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Cells, the microscopic building blocks of the human body, operate like a sophisticated symphony orchestra, finely orchestrating numerous life processes. In this diminutive yet intricate world, ribosomes function as conductors, guiding the synthesis of proteins—the essential constituents of life. However, disruptions in ribosomal function are frequently linked to cellular dysfunction, intimately intertwining them with the onset and progression of various diseases.
Anomalies in cellular ribosomes have a close correlation with several diseases, including:
Diamond-Blackfan Anemia: A rare genetic disorder appearing in infancy, Diamond-Blackfan anemia is associated with mutations or defects in ribosomal proteins. These disruptions impede normal protein synthesis, leading to abnormal red blood cell development and resulting in anemia.
Cancer: The critical role of ribosomes in protein synthesis has spurred intense investigation into their relationship with cancer. Cancer cells often exhibit abnormalities in ribosomal function, such as heightened protein synthesis and aberrant expression of specific ribosomal proteins, potentially contributing to the rapid growth and division of cancer cells.
Multiple Myeloma: This cancer, characterized by abnormal proliferation of plasma cells in the bone marrow, may involve ribosomal abnormalities impacting normal cellular regulation and growth.
Given the association between ribosomal abnormalities and various diseases, a comprehensive understanding of ribosomal structure, function, and their roles in cells and diseases is imperative. Techniques for ribosomal analysis facilitate the identification of specific ribosomal changes associated with disease states, aiding in the discovery of potential biomarkers for early disease diagnosis and monitoring.
Current Techniques in Ribosomal Analysis
Ribosome RNA Sequencing: A high-throughput sequencing technique used to analyze the composition of ribosomal RNA. By determining the expression levels and modification states of ribosomal RNA, researchers can comprehend gene expression regulation in cells under different conditions.
Ribosomal Protein Mass Spectrometry: Mass spectrometry is employed to identify and quantify ribosomal proteins. Separating and digesting ribosomal proteins and analyzing the resulting peptide fragments using a mass spectrometer provide valuable information about ribosomal protein composition and function.
Cryo-Electron Microscopy (Cryo-EM): This technique provides high-resolution images of ribosomal structures, aiding scientists in gaining a deep understanding of the three-dimensional structure of ribosomes and their intricate regulation in protein synthesis.
Ribosome Profiling (Ribo-Seq): Also known as Ribo-Seq, this technique explores translational levels by measuring nucleotide fragments bound to ribosomes. Ribo-Seq primarily targets mRNA sequences protected by ribosomes during the translation process, distinguishing it from RNA-Seq, which sequences all mRNA in a given sample.
As pivotal contributors to cellular protein synthesis, ribosomal abnormalities are intricately linked to various diseases. Advanced ribosomal analysis techniques enable scientists to explore the composition and function of ribosomes, revealing their crucial roles in cell biology and disease occurrence. In-depth research in this field not only provides novel insights into fundamental science but also offers robust support for the future treatment and prevention of diseases.
Extracellular vesicles (EVs), particularly exosomes, represent a crucial subgroup in cellular communication. First proposed by Johnstone et al. in 1983 during the study of erythrocyte differentiation, exosomes were officially identified in 1987 through ultracentrifugation. These membrane-bound small bodies, released from cells through the fusion of multivesicular bodies with the cell membrane, range in diameter from 40 nm to 100 nm. Exosomes display diverse shapes, including flat or spherical bodies, some exhibiting a cup-shaped morphology, especially in bodily fluids where they predominantly appear as spherical entities.
Certain proteins overexpressed in tumor cells may also be found in exosomes, and their composition varies depending on the cell origin, expressing unique biological proteins. Tumor-derived exosomes (Tex) play a pivotal role in tumor development, carrying a significant amount of mRNA and microRNA (miRNA). Initially considered cellular waste "garbage bags," exosomes are actively secreted by immune cells, stem cells, and tumor cells under physiological and pathological conditions, facilitating the transport of biomolecules and contributing to tumor pathogenesis.
