Biology Approach Research Articles

LncRNA HOXA-AS3 promotes cell proliferation and invasion via targeting miR-218-5p/FOXP1 axis in osteosarcoma

Osteosarcoma is an aggressive form of bone cancer and affects the health in children and adolescents. Although conventional treatment improves the osteosarcoma survival, some patients have metastasis and drug resistance, leading to a worse prognosis. Therefore, it is necessary to explore the molecular mechanism of osteosarcoma occurrence and progression, which could discover the novel treatment for osteosarcoma. Long noncoding RNAs (lncRNAs) have been reported to regulate osteosarcoma occurrence and malignant progression. LncRNA HOXA-AS3 facilitates the tumorigenesis and progression in a variety of human cancers. However, the underlying mechanism of lncRNA HOXA-AS3-induced oncogenesis is poorly determined in osteosarcoma. To address this point, we utilized several cellular biological strategies and molecular approaches to explore the biological functions and mechanisms of lncRNA HOXA-AS3 in osteosarcoma cells. We found that lncRNA HOXA-AS3 facilitates cell proliferation and invasion via targeting miR-218-5p/FOXP1 axis in osteosarcoma. In conclusion, lncRNA HOXA-AS3 could be a promising target for osteosarcoma treatment.

Carbon dioxide removal and net zero emissions in Africa: an integrated assessment modelling based on three different land-based negative emission solutions

Abstract As the remaining carbon budget for limiting warming to 1.5 °C rapidly diminishes, it is clear that, besides decarbonization, the world will need to remove 100–1000 GtCO2 from the atmosphere by the end of the century. Yet, Africa, where many carbon removal schemes are planned, remains a ‘blindspot’ in existing studies. There is limited understanding of the trade-offs and synergies associated with carbon removal within Africa’s energy-land-water system. To address this research gap, we model a stylized net-zero emissions (NZEs) in Africa by 2050, with focus on three land-based biological carbon removal approaches: afforestation/reforestation (AR), bioenergy with carbon capture and storage (BECCS), and biochar. We find that by 2050, the total gross carbon removal is projected to reach 1.2 GtCO2 yr−1 when all three carbon removal approaches are available, and 0.5 GtCO2 yr−1 when Africa relies solely on AR. Pursuing NZE with only AR or AR alongside biochar in Africa would be the most expensive mitigation option but they lead to the lowest residual fossil fuel and industry CO2 emissions. An NZE by 2050 in Africa could reduce cropland by 30%–40% from 2020 to 2050, depending on the carbon dioxide removal deployment strategy adopted. Southern Africa would be particularly affected, facing significant challenges in balancing food security with climate goals. The highest increase in staple food prices will occur under AR only, while the availability of AR-BECCS-biochar produces the lowest rise in staple food prices. Our findings highlight the need for balanced and region-specific carbon dioxide removal strategies to ensure climate and other sustainability goals are met.

How can the diterpene synthase CotB2V80L alter the product profile?

Structural diversity of diterpenes is mediated by the enigmatic family of diterpene synthases. The overall enzymatic contribution hereby lies in a carefully concerted chemistry of highly reactive carbocation intermediates mainly guided by aromatic and polar amino acid side chains and the pyrophosphate cofactor. To date several studies aimed to shed light on the mechanism underlining terpene synthases chemistry. Specifically, the diterpene synthase CotB2 serves as model enzyme for detailed mutagenesis studies. Here we investigate the catalytic mechanism of CotB2 variant V80L in a holistic, biochemical, structural, and computational biology approach. We were able to identify an altered product profile compared to CotB2WT for the substrates geranylgeranyl diphosphate and farnesyl diphosphate. Moreover, we solved the crystal structure, and shed further light on terpene synthase chemistry by modelling of the substrate and intermediate binding.

