Dental stem cell-derived extracellular vesicles as promising therapeutic agents in the treatment of diseases

Dental stem cells (DSCs), an important source of mesenchymal stem cells (MSCs), can be easily obtained by minimally invasive procedures and have been used for the treatment of various diseases. Classic paradigm attributed the mechanism of their therapeutic action to direct cell differentiation after targeted migration, while contemporary insights into indirect paracrine effect opened new avenues for the mystery of their actual low engraftment and differentiation ability in vivo. As critical paracrine effectors, DSC-derived extracellular vesicles (DSC-EVs) are being increasingly linked to the positive effects of DSCs by an evolving body of in vivo studies. Carrying bioactive contents and presenting therapeutic potential in certain diseases, DSC-EVs have been introduced as promising treatments. Here, we systematically review the latest in vivo evidence that supports the therapeutic effects of DSC-EVs with mechanistic studies. In addition, current challenges and future directions for the clinical translation of DSC-EVs are also highlighted to call for more attentions to the (I) distinguishing features of DSC-EVs compared with other types of MSC-EVs, (II) heterogeneity among different subtypes of DSC-derived EVs, (III) action modes of DSC-EVs, (IV) standardization for eligible DSC-EVs and (V) safety guarantee for the clinical application of DSC-EVs. The present review would provide valuable insights into the emerging opportunities of DSC-EVs in future clinical applications.

Mimicking Enzymes: Taking Advantage of the Substrate-Recognition Properties of Metalloporphyrins in Supramolecular Catalysis

The present review describes the most relevant advances dealing with supramolecular catalysis in which metalloporphyrins are employed as substrate-recognition sites in the second coordination sphere of the catalyst. The kinetically-labile interaction between metalloporphyrins (typically, those derived from zinc) and nitrogen- or oxygen-containing substrates is energetically comparable to those non-covalent interactions (i.e. hydrogen bonding) found in enzymes enabling substrate-preorganization. Much inspired from this host-guest phenomena, the catalytic systems described in this account display unique activities, selectivities and action modes difficult to reach applying purely covalent strategies.

Comparison of Biochemical Characteristics, Action Models, and Enzymatic Mechanisms of a Novel Exolytic and Two Endolytic Lyases with Mannuronate Preference

Recent explorations of tool-like alginate lyases have been focused on their oligosaccharide-yielding properties and corresponding mechanisms, whereas most were reported as endo-type with α-L-guluronate (G) preference. Less is known about the β-D-mannuronate (M) preference, whose commercial production and enzyme application is limited. In this study, we elucidated Aly6 of Flammeovirga sp. strain MY04 as a novel M-preferred exolytic bifunctional lyase and compared it with AlgLs of Pseudomonas aeruginosa (Pae-AlgL) and Azotobacter vinelandii (Avi-AlgL), two typical M-specific endolytic lyases. This study demonstrated that the AlgL and heparinase_II_III modules play indispensable roles in determining the characteristics of the recombinant exo-type enzyme rAly6, which is preferred to degrade M-enriched substrates by continuously cleaving various monosaccharide units from the nonreducing end, thus yielding various size-defined ΔG-terminated oligosaccharides as intermediate products. By contrast, the endolytic enzymes Pae-rAlgL and Avi-rAlgL varied their action modes specifically against M-enriched substrates and finally degraded associated substrate chains into various size-defined oligosaccharides with a succession rule, changing from ΔM to ΔG-terminus when the product size increased. Furthermore, site-directed mutations and further protein structure tests indicated that H195NHSTW is an active, half-conserved, and essential enzyme motif. This study provided new insights into M-preferring lyases for novel resource discoveries, oligosaccharide preparations, and sequence determinations.

Mechanisms Affecting the Biosynthesis and Incorporation Rate of Selenocysteine

Selenocysteine (Sec) is the 21st non-standard proteinogenic amino acid. Due to the particularity of the codon encoding Sec, the selenoprotein synthesis needs to be completed by unique mechanisms in specific biological systems. In this paper, the underlying mechanisms for the biosynthesis and incorporation of Sec into selenoprotein were comprehensively reviewed on five aspects: (i) the specific biosynthesis mechanism of Sec and the role of its internal influencing factors (SelA, SelB, SelC, SelD, SPS2 and PSTK); (ii) the elements (SECIS, PSL, SPUR and RF) on mRNA and their functional mechanisms; (iii) the specificity (either translation termination or translation into Sec) of UGA; (iv) the structure–activity relationship and action mechanism of SelA, SelB, SelC and SelD; and (v) the operating mechanism of two key enzyme systems for inorganic selenium source flow before Sec synthesis. Lastly, the size of the translation initiation interval, other action modes of SECIS and effects of REPS (Repetitive Extragenic Palindromic Sequences) that affect the incorporation efficiency of Sec was also discussed to provide scientific basis for the large-scale industrial fermentation for the production of selenoprotein.

