Biological Purposes Research Articles

The nucleolin antagonist N6L and paclitaxel combination treatment could be a new promising therapeutic strategy for pancreatic ductal adenocarcinoma therapy.

Pancreatic cancer (PCa) is one of the most devastating cancers with few clinical signs and no truly effective therapy. In recent years, our team has demonstrated that nucleolin antagonists such as N6L could be a therapeutic alternative for this disease. In order to study a possible clinic development of N6L (multivalent pseudopeptide), we undertook to study the effect of combination of N6L with chemotherapies classically used for PCa on the survival of pancreatic cancer cells. Thus, the combined effect of N6L with either gemcitabine, FOLFOX and paclitaxel (PTX) on the survival of PANC-1, Mia-PaCa-2 and BxPC3 was studied and shown additive effect. In addition, analysis of the data by Combenefit software indicate that there are synergistic effects between N6L and the 3 chemotherapy molecules tested with more sensitive effects with the N6L-PTX combination. This result was confirmed by associating N6L and paclitaxel on porous calcium carbonate particles loaded with cyclodextrin (CD) encapsulating PTXl and carrying N6L at their surface. Porous calcium carbonate particles present highly benefits for biological purposes because of their large surface area and their high stability in neutral media. As for CD, it presents the advantage of owing hydrophilic exterior and a less polar cavity in the center. We have then combined the advantageous features of both porous and negatively charged surfaces of calcium carbonate (CaCO3) particles and host molecules CD for developing carrier enabling all at once the loading of PTX (hydrophobic drug) and N6L (cationic drug). This association generates water-soluble particles capable of targeting via N6L and delivering paclitaxel to tumor cells.

A dual-mode biosensor for microRNA detection based on DNA tetrahedron-gated nanochannels.

Abiosensor based on solid-state nanochannels of anodic aluminum oxide (AAO) membrane for both electrochemical and naked-eye detection of microRNA-31 (MiR-31) is proposed. For this purpose, MoS2 nanosheets, which possess different adsorption capabilities to single-stranded and double-stranded nucleic acids, are deposited onto the top surface of the AAO membrane. Moreover,multi-functional DNA nanostructure have been designed by linking a G-rich sequence for folding to a G-quadruplex at three vertices and a complementary sequence of MiR-31 at the other one vertex of a DNA tetrahedron. In the absence of MiR-31, the tetrahedron DNAzyme probe formed after the addition of hemin can mediate the deposition of insoluble on MoS2/AAO, which not only enables the color change of the membrane but also gates the transport of K3[Fe(CN)6] across the nanochannels. Therefore, the detection of MiR-31 is realized by both visual observation of the brown color and measuring the electrochemical redox current of [Fe(CN)6]3-. Using this biosensor, a detection limit as low as 0.06fM is achieved. Thedual-mode detection method also exhibits good specificity, reproducibility, and stability, demonstrating potential application in the diagnosis of oral squamous cell carcinoma and other related biological purposes.

Botulinum Toxin: A Comprehensive Review of Its Molecular Architecture and Mechanistic Action.

Botulinum toxin (BoNT), the most potent substance known to humans, likely evolved not to kill but to serve other biological purposes. While its use in cosmetic applications is well known, its medical utility has become increasingly significant due to the intricacies of its structure and function. The toxin's structural complexity enables it to target specific cellular processes with remarkable precision, making it an invaluable tool in both basic and applied biomedical research. BoNT's potency stems from its unique structural features, which include domains responsible for receptor recognition, membrane binding, internalization, and enzymatic cleavage. This division of labor within the toxin's structure allows it to specifically recognize and interact with synaptic proteins, leading to precise cleavage at targeted sites within neurons. The toxin's mechanism of action involves a multi-step process: recognition, binding, and catalysis, ultimately blocking neurotransmitter release by cleaving proteins like SNAP-25, VAMP, and syntaxin. This disruption in synaptic vesicle fusion causes paralysis, typically in peripheral neurons. However, emerging evidence suggests that BoNT also affects the central nervous system (CNS), influencing presynaptic functions and distant neuronal systems. The evolutionary history of BoNT reveals that its neurotoxic properties likely provided a selective advantage in certain ecological contexts. Interestingly, the very features that make BoNT a potent toxin also enable its therapeutic applications, offering precision in treating neurological disorders like dystonia, spasticity, and chronic pain. In this review, we highlight the toxin's structural, functional, and evolutionary aspects, explore its clinical uses, and identify key research gaps, such as BoNT's central effects and its long-term cellular impact. A clear understanding of these aspects could facilitate the representation of BoNT as a unique scientific paradigm for studying neuronal processes and developing targeted therapeutic strategies.