Chronic inflammation: Cross linking insights from Ayurvedic Sciences, a silver lining to systems biology and personalized medicine

Precision in personalized medicine is a crucial subject that needs comprehensive discussion and scientific validation. Traditional healthcare approaches like the Ayurvedic Sciences are often contextually linked with personalized medicine. However, it is unfortunate that this knowledge concerning Ayurveda and personalized medicine is restricted to applying systems biology techniques to 'prakriti' the phenotypic expression and characterization detailed in the literature. There are other significant constructs besides prakruti that interest an Ayurvedic physician, which accounts for crafting precision in evidence-based medicinal practices. There is this influential model of Ayurvedic healthcare practice wherein the physician maps specific personalized characters in addition to prakruti to deduce the host responses to endogenous and exposome conditions. Subsequently, tailored protocols are administered that bring about holistic, personalized outcomes.The review aimed to determine the effective methods for integrating Systems Biology, Ayurvedic Sciences, and Personalized Medicine (precision medicinebased). Ayurveda adopts a holistic approach, considering multiple variables and their interconnections, while the modern reductionist approach focuses on understanding complex details of smaller parts through rigorous experimentation. Despite seeming extremes, ongoing research on lifestyle, gut health, and spiritual well-being highlights the evolving intersection between traditional Ayurvedic practices and modern science. The current focus is on developing the fundamental concept of Ayurveda Biology by incorporating Systems Biology techniques.Challenges in this integration include understanding diverse data types, bridging interdisciplinary knowledge gaps, and addressing technological limitations and ethical concerns. Overcoming these challenges will require interdisciplinary collaboration, innovative methodologies, substantial investment in technology, and cultural sensitivity to preserve Ayurveda's core principles while leveraging modern scientific advancements. The focus of discussions and debates on such collaborations should be breakthrough clinical models, such as chronic inflammation, which can be objectively related to specific stages of disease manifestations described in Ayurveda. Validating patient characteristics with systems biology approaches, particularly in shared pathologies like chronic inflammation, is crucial for bringing prediction and precision to personalized medicine

Regeneration of Osteochondral Lesion of the Talus with Retrograde Drilling Technique: An In Vitro Pilot Study

Background: Retrograde Drilling (RD) is a surgical technique employed for osteochondral lesions of the talus (OCLTs) to reach the subchondral bone lesion from behind, thus preserving cartilage integrity. The aim of the present pilot study was to set up an in vitro model of OCLTs to evaluate the regenerative potential of biological approaches that could be associated with the RD technique. Methods: For this purpose, an OCLT was created in human osteochondral specimens, to try to mimic the RD technique, and to compare the regenerative potential of two biological treatments. For this purpose, three groups of treatments were performed in vitro: (1) no treatment (empty defect); (2) autologous bone graft (ABG); (3) hyaluronic membrane enriched with autologous bone marrow cells. Tissue viability; production of Collagen I and II, Vascular Endothelial Growth Factor, and Aggrecan; and histological and microCT evaluations were performed after 30 days of culture in normal culture conditions. Results: It was observed that Group 3 showed the highest viability, and Group 2 showed the highest protein production. From a histological and microtomographic point of view, it was possible to appreciate the structure of the morcellized bone with which the defect of Group 2 was filled, while it was not yet possible to observe the deposition of mineralized tissue in Group 3. Conclusions: To conclude, this pilot study shows the feasibility of an alternative in vitro model to evaluate and compare the regenerative potential of two biological scaffolds, trying to mimic the RD technique as much as possible. The tissues remained vital for up to 4 weeks and both ABG and hyaluronic acid-based scaffolds stimulated the release of proteins linked to regenerative processes in comparison to the empty defect group.

