Summary

The advent of biopharmaceuticals in current medicine brought enormous benefits to the treatment of life-threatening human diseases (e.g., cancer, diabetes and neurodegenerative disorders), and improved the well-being of many people worldwide. The global portfolio of these therapeutic products include proteins and antibodies, nucleic acids, and cell-based products, and continues to expand at a rapid pace - approvals in the period 2015-2018 essentially double the typical five-yearly historical approval pace (G. Walsh, Nat. Biotechnol., 36:1136-1145, 2018) -, representing a significant share of the entire market of pharmaceuticals.

Innovation in the (bio)pharmaceutical industry has been driven towards the development of cost-effective manufacturing processes, envisaging the delivery of products in high quantity, with superior quality (purity), and high specificity, with the ultimate goal of benefiting patients. Progress in this direction have resulted from the application of novel technologies in the upstream stage (high-throughput, single-use devices, statistical optimization of media and fermentation conditions, QbD, and continuous processing), while at the downstream level, chromatography has evolved through the development of new resins and ligands, coupled with advances in process modelling, operating and control strategies.

An emerging trend is the application of alternative solvents such as ionic liquids and deep eutectic solvents, in which their structure and physicochemical properties can be tuned to address unmet needs in (bio)pharmaceutical research. These compounds may be derived from natural and reneawable sources and hold great promise in the development of efficient, sustainable and cost-effective biopharmaceuticals purification processes.

This Entry Collection aims to provide the latest progresses achieved in pharmaceuticals bioprocessing. We welcome submissions of original research, comprehensive reviews and perspectives, including, but not limited, to the following fields:

- Upstream processing (genetic engineering, systems biology, difficult-to-express proteins, expression conditions, Quality by Design approaches, process analytical technologies);

- Chromatographic purification methods (process modelling and control, continuous bioprocessing, design and characterization of resins and ligands, new formats);

- Alternative purification methods (aqueous biphasic systems, filtration, crystallization, precipitation);

- Application of neoteric solvents in upstream and downstream stages;

- Analytical characterization of biopharmaceuticals (stability, post-translational modifications, biological activity, immunogenicity); 