Protective Role of Vitamin B6 Against Teratogenic Effects Induced by Lead in Chick Embryo.

Heavy metals like lead (Pb) have been used by humans for a very long time, but throughout the industrial revolution, their use expanded, increasing exposure to the metal. Lead, however, has no biological purpose in the human body and is hazardous when it gets into soft tissues and organs. Lead is still used in a variety of industries, including battery manufacturing and car maintenance, despite efforts to limit its usage. This study investigates the teratogenic and morphometric effects of lead on chick embryos and the potential ameliorative effects of vitamin B6. Two hundred fertilized eggs from the golden black chicken were divided into four groups: control, lead acetate, vitamin B6, and lead + vitamin B6. On the 14th day, embryos were analyzed. Significant reductions in body weight and size were observed in the lead-exposed group (33.93 ± 1.27 g) compared to the control (41.12 ± 0.97 g). Pronounced deformities included rudimentary beaks, protruding eyes, tridactyl limbs, hydrocephaly, and neck deformities. Appendicular deformities like phocomelia, amelia, and abnormal phalanges growth were also noted. Vitamin B6 demonstrated therapeutic benefits, significantly improving mean embryo weight in the Lead + Vitamin B6 group (42.37 ± 0.99 g). The lead-exposed group showed a reduction in maxilla length (3.61 ± 1.30 mm) compared to the Lead + Vitamin B6 group (7.57 ± 0.79 mm). This group also showed reduced severity of muscular dystrophy and bone thinning, with signs of recovery in beak and bone sizes. The study highlights vitamin B6's beneficial impact in mitigating lead's toxic effects on chick embryonic development.

A fluorescent magnetic nanocrystalline cellulose nanosensor based on rhodamine B for Fe3+ ion detection

This research introduces a nanosensor specifically designed for the detection of Fe3+ ions in aqueous solutions. The sensor is created using magnetic nanoparticles that have been functionalized with rhodamine B (RB). The Z-average particle size was 235.8, 287.3, and 121.6 for NCC, NCC@Fe3O4, and NCC@Fe3O4@RB indicating successful mitigation of magnetic aggregation by NCC and RB. The resulting structure, NCC@Fe3O4@RB, acts as a fluorescent probe that emits strong fluorescence under ultraviolet light, demonstrating its potential as an efficient tool for Fe3+ ion detection in water. The NCC@Fe3O4@RB fluorescent probe had a limit of detection (LOD) of 1 × 10−5 M, with linearity at concentrations of 1 × 10−4–5 × 10−3 M. Upon introduction of iron ions to a solution containing NCC@Fe3O4@RB, they form complexes by binding with the weak-field ligands (such as nitrogen and oxygen) present within the structure of NCC@Fe3O4@RB. This interaction involves a high-spin coordination process, leading to the self-assembly of Fe3+ ions on the surface of NCC@Fe3O4@RB. The magnetization saturation (Ms) for NCC@Fe3O4, NCC@Fe3O4@NH2, and NCC@Fe3O4@RB was measured 44.7, 43.1, and 40.5 emu/g, respectively. As a result, single electrons are generated, which leads to increased paramagnetism, ultimately quenching the fluorescence. This fluorescence quenching effect caused by Fe3+ ions make the NCC@Fe3O4@RB fluorescent probe an efficient detector of Fe3+ ions in water. The main benefit of this fluorescence quenching mechanism lies in its ability to specifically target Fe3+ ions, without being influenced by the presence of other metal ions. This specificity guarantees that fluorescent probes utilizing magnetic fluorescence nanoparticles are highly efficient in detecting iron ions in water-based solutions, making them a valuable tool for environmental and biological purposes.

