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Discovery and characterization of a novel poly-mannuronate preferred alginate lyase: The first member of a new polysaccharide lyase family

Alginate is one of the most important marine colloidal polysaccharides, and its oligosaccharides have been proven to possess diverse biological functions. Alginate lyases could specifically degrade alginate and therefore serve as desirable tools for the research and development of alginate. In this report, a novel catalytic domain, which demonstrated no significant sequence similarity with all previously defined functional domains, was verified to exhibit a random endo-acting lyase activity to alginate. The action pattern analysis revealed that the heterologously expressed protein, named Aly44A, preferred to degrade polyM. Its minimum substrates and the minimum products were identified as unsaturated alginate trisaccharides and disaccharides, respectively. Based on the sequence novelty of Aly44A and its homologs, a new polysaccharide lyase family (PL44) was proposed. The discovery of the novel enzyme and polysaccharide lyase family provided a new entrance for the gene-mining and acquiring of alginate lyases, and would facilitate to the utilization of alginate and its oligosaccharides.

Probable antibody-mediated rejection in kidney transplantation is a rare and challenging phenotype to define: Findings from a single-center study

The Banff 2022 consensus introduced probable antibody-mediated rejection (AMR), characterized by mild AMR histologic features and human leukocyte antigen (HLA) donor-specific antibody (DSA) positivity. In a single-center observational cohort study of 1891 kidney transplant recipients transplanted between 2004 and 2021, 566 kidney biopsies were performed in 178 individual HLA-DSA–positive transplants. Evaluated at time of the first HLA-DSA–positive biopsy of each transplant (N = 178), 84 of the 178 (47.2%) of first biopsies were scored as no AMR, 22 of the 178 (12.4%) as probable AMR, and 72 of the 178 (40.4%) as AMR. The majority (77.3%) of probable AMR cases were first diagnosed in indication biopsies. Probable AMR was associated with lower estimated glomerular filtration rate (mL/min/1.73m2) than no AMR (20.2 [8.3-32.3] vs 40.1 [25.4-53.3]; P = .001). The one-year risk of (repeat) AMR was similar for probable AMR and AMR (subdistribution hazard ratio (sHR), 0.99; 0.42-2.31; P = .97) and higher than after no AMR (sHR, 3.05; 1.07-8.73; P = .04). Probable AMR had a higher five-year risk of transplant glomerulopathy vs no AMR (sHR, 4.29; 0.92-19.98; P = 06), similar to AMR (sHR, 1.74; 0.43-7.04; P = .44). No significant differences in five-year risk of graft failure emerged between probable AMR and AMR (sHR, 1.14; 0.36-3.58; P = .82) or no AMR (sHR, 2.46; 0.78-7.74; P = .12). Probable AMR is a rare phenotype, however, sharing significant similarities with AMR in this single-center study. Future studies are needed to validate reproducible diagnostic criteria and associated clinical outcomes to allow for defining best management of this potentially relevant phenotype.

Enhancing predictions of protein stability changes induced by single mutations using MSA-based Language Models.

Protein Language Models offer a new perspective for addressing challenges in structural biology, while relying solely on sequence information. Recent studies have investigated their effectiveness in forecasting shifts in thermodynamic stability caused by single amino acid mutations, a task known for its complexity due to the sparse availability of data, constrained by experimental limitations. To tackle this problem, we introduce two key novelties: leveraging a Protein Language Model that incorporates Multiple Sequence Alignments to capture evolutionary information, and using a recently released mega-scale dataset with rigorous data pre-processing to mitigate overfitting. We ensure comprehensive comparisons by fine-tuning various pre-trained models, taking advantage of analyses such as ablation studies and baselines evaluation. Our methodology introduces a stringent policy to reduce the widespread issue of data leakage, rigorously removing sequences from the training set when they exhibit significant similarity with the test set. The MSA Transformer emerges as the most accurate among the models under investigation, given its capability to leverage co-evolution signals encoded in aligned homologous sequences. Moreover, the optimized MSA Transformer outperforms existing methods and exhibits enhanced generalization power, leading to a notable improvement in predicting changes in protein stability resulting from point mutations. Code and data at https://github.com/RitAreaSciencePark/PLM4Muts. Supplementary Information is available at Bioinformatics online.