Exosomes possess distinct biological characteristics, including their small size, allowing evasion of mononuclear phagocytes and traversal of vascular barriers, making them prevalent in bodily fluids. Their phospholipid bilayer structure provides biological stability, rendering them resistant to degradation. Tumor cells secrete more exosomes than normal cells, exhibiting high heterogeneity in size and surface proteins, valuable for distinguishing between different tumors and normal cells.
Within the tumor microenvironment, exosomes play a critical role in cellular communication, influencing tumor initiation, development, metastasis, immune evasion, and drug resistance.
Exosomes for Plastic and Cosmetic
However, cancer therapy by exosomes not only plays a role in the functional research and diagnostic applications of major diseases such as malignant tumors but also garners attention in the field of medical aesthetics. Positioned as "anti-aging treasures" and a "revolutionary innovative technology," exosomes are considered the "fountain of youth" in beauty enhancement. Their applications extend beyond functional skincare to include anti-aging, regenerative repair, and addressing issues like skin aging, texture improvement, skin tone alteration, and hair loss.
The "2022-2040 Exosome Therapy Market Report" by Roots Analysis forecasts a 41% annual growth rate in the exosome therapy market. Exosome beauty therapy, utilizing exosomes rich in ribonucleic acid (RNA) and membrane proteins, involves topical application or skin introduction. Through exosome signaling and nutrient delivery, it regulates cells, promotes continuous regeneration, and improves skin beauty, with applications in anti-aging, whitening, sensitive repair, inflammation repair, and scar repair.
On the market, exosomes are available in three forms:
* Frozen exosomes: Primarily for laboratory research, unsuitable for large-scale production due to complex storage and application requirements.
* Freeze-dried powder exosomes: Susceptible to loss of activity due to changes in membrane structure during vacuum freezing.
* Vitalized exosomes: Suspended in a liquid matrix, maintaining structural integrity and activity at an optimal temperature of 37°C, suitable for storage, transportation, and use.
These forms are closely linked to upstream exosome analysis technologies, including isolation, purification, engineering, and manufacturing. Exosome analysis facilitates the discovery of new biomarkers, providing additional options for early disease diagnosis and treatment.
In cancer immunotherapy, the spotlight has fallen on STING as a pivotal target of recent interest. Biopharmaceutical companies worldwide are vigorously developing innovative therapies targeting STING with the goal of activating immune pathways to combat cancer cells.
While these STING agonists have demonstrated promise in preclinical studies, a perplexing phenomenon has emerged in certain clinical trials. Contrary to expectations, drugs designed to activate the STING pathway have not consistently yielded the desired benefits for advanced cancer patients. For instance, a Phase 1 clinical trial assessing STING agonists reported only one out of 47 patients with advanced or metastatic cancer displaying a definitive partial response. In another Phase 1 clinical trial involving a STING agonist co-administered with a PD-1 inhibitor, the overall remission rate for advanced cancer patients hovered around 10%.
So, what accounts for the unexpected outcomes of STING agonists in the fight against cancer? In their quest for answers, researchers at the Memorial Sloan Kettering Cancer Center, in collaboration with Weill Cornell Medicine, have uncovered a counterintuitive possibility—drugs inhibiting STING activation may prove more beneficial to patients with advanced cancer than STING activators.
This revelation hinges on the nature of the STING signaling pathway itself. Within the human body, the presence of double-stranded DNA molecules in the cytoplasmic matrix serves as an early warning signal, indicating the intrusion of pathogens, the existence of cancer cells, or cell rupture. Once intracellular sensors detect cytoplasmic DNA, they activate the STING protein, which, in turn, triggers the expression of inflammation-associated genes, igniting an innate immune response that shields the body from foreign invaders and abnormal cells—a pivotal process in anti-tumor immunity.
However, the new study suggests that cancer cells disrupt the STING signaling pathway, creating an immunosuppressive tumor microenvironment. Particularly in advanced cancer stages, where cancer cells exhibit high chromosomal instability, the STING pathway remains persistently active, leading to "desensitization." This, in turn, rewires the downstream signaling pathway, inducing endoplasmic reticulum stress—a favorable environment for cancer cell metastasis.