Comparative evaluation of biological control programs and chemical pesticides for managing insect and mite pests in cucumber greenhouses: a sustainable approach for enhanced pest control and yield

BackgroundCucumber plants are susceptible to several economically damaging pests, including whiteflies, aphids, thrips and spider mites. This study aimed to evaluate the efficacy of two biological control programs, utilizing different releases of bio-agents, in comparison with chemical control method. The bio-agents used were the aphid parasitoid Aphelinus albipodus Hayat and Fatima (Hymenoptera: Aphelinidae), the green lacewing Chrysoperla carnea (Steph.) (Neuroptera: Chrysopidae) and the predatory mite Phytoseiulus persimilis Athias-Henriot (Acari: Phytoseiidae) in two release rates; low and high. Additionally, a chemical pesticides treatment was included for comparison in managing the pests in cucumber greenhouses during the winter seasons of 2022 and 2023, in Egypt. Abundances of whitefly, aphids, thrips and spider mites were recorded weekly throughout the study.ResultsThe aphid population in the greenhouse with high release rate (BIO 2) showed the highest reduction, with percentages of 84.55 and 89.88% in 2022 and 2023, respectively. Both greenhouse with low release rate (BIO 1) and BIO 2 exhibited significant reductions in the whitefly population, with proportions of 71.31 and 72.01% in 2022, and 82.05 and 85.94% in 2023, respectively. The thrips population also experienced notable reductions in both BIO 1 and BIO 2 greenhouses, with percentages of 72.08 and 75.71% in 2022, and 59.93 and 61.38% in 2023, respectively. However, the pesticide treatment demonstrated the lowest reduction in populations of aphids, whitefly and thrips in both seasons. Nevertheless, in all treatments in the two evaluated seasons, the high release rate of the predatory mite, P. persimilis (15 individuals/m2), proved to be highly effective in maintaining the mite populations below the economic threshold level. However, the population density of the two-spotted spider mite, Tetranychus urticae Koch. (Acari: Tetranychidae), increased in the pesticide-treated greenhouse, indicating the development of resistance to pesticides. Although the tested programs resulted in similar yields, the biological control approach offered the advantage of pesticide-free produce and reduced production costs.ConclusionFor pest management in cucumber growing in greenhouses during winter, it is recommended to use biological control agents at a low release rate at the early occurrence of pests. This approach can help minimize pest populations effectively.

The identification of biomarkers for Alzheimer's disease using a systems biology approach based on lncRNA-circRNA-miRNA-mRNA ceRNA networks

In addition to being the most prevalent form of neurodegeneration among the elderly, AD is a devastating multifactorial disease. Currently, treatments address only its symptoms. Several clinical studies have shown that the disease begins to manifest decades before the first symptoms appear, indicating that studying early changes is crucial to improving early diagnosis and discovering novel treatments. Our study used bioinformatics and systems biology to identify biomarkers in AD that could be used for diagnosis and prognosis. The procedure was performed on data from the GEO database, and GO and KEGG enrichment analysis were performed. Then, we set up a network of interactions between proteins. Several miRNA prediction tools including miRDB, miRWalk, and TargetScan were used. The ceRNA network led to the identification of eight mRNAs, four circRNAs, seven miRNAs, and seven lncRNAs. Multiple mechanisms, including the cell cycle and DNA replication, have been linked to the promotion of AD development by the ceRNA network. By using the ceRNA network, it should be possible to extract prospective biomarkers and therapeutic targets for the treatment of AD. It is possible that the processes involved in DNA cell cycle and the replication of DNA contribute to the development of Alzheimer's disease.

Molecular Insights into the Regulatory Landscape of Protein Kinase C-Related Kinase-2 (PRK2/PKN2) Using Targeted Small Compounds

The protein kinase C-related kinases (PRKs, also termed PKNs) are important in cell migration, cancer, hepatitis C infection, and nutrient sensing. They belong to a group of protein kinases called AGC kinases that share common features like a C-terminal extension to the catalytic domain comprising a hydrophobic motif. PRKs are regulated by N-terminal domains, a pseudosubstrate sequence, Rho-binding domains and a C2 domain involved in inhibition and dimerization, while Rho and lipids are activators. We investigated the allosteric regulation of PRK2 and its interaction with its upstream kinase PDK1 using a chemical biology approach. We confirmed the PIF-mediated docking interaction of PRK2 with PDK1 and showed that this interaction can be modulated allosterically. We showed that the polypeptide PIFtide and a small compound binding to the PIF-pocket of PRK2 were allosteric activators, by displacing the pseudosubstrate PKL region from the active site. In addition, a small compound binding to the PIF-pocket allosterically inhibited the catalytic activity of PRK2. Together, we confirmed the docking interaction and allostery between PRK2 and PDK1 and described an allosteric communication between the PIF-pocket and the active site of PRK2, both modulating the conformation of the ATP-binding site and the pseudosubstrate PKL-binding site. Our study highlights the allosteric modulation of the activity and the conformation of PRK2 in addition to the existence of at least two different complexes between PRK2 and its upstream kinase PDK1. Finally, the study highlights the potential for developing allosteric drugs to modulate PRK2 kinase conformations and catalytic activity.