Exploring the Potential of Echinococcus Granulosus Antigens in Immunotherapy for Cancer

Background: Echinococcus granulosus, intrigues researchers due to its unique biology and immunogenicity. Recent studies show a negative relationship between echinococcosis incidence and cancer progression, emphasizing significant similarities between E. granulosus and cancer antigens. This article will review the anti-cancer effects of E. granulosus antigens and their application in cancer immunotherapy. Main Body: It begins with an introduction, highlighting the significance of E. granulosus antigens in contemporary cancer treatment. Subsequently, an overview of hydatid cysts, the source of these antigens, elucidating their structure and immunogenic properties is provided. Our review extends to the interactions between echinococcosis and both the innate and acquired immune systems, shedding light on the mechanisms involved. We delve into the intriguing connections between echinococcosis and cancer, exploring the direct and indirect anti-cancer effects of these antigens and their potential in cancer immunotherapy. To offer a balanced perspective, we also weigh the pros and cons of using E. granulosus antigens in cancer therapy. Conclusion: In conclusion, the promising attributes of E. granulosus antigens, as highlighted throughout this review, suggest a bright future for their utilization in cancer therapy. Their ability to trigger potent immune responses and target cancer cells holds great potential for the development of effective and tailored therapies, offering new hope for improved cancer treatment outcomes. Further research and clinical trials are needed to fully realize the potential of E. granulosus antigens in the field of cancer immunotherapy.

Exploring Indonesia's Vernacular Architecture: Comparison of Environment and Culture Responsiveness

Culture, region, and climate are three fundamental aspects that influence vernacular architecture. As the largest archipelagic country in the world, Indonesia is rich in diversity of vernacular architecture, originating from different cultural backgrounds and natural characteristics. It is interesting to examine whether significant similarities or differences are reflected in two vernacular houses formed from other cultures, regions, and topographies, even though they have the same function: residence. In this research, architectural comparisons were made between Sundanese traditional houses with the natural character of the mountains in West Java and Banjar traditional houses in the coastal region of South Kalimantan. Data was obtained through the literature review and then analyzed using Bentley's theory of three aspects — functional-constructional, environmental, and socio-cultural; as well as seven criteria — permeability, variety, readability, robustness, visual suitability, richness, and personalization. The research results show that the differences between these two vernacular architectures are visible from the use of materials and the type of foundation used. Apart from that, an interesting fact was discovered that even though both of them have different cultures and regions, the shape of the roof, the position of openings such as windows and doors, and the location of the buildings in the same housing complex, these two vernacular architectures have similarities. It is analyzed that this is the response of both communities that is reflected in each of their vernacular architecture to the environment in the same climate, namely the tropical climate.

Comparative Analysis of Educational Policies of China and Pakistan:A Systematic Literature Review

This paper presents a systematic literature review that offers a comparative analysis of the educational policies of China and Pakistan. The review delves into the historical context, policy formulation, implementation strategies, and outcomes of educational reforms in both countries. To ensure a comprehensive and current analysis, studies published between 2000 and 2023 were included. Data were meticulously extracted from peer-reviewed journal articles, government reports, and policy documents. The selected studies were thoroughly analyzed to identify key themes and patterns, employing a comparative framework to synthesize the data focusing on policy formulation, implementation, and outcomes. This detailed comparative analysis highlights significant differences and similarities between the two nations' educational systems, providing valuable insights into how each country addresses its unique educational challenges and opportunities. By examining these aspects, the review offers a comprehensive understanding of the educational landscapes of China and Pakistan, shedding light on the successes and shortcomings of their respective educational policies. The findings suggest that both countries can learn valuable lessons from each other's experiences, thereby enhancing their educational frameworks. This study contributes to the broader discourse on global educational development, emphasizing the importance of tailored policy responses to meet diverse educational needs.

Sebuah Kajian Perbandingan: Telaah Kehidupan Komunitas Vinsensian dalam Tradisi Balale’ Suku Dayak Kanayatn

This research aims to explore the conceptual and practical aspects of community in the Balale' tradition of the Dayak Kanayatn tribe, with reference to the thought of St. Vincent as reflected in his letters and the principles of the constitution of the Congregation of the Mission (CM). Thus, the purpose of this research is to identify and analyze the concepts of community that exist in the traditional culture of the Dayak Kanayatn tribe, while exploring Vincent's view of community. Then, positive community values are developed that can contribute to the advancement of Indonesian civilization. The research method used is a literature study. The researcher can explore the thoughts and practices of community from both traditional and philosophical perspectives. A thorough analysis of these concepts reveals significant similarities between the Dayak Kanayatn tribal community and the concept of Vincentian community, where both emphasize the importance of solidarity, cooperation, and family spirit in creating Bonum Communae or the common good. In this context, an attempt is made to integrate the concepts of community found in the Balale' tradition with the Vincentian view, with the aim of producing a value framework that can organize and strengthen a just, prosperous, and welfare common life. Through this research, it is hoped to make a meaningful contribution to the discovery and development of positive community values for the Indonesian state, which in turn will support the creation of an advanced and civilized Indonesian society.

