Cureus. 2024 Mar 15;16(3):e56223. doi: 10.7759/cureus.56223. eCollection 2024 Mar.

ABSTRACT

In this paper we synthesize an expansive body of literature examining the multifaceted influence of chiropractic care on processes within and modulators of the neuroendocrine-immune (NEI) system, for the purpose of generating an inductive hypothesis regarding the potential impacts of chiropractic care on integrated physiology. Taking a broad, interdisciplinary, and integrative view of two decades of research-documented outcomes of chiropractic care, inclusive of reports ranging from systematic and meta-analysis and randomized and observational trials to case and cohort studies, this review encapsulates a rigorous analysis of research and suggests the appropriateness of a more integrative perspective on the impact of chiropractic care on systemic physiology. A novel perspective on the salutogenic, health-promoting effects of chiropractic adjustment is presented, focused on the improvement of physical indicators of well-being and adaptability such as blood pressure, heart rate variability, and sleep, potential benefits that may be facilitated through multiple neurologically mediated pathways. Our findings support the biological plausibility of complex benefits from chiropractic intervention that is not limited to simple neuromusculoskeletal outcomes and open new avenues for future research, specifically the exploration and mapping of the precise neural pathways and networks influenced by chiropractic adjustment.

PMID:38618450 | PMC:PMC11016242 | DOI:10.7759/cureus.56223

Interface Focus. 2024 Apr 12;14(2):20230082. doi: 10.1098/rsfs.2023.0082. eCollection 2024 Apr 15.

ABSTRACT

Radular teeth have to cope with wear, when interacting with ingesta. In some molluscan taxa, wear-coping mechanisms, related to the incorporation of high contents of iron or silica, have been previously determined. For most species, particularly for those which possess radulae without such incorporations, wear-coping mechanisms are understudied. In the present study, we documented and characterized the wear on radular teeth in the model species Loligo vulgaris (Cephalopoda). By applying a range of methods, the elementary composition and mechanical properties of the teeth were described, to gain insight into mechanisms for coping with abrasion. It was found that the tooth regions that are prone to wear are harder and stiffer. Additionally, the surfaces interacting with the ingesta possessed a thin coating with high contents of silicon, probably reducing abrasion. The here presented data may serve as an example of systematic study of radular wear, in order to understand the relationship between the structure of radular teeth and their properties.

PMID:38618237 | PMC:PMC11008966 | DOI:10.1098/rsfs.2023.0082

Interface Focus. 2024 Apr 12;14(2):20230056. doi: 10.1098/rsfs.2023.0056. eCollection 2024 Apr 15.

ABSTRACT

Mandible morphology has an essential role in biting performance, but the mandible cuticle can have regional differences in its mechanical properties. The effects of such a heterogeneous distribution of cuticle material properties in the mandible responses to biting loading are still poorly explored in chewing insects. Here, we tested the mechanical properties of mandibles of the ant species Formica cunicularia by nanoindentation and investigated the effects of the cuticular variation in Young's modulus (E) under bite loading with finite-element analysis (FEA). The masticatory margin of the mandible, which interacts with the food, was the hardest and stiffest region. To unravel the origins of the mechanical property gradients, we characterized the elemental composition by energy-dispersive X-ray spectroscopy. The masticatory margin possessed high proportions of Cu and Zn. When incorporated into the FEA, variation in E effectively changed mandible stress patterns, leading to a relatively higher concentration of stresses in the stiffer mandibular regions and leaving the softer mandible blade with relatively lower stress. Our results demonstrated the relevance of cuticle E heterogeneity in mandibles under bite loading, suggesting that the accumulation of transition metals such as Cu and Zn has a relevant correlation with the mechanical characteristics in F. cunicularia mandibles.

PMID:38618235 | PMC:PMC11008963 | DOI:10.1098/rsfs.2023.0056

Interface Focus. 2024 Apr 12;14(2):20230048. doi: 10.1098/rsfs.2023.0048. eCollection 2024 Apr 15.

ABSTRACT

Leafcutter ant colonies are divided into castes with the individuals performing different tasks, based mostly on size. With the mandibles, the small minims care for the brood or the fungus, whereas the larger minors and mediae cut and transport plant material, with the ant size positively related to the material size. The mechanical properties and composition of the mandible cuticle have been previously tested in the soldiers as the largest caste, revealing that the cutting edges contained high contents of the cross-linking transition metal zinc (Zn). With regard to the smaller castes, no data are present. To study how the mandible size and function relates to its mechanical properties, we here tested the mandibles of minims, minors and mediae by nanoindentation. We found that the hardness (H) and Young's modulus (E) values increased with increasing ant size and that the mandible cutting edges in each caste have the highest H- and E-values. To gain insight into the origins of these properties, we characterized the elemental composition by energy-dispersive X-ray analysis, revealing that minors and mediae possessed higher content of Zn in the cutting edges in contrast to the minims containing significantly less Zn. This shows, that Zn content relates to higher mechanical property values. Additionally, it shows that all of these parameters can differ within a single species.