Bioinformatic Prediction and High Throughput In Vivo Screening to Identify Cis-Regulatory Elements for the Development of Algal Synthetic Promoters.

Algae biotechnology holds immense promise for revolutionizing the bioeconomy through the sustainable and scalable production of various bioproducts. However, their development has been hindered by the lack of advanced genetic tools. This study introduces a synthetic biology approach to develop such tools, focusing on the construction and testing of synthetic promoters. By analyzing conserved DNA motifs within the promoter regions of highly expressed genes across six different algal species, we identified cis-regulatory elements (CREs) associated with high transcriptional activity. Combining the algorithms POWRS, STREME, and PhyloGibbs, we predicted 1511 CREs and inserted them into a minimal synthetic promoter sequence in 1, 2, or 3 copies, resulting in 4533 distinct synthetic promoters. These promoters were evaluated in vivo for their capacity to drive the expression of a transgene in a high-throughput manner through next-generation sequencing post antibiotic selection and fluorescence-activated cell sorting. To validate our approach, we sequenced hundreds of transgenic lines showing high levels of GFP expression. Further, we individually tested 14 identified promoters, revealing substantial increases in GFP expression─up to nine times higher than the baseline synthetic promoter, with five matching or even surpassing the performance of the native AR1 promoter. As a result of this study, we identified a catalog of CREs that can now be used to build superior synthetic algal promoters. More importantly, here we present a validated pipeline to generate building blocks for innovative synthetic genetic tools applicable to any algal species with a sequenced genome and transcriptome data set.

Bioinformatic Prediction and High Throughput In Vivo Screening to Identify Cis-Regulatory Elements for the Development of Algal Synthetic Promoters.

Algae biotechnology holds immense promise for revolutionizing the bioeconomy through the sustainable and scalable production of various bioproducts. However, their development has been hindered by the lack of advanced genetic tools. This study introduces a synthetic biology approach to develop such tools, focusing on the construction and testing of synthetic promoters. By analyzing conserved DNA motifs within the promoter regions of highly expressed genes across six different algal species, we identified cis-regulatory elements (CREs) associated with high transcriptional activity. Combining the algorithms POWRS, STREME, and PhyloGibbs, we predicted 1511 CREs and inserted them into a minimal synthetic promoter sequence in 1, 2, or 3 copies, resulting in 4533 distinct synthetic promoters. These promoters were evaluated in vivo for their capacity to drive the expression of a transgene in a high-throughput manner through next-generation sequencing post antibiotic selection and fluorescence-activated cell sorting. To validate our approach, we sequenced hundreds of transgenic lines showing high levels of GFP expression. Further, we individually tested 14 identified promoters, revealing substantial increases in GFP expression─up to nine times higher than the baseline synthetic promoter, with five matching or even surpassing the performance of the native AR1 promoter. As a result of this study, we identified a catalog of CREs that can now be used to build superior synthetic algal promoters. More importantly, here we present a validated pipeline to generate building blocks for innovative synthetic genetic tools applicable to any algal species with a sequenced genome and transcriptome data set.

Structure analysis of the telomere resolvase from the Lyme disease spirochete Borrelia garinii reveals functional divergence of its C-terminal domain.