Natural Language Processing Approaches to Text Data Augmentation: A Computational Linguistic Analysis

In the context of Natural Language Processing (NLP) tasks, problems such as insufficient or skewed data are frequently encountered. One practical solution to this problem is to generate additional textual data. Text Data Augmentation (TDA) refers to small changes made to accessible text at the character, word, or sentence level to generate synthetic data that is subsequently inserted into data loaders to train the model. By producing synthetic data, models can learn from a larger range of instances and, hence, enhance their resilience and generalization skills. Despite the fact that the entire NLP community has extensively studied many NLP DA approaches, recent research on the subject suggests that the relationship between the several DA techniques now in use is not entirely known in practice. Therefore, this study applies and extends the advances of TDA to encounter and cover varied tools on multiple settings or contexts. To carry out a thorough practical implementation of NLP DA approaches, comparing the way they perform and highlighting some of the significant similarities and differences in these various scenarios, this work depends on different tools of easy data augmentation and neural-based augmentation. This study suggests that some typical DA techniques might not be suitable in some circumstances or text environments. Specifically, according to the initial results, the context and word count of a text may have a significant impact on the quality of the synthetic data.

Hyperacusis questionnaire and event-related potential correlation in migraine patients

This study aims to investigate auditory hypersensitivity and cortical function in migraine patients using the Hyperacusis Questionnaire and the Event-Related Potential (ERP) technique. The study analyzes alterations in the latency and amplitude of the event-related potentials MMN and P300 components. The findings contribute to a better understanding of the physiological relationship between migraine and auditory hypersensitivity. Seventeen migraine patients were admitted to the outpatient clinic of the Department of Otorhinolaryngology-Head and Neck Surgery at Peking University People’s Hospital from June 2023 to September 2023. Nineteen matched healthy subjects were also selected. All participants underwent the pure tone audiometry and the auditory brainstem response test to determine hearing thresholds, the Hyperacusis Questionnaire, the Tinnitus Handicap Inventory, and an ERP examination. The Oddball classical paradigm was used as the stimulation task, and electroencephalography signals were recorded synchronously. The scores of the Hyperacusis Questionnaire, latency and amplitude of MMN and P300 component were compared between the migraine group and the control group, and their correlation was analyzed. The latency of MMN at the Fz and Cz sites in migraine patients was significantly shorter than that in the control group (P < 0.05), and the amplitudes were significantly higher than those in the control group (P < 0.05). The variances in latency and amplitude of P300 at Cz and Pz sites in migraine patients were not statistically significant when compared with the control group. (P > 0.05). The Hyperacusis Questionnaire was negatively correlated with MMN latency, with a correlation coefficient of − 0.374 (P = 0.025), and positively correlated with MMN amplitude, with a correlation coefficient of 0.378 (P = 0.023). There was no significant similarity between the Hyperacusis Questionnaire and P300 latency and amplitude (P > 0.05). Overall, auditory hypersensitivity was enhanced in individuals with migraines compared to healthy individuals, leading to faster information processing, while there may be less impairment in cognitive function.

A methodology to globally assess ectodomain shedding using soluble fractions from the mouse brain.

Ectodomain shedding (ES) is a fundamental process involving the proteolytic cleavage of membrane-bound proteins, leading to the release of soluble extracellular fragments (shed ectodomains) with potential paracrine and autocrine signaling functions. In the central nervous system (CNS), ES plays pivotal roles in brain development, axonal regulation, synapse formation, and disease pathogenesis, spanning from cancer to Alzheimer's disease. Recent evidence also suggests its potential involvement in neurodevelopmental conditions like autism and schizophrenia. Past investigations of ES in the CNS have primarily relied on cell culture supernatants or cerebrospinal fluid (CSF) samples, but these methods have limitations, offering limited insights into how ES is modulated in the intact brain parenchyma. In this study, we introduce a methodology for analyzing shed ectodomains globally within rodent brain samples. Through biochemical tissue subcellular separation, mass spectrometry, and bioinformatic analysis, we show that the brain's soluble fraction sheddome shares significant molecular and functional similarities with in vitro neuronal and CSF sheddomes. This approach provides a promising means of exploring ES dynamics in the CNS, allowing for the evaluation of ES at different developmental stages and pathophysiological states. This methodology has the potential to help us deepen our understanding of ES and its role in CNS function and pathology, offering new insights and opportunities for research in this field.