Plant Mediated Biosynthesis of Zinc Oxide Nanoparticle Using Aegle marmelos (Bael) Leaf Extract to Study its Antibacterial Activity and Chromium Adsorption

Nanoparticle is a miraculous material of this modern era due to their exceptional applications in various sectors (pharmaceutical, medical, cosmetics, paints, waste treatment process, etc.). In current study, zinc oxide nanoparticles (ZnO NPs) was synthesised using a green approach with Aegle marmelos (Bael) plant leaf extract as reducing agent. Characteristics of synthesised ZnO nanoparticles were examined with Fourier Transform Infrared Spectroscopy and UV-visible spectroscopy. The UV-vis spectroscopy study confirmed the formation of nanoparticles, showed a peak between 220-230 nm. FTIR spectroscopy was used to detect the specific functional groups involved in reducing and stabilizing during the biosynthesis process. Various applications were performed like; antibacterial properties and chromium metal adsorption. Antibacterial activity were analysed using well diffusion method. Nanoparticles of Zinc oxide were highly effective against gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) and gram-negative bacteria (Escherichia coli and Salmonella typhi). So, they can be used as an excellent antibacterial agent for biological purposes. In metal removal, zinc oxide nanoparticle removes about 50% of the chromium from water through adsorption. Current study showed synthesis of ZnO nanoparticle through green approach will have great potential in antibacterial activity and treatment of chromium metal contaminated water.

Complex interplay between the microfluidic and optical properties of Hoplia sp. beetles

BackgroundAll living organisms exist in a world affected by many external influences, especially water and light. Photonic nanostructures present in certain insects, have evolved over time in response to diverse environmental conditions, facilitating communication within and between species, camouflage, thermoregulation, hydration, and more. Up to now, only a few insect species have been discovered whose elytron changes its color due to permeation of water (or its vapor) through cuticle.ResultsHere we report on a scarabaeid beetle Hoplia argentea remarkable in its ability to shift from green to brownish-red when exposed to water, demonstrating reversible changes. Here we show that elytron and scales form a complex and efficient micro/nano-optofluidic system. Water is channeled into the elytral lacunae, then transported internally to the petals of the scales, where it is wicked inside each scale, pushing the entrapped air out. Wicking is a very fast process, occurring during a few seconds. The advantage of this principle is in extremely high pressure (approximately 15 bar) produced by capillary forces, which expediates permeation of air. We present optical models that explain the physical mechanisms behind the coloration, detailing how superhydrophilic properties influence optical behavior.ConclusionSpecies within the genus Hoplia exhibit diverse coloration strategies, likely linked to their specific ecological niches. These organisms have evolved intricate optical and microfluidic systems that facilitate rapid alterations in body coloration, potentially serving purposes such as environmental camouflage and thermoregulation. Studying microfluidic and optical properties of the elytra will not only enhance our understanding of the biological purposes behind color change but also inspires design of artificial biomimetic devices. Dynamic fluid flow patterns, described in this paper, are fairly constant and unique and can be used in security applications as a, so called, physically unclonable functions (PUF). More broadly, this kind of microfluidic system can be used for controlled drug release, sensing, hydraulic and pneumatic pumping.

Redundant pathways for removal of defective RNA polymerase II complexes at a promoter-proximal pause checkpoint.

The biological purpose of Integrator and RNA polymerase II (RNAPII) promoter-proximal pausing remains uncertain. Here, we show that loss of INTS6 in human cells results in increased interaction of RNAPII with proteins that can mediate its dissociation from the DNA template, including the CRL3ARMC5 E3 ligase, which ubiquitylates CTD serine5-phosphorylated RPB1 for degradation. ARMC5-dependent RNAPII ubiquitylation is activated by defects in factors acting at the promoter-proximal pause, including Integrator, DSIF, and capping enzyme. This ARMC5 checkpoint normally curtails a sizeable fraction of RNAPII transcription, and ARMC5 knockout cells produce more uncapped transcripts. When both the Integrator and CRL3ARMC5 turnover mechanisms are compromised, cell growth ceases and RNAPII with high pausing propensity disperses from the promoter-proximal pause site into the gene body. These data support a model in which CRL3ARMC5 functions alongside Integrator in a checkpoint mechanism that removes faulty RNAPII complexes at promoter-proximal pause sites to safeguard transcription integrity.