PMID:38618230 | PMC:PMC11008964 | DOI:10.1098/rsfs.2023.0048

Bio Protoc. 2024 Apr 5;14(7):e4966. doi: 10.21769/BioProtoc.4966. eCollection 2024 Apr 5.

ABSTRACT

Contractile injection systems (CISs), one of the most important bacterial secretion systems that transport substrates across the membrane, are a collection of diverse but evolutionarily related macromolecular devices. Numerous effector proteins can be loaded and injected by this secretion complex to their specific destinations. One group of CISs called extracellular CIS (eCIS) has been proposed as secretory molecules that can be released from the bacterial cytoplasm and attack neighboring target cells from the extracellular environment. This makes them a potential delivery vector for the transportation of various cargos without the inclusion of bacterial cells, which might elicit certain immunological responses from hosts. We have demonstrated that the Photorhabdus virulence cassette (PVC), which is a typical eCIS, could be applied as an ideal vector for the translocation of proteinaceous cargos with different physical or chemical properties. Here, we describe the in-depth purification protocol of this mega complex from Escherichia coli. The protocol provided is a simpler, faster, and more productive way of generating the eCIS complexes than available methodologies reported previously, which can facilitate the subsequent applications of these nanodevices and other eCIS in different backgrounds.

PMID:38618175 | PMC:PMC11006799 | DOI:10.21769/BioProtoc.4966

Integr Med (Encinitas). 2024 Mar;23(1):28-31.

ABSTRACT

Traditional medicine, exemplified by systems such as Ayurveda, inherently adopts a holistic framework. This framework extends beyond mere consideration of the human body to encompass broader systems of health, integrating elements of nature, particularly plants. Over time, there has been a notable integration between traditional medical philosophies and modern scientific methodologies. This integration is evident in published works that blend these disciplines, resulting in the creation of innovative terminology, such as «Ayurnutrigenomics». Concurrently, the lexicon within medical science has evolved to highlight the connection of body systems, as illustrated by terms like «gut-brain axis», which emphasize the relationship between physiological and psychological factors. This integration of perspectives is further demonstrated by terms such as «psychoneuroendocrine» and «mind-heart-body», reflecting a holistic approach to health. Alongside the emergence of these novel terms, there has been a proliferation of literature exploring the diverse functions of plants, particularly focusing on phytonutrients such as those found in the polyphenol category of compounds. In many ways, these emerging findings suggest a fundamental relationship between humans and plants, aligning with the principles of traditional medicine and indicating a profound connection between the two. Thus, in harmony with the increasing recognition of the interconnectedness between human systems biology, the study of phytochemicals, and the ability of plants to influence neuroendocrine responses, this article proposes a new term: the phytoneuroendocrine system.

PMID:38618161 | PMC:PMC11007616

Front Pharmacol. 2024 Mar 28;15:1347047. doi: 10.3389/fphar.2024.1347047. eCollection 2024.

ABSTRACT

Metformin is the initial medication recommended for the treatment of type 2 diabetes mellitus (T2DM). In addition to diabetes treatment, the function of metformin also can be anti-aging, antiviral, and anti-inflammatory. Nevertheless, further exploration is required to fully understand its mode of operation. Historically, the liver has been acknowledged as the main location where metformin reduces glucose levels, however, there is increasing evidence suggesting that the gastrointestinal tract also plays a significant role in its action. In the gastrointestinal tract, metformin effects glucose uptake and absorption, increases glucagon-like peptide-1 (GLP-1) secretion, alters the composition and structure of the gut microbiota, and modulates the immune response. However, the side effects of it cannot be ignored such as gastrointestinal distress in patients. This review outlines the impact of metformin on the digestive system and explores potential explanations for variations in metformin effectiveness and adverse effects like gastrointestinal discomfort.

PMID:38617792 | PMC:PMC11010946 | DOI:10.3389/fphar.2024.1347047

ACS Omega. 2024 Mar 26;9(14):16311-16321. doi: 10.1021/acsomega.3c10459. eCollection 2024 Apr 9.

ABSTRACT

Alzheimer's disease (AD) is the most common type of dementia, affecting over 50 million people worldwide. Currently, most approved medications for AD inhibit the activity of acetylcholinesterase (AChE), but these treatments often come with harmful side effects. There is growing interest in the use of natural compounds for disease prevention, alleviation, and treatment. This trend is driven by the anticipation that these substances may incur fewer side effects than existing medications. This research presents a computational approach combining machine learning with structural modeling to discover compounds from medicinal mushrooms with a high potential to inhibit the activity of AChE. First, we developed a deep neural network capable of rapidly screening a vast number of compounds to indicate their potential to inhibit AChE activity. Subsequently, we applied deep learning models to screen the compounds in the BACMUSHBASE database, which catalogs the bioactive compounds from cultivated and wild mushroom varieties local to Thailand, resulting in the identification of five promising compounds. Next, the five identified compounds underwent molecular docking techniques to calculate the binding energy between the compounds and AChE. This allowed us to refine the selection to two compounds, erinacerin A and hericenone B. Further analysis of the binding energy patterns between these compounds and the target protein revealed that both compounds displayed binding energy profiles similar to the combined characteristics of donepezil and galanthamine, the prescription drugs for AD. We propose that these two compounds, derived from Hericium erinaceus (also known as lion's mane mushroom), are suitable candidates for further research and development into symptom-alleviating AD medications.

