Nanobodies' duo facilitates ultrasensitive serum HER-2/neu immunoassays via enhanced avidity interactions.

Background: Existing liquid biopsy assays for protein biomarkers of cancer are mostly based on antibodies (Ab) contributing unfavorably to their high cost. Easy to express and modify in vitro, nanobodies may be a cost-effective alternative to Ab.

Results: We show that serum HER-2/neu, a biomarker and target of aggressive HER-2/neu(+) cancers, can be accurately detected in a 1.

Plug-and-play nucleic acid-mediated multimerization of biparatopic nanobodies for molecular imaging.

In cancer molecular imaging, selecting binders with high specificity and affinity for biomarkers is paramount for achieving high-contrast imaging within clinical time frames. Nanobodies have emerged as potent candidates, surpassing antibodies in pre-clinical imaging due to their convenient production, rapid renal clearance, and deeper tissue penetration. Multimerization of nanobodies is a popular strategy to enhance their affinity and pharmacokinetics; however, traditional methods are laborious and may yield heterogeneous products.

Dual-Targeting of the HER2 Cancer Receptor with an Antibody-Directed Enzyme and a Nanobody-Guided MMAE Prodrug Scaffold.

Antibody-enzyme conjugates have shown potential as tissue-specific prodrug activators by antibody-directed enzyme prodrug therapy (ADEPT), but the approach met challenges clinically due to systemic drug release. Here, we report a novel dual-targeting ADEPT system (DuADEPT) which is based on active cancer receptor targeting of both a trastuzumab-sialidase conjugate (Tz-Sia) and a highly potent sialidase-activated monomethyl auristatin E (MMAE) prodrug scaffold. The scaffold is based on a four-way junction of the artificial nucleic acid analog acyclic (L)-threoninol nucleic acid ((L)-aTNA) which at the ends of its four arms carries one nanobody targeting HER2 and three copies of the prodrug.

RNA nanostructures for targeted drug delivery and imaging.

The RNA molecule plays a pivotal role in many biological processes by relaying genetic information, regulating gene expression, and serving as molecular machines and catalyzers. This inherent versatility of RNA has fueled significant advancements in the field of RNA nanotechnology, driving the engineering of complex nanoscale architectures toward biomedical applications, including targeted drug delivery and bioimaging. RNA polymers, serving as building blocks, offer programmability and predictability of Watson-Crick base pairing, as well as non-canonical base pairing, for the construction of nanostructures with high precision and stoichiometry.

Biased activation of the receptor tyrosine kinase HER2.

HER2 belongs to the ErbB sub-family of receptor tyrosine kinases and regulates cellular proliferation and growth. Different from other ErbB receptors, HER2 has no known ligand. Activation occurs through heterodimerization with other ErbB receptors and their cognate ligands.

Mass versus personalized medicine against COVID-19 in the "system sciences" era.

The importance of personalized/precision medicine for targeted therapies and improved outcomes both in terms of efficacy and safety in health care is by now grounded. We here discuss the current landscape of personalized medicine approaches against SARS-CoV-2. A schematic of the approach is illustrated in the figure in the text.

From Soft to Hard Biomimetic Materials: Tuning Micro/Nano-Architecture of Scaffolds for Tissue Regeneration.

Failure of tissues and organs resulting from degenerative diseases or trauma has caused huge economic and health concerns around the world. Tissue engineering represents the only possibility to revert this scenario owing to its potential to regenerate or replace damaged tissues and organs. In a regeneration strategy, biomaterials play a key role promoting new tissue formation by providing adequate space for cell accommodation and appropriate biochemical and biophysical cues to support cell proliferation and differentiation.

Site-specific nanobody-oligonucleotide conjugation for super-resolution imaging.

Camelid single-domain antibody fragments, also called nanobodies, constitute a class of binders that are small in size (~15 kDa) and possess antigen-binding properties similar to their antibody counterparts. Facile production of recombinant nanobodies in several microorganisms has made this class of binders attractive within the field of molecular imaging. Particularly, their use in super-resolution microscopy has improved the spatial resolution of molecular targets due to a smaller linkage error.

SARS-CoV-2 Omicron variant: A next phase of the COVID-19 pandemic and a call to arms for system sciences and precision medicine.

Since early 2020, coronavirus diseases 2019 (COVID-19) infection pandemic/endemic is constantly surprising health experts because of continuous variations in the structures of severe acute respiratory coronavirus 2 (SARS-CoV-2) in the form of newly emerged variants. Such mutations have exhibited high mortality and severity due to the newly emerged more infectious sites of SARS-CoV-2, making viral infection more transmissible, infectious, and severe. Recently, SARS-CoV-2 mutated to another variant, namely, Omicron (B.

Extracellular pH, osmolarity, temperature and humidity could discourage SARS-CoV-2 cell docking and propagation intercellular signaling pathways.

The COVID-19 pandemic and its virus variants continue to pose a serious and long-lasting threat worldwide. To combat the pandemic, the world's largest COVID-19 vaccination campaign is currently ongoing. As of July 19 2021, 26.

Intrinsically Conductive Polymers for Striated Cardiac Muscle Repair.

One of the most important features of striated cardiac muscle is the excitability that turns on the excitation-contraction coupling cycle, resulting in the heart blood pumping function. The function of the heart pump may be impaired by events such as myocardial infarction, the consequence of coronary artery thrombosis due to blood clots or plaques. This results in the death of billions of cardiomyocytes, the formation of scar tissue, and consequently impaired contractility.

MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti-COVID-19 Therapeutics.