HcN57, A Novel Unusual Acidic Silk-Like Matrix Protein from Hyriopsis cumingii, Participates in Framework Construction and Nacre Nucleation During Nacreous Layer Formation.

In the classic molecular model of nacreous layer formation, unusual acidic matrix proteins rich in aspartic acid (Asp) residues are essential for nacre nucleation due to their great affinity for binding calcium. However, the acidic matrix proteins discovered in the nacreous layer so far have been weakly acidic with a high proportion of glutamate. In the present study, several silk-like matrix proteins, including the novel matrix protein HcN57, were identified in the ethylenediaminetetraacetic acid-soluble extracts of the nacreous layer of Hyriopsis cumingii. HcN57 is a highly repetitive protein that consists of a high proportion of alanine (Ala, 34.4%), glycine (Gly, 22.5%), and serine (Ser, 11.4%). It forms poly Ala blocks, GlynX repeats, an Ala-Gly repeat, and a Ser-Ala-rich region, exhibiting significant similarity to silk proteins found in spider species. The expression of HcN57 was specifically located in the dorsal epithelial cells of the mantle pallium and mantle center. Notably, expression of HcN57 was relatively high during nacreous layer regeneration and pearl nacre deposition, suggesting HcN57 is a silk matrix protein in the nacreous layer. Importantly, HcN57 also contains a certain content of Asp residues, making it an unusual acidic matrix protein present in the nacreous layer. These Asp residues are mainly distributed in three large hydrophilic acidic regions, which showed inhibitory activity against aragonite deposition and morphological regulation of calcite in vitro. Moreover, HcN57-dsRNA injection resulted in failure of nacre nucleation in vivo. Taken together, our results show that HcN57 is a bifunctional silk protein with poly Ala blocks and Gly-rich regions that serve as space fillers within the chitinous framework to prevent crystallization at unnecessary nucleation sites and Asp-rich regions that create a calcium ion supersaturated microenvironment for nucleation in the center of nacre tablets. These observations contribute to a better understanding of the mechanism by which silk proteins regulate framework construction and nacre nucleation during nacreous layer formation.

Divergence and convergence: a cross-generational study on local food consumption

In the context of the expanding local food market, grasping the evolutionary trajectory of consumer purchasing behavior is crucial for understanding market dynamics. This study adopts a cross-generational perspective to delve into and elucidate the similarities and differences in local food consumption behaviors between Gen Z and Gen Y. Through the analysis of online survey data from 251 individuals of Gen Z and 319 of Gen Y and utilizing the Theory of Planned Behavior as a theoretical framework, and the study identifies eight key variables. The findings reveal that while Gen Z and Gen Y exhibit a range of common characteristics in their choice of local food,including attention to word of mouth, health consciousness, subjective norms, perceived behavioral control, and attitude.there is a significant divergence in their motivating factors for purchasing. Specifically, convenience is the primary driver for Gen Z when selecting local food; conversely, price is the decisive factor in the decision-making process of Gen Y. By unveiling these significant differences and similarities, the research offers significant understanding beneficial to the food sector, particularly in formulating market strategies targeted at different generations.

Investigation into the fabrication of plant-based simulant connective tissue utilizing algae polysaccharide-derived hydrogel

Connective tissue is an important component of meat products that provides support to animal muscles. Hydrogels are considered a promising alternative to connective tissues and simulate actual products by adjusting the gel texture and mouthfeel. This study used soybean protein isolate (SPI), corn starch (CS), konjac glucomannan (KGM), and seaweed powder (SP) as raw materials to examine the effect of different added SP and KGM concentrations on the gel texture. The G' of the gel increased five-fold when the SP and KGM concentration was increased from 1 % to 3 %. The results of mechanical property tests showed that with the addition of SP, the gel hardness increased from 316.00 g to 1827.23 g and the tensile strength increased from 0.027 MPa to 0.089 MPa. Sensory evaluation showed that the samples with 2 % SP and KGM presented the highest overall acceptability score and the most significant similarity to real connective tissue. The connective tissue simulants exhibited excellent water-holding capacity (>90 %), significantly increasing their juiciness. SEM indicated that 2 % KGM addition improved gel network structure stability. The results demonstrate the potential of seaweed polysaccharide-derived hydrogels as connective tissue mimics. This provides a new strategy for the preparation of high mechanical strength hydrogels and lays the foundation for structural diversification of plant-based meat.