Comparison of YAG:Nd3+-Yb3+ nanothermometers synthesized by Pechini and solvothermal methods

Luminescence intensity ratio-based nanothermometry is a widely studied thermal sensing technique in the literature. Regarding biological purposes, it is essential to have thermal probes that are efficient in this type of environment. Thermal bioprobes demand highly crystallized nanocrystals, commonly smaller than 100 nm, with luminescence emissions in the near-infrared range that are not significantly absorbed by biological tissues. Several nanomaterials that have been studied for nanothermometry do not meet the requirements for this type of applications. Accordingly, researches are needed to develop suitable and reliable nanothermometers for thermal sensing. Therefore, our goal was to investigate the impact of Nd3+-Yb3+ co-doping on the thermometric performance of YAG matrix, a promising crystal because it presents a host structure favoring the insertion of lanthanide ions, which provide its luminescent features. In order to achieve this purpose, we first synthesized YAG:Nd3+-Yb3+ nanocrystals through a generic route - called modified Pechini method - to screen their thermal properties. Our results show that YAG:Nd3+-Yb3+ nanocrystals have the potential to work in vivo environments. The nanothermometers investigated here are excited in the first biological window (BW-I) at 805 nm with luminescence emissions within the BW-II, at 1030.5 and 1064 nm. By co-doping the YAG matrix with different Nd3+-Yb3+ concentrations, we studied the energy transfer process between the dopant ions and their impact on thermometry efficiency. By the efficient coupling of the Nd3+-Yb3+ pair, we improved the Sr value by a factor of 3 of YAG compounds up to 0.6 %.K−1. We then synthesized YAG:Nd3+-Yb3+ nanocrystals using a second type of synthesis, by solvothermal means, in order to obtain individual nanocrystals, well dispersed in aqueous solutions, and to adapt their morphology and size for biological purposes. Therefore, we compared the structural and luminescence properties and thermometry efficiencies of YAG:Nd3+-Yb3+ nanocrystals obtained through two distinct processes and showed that the nanothermometry properties are not affected by the synthesis method.

Selective pH-Responsive Conjugation between a Pair of De Novo Discovered Peptides.

There is a demand for site-selective peptide/protein conjugation chemistry that is fully reversible in a stimulus-responsive manner. The contemporary methods for site-selective protein modification enable the preparation of homogeneous protein-small molecule conjugates, which are indispensable for drug delivery and chemical biology purposes, but such chemistries are usually irreversible. In contrast, the existing reversible protein labeling techniques are generally not site-selective. Here, we report an mRNA display-enabled de novo discovery of a pair of peptides which selectively react with each other to form a conjugate that is stable under neutral conditions (pH 7.5) but rapidly dissociates into the constituents at pH 10. A Cys thiol of peptide CP1 rapidly reacts (k1 = 340 M-1·s-1) with the isothiocyanate moiety in partner ITC6 to furnish a stable dithiocarbamate (t1/2 = 6 h at pH 7.5). We show that the pH-responsive nature of the reaction (conjugate's t1/2 = 5 min at pH 10) can be leveraged to utilize ITC6 (1) as a pull-down handle to selectively isolate CP1 from cell lysates and (2) as a temporary protecting group to protect CP1 from nonspecific Cys labeling reagents such as iodoacetamide. Altogether, the chemistry developed here complements the existing approaches and is applicable in a variety of chemical biology settings where selective reversible reactions are needed.

Microwave-assisted synthesis of copper oxide nanoparticles using an Andrographis paniculata leaf extract: Characterization and multifunctional biological activities