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Entries
Topic Review
Metabolomics and Bladder Cancer
In the last decade, metabolomics has tried to assert its value in the bladder cancer field. Due to the current invasive diagnostic techniques, such as cystoscopy and the continuous monitoring patients must undergo, the introduction of non-invasive urinary biomarkers for monitoring this disease would be advantageous. This section represents a collection of all the metabolic information that various studies have obtained in recent years on bladder cancer, with particular attention to discovering biomarkers in urine for the diagnosis of this disease. In principle, they would complement cystoscopy or, at best, replace it. However, evaluating the different degrees of reproducibility that the experiments have shown in the indication of biomarkers, a synthesis was proposed to obtain a consensus list that is more reliable to become a guideline for clinical practice.
  • 481
  • 11 Nov 2021
Topic Review
Adipose Tissue Mitochondria
Mitochondria play a key role in maintaining energy homeostasis in metabolic tissues, including adipose tissues. The two main types of adipose tissues are the white adipose tissue (WAT) and the brown adipose tissue (BAT). WAT primarily stores excess energy, whereas BAT is predominantly responsible for energy expenditure by non-shivering thermogenesis through the mitochondria. WAT in response to appropriate stimuli such as cold exposure and β-adrenergic agonist undergoes browning wherein it acts as BAT, which is characterized by the presence of a higher number of mitochondria. 
  • 918
  • 10 Nov 2021
Topic Review
Xylitol Biosynthesis in the Yeast Candida
Xylitol is an industrially important chemical due to its commercial applications. The use of xylitol as a sweetener as well as its utilization in biomedical applications has made it a high value specialty chemical.
  • 585
  • 09 Nov 2021
Topic Review
Application of Nanotechnologies in Ischemic Heart Disease
Nanotechnology focuses on atomic and molecular structures with dimensions of 0.1–100 nm. The resulting nanomaterials exhibit distinct mechanical, electrical, thermal, magnetic and imaging features that facilitate novel and unique applications in different branches of science, such as nanomedicine, nanobiology and nanobiotechnology.
  • 455
  • 09 Nov 2021
Topic Review
Eggshell Membrane Ameliorates Hyperuricemia
Hyperuricemia is the primary cause of gouty arthritis and other metabolic disorders. Eggshell membrane (EM) is an effective and safe supplement for curing pain and stiffness connected with osteoarthritis. However, the effect of EM on hyperuricemia is unclear. This study determines the effects of EM on potassium oxonate-injected hyperuricemia. Uric acid, creatinine, blood urea nitrogen concentrations in the serum, and xanthine oxidase activity in the liver are measured. Protein levels of renal urate transporter 1 (URAT1), organic anion transporters 1 (OAT1), glucose transporter 9 (GLUT9), and ATP-binding cassette transporter G2 (ABCG2) in the kidney are determined with renal histopathology. The results demonstrate that EM reduces serum uric acid levels and increases urine uric acid levels in hyperuricemic rats. Moreover, EM downregulates renal URAT1 protein expression, upregulates OAT1 and ABCG2, but does not change GLUT9 expression. Additionally, EM does not change xanthine oxidase activity in the liver or the serum. EM also decreases uric acid uptake into oocytes expressing hURAT1. Finally, EM markedly reduces renal inflammation and serum interleukin-1β levels. These findings suggest that EM exhibits antihyperuricemic effects by promoting renal urate excretion and regulating renal urate transporters. Therefore, EM may be useful in the prevention and treatment of gout and hyperuricemia.
  • 708
  • 08 Nov 2021
Topic Review
Chitosan Nanostructures
Chitosan (CS) is a natural polymer with a positive charge, a deacetylated derivative of chitin. Chitosan nanostructures (nano-CS) have received increasing interest due to their potential applications and remarkable properties. 
  • 569
  • 04 Nov 2021
Topic Review
Medication for Macular Degeneration
Age-related macular degeneration (AMD) is central vision loss with aging, was the fourth main cause of blindness in 2015, and has many risk factors, such as cataract surgery, cigarette smoking, family history, hypertension, obesity, long-term smart device usage, etc. In general, AMD drug candidates from natural products are more effective at treating early and intermediate AMD.
  • 530
  • 05 Nov 2021
Topic Review
Antimicrobial Activity of Gemini Surfactants
Gemini cationic surfactants (GS) are constructed from two alkylammonium monomeric salts linked by a spacer.They exhibit significant surface, aggregation and antimicrobial properties. Due to the fact that, in order to achieve the desired utility effect, the minimal concentration of compounds are used, they are in line with the principle of greenolution (green evolution) in chemistry. The obtained results indicate that the synthesized compounds are effective microbicides with a broad spectrum of biocidal activity and are active against Escherichia coli, Staphylococcus aureus, yeast Candida albicans, molds Aspergillus niger and Penicillium chrysogenum. These compounds constitute a new, interesting class of microbicides with a broad spectrum of biocidal activity.
  • 658
  • 28 Jan 2022
Topic Review
Umbilical Cord-Derived Wharton’s Jelly in Orthopedic Regenerative Medicine
Wharton’s jelly (WJ) is an allogenic tissue comprised of connective tissue located within the umbilical cord. Wharton’s jelly resists torsional and compressive stresses during fetal development levied upon the umbilical vessels. The primitive mesenchymal stem cells reside within the UC-derived WJ [15]. These perinatal MSCs resemble embryonic stem cells (ESCs) but exhibit many properties of adult MSCs. Wharton’s jelly-derived mesenchymal stem cells (WJSCs) exhibit lower expression levels of pluripotent markers compared to ESCs, indicating multipotency rather than pluripotency [16,17]. Wharton’s jelly contains the highest concentration of MSCs/mL compared to other tissue types.
  • 619
  • 08 Nov 2021
Topic Review
Rhus trilobata Nutt. (Anacardiaceae)
Rhus trilobata (RHTR) is a medicinal plant with cytotoxic activity in different cancer cell lines. However, the active compounds in this plant against ovarian cancer are unknown. In this study, we aimed to evaluate the antineoplastic activity of RHTR and identify its active metabolites against ovarian cancer. The aqueous extract (AE) and an active fraction (AF02) purified on C18-cartridges/ethyl acetate decreased the viability of SKOV-3 cells at 50 and 38 μg/mL, respectively, compared with CHO-K1 (> 50 μg/mL) in MTT assays and generated changes in the cell morphology with apoptosis induction in Hemacolor® and TUNEL assays (p ≤ 0.05, ANOVA). The metabolite profile of AF02 showed a higher abundance of flavonoid and lipid compounds compared with AE by UPLC-MS. Gallic acid and myricetin were the most active compounds in RHTR against SKOV-3 cells at 50 and 166 μg/mL, respectively (p ≤ 0.05, ANOVA). Antineoplastic studies in Nu/Nu female mice with subcutaneous SKOV-3 cells xenotransplant revealed that 200 mg/kg/i.p. of AE and AF02 inhibited ovarian tumor lesions from 37.6% to 49% after 28 days (p ≤ 0.05, ANOVA). In conclusion, RHTR has antineoplastic activity against ovarian cancer through a cytostatic effect related to gallic acid and myricetin. Therefore, RHTR could be a complementary treatment for this pathology.
  • 568
  • 05 Nov 2021
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