Borrelia spirochetes are the causative agents of Lyme disease and relapsing fever, two of the most common tick-borne illnesses. A characteristic feature of these spirochetes is their highly segmented genomes which consists of a linear chromosome and a mixture of up to approximately 24 linear and circular extrachromosomal plasmids. The complexity of this genomic arrangement requires multiple strategies for efficient replication and partitioning during cell division, including the generation of hairpin ends found on linear replicons mediated by the essential enzyme ResT, a telomere resolvase. Using an integrative structural biology approach employing advanced modelling, circular dichroism, X-ray crystallography and small-angle X-ray scattering, we have generated high resolution structural data on ResT from B. garinii. Our data provides the first high-resolution structures of ResT from Borrelia spirochetes and revealed active site positioning in the catalytic domain. We also demonstrate that the C-terminal domain of ResT is required for both transesterification steps of telomere resolution, and is a requirement for DNA binding, distinguishing ResT from other telomere resolvases from phage and bacteria. These results advance our understanding of the molecular function of this essential enzyme involved in genome maintenance in Borrelia pathogens.

Salt-tolerant plant growth-promoting bacteria as a versatiletool for combating salt stress in crop plants.

Soil salinization poses a great threat to global agricultural ecosystems, and finding ways to improve the soils affected by salt and maintain soil health and sustainable productivity has become a major challenge. Various physical, chemical and biological approaches are being evaluated to address this escalating environmental issue. Among them, fully utilizing salt-tolerant plant growth-promoting bacteria (PGPB) has been labeled as a potential strategy to alleviate salt stress, since they can not only adapt well to saline soil environments but also enhance soil fertility and plant development under saline conditions. In the last few years, an increasing number of salt-tolerant PGPB have been excavated from specific ecological niches, and various mechanisms mediated by such bacterial strains, including but not limited to siderophore production, nitrogen fixation, enhanced nutrient availability, and phytohormone modulation, have been intensively studied to develop microbial inoculants in agriculture. This review outlines the positive impacts and growth-promoting mechanisms of a variety of salt-tolerant PGPB and opens up new avenues to commercialize cultivable microbes and reduce the detrimental impacts of salt stress on plant growth. Furthermore, considering the practical limitations of salt-tolerant PGPB in the implementation and potential integration of advanced biological techniques in salt-tolerant PGPB to enhance their effectiveness in promoting sustainable agriculture under salt stress are also accentuated.

Structural details of helix-mediated TDP-43 C-terminal domain multimerization.

The primarily disordered C-terminal domain (CTD) of TAR DNA binding protein-43 (TDP-43), a key nuclear protein in RNA metabolism, forms neuronal inclusions in several neurodegenerative diseases. A conserved region (CR, spanning residues 319-341) in CTD forms transient helix-helix contacts important for its higher-order oligomerization and function that are disrupted by ALS-associated mutations. However, the structural details of CR assembly and the explanation for several ALS-associated variants' impact on phase separation and function remain unclear due to challenges in analyzing the dynamic association of TDP-43 CTD using traditional structural biology approaches. By employing an integrative approach, combining biophysical experiments, biochemical assays, AlphaFold2-Multimer (AF2-Multimer), and atomistic simulations, we generated structural models of helical oligomerization of TDP-43 CR. Using NMR, we first established that the native state of TDP-43 CR under physiological conditions is α-helical. Next, alanine scanning mutagenesis revealed that while hydrophobic residues in the CR are important for CR assembly, phase separation and TDP-43 nuclear retention function, polar residues down regulate these processes. Finally, pairing AF2-Multimer modeling with AAMD simulations indicated that dynamic, oligomeric assemblies of TDP-43 that are stabilized by a methionine-rich core with specific contributions from a tryptophan/leucine pair. In conclusion, our results advance the structural understanding of the mechanisms driving TDP-43 function and provide a window into the initial stages of its conversion into pathogenic aggregates.