This research delves into the environmentally friendly production of copper nanoparticles (CuNPs) using Andrographis paniculata leaf extract (Ap-CuNPs) and their thorough assessment for possible biological purposes. CuNPs were synthesised through a microwave-assisted method using Andrographis paniculata leaf extract. Characterization techniques included ultraviolet spectroscopy (UVVis), FT-IR spectroscopy, SEM, EDAX, XRD, particle size analysis, and zeta potential measurement. Biological activities were assessed through antioxidant (DPPH and H2O2 assays), anti-inflammatory (BSA and egg albumin denaturation assays), antimicrobial, cytotoxic (brine shrimp lethality and MTT assays), and wound healing (scratch assay) tests. Characterization confirmed the formation of Ap-CuNPs with a plasmon resonance peak at 550 nm, the presence of phytochemical capping agents, and high crystallinity. The average particle size was 69.1 nm, with a zeta potential of −12.1 mV. Ap-CuNPs exhibited significant antioxidant activity, with 88.62 % inhibition in the DPPH assay, in the H2O2 assay, which assesses the capacity to scavenge hydrogen peroxide, the Ap-CuNPs achieved 86.3 % inhibition at the same concentration. and anti-inflammatory activity, with 80 % inhibition in the BSA assay. Antimicrobial tests revealed strong activity against gram-negative bacteria in the 22 mm inhibition zone for Pseudomonas sp., for S. aureus, the inhibition zones were 9 mm. Cytotoxicity assessments revealed minimal effects at low concentrations, with 200 μg/ml identified as the optimal dose for wound healing. In vitro wound scratch assays demonstrated enhanced fibroblast migration and wound closure at this concentration.

Silicon Nanowire Biosensors for Diabetes Mellitus Monitoring

The main goal of this research is the development of a label-free biosensor for the detection of diabetes mellitus (DM) using the target molecule retinol-binding protein 4 (RBP4). The enzyme-linked immunosorbent assay (ELISA) approach, currently used to detect DM, is time-consuming and difficult. As a result, label-free biosensors are being considered as an alternative. In this research, silicon nanowires (SiNWs) were selected as the transducer for this biosensor due to their low cost, real-time analysis capability, high sensitivity, and low detection limit. The SiNWs were created using conventional lithography, reactive ion etching (RIE), and physical vapor deposition (PVD), and then dripped with a gold nanoparticle solution to create gold-decorated SiNWs. The surface of the gold-decorated SiNWs was functionalized using 3-aminothiophenol and glutaraldehyde solutions before being immobilized with DM RBP4 antibodies and targets. The electrical characterization of the gold nanoparticle decorated SiNWs biosensor revealed good performance in DM detection. The pH tests confirmed that the SiNWs acted as a transducer, with current proportional to the DM RBP4 concentration. The estimated limit of detection (LOD) and sensitivity for detecting DM RBP4 binding were 0.076 fg/mL and 8.92 nA(g/mL)-1, respectively. This gold nanoparticle decorated SiNWs biosensor performed better than other methods and enabled efficient, accurate, and direct detection of DM. The SiNWs could be used as a distinctive electrical protein biosensor for biological diagnostic purposes. In conclusion, gold nanoparticle deposition offers effective label-free, direct, and high-accuracy DM detection, outperforming previous approaches. Thus, these SiNWs serve as novel electrical protein biosensors for future biological diagnostic applications.

Biosynthesis of gold nanoparticles from Martynia annua aqueous leaves extract, its antioxidant potential and antimicrobial ability against selected wound pathogens

The field of nanotechnology has great potential within the realm of modern nanoscience and technology. Ecologically responsible nanoparticle production requires the careful selection of a solvent that is ecologically acceptable, together with the use of reducing and stabilizing chemicals that are also environmentally beneficial. The utilization of gold nanoparticles has been widely investigated in the fields of separation sciences and illness diagnosis for biological purposes. The objective of this study is to synthesize gold nanoparticles utilizing a Water-based Leaf Extract from the Martynia annua Plant in an ecologically sustainable manner. X-ray diffraction, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) were employed to analyze the morphological characteristics, stability, and crystalline structure of the produced nanoparticles. The experimental results validate the commencement of the gold ion reduction process by the detected change in color of the reaction mixture to a deep purple colour. Moreover, the synthesis was confirmed by the use of UV–visible spectrometry, within the wavelength region of 584 nm. The zeta potential of the produced nanoparticles is reported to be −31 mV, while the average diameter of the particles is about 21 nm. The synthesized particles exhibit significant antioxidant capacity in comparison to the standard. Further AuNPs shows strong antibacterial potential against Escherichia coli, Staphylococcus aureus, Streptococcus sp, Bacillus subtilis, and Enterococcus sp was 53.94 µg/mL, 78.02 µg/mL, 55.47 µg/mL, 55.83 µg/mL, and 95.24 µg/mL respectively Synthesized particles demonstrate substantial cytotoxicity against A549 human lung cancer cells and it shows the inhibitory concentration at 20 µg/ml. The results indicated a significant decrease in cell viability, which was directly linearly related to the dosage of particles. The Martynia annua plant mediated gold nanoparticles exhibit potent antioxidant and antibacterial properties effectively combating specific wound infections.

