Fenton chemistry leading to the formation of reactive oxygen species (ROS) causing cellular damage.

Lactoyl leucine and isoleucine are bioavailable alternatives for canonical amino acids in cell culture media.

Increasing demands for protein-based therapeutics such as monoclonal antibodies, fusion proteins, bispecific molecules, and antibody fragments require researchers to constantly find innovative solutions. To increase yields and decrease costs of next generation bioprocesses, highly concentrated cell culture media formulations are developed but often limited by the low solubility of amino acids such as tyrosine, cystine, leucine, and isoleucine, in particular at physiological pH. This study sought to investigate highly soluble and bioavailable derivatives of leucine and isoleucine that are applicable for fed-batch processes.

Use of 5-Thio-L-Fucose to modulate binding affinity of therapeutic proteins.

The reduction of antibody core-fucosylation is known to enhance antibody-dependent cellular cytotoxicity (ADCC). In this study, 5-Thio-l-Fucose (ThioFuc) was investigated as a media and feed supplement for modulating the fucosylation profile of therapeutic proteins and, thereby, improving the resulting effector functions. Glycan analysis of five different therapeutic proteins produced by a diverse set of Chinese hamster ovary cell lines demonstrated a clone dependent impact of ThioFuc treatment.

Targeted Modification of the Foot-And-Mouth Disease Virus Genome for Quick Cell Culture Adaptation.

Foot-and-mouth disease virus (FMDV) causes the highly contagious foot-and-mouth disease, which is characterized by the appearance of vesicles in and around the mouth and feet of cloven-hoofed animals. BHK-21 cells are the cell line of choice for the propagation of FMDV for vaccine production worldwide but vary in their susceptibility for different FMDV strains. Previous studies showed that the FMDV resistance of a certain BHK cell line can be overcome by using a closely related but permissive cell line for the pre-adaptation of the virus, but the adapted strains were found to harbor several capsid mutations.

Modeling Diet-Induced Metabolic Syndrome in Rodents.

Standardized animal models represent one of the most valuable tools available to understand the mechanism underlying the metabolic syndrome (MetS) and to seek for new therapeutic strategies. However, there is considerable variability in the studies conducted with this essential purpose. This review presents an updated discussion of the most recent studies using diverse experimental conditions to induce MetS in rodents with unbalanced diets, discusses the key findings in metabolic outcomes, and critically evaluates what we have been learned from them and how to advance in the field.

Reactivity and degradation products of tryptophan in solution and proteins.

Tryptophan is one of the essential mammalian amino acids and is thus a required component in human nutrition, animal feeds, and cell culture media. However, this aromatic amino acid is highly susceptible to oxidation and is known to degrade into multiple products during manufacturing, storage, and processing. Many physical and chemical processes contribute to the degradation of this compound, primarily via oxidation or cleavage of the highly reactive indole ring.

Synthesis of new lophine-carbohydrate hybrids as cholinesterase inhibitors: cytotoxicity evaluation and molecular modeling.

In this study, we synthesized nine novel hybrids derived from d-xylose, d-ribose, and d-galactose sugars connected by a methylene chain with lophine. The compounds were synthesized by a four-component reaction to afford the substituted imidazole moiety, followed by the displacement reaction between sugar derivatives with an appropriate -alkylamino-lophine. All the compounds were found to be the potent and selective inhibitors of BuChE activity in mouse serum, with compound (a d-galactose derivative) being the most potent inhibitor (IC = 0.

Quinolines derivatives as promising new antifungal candidates for the treatment of candidiasis and dermatophytosis.

Fungal infections have emerged as a current serious global public health problem. The main problem involving these infections is the expansion of multidrug resistance. Therefore, the prospection of new compounds with efficacy antifungal becomes necessary.

Keto leucine and keto isoleucine are bioavailable precursors of their respective amino acids in cell culture media.

Highly concentrated cell culture media formulations are essential to develop next generation bioprocesses used to produce therapeutic monoclonal antibodies, fusion proteins, bispecific molecules and mAb fragments. Although cysteine/cystine and tyrosine are the first components preventing the development of highly concentrated complex cell culture media, leucine and isoleucine were identified as the next critical amino acids due to their limited solubility. This work sought to investigate highly soluble and readily bioavailable derivatives of both amino acids that may be used in batch, fed-batch or perfusion processes.

A short overview on mycophenolic acid pharmacology and pharmacokinetics.

Immunosuppressive therapy is used in solid organ transplant treatment, and mycophenolic acid (MPA) is one of the immunosuppressive drugs most used worldwide. It is a potent, selective, non-competitive, and reversible inosine monophosphate dehydrogenase (IMPDH) inhibitor that acts to inhibit guanine synthesis. To improve solubility, MPA is used as the prodrug mycophenolate mofetil (MMF) or as an enteric-coated mycophenolate sodium salt (EC-MPS).

Amyloid-β oligomers in cellular models of Alzheimer's disease.

Amyloid-β (Aβ) dysmetabolism is tightly associated with pathological processes in Alzheimer's disease (AD). Currently, it is thought that, in addition to Aβ fibrils that give rise to plaque formation, Aβ aggregates into non-fibrillar soluble oligomers (AβOs). Soluble AβOs have been extensively studied for their synaptotoxic and neurotoxic properties.