Over 313,000 SARS-CoV-2 positive cases have been confirmed in Italy as of 30 September 2020, and the number of deaths exceeding thirty-five thousand makes Italy among the list of most significantly affected countries in the world. Such an enormous occurrence of infections and death raises the urgent demand for effective available treatments. Discovering the cellular/molecular mechanisms of SARS-CoV-2 pathogenicity is of paramount importance to understand how the infection becomes a disease and how to plan any therapeutic approach.

3D Printing Decellularized Extracellular Matrix to Design Biomimetic Scaffolds for Skeletal Muscle Tissue Engineering.

Functional engineered muscles are still a critical clinical issue to be addressed, although different strategies have been considered so far for the treatment of severe muscular injuries. Indeed, the regenerative capacity of skeletal muscle (SM) results inadequate for large-scale defects, and currently, SM reconstruction remains a complex and unsolved task. For this aim, tissue engineered muscles should provide a proper biomimetic extracellular matrix (ECM) alternative, characterized by an aligned/microtopographical structure and a myogenic microenvironment, in order to promote muscle regeneration.

Information-Driven Design as a Potential Approach for 3D Printing of Skeletal Muscle Biomimetic Scaffolds.

Severe muscle injuries are a real clinical issue that still needs to be successfully addressed. Tissue engineering can represent a potential approach for this aim, but effective healing solutions have not been developed yet. In this regard, novel experimental protocols tailored to a biomimetic approach can thus be defined by properly systematizing the findings acquired so far in the biomaterials and scaffold manufacturing fields.

Harnessing Inorganic Nanoparticles to Direct Macrophage Polarization for Skeletal Muscle Regeneration.

Modulation of macrophage plasticity is emerging as a successful strategy in tissue engineering (TE) to control the immune response elicited by the implanted material. Indeed, one major determinant of success in regenerating tissues and organs is to achieve the correct balance between immune pro-inflammatory and pro-resolution players. In recent years, nanoparticle-mediated macrophage polarization towards the pro- or anti-inflammatory subtypes is gaining increasing interest in the biomedical field.

Smart ECM-Based Electrospun Biomaterials for Skeletal Muscle Regeneration.

The development of smart and intelligent regenerative biomaterials for skeletal muscle tissue engineering is an ongoing challenge, owing to the requirement of achieving biomimetic systems able to communicate biological signals and thus promote optimal tissue regeneration. Electrospinning is a well-known technique to produce fibers that mimic the three dimensional microstructural arrangements, down to nanoscale and the properties of the extracellular matrix fibers. Natural and synthetic polymers are used in the electrospinning process; moreover, a blend of them provides composite materials that have demonstrated the potential advantage of supporting cell function and adhesion.

Turning regenerative technologies into treatment to repair myocardial injuries.

Regenerative therapies including stem cell treatments hold promise to allow curing patients affected by severe cardiac muscle diseases. However, the clinical efficacy of stem cell therapy remains elusive, so far. The two key roadblocks that still need to be overcome are the poor cell engraftment into the injured myocardium and the limited knowledge of the ideal mixture of bioactive factors to be locally delivered for restoring heart function.

Inflamm-aging microRNAs may integrate signals from food and gut microbiota by modulating common signalling pathways.

Human gut microbiota, which comprises an extremely diverse and complex community of microorganisms inhabiting the intestinal tract, may be associated with inflammation and age-related chronic health conditions. However, the mechanism underlying this association is only recently beginning to emerge. Transfer and modulation of gene expression by diet-derived microRNAs (miRs) in mammals might be involved in this communication.

Exploring the roles of MSCs in infections: focus on bacterial diseases.

Despite human healthcare advances, some microorganisms continuously react evolving new survival strategies, choosing between a commensal fitness and a pathogenic attitude. Many opportunistic microbes are becoming an increasing cause of clinically evident infections while several renowned infectious diseases sustain a considerable number of deaths. Besides the primary and extensively investigated role of immune cells, other cell types are involved in the microbe-host interaction during infection.

The Activity of L. Essential Oil on Inflammation.

The use of herbs with medicinal value and biomedical effects has increased tremendously in the last years. However, inadequate basic knowledge of their mode of action is the main issue related to phytotherapy, although they have shown promising potential. To provide insights into these important issues, we tested here on appropriate models the efficacy of essential oil (Aa-EO) for anti-inflammatory properties.

α-Linolenic Acid Reduces TNF-Induced Apoptosis in C2C12 Myoblasts by Regulating Expression of Apoptotic Proteins.

Impaired regeneration and consequent muscle wasting is a major feature of muscle degenerative diseases. Nutritional interventions such as adjuvant strategy for preventing these conditions are recently gaining increasing attention. Ingestion of n3-polyunsaturated fatty acids has been suggested as having a positive impact on muscle diseases.

How Diet Intervention via Modulation of DNA Damage Response through MicroRNAs May Have an Effect on Cancer Prevention and Aging, an in Silico Study.

The DNA damage response (DDR) is a molecular mechanism that cells have evolved to sense DNA damage (DD) to promote DNA repair, or to lead to apoptosis, or cellular senescence if the damage is too extensive. Recent evidence indicates that microRNAs (miRs) play a critical role in the regulation of DDR. Dietary bioactive compounds through miRs may affect activity of numerous genes.

Three-dimensional imaging technologies: a priority for the advancement of tissue engineering and a challenge for the imaging community.

Tissue engineering/regenerative medicine (TERM) is an interdisciplinary field that applies the principle of engineering and life sciences to restore/replace damaged tissues/organs with in vitro artificially-created ones. Research on TERM quickly moves forward. Today newest technologies and discoveries, such as 3D-/bio-printing, allow in vitro fabrication of ex-novo made tissues/organs, opening the door to wide and probably never-ending application possibilities, from organ transplant to drug discovery, high content screening and replacement of laboratory animals.