Aptamer Insights in Targeting and Designing of Therapeutic Drugs.

In the therapy of chronic and dangerous conditions like as cancer, heart disease, neurological illnesses, or retinal angiopathy, we frequently require most effective dosage schedule with adequate precision and sufficient therapeutic potential. Among these entities with the capacity to behave in a target-specific way are aptamers. Usually, they are produced by an iterative screening procedure named “Systemic Evolution of Ligands by Exponential Enrichment (SELEX)” which is used to complicate nucleic acid libraries. For several biological purposes, including targeted treatment, aptamers are potential and could be easily molded into desirable needs and also be tested in a manner that is not very extravagant or pricey. Chemical modification can be employed to enhance their pharmacological actions or prevent enzymatic degradation, hence guaranteeing their chemical integrity and bioavailability in a physiological setting. The recent advancements made in drug targeting and design with the use of aptamers are the main topic of this review. This review will highlight current developments and go over prospects and problems in the fields of aptamer-based targeted therapy, including aptamer therapeutics.

Entropy optimization on EMHD Casson Williamson penta-hybrid nanofluid over porous exponentially vertical cone

Present inquiry explores steady electro magneto hydrodynamic flow on porous exponentially vertical cone of Casson Williamson nanofluid. In this novel research work, we have successfully developed a multipurpose and adaptable penta-hybrid nanofluid by mixing nanoparticles of silver (Ag), gold (Au), magnesium oxide (MgO), copper (Cu), titanium dioxide (TiO2) with base fluid and are used in many innovative applications, including coatings, sensors, energy storage, water purification, enhanced heat transfer, biological purposes and lubricants. Numerous industries can benefit considerably from the combined features of these nanoparticles, which can improve the base fluid’s functioning and performance. Further, it aims to determine thermal and mass transportation of penta-hybrid nanofluid. The controlling PDEs can be turned into non-linear ODEs via similarity conversions, solved using fifth order Runge-Kutta-Fehlberg technique via shooting technique. Penta-hybrid nanofluid/ C2H6O2is excelled in heat transport to greater extent than other hybrid nanofluids with 62.6 %. Moreover, entropy generation rate is performed, and irreversibility demonstrates that, compared to previous efforts, total entropy generation rate minimize energy loss by 247.16 % in present study. Estimating impact of flow patterns and transmission rates are useful application with varied industrial and engineering applications, environmental restoration, and biomedical applications such as targeted medication administration.

A Brief Review Article on Carica papaya and its Medical Advantages

Carica papaya is a member of the Caricaceae family and is frequently referred to as "papaya." Carica papaya has been utilized in Ayurvedic therapy for centuries. It has anti-inflammatory, antioxidant, diuretic, antibacterial, abortifacient, vermifuge, hypoglycemia, antifungal, anthelminthic, and hypoglycemic properties. Immunomodulatory, and so forth. Scientific research suggests that they have a diverse biological purpose that sustains their existence. Traditionally, it has been used to treat a variety of ailments It is used to cure a variety of infections such as dengue fever, warts, corns, sinuses, skin inflammation, diabetes, glandular tumors, blood pressure, digestive disorders, constipation, antibacterial, antifertility, anti-HIV, expel worms, excite regeneration organs, and many more. The current study is on the nutritional content, health benefits, medicinal benefits, and synthetic elements of papaya.

Exploring Valeriana species: Unraveling anticonvulsant potential through phytochemistry and pharmacology