Dr. Samuel Bakhoum, co-corresponding author of the study, analogizes this phenomenon, "think of STING signaling as a car alarm. If it rarely sounds, the loud noise will grab your attention. But if it keeps going off, you become accustomed to it and tune it out."
To understand the interactions between cancer cells and immune cells in the tumor microenvironment, another co-corresponding author, Dr. Ashley Laughney, led the team in developing a specialized computational tool named "Contact Tracing". This tool predicts cell-cell interactions and assesses how ligand-receptor interactions influence signal-receiving cells based on single-cell sequencing data.
Dr. Laughney highlights a significant discovery, "one of our most crucial findings is that altering the degree of chromosomal instability or activating STING significantly changes the response within the tumor and its surroundings."
The researchers confirmed the link between chromosomal instability-driven cancer cell metastasis and STING signaling in mouse models implanted with various tumor cells, as well as in human healthy cells and tumor samples. These findings also open the door to innovative therapeutic concepts—for advanced cancer patients with chromosomal instability, activating STING may prove ineffective due to cellular desensitization". In such cases, inhibiting STING could be a promising alternative.
In experimental settings, the researchers administered STING inhibitors to mouse models of melanoma, breast cancer, and colorectal cancer, effectively reducing metastasis driven by chromosomal instability.
Additionally, these insights suggest that by identifying tumors still capable of robust responses to STING activation, clinicians can select patients who would genuinely benefit from STING agonist therapy.
Antibodies, the extraordinary proteins that serve as the frontline troops of the human immune system, have recently gained attention for their ability to combat tiny compounds known as haptens. Because of their small size, these elusive targets present particular difficulty for the immune system to identify as foreign invaders. However, researchers' inventiveness has resulted in the creation of several techniques to bypass this barrier and unleash the full potential of hapten antibodies.
The search for hapten antibodies has been accompanied by a slew of novel techniques, injecting a burst of creativity into the field. To increase immunogenicity, one technique involves connecting haptens to bigger carrier molecules such as proteins or polymeric materials. Adjuvants, which operate as immune system enhancers, are another strategy used to stimulate a more robust response. Furthermore, anti-hapten antibodies, a subset of antibodies that recognize and bind to haptens, have emerged as a potent tool in the search for hapten-specific antibodies.
Hapten-specific antibodies offer a wide range of uses, ranging from biotechnology to diagnostics and therapies. One of the most interesting areas is the development of small-molecule antibody therapies, a new class of antibodies designed to target and neutralize disease-causing small-molecules. These small-molecule antibodies have distinct advantages over standard small-molecule medications, including increased specificity and affinity for their targets, which reduces the likelihood of off-target effects and increases efficacy.
With the growing demand for small-molecule antibody therapies, specialist services that offer custom antibody generation against a wide range of small compounds have emerged. Creative Biolabs is a US-based biotech company that specializes in small-molecule antibody design and development and can provide a series of services related to small-molecule antibodies. These services use a potent combination of immunization and screening approaches to create antibodies with exceptional specificity and affinity for the target. The resulting antibodies can then be fine-tuned for a wide range of applications, from in vitro diagnostics to therapeutic treatments, opening up a world of possibilities for researchers.
Finally, the development of hapten-specific antibodies has sparked a surge of innovation in the fields of small-molecule antibody therapies and diagnostics, holding enormous potential for the detection and treatment of a wide range of disorders. Access to these cutting-edge tools has been democratized by the availability of specialist small-molecule antibody development services, allowing researchers and enterprises to adapt antibodies to their unique needs. As the research progresses, the potential for small-molecule antibodies to make even larger strides in the near future grows.
Therapeutics based on macromolecular proteins and peptides have successfully been efficiently applied to treat serious human diseases. With the development of biotechnologies, a great number of authorized protein therapeutics and drug products have been utilized in clinical research over the last few decades. However, the main issue that needs to be resolved currently for protein therapeutics is the short half-lives caused by fast degradation in serum and quick elimination during clinical application due to enzymatic degradation, renal clearance, liver metabolism, and immunogenicity.