Shared and unique transcriptomic signatures of antidepressant and probiotics action in the mammalian brain.

Understanding the shared and divergent mechanisms across antidepressant (AD) classes and probiotics is critical for improving treatment for mood disorders. Here we examine the transcriptomic effects of bupropion (NDRI), desipramine (SNRI), fluoxetine (SSRI) and a probiotic formulation (Lacidofil®) on 10 regions across the mammalian brain. These treatments massively alter gene expression (on average, 2211 differentially expressed genes (DEGs) per region-treatment combination), highlighting the biological complexity of AD and probiotic action. Intersection of DEG sets against neuropsychiatric GWAS loci, sex-specific transcriptomic portraits of major depressive disorder (MDD), and mouse models of stress and depression reveals significant similarities and differences across treatments. Interestingly, molecular responses in the infralimbic cortex, basolateral amygdala and locus coeruleus are region-specific and highly similar across treatments, whilst responses in the Raphe, medial preoptic area, cingulate cortex, prelimbic cortex and ventral dentate gyrus are predominantly treatment-specific. Mechanistically, ADs concordantly downregulate immune pathways in the amygdala and ventral dentate gyrus. In contrast, protein synthesis, metabolism and synaptic signaling pathways are axes of variability among treatments. We use spatial transcriptomics to further delineate layer-specific molecular pathways and DEGs within the prefrontal cortex. Our study reveals complex AD and probiotics action on the mammalian brain and identifies treatment-specific cellular processes and gene targets associated with mood disorders.

No evidence for niche competition in the extinction of the South American saber-tooth species

The end of South American isolation during the Great American Biotic Interchange (GABI) promoted the contact between South and North American saber-tooth forms that evolved in isolation. This contact may have driven saber-tooth species to a competitive interaction, resulting in the extinction of the South American saber-tooth form. Here, we used paleoclimatic data to compare the climatic niche of the saber-tooth forms Thylacosmilus atrox (from South America), Smilodon fatalis, and Smilodon populator (both originally from North America). We evaluated niche width, overlap, and similarity to infer potential geographic distribution overlap and competition between these North and South American predators. To do so, we obtained the climatic variables from sites where occurrence fossil records were available. Our results suggest that T. atrox had a narrower climatic niche compared to Smilodon species. Although we found a significant climatic niche overlap and similarity between S. fatalis and T. atrox, it seems unlikely that both species have co-occurred. Low niche overlap and similarity between T. atrox and S. populator dismiss competitive interaction between them. Moreover, climatic niche and low tolerance for environmental changes may have been the cause of the South American saber-tooth extinction.

Grapevine (Vitis vinifera L.) Germplasm from Siena (Italy) Includes Rare Strains and Reveals Population Structuring

Molecular characterization was carried out on samples of historical grapevine populations that were gathered from within and around the medieval walls of Siena. Forty-nine grapevines were selected based on their age, historical site of growth, grapevines’ ampelography, and for being relict accessions, obsolete to cultivation. SSR profiling data were compared to 44 known grapevines, revealing six functional genetic groups with significant similarity to grapevine types generally grown in Tuscany. The Sienese germplasm is enriched with rare grapevines at risk of extinction, such as Zuccaccio, Gorgottesco, Tenerone, Prugnolo gentile, Occhio di Pernice, Procanico, Rossone, Mammolo, and Canina. Population genetics analysis revealed the existence of five subpopulations structure (-k5) in analogy with cluster analysis.

Complete S1 glycoprotein analysis of two distinct groups of GI-19 (QX) infectious bronchitis virus from Indonesia: Molecular phylogenetic and in-silico approaches