Construction of lignan glycosides biosynthetic network in Escherichia coli using mutltienzyme modules

BackgroundDue to the complexity of the metabolic pathway network of active ingredients, precise targeted synthesis of any active ingredient on a synthetic network is a huge challenge. Based on a complete analysis of the active ingredient pathway in a species, this goal can be achieved by elucidating the functional differences of each enzyme in the pathway and achieving this goal through different combinations. Lignans are a class of phytoestrogens that are present abundantly in plants and play a role in various physiological activities of plants due to their structural diversity. In addition, lignans offer various medicinal benefits to humans. Despite their value, the low concentration of lignans in plants limits their extraction and utilization. Recently, synthetic biology approaches have been explored for lignan production, but achieving the synthesis of most lignans, especially the more valuable lignan glycosides, across the entire synthetic network remains incomplete.ResultsBy evaluating various gene construction methods and sequences, we determined that the pCDF-Duet-Prx02-PsVAO gene construction was the most effective for the production of (+)-pinoresinol, yielding up to 698.9 mg/L after shake-flask fermentation. Based on the stable production of (+)-pinoresinol, we synthesized downstream metabolites in vivo. By comparing different fermentation methods, including “one-cell, one-pot” and “multicellular one-pot”, we determined that the “multicellular one-pot” method was more effective for producing (+)-lariciresinol, (-)-secoisolariciresinol, (-)-matairesinol, and their glycoside products. The “multicellular one-pot” fermentation yielded 434.08 mg/L of (+)-lariciresinol, 96.81 mg/L of (-)-secoisolariciresinol, and 45.14 mg/L of (-)-matairesinol. Subsequently, ultilizing the strict substrate recognition pecificities of UDP-glycosyltransferase (UGT) incorporating the native uridine diphosphate glucose (UDPG) Module for in vivo synthesis of glycoside products resulted in the following yields: (+)-pinoresinol glucoside: 1.71 mg/L, (+)-lariciresinol-4-O-d-glucopyranoside: 1.3 mg/L, (+)-lariciresinol-4’-O-d-glucopyranoside: 836 µg/L, (-)-secoisolariciresinol monoglucoside: 103.77 µg/L, (-)-matairesinol-4-O-d-glucopyranoside: 86.79 µg/L, and (-)-matairesinol-4’-O-d-glucopyranoside: 74.5 µg/L.ConclusionsBy using various construction and fermentation methods, we successfully synthesized 10 products of the lignan pathway in Isatis indigotica Fort in Escherichia coli, with eugenol as substrate. Additionally, we obtained a diverse range of lignan products by combining different modules, setting a foundation for future high-yield lignan production.

DAMP-ing IBD: Extinguish the Fire and Prevent Smoldering.

In inflammatory bowel diseases (IBD), the most promising therapies targeting cytokines or immune cell trafficking demonstrate around 40% efficacy. As IBD is a multifactorial inflammation of the intestinal tract, a single-target approach is unlikely to solve this problem, necessitating an alternative strategy that addresses its variability. One approach often overlooked by the pharmaceutically driven therapeutic options is toaddress the impact of environmental factors. This is somewhat surprising considering that IBD is increasingly viewed as a condition heavily influenced by such factors, including diet, stress, and environmental pollution-often referred to as the "Western lifestyle". In IBD, intestinal responses result from a complex interplay among the genetic background of the patient, molecules, cells, and the local inflammatory microenvironment where danger- and microbe-associated molecular patterns (D/MAMPs) provide an adjuvant-rich environment. Through activating DAMP receptors, this array of pro-inflammatory factors can stimulate, for example, the NLRP3 inflammasome-a major amplifier of the inflammatory response in IBD, and various immune cells via non-specific bystander activation of myeloid cells (e.g., macrophages) and lymphocytes (e.g., tissue-resident memory T cells). Current single-target biological treatment approaches can dampen the immune response, but without reducing exposure to environmental factors of IBD, e.g., by changing diet (reducing ultra-processed foods), the adjuvant-rich landscape is never resolved and continues to drive intestinal mucosal dysregulation. Thus, such treatment approaches are not enough to put out the inflammatory fire. The resultant smoldering, low-grade inflammation diminishes physiological resilience of the intestinal (micro)environment, perpetuating the state of chronic disease. Therefore, our hypothesis posits that successful interventions for IBD must address the complexity of the disease by simultaneously targeting all modifiable aspects: innate immunity cytokines and microbiota, adaptive immunity cells and cytokines, and factors that relate to the (micro)environment. Thus the disease can be comprehensively treated across the nano-, meso-, and microscales, rather than with a focus on single targets. A broader perspective on IBD treatment that also includes options to adapt the DAMPing (micro)environment is warranted.