After putting in a lot of effort over the years, researchers have discovered some effective strategies for extending the half-life of protein therapeutics and biopharmaceutical products, such as polymers in drug half-life extension. Polymer conjugation is one of the widely used and efficient techniques in drug half-life extension research, and PEGylation in drug half-life extension is an efficient method for improving pharmacokinetic properties owing to its highly hydrophilic and mostly non-toxic features.
As protein engineering technology advances, bioactive natural protein conjugation, due to its lower toxic side effects, is becoming more accepted as a competitive method to prolong the half-life of drugs. Currently, diverse technologies of bioactive natural protein conjugation are being developed for the half-life extension of drug research, including:
* Albumin-based half-life extension
Albumin conjugation has been extensively used in a variety of protein drugs on the market.
* Fc-Fusion-based half-life extension
The Fc-Fusion technique works well for most therapeutic protein modifications.
* Transferrin fusion-based half-life extension
Transferrin fusion, a novel method to realize half-life extension, has potential clinical application.
In addition, lack of efficacy continues to be a major driver of drug candidate attrition. The drug half-life assay, as the first essential step in drug development to determine the half-life of drugs, is an essential strategy for selecting suitable drug candidates for clinical trials. In this case, many CRO companies are working hard to provide a variety of assays for improving the evaluation of drug candidates, as did Creative Biolabs. Having updated their advanced and comprehensive half-life assay platform, they are confident in providing high-quality half-life assay services to global customers, including but not limited to drug half-life in vitro and in vivo detection services.
Creative Biolabs, as a global CRO company focusing on drug development for years, has accumulated extensive experience in half-life extension and won a prominent reputation from customers all over the world. Scientists at Creative Biolabs continue to improve its half-life extension technologies in order to provide customers with the best drug half-life extension services, contributing to accelerating drug development.
Cancer has been a leading cause of death worldwide for decades, accounting for nearly one in every six deaths and posing a serious threat to people's health. A great number of plans and approaches have been approved to support the improvement of cancer cure rates with ongoing research on cancer treatment.
A recent study demonstrated that γδ T-cells were found to be the most prognostically beneficial immune cell subset in tumor infiltrates from 18,000 tumors across 39 malignancies, which makes γδ T-cells a kind of highly promising effector cell compartment for cancer immunotherapy. At present, γδ T cells have indicated powerful anti-tumor efficacy against breast cancer, colon cancer, lung cancer, leukemia, and others.
As innate immune cells, indeed, gamma delta T cells can recognize tumor cells independently of human leukocyte antigen (HLA) restriction and quickly produce abundant cytokines and potent cytotoxicity in response to malignancies. Gamma delta T cells have several favorable features for the development of T cell-based therapy for cancer, which are listed below:
* Gamma delta T cells recognize a broad spectrum of antigens on various cancer cells.
* Gamma delta T cells recognize their target cells independent of the major histocompatibility complex (MHC).
* Gamma delta T cells are distributed in various tissues and can quickly respond to target tumor cells.
* Gamma delta T cells interact with other immune cells such as B cells to drive a cascade of immune responses against tumors.
Isolating and purifying functional and specific gamma delta T cell populations from a complex biological sample is crucial for understanding the biological function of gamma delta T cells and creating gamma delta T cell-based therapies. Therefore, outstanding technologies for T cell isolation play a critical role. Magnetic bead cell sorting (MACS) is a frequent, efficient, and quick method for isolating uncontaminated gamma delta T lymphocytes from human peripheral blood mononuclear cells (PBMCs).
In addition, due to the essential function of gamma delta T cells in several diseases, a T cell cytotoxicity test is necessary for testing gamma delta T cell activity and cytotoxicity. The normal cytotoxicity tests include the LDH cytotoxicity test, flow cytometry-based cytotoxicity test, and impedance-based label-free real-time cytotoxicity assay, in which the LDH cytotoxicity test is one of the most commonly used methods for cell cytotoxicity detection.
Creative Biolabs is a biotechnology business that focuses on the discovery of gamma delta T cells to combat human cancers. They established and optimized robust platforms in-house for the selective isolation and expansion of anticancer gamma delta T cell populations from human tissues. Furthermore, they offer preclinical research services to assess the safety and efficacy of gamma delta T cell-based cancer immunotherapy.