Background and aims: The Valerianaceae comprises about 300 species of annual and perennial plants found worldwide. Several species are utilized for biological purposes, while others are consumed. The various Valeriana species have different therapeutic effects, including sleep aid, sedative and anxiolytic, and anticonvulsant effects. The study intends to review the phytochemistry, pharmacological activities, and molecular pathways of these plants to explore their potential as therapeutic options for seizures and epilepsy. Methods: Until 2023, all relevant information about Valeriana species was gathered from PubMed, Scopus, Web of Science, and Embase. Valerianaceae, Valeriana, valeric acid, and Valeriana officinalis, phytochemical composition, in vivo investigations, epilepsy, neuroprotective, anticonvulsant, GABA, seizure, and preclinical and clinical research were among the search terms utilized for this review. Results: Based on the results obtained from the studies conducted in this field, significant anticonvulsant effects of various compounds extracted from the Valeriana species have been observed in multiple animal models, including pentylenetetrazole (PTZ)- and maximal electroshock (MES)-induced seizures in mice, rats, and zebrafish. It has also been determined that the molecular and pharmacological mechanisms involved in these anti-epileptic effects are increasing the GABA pathway, inhibiting the NMDA receptor and adenosine pathways, and nitric oxide (NO) modulation. Moreover, these compounds synergize with clonazepam, diazepam, phenobarbital, and phenytoin. Conclusion: It is recommended to prepare proper drug forms and study its anticonvulsant effects in clinical studies.

Development of Leptolyngbya sp. BL0902 into a model organism for synthetic biological research in filamentous cyanobacteria.

Cyanobacteria have great potential in CO2-based bio-manufacturing and synthetic biological studies. The filamentous cyanobacterium, Leptolyngbya sp. strain BL0902, is comparable to Arthrospira (Spirulina) platensis in commercial-scale cultivation while proving to be more genetically tractable. Here, we report the analyses of the whole genome sequence, gene inactivation/overexpression in the chromosome and deletion of non-essential chromosomal regions in this strain. The genetic manipulations were performed via homologous double recombination using either an antibiotic resistance marker or the CRISPR/Cpf1 editing system for positive selection. A desD-overexpressing strain produced γ-linolenic acid in an open raceway photobioreactor with the productivity of 0.36 g·m-2·d-1. Deletion mutants of predicted patX and hetR, two genes with opposite effects on cell differentiation in heterocyst-forming species, were used to demonstrate an analysis of the relationship between regulatory genes in the non-heterocystous species. Furthermore, a 50.8-kb chromosomal region was successfully deleted in BL0902 with the Cpf1 system. These results supported that BL0902 can be developed into a stable photosynthetic cell factory for synthesizing high value-added products, or used as a model strain for investigating the functions of genes that are unique to filamentous cyanobacteria, and could be systematically modified into a genome-streamlined chassis for synthetic biological purposes.

High interspecific variability in ice nucleation activity suggests pollen ice nucleators are incidental

Abstract. Ice-nucleating macromolecules (INMs) produced by plant pollen can nucleate ice at warm temperatures and may play an important role in weather- and climate-relevant cloud glaciation. INMs have also proved useful for mammalian cell and tissue model cryopreservation. The high ice nucleation (IN) activity of some INMs indicates an underlying biological function, either freezing tolerance or bioprecipitation-mediated dispersal. Here, using the largest study of pollen ice nucleation to date, we show that phylogenetic proximity, spermatophyte subdivision, primary growth biome, pollination season, primary pollination method, desiccation tolerance and native growth elevation do not account for the IN activity of INMs released from different plant species' pollen. The results suggest that these macromolecules are produced by plants for a purpose unrelated to ice nucleation and have an incidental ability to nucleate ice. This ability may have been adapted by some species for specific biological purposes, producing exceptional ice nucleators. Pollen INMs may be more active, widespread in nature, and diverse than previously thought.

Turn-on protein switches for controlling actin binding in cells

Within a shared cytoplasm, filamentous actin (F-actin) plays numerous and critical roles across the cell body. Cells rely on actin-binding proteins (ABPs) to organize F-actin and to integrate its polymeric characteristics into diverse cellular processes. Yet, the multitude of ABPs that engage with and shape F-actin make studying a single ABP’s influence on cellular activities a significant challenge. Moreover, without a means of manipulating actin-binding subcellularly, harnessing the F-actin cytoskeleton for synthetic biology purposes remains elusive. Here, we describe a suite of designed proteins, Controllable Actin-binding Switch Tools (CASTs), whose actin-binding behavior can be controlled with external stimuli. CASTs were developed that respond to different external inputs, providing options for turn-on kinetics and enabling orthogonality and multiplexing. Being genetically encoded, we show that CASTs can be inserted into native protein sequences to control F-actin association locally and engineered into structures to control cell and tissue shape and behavior.