Infectious bronchitis (IB) is an important viral disease that impacts poultry productivity, according to many studies. The main important infectious bronchitis virus (IBV) protein, spike glycoprotein subunit 1 (S1), plays a role in pathogenicity and immunogenicity. Conventional molecular detection and analysis of the S1 gene still face many challenges due to its hypervariability. In Indonesia, there were only a few reports on partial S1 gene analysis of IBVs; thus far, there have been no phylogenetic or in-silico approaches to their S1 complete gene. This study aims to reveal molecular pathogenicity and immunogenicity features on the S1 complete gene of IBVs from Indonesia. We analyzed fourteen IBV isolates using conventional RT-PCR and Sanger sequencing and then aligned their verified S1 complete sequences with other Indonesian GI-19 IBVs from Genbank for molecular phylogenetic and in-silico analysis. Phylogenetic analysis consisted of amino acid polymorphism and identity, as well as phylogenetic tree construction. As part of the in-silico analysis, we used proteins that have homology and immunoinformatic predictions (B-cell epitope and N-glycosylation). Molecular phylogenetic analysis revealed the division of the Indonesian GI-19 IBVs into two distinct groups. These groups had different amino acid variations at receptor binding sites, hypervariable antigenic sites, and cleavage sites. We also calculated the amino acid identity at 95.4–98.3%. In-silico studies revealed significant similarities in B-cell epitopes, distinct N-glycosylation sites, and the suggestion of a homotrimer protein structure. We found that the S1 full gene of two different groups of GI-19 IBVs (QX strain) from Indonesia predicted changes in their pathogenicity and immunogenicity.

Comparing Finnish and Chinese national teacher education frameworks from the teacher competency perspective

ABSTRACT Finnish and Chinese teacher education have gained worldwide attention because of their pupils’ significant achievements in international assessments. Focusing on the manifestations of teacher competencies in the respective teacher education frameworks, this article compares Finnish and Chinese teacher education and their curricular traditions. The mixed-method analysis of the two national frameworks draws attention to significant differences and similarities. Due to particular cultural contexts, while the Chinese Framework emphasises ethics, student management, and assessment competencies, Finnish teacher education focuses comparatively more on adaptive teaching, innovation, and partnering. The competencies of subject matters, pedagogy and subject didactics, teaching technologies, communication, multidisciplinarity, reflection and inquiry, and professional development are emphasised in both countries. This article provides insights into manifestations of teacher competencies in the context of hybrid curriculum traditions in Finland and China through adapting and applying an international framework, offering alternative perspectives on quality teacher education beyond Anglo-American approaches.

Coupled membranes: a mechanism of frequency filtering and transmission in the field cricket ear evidenced by micro-computed tomography, laser Doppler vibrometry and finite element analysis.

Many animals employ a second frequency filter beyond the initial filtering of the eardrum (or tympanal membrane). In the field cricket ear, both the filtering mechanism and the transmission path from the posterior tympanal membrane (PTM) have remained unclear. A mismatch between PTM vibrations and sensilla tuning has prompted speculations of a second filter. PTM coupling to the tracheal branches is suggested to support a transmission pathway. Here, we present three independent lines of evidence converging on the same conclusion: the existence of a series of linked membranes with distinct resonant frequencies serving both filtering and transmission functions. Micro-computed tomography (µ-CT) highlighted the 'dividing membrane (DivM)', separating the tracheal branches and connected to the PTM via the dorsal membrane of the posterior tracheal branch (DM-PTB). Thickness analysis showed the DivM to share significant thinness similarity with the PTM. Laser Doppler vibrometry indicated the first of two PTM vibrational peaks, at 6 and 14 kHz, originates not from the PTM but from the coupled DM-PTB. This result was corroborated by µ-CT-based finite element analysis. These findings clarify further the biophysical source of neuroethological pathways in what is an important model of behavioural neuroscience. Tuned microscale coupled membranes may also hold biomimetic relevance.

Comparative Metabolomics and Network Pharmacology Analysis Reveal Shared Neuroprotective Mechanisms of Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb.

Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb., two nootropics, are recognized in Indian Ayurvedic texts. Studies have attempted to understand their action as memory enhancers and neuroprotectants, but many molecular aspects remain unknown. We propose that Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb. share common neuroprotective mechanisms. Mass spectrometry-based untargeted metabolomics and network pharmacology approach were used to identify potential protein targets for the metabolites from each extract. Phytochemical analyses and cell culture validation studies were also used to assess apoptosis and ROS activity using aqueous extracts prepared from both herbal powders. Further, docking studies were also performed using the LibDock protocol. Untargeted metabolomics and network pharmacology approach unveiled 2751 shared metabolites and 3439 and 2928 non-redundant metabolites from Bacopa monnieri and Centella asiatica extracts, respectively, suggesting a potential common neuroprotective mechanism among these extracts. Protein-target prediction highlighted 92.4% similarity among the proteins interacting with metabolites for these extracts. Among them, kinases mapped to MAPK, mTOR, and PI3K-AKT signaling pathways represented a predominant population. Our results highlight a significant similarity in the metabolome of Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb., and their potential protein targets may be attributed to their common neuroprotective functions.