Institute of Life Sciences

Ehretia asperula Zoll. et Mor. (“Xạ đen”) is a valuable medicinal plant widely used in traditional Vietnamese medicine due to its rich content of bioactive compounds. This study investigated the phytochemical composition, antioxidant activity, and genetic diversity of samples collected from three regions in Vietnam. ITS marker and methods for quantifying secondary metabolites were used to assess the genetic diversity and chemical composition of E. asperula across different collection sites. Although ITS1 sequence analysis showed no significant genetic variation among accessions, there were notable differences in secondary metabolite content. Plants from Hoa Binh province contained the highest levels of total phenolic, flavonoids, and rosmarinic acid, followed by those from Dong Nai and Vinh Phuc provinces. Among the tested solvents, an ethanol-water (30 : 70, v/v) proved most effective for extracting the targeted compounds. In addition, a micropropagation protocol was successfully established using nodal explants from the plants collected from Hoa Binh province. Optimal surface sterilization was achieved with 0.1% HgCl2 for 16 min. Shoots were most efficiently regenerated from nodal explants on MS medium supplemented with 3.0 mg l−1 kinetin. Shoot proliferation was most effective on MS medium supplemented with 1.5 mg l−1 2-isopentenyladenine, while root induction reached 100% efficiency on MS medium containing 1.0 mg l−1 indole-3-butyric acid. These findings highlight the potential of E. asperula as a sustainable natural antioxidant source and support its continued use in traditional medicine.

The increasing prevalence of diabetes and obesity worldwide has spurred the design of innovative therapeutic approaches. Stimuli-responsive biomaterials have emerged as promising tools for targeted and controlled delivery of therapeutics. These materials have the ability to respond dynamically to specific external or internal stimuli and interact with the body at specific focal points by facilitating cellular pathways like drug release, biochemical signals, electrical signal transmission, cell loading, and mechanical stress modulation, thereby providing innovative solutions for drug delivery that can significantly improve patient outcomes. Ongoing advancements in this field are expected to pave the way for smarter therapeutics that are both effective and patient-centric. This chapter systematically elucidates the presence of physical stimulus-responsive biomaterials and chemical stimulus-responsive biomaterials used to manage diabetes and obesity. Moreover, it delves deeply into how stimuli-responsive materials can mimic natural insulin production in response to blood glucose levels, which helps to manage diabetes.

ABSTRACT The majority of RNAs transcribed from the genome are non-coding RNAs (ncRNAs) that are involved in regulating the expression of protein-coding genes. However, a growing body of research highlights several novel microproteins encoded by unconventional ncRNAs such as long non-coding RNAs and circular RNAs (circRNAs) as important regulators of disease and development. Although several circRNAs have recently been reported to translate into functional peptides in diverse tissues, their roles in skeletal muscle remain largely unexplored. In this study, polyribosome-associated RNA sequencing and publicly available translatable circRNAs from the riboCIRC database were curated to discover potential protein-coding circRNAs in mouse C2C12 skeletal muscle cells. We validated a few circRNAs with high potential of translating into proteins in mouse C2C12 cells, including circular Smad1 ( circSmad1 ) that encodes a 194 amino acid peptide called circSmad1-194aa. Interestingly, silencing of circSmad1 in C2C12 cells resulted in loss of myotube fusion and maturation. CircSmad1-194aa was found to contain the DNA-binding SMAD1-MH1 domain that localized into the nucleus during myogenesis. Moreover, CircSmad1-194aa associates with the BMP-responsive element (BRE) in the Id1 promoter that is known to inhibit Myod1 -driven myoblast differentiation. We propose that circSmad1-194aa promotes myogenesis by masking Id1 -BRE from SMAD complex interaction, leading to suppression of ID1 expression and upregulation of MYOD1. Together, our findings identify circSmad1-194aa as a novel regulator of skeletal muscle differentiation and highlight the potential for the discovery of other functional circRNA-derived peptides in muscle pathophysiology. HIGHLIGHTS RNA-seq discovers hundreds of polysome-associated circRNAs in mouse C2C12 myoblasts Protein-coding circRNAs exhibit myogenesis-specific expression CircSmad1 is abundant, methylated, and translated into a 194aa polypeptide CircSmad1 -encoded polypeptide promotes myogenesis GRAPHICAL ABSTRACT