Long noncoding RNA GAS5 in age-related diseases

: Aging refers to a natural process and a universal phenomenon in all cells, tissues, organs and the whole organism. Long non-coding RNAs (lncRNAs) are non-coding RNAs with the length of 200 nucleotides. LncRNA growth arrest-specific 5 (lncRNA GAS5) is often down-regulated in cancer. The accumulation of lncRNA GAS5 has been found to be able to inhibit cancer growth, invasion and metastasis, while enhancing the sensitivity of cells to chemotherapy drugs. LncRNA GAS5 can be a signaling protein, which is specifically transcribed under different triggering conditions. Subsequently, it is involved in signal transmission in numerous pathways as a signal node. LncRNA GAS5, with a close relationship to multiple miRNAs, was suggested to be involved in the signaling pathway under three action modes (i.e., signal, bait and guidance). LncRNA GAS5 was found to be involved in different age-related diseases (e.g., rheumatoid arthritis, type 2 diabetes, atherosclerosis, osteoarthritis, osteoporosis, multiple sclerosis, cancer etc.). This study mainly summarized the regulatory effect exerted by lncRNA GAS5 on age-related diseases.

Knowledge of preservice elementary teachers on fractions

In this paper, we studied the knowledge on didactic contents reflected by future elementary teachers when answering questions related to teaching and learning fractions. Following a qualitative methodology, specifically a case study, 9 senior pre-service elementary teachers were interviewed using a structured approach. The topic was presented to the subjects using a narrative they had previously written on how to initiate the concept of fractions with school children. After reading it, they were asked questions regarding task design, learning objectives, and mistakes and difficulties. Results identified two trends in the participants’ knowledge: a procedural or technical trend in which the stated knowledge emphasizes procedures, processes, or action modes, and a conceptual or cognitive trend in which the stated knowledge emphasizes the functional understanding of fractions and their relationships. As a conclusion, it is essential that initial teacher training emphasizes mathematical as well as didactic contents.

Comparison of the Values of a Novel Exolytic and Two Endolytic Alginate Lyases with Mannuronate Preference for Direct Preparation of Oligosaccharides, Action Modes, and Underlying Catalytic Mechanisms

Recent exploration of tool-like alginate lyases has focused on their oligosaccharide products and corresponding substrate action modes, and most were characterized as endolytic lyases with guluronate (G) preference. Herein, we elucidated a novel exolytic lyase, Aly-6, and two typical endolytic lyases, AlgL-Pae and AlgL-Avi, all with mannuronate (M) preferences. AlgL and heparinase_II_III modules play essential roles in determining the similar characteristics of these enzymes, although they are quite different in sequence characteristics. Aly-6 degraded substrates completely by continuously cleaving various monosaccharide units from nonreducing ends and producing various size-defined ΔG-terminated oligosaccharide fractions as intermediate alginate digests, which was inhibited by fluorescent labeling of reducing ends. Distinctly, AlgL-Pae and AlgL-Avi varied their action modes toward associated alginate substrates and therefore eventually degraded alginate into various size-defined oligosaccharide products with a specific structure-based succession rule. This study provided new insights into the action modes, associated mechanisms, and enzyme applications of M-preferred lyases.

Circular RNAs and Cardiovascular Regeneration

circular RNAs (circRNAs) are a type of non-coding RNAs that are widely present in eukaryotic cells. They have the characteristics of stable structure, high abundance, and cell or tissue specific expression. circRNAs are single-stranded RNAs that are covalently back spliced to form closed circular loops. They may participate in gene expression and regulation through a variety of action modes. circRNAs can encode proteins or function by acting as miRNA sponges for protein translation. Since 2016, a growing number of research studies have shown that circRNAs play important role in the pathogenesis of cardiovascular disease. With the construction of circRNA database, the differential expression of circRNAs in the heart tissue samples from different species and the gradual elucidation of its mode of action in disease may become an ideal diagnosis biomarker and an effective therapeutic target. What can be expected surely has a broader application prospect. In this review, we summarize recent publications on circRNA biogenesis, expression profiles, functions, and the most recent studies of circRNAs in the field of cardiovascular diseases with special emphasis on cardiac regeneration.

New Clinical Applications of Electrolyzed Water: A Review

As the situation of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is still deteriorating, there has been a huge increase in the demand and use of disinfectants. Electrolyzed water (EW), as a novel broad-spectrum disinfectant and cleaner, has been widely used for several years. EW can be produced in an electrolysis chamber which contains dilute salt and tap water. It is an effective antimicrobial and antibiofilm agent, with several advantages such as on-the-spot, cheap, environmentally friendly and safe for human beings. Therefore, EW holds potential significance for high-risk settings in hospitals and other clinical facilities. EW can also be applied for wound healing, advanced tissue care, and dental clinics. The present review article highlights the latest developments and new perspectives of EW, especially in clinical fields. Furthermore, the main action modes of antibiofilm and antimicrobial will be summarized.