Demystifying the potential of lipid-based nanocarriers in targeting brain malignancies.

Drug targeting for brain malignancies is restricted due to the presence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), which act as barriers between the blood and brain parenchyma. Certainly, the limited therapeutic options for brain malignancies have made notable progress with enhanced biological understanding and innovative approaches, such as targeted therapies and immunotherapies. These advancements significantly contribute to improving patient prognoses and represent a promising shift in the landscape of brain malignancy treatments. A more comprehensive understanding of the histology and pathogenesis of brain malignancies is urgently needed. Continued research focused on unraveling the intricacies of brain malignancy biology holds the key to developing innovative and tailored therapies that can improve patient outcomes. Lipid nanocarriers are highly effective drug delivery systems that significantly improve their solubility, bioavailability, and stability while also minimizing unwanted side effects. Surface-modified lipid nanocarriers (liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, lipid nanocapsules, lipid-polymer hybrid nanocarriers, lipoproteins, and lipoplexes) are employed to improve BBB penetration and uptake through various mechanisms. This systematic review illuminates and covers various topics related to brain malignancies. It explores the different methods of drug delivery used in treating brain malignancies and delves into the benefits, limitations, and types of brain-targeted lipid-based nanocarriers. Additionally, this review discusses ongoing clinical trials and patents related to brain malignancy therapies and provides a glance into future perspectives for treating this condition.

Germination and biological adaptation approaches as salt-stress tolerance process in selected paddy cultivars under salinity stress

Cultivating productive paddy crops on salty soil to maximise production is a challenging approach to meeting the world's growing food demand. Thus, determining salinity tolerance rates in specific paddy cultivars is urgently needed. In this study, the salt tolerance traits of selected paddy cultivars, ADT45 and ADT39, were investigated by analysing germination, metabolites (pigments and biomolecules), and enzymatic (Superoxide dismutase (SOD), Catalase (CAT), and Peroxidase (POD) adaptation strategies as salt-stress tolerance mechanisms. This study found that salinity-induced reactive oxygen species (ROS) were efficiently detoxified by the antioxidant enzymes Superoxide dismutase (SOD), Catalase (CAT), and Peroxidase (POD) in ADT45 paddy varieties, followed by ADT39. Salinity stress had a significant impact on pigments and essential biomolecules in ADT45 and ADT39 paddy cultivars, including total chlorophyll, anthocyanin, carotenoids, ascorbic acid, hydrogen peroxide (H2O2), malondialdehyde, and proline. ADT45 demonstrated a significant relationship between H2O2 and antioxidant enzyme levels, followed by ADT39 paddy but not IR64. Morphological, physiological, and biochemical analyses revealed that ADT45, followed by ADT39, is a potential salt-tolerant rice cultivar.

Leveraging Quantitative Systems Pharmacology and Artificial Intelligence to advance treatment of Chronic Kidney Disease Mineral Bone Disorder.