Achieving selective oxygenation chemistry offers a powerful strategy for streamlining routes to complex target molecules, yet the development of site-selective C-H functionalization reactions remain a significant challenge. Several enzyme families are capable of catalyzing C-H hydroxylation reactions and, in principle, provide an attractive solution for achieving selective oxidative transformations. In practice, however, the difficulty of identifying a biocatalyst suited to a specific synthetic target often renders chemoenzymatic strategies impractical. For example, biosynthetic enzymes such as CitB and ClaD can mediate site-selective benzylic hydroxylation, enabling access to select natural products that share structural features with their native substrates. Nonetheless, such approaches typically lack generality and do not readily extend to broader collections of natural products. Here, we explore the previously unstudied natural sequence space of the hydroxylases CitB and ClaD to generate a bespoke panel of uncharacterized enzymes that collectively expand the scope of this chemoenzymatic strategy. Development of this curated biocatalyst panel enabled the synthesis of six natural products, demonstrating that assembling this enzyme collection effectively derisks the use of biocatalysis in synthetic campaigns.

BackgroundGlobally, multiple SARS-CoV-2 vaccines received emergency authorization, primarily based on adenoviral vector, mRNA, or inactivated virus platforms. Among them, Covaxin, an inactivated vaccine, was widely used in India and several Southeast Asian countries. Due to their emergency rollout in 2021, the long-term immunogenicity data to assess the impact of these vaccinations have been limited. This study investigated the prolonged immune responses induced by Covaxin, an inactivated virus-based COVID-19 vaccine, in 250 individuals monitored for 2 years.MethodsThis longitudinal study (January 2021–January 2023) tracked 250 participants, collecting blood at seven time points. We measured SARS-CoV-2 spike RBD IgG and neutralizing antibodies using ECLIA and surrogate virus neutralization tests, respectively. We also assessed cellular immunity in a subset of Covaxin recipients through flow cytometry of spike protein-stimulated lymphocytes.ResultsAnti-RBD IgG levels declined rapidly post-vaccination. A significant rise was observed following Omicron infection, with sustained high antibody titers and high virus neutralization capacity. Covaxin recipients demonstrated high CD4+ T-cell activity during the Omicron wave, correlating with mild or asymptomatic infections. These findings suggest that Omicron exposure may have served as a natural booster and hold potential for next-generation vaccine development for COVID. Enhanced T-cell responses, particularly after the third dose, further underscored the vaccine’s ability to maintain cellular immunity. Compared with Covishield, Covaxin elicited milder immune responses, possibly contributing to its favorable safety profile.ConclusionsOverall, this study provides one of the first longitudinal analyses of the humoral and T-cell responses to Covaxin, a vaccine widely administered in India and neighboring Southeast Asian countries.

Chitin, poly-N-acetyl-d-glucosamine,is an abundant polysaccharide produced by fungal cell walls, insectepicuticles, and nematode cuticles. Its immunomodulatory functionhas curious attributes: paradoxically opposing host responses usingdifferent host receptors, resulting in immunostimulatory or immunosuppressiveproperties depending on the size/length of the oligomers as well asacetylation levels, have been reported in the literature. Here, wedemonstrate that hepta-N-acetyl chitoheptaose (7-mer)is a TLR2 ligand, while the 8-mer activates immune cells through TLR4,and the 6-mer is a relatively poor ligand for both TLR2 and TLR4 ingenerating inflammatory host cytokines. A significantly enhanced inflammatoryresponse, characterized by increased TNF-α, IL-1β, IL-6,and IL-10, was a feature of only the 8-mer, while the 6- and 7-mersinduced modest activation in both HEK cells (transfected with specificTLRs) and human THP2 cells in vitro. The translationalsignificance of these features was addressed in an experimental modelof sepsis using the Cecal Ligation Puncture (CLP) protocol, a murinemodel considered a gold standard for human sepsis. More significantly,therapeutic rather than prophylactic administration, which simulatesthe real-life scenario of human and animal sepsis, of the 7 mer, ratherthan the 6- or 8-mer residues of chitin oligomer, significantly protectedmice against sepsis, as shown by decreased mortality and decreasedinduction of inflammatory cytokines. These findings suggest that modulationof immune response by chito-polysaccharides in vivo is precisely calibrated.