Chronic kidney disease mineral bone disorder (CKD-MBD) is a complex clinical syndrome responsible for the accelerated cardiovascular mortality seen in individuals afflicted with CKD. Current approaches to therapy have failed to improve clinical outcomes adequately, likely due to targeting surrogate biochemical parameters as articulated by the guideline developer, KDIGO (Kidney Disease: Improving Global Outcomes). We hypothesized that using a Systems Biology Approach combining machine learning with mathematical modeling, we could test a novel approach to therapy targeting the abnormal movement of mineral out of bone and into soft tissue that is characteristic of CKD-MBD. The mathematical model describes the movement of calcium and phosphate between body compartments in response to standard therapeutic agents. The machine learning technique we applied is Reinforcement Learning (RL). We compared calcium, phosphate, PTH, and mineral movement out of bone and into soft tissue under four scenarios: standard approach (KDIGO), achievement of KDIGO guidelines using RL (RLKDIGO), targeting abnormal mineral flux (RLFLUX), and combining achievement of KDIGO guidelines with minimization of abnormal mineral flux (RLKDIGOFLUX). We demonstrate through simulations that explicitly targeting abnormal mineral flux significantly decreases abnormal mineral movement compared to standard approach while achieving acceptable biochemical outcomes. These investigations highlight the limitations of current therapeutic targets, primarily secondary hyperparathyroidism, and emphasize the central role of deranged phosphate homeostasis in the genesis of the CKD-MBD syndrome.

Bacterially expressed full length Hemagglutinin of Avian Influenza Virus H5N1 forms oligomers and exhibits hemagglutination

Avian influenza poses a significant global health threat, with the potential for widespread pandemics and devastating consequences. Hemagglutinin (HA), a critical surface glycoprotein of influenza viruses, plays a pivotal role in viral entry and serves as a primary target for subunit vaccine development. In this study, we successfully cloned, expressed, and purified hemagglutinin from the circulating strain of H5N1 influenza virus using a robust molecular biology approach. The cloning process involved insertion of the synthetic HA gene into the pET21b vector, confirmed through double digestion and sequencing. SDS-PAGE analysis confirmed the presence of the expected 60 kDa protein band post-induction. Following expression, the protein was subjected to purification via Ni-NTA affinity chromatography, yielding pure protein fractions. Native PAGE analysis confirmed the protein's oligomeric forms, essential for optimal antigenicity. Western blot analysis further validated protein identity using anti-His and anti-HA antibodies. MALDI-TOF analysis confirmed the protein's sequence integrity, while hemagglutination assay demonstrated its biological activity in binding to N-acetyl neuraminic acid. These findings underscore the potential of recombinant hemagglutinin as a valuable antigen for diagnosis and biochemical assays as well as for vaccine development against avian influenza. In conclusion, this study represents a critical guide for bacterial production of H5N1 HA, which can be a cost-effective and simpler strategy compared to mammalian protein expression. Further research into optimizing vaccine candidates and production methods will be essential in combating the ongoing threat of avian influenza pandemics.

Dysregulated proteasome activity and steroid hormone biosynthesis are associated with mortality among patients with acute COVID-19

The persistence of coronavirus disease 2019 (COVID-19)-related hospitalization severely threatens medical systems worldwide and has increased the need for reliable detection of acute status and prediction of mortality. We applied a systems biology approach to discover acute-stage biomarkers that could predict mortality. A total 247 plasma samples were collected from 103 COVID-19 (52 surviving COVID-19 patients and 51 COVID-19 patients with mortality), 51 patients with other infectious diseases (IDCs) and 41 healthy controls (HCs). Paired plasma samples were obtained from survival COVID-19 patients within 1 day after hospital admission and 1–3 days before discharge. There were clear differences between COVID-19 patients and controls, as well as substantial differences between the acute and recovery phases of COVID-19. Samples from patients in the acute phase showed suppressed immunity and decreased steroid hormone biosynthesis, as well as elevated inflammation and proteasome activation. These findings were validated by enzyme-linked immunosorbent assays and metabolomic analyses in a larger cohort. Moreover, excessive proteasome activity was a prominent signature in the acute phase among patients with mortality, indicating that it may be a key cause of poor prognosis. Based on these features, we constructed a machine learning panel, including four proteins [C-reactive protein (CRP), proteasome subunit alpha type (PSMA)1, PSMA7, and proteasome subunit beta type (PSMB)1)] and one metabolite (urocortisone), to predict mortality among COVID-19 patients (area under the receiver operating characteristic curve: 0.976) on the first day of hospitalization. Our systematic analysis provides a novel method for the early prediction of mortality in hospitalized COVID-19 patients.