PMID:38617639 | PMC:PMC11007777 | DOI:10.1021/acsomega.3c10459

iScience. 2024 Mar 26;27(4):109567. doi: 10.1016/j.isci.2024.109567. eCollection 2024 Apr 19.

ABSTRACT

The human respiratory system is a complex and important system that can suffer a variety of diseases. Single-cell sequencing technologies, applied in many respiratory disease studies, have enhanced our ability in characterizing molecular and phenotypic features at a single-cell resolution. The exponentially increasing data from these studies have consequently led to difficulties in data sharing and analysis. Here, we present scMoresDB, a single-cell multi-omics database platform with extensive omics types tailored for human respiratory diseases. scMoresDB re-analyzes single-cell multi-omics datasets, providing a user-friendly interface with cross-omics search capabilities, interactive visualizations, and analytical tools for comprehensive data sharing and integrative analysis. Our example applications highlight the potential significance of BSG receptor in SARS-CoV-2 infection as well as the involvement of HHIP and TGFB2 in the development and progression of chronic obstructive pulmonary disease. scMoresDB significantly increases accessibility and utility of single-cell data relevant to human respiratory system and associated diseases.

PMID:38617561 | PMC:PMC11015448 | DOI:10.1016/j.isci.2024.109567

Biophys Rev (Melville). 2024 Apr 10;5(2):021301. doi: 10.1063/5.0179125. eCollection 2024 Jun.

ABSTRACT

Rapid advances in tissue engineering have resulted in more complex and physiologically relevant 3D in vitro tissue models with applications in fundamental biology and therapeutic development. However, the complexity provided by these models is often not leveraged fully due to the reductionist methods used to analyze them. Computational and mathematical models developed in the field of systems biology can address this issue. Yet, traditional systems biology has been mostly applied to simpler in vitro models with little physiological relevance and limited cellular complexity. Therefore, integrating these two inherently interdisciplinary fields can result in new insights and move both disciplines forward. In this review, we provide a systematic overview of how systems biology has been integrated with 3D in vitro tissue models and discuss key application areas where the synergies between both fields have led to important advances with potential translational impact. We then outline key directions for future research and discuss a framework for further integration between fields.

PMID:38617201 | PMC:PMC11008916 | DOI:10.1063/5.0179125

Quant Plant Biol. 2024 Apr 3;5:e3. doi: 10.1017/qpb.2024.3. eCollection 2024.

ABSTRACT

The idea that plants would be efficient, frugal or optimised echoes the recurrent semantics of 'blueprint' and 'program' in molecular genetics. However, when analysing plants with quantitative approaches and systems thinking, we instead find that plants are the results of stochastic processes with many inefficiencies, incoherence or delays fuelling their robustness. If one had to highlight the main value of quantitative biology, this could be it: plants are robust systems because they are not efficient. Such systemic insights extend to the way we conduct plant research and opens plant science publication to a much broader framework.

PMID:38617131 | PMC:PMC11016357 | DOI:10.1017/qpb.2024.3

Plant Commun. 2024 Apr 13:100920. doi: 10.1016/j.xplc.2024.100920. Online ahead of print.

ABSTRACT

Stress Knowledge Map (SKM, https://skm.nib.si) is a publicly available resource containing two complementary knowledge graphs describing current knowledge of biochemical, signalling, and regulatory molecular interactions in plants: a highly curated model of plant stress signalling (PSS, 543 reactions) and a large comprehensive knowledge network (CKN, 488,390 interactions). Both were constructed by domain experts through systematic curation of diverse literature and database resources. SKM provides a single entrypoint for plant stress response investigations and the related growth trade-offs as well as interactive exploration of current knowledge. PSS is also formulated as qualitative and quantitative models for systems biology, and thus represents a starting point of a plant digital twin. Here, we describe the features of SKM and show, through two case studies, how it can be used for complex analyses, including systematic hypothesis generation, design of validation experiments, or to gain new insights into experimental observations in plant biology.

PMID:38616489 | DOI:10.1016/j.xplc.2024.100920

Carbohydr Polym. 2024 Jul 1;335:122046. doi: 10.1016/j.carbpol.2024.122046. Epub 2024 Mar 15.

ABSTRACT

Currently, purification step in the recombinant protein manufacture is still a great challenge and its cost far outweighs those of the upstream process. In this study, a functionalized cellulose-based monolith was constructed as an efficient affinity adsorbent for one-step purification of recombinant proteins. Firstly, the fundamental cellulose monolith (CE monolith) was fabricated based on thermally induced phase separation, followed by being modified with nitrilotriacetic acid anhydride through esterification to give NCE monolith. After chelating with Ni2+, the affinity adsorbent NCE-Ni2+ monolith was obtained, which was demonstrated to possess a hierarchically porous morphology with a relatively high surface area, porosity and compressive strength. The adsorption behavior of NCE-Ni2+ monolith towards β2-microglobulin with 6 N-terminus His-tag (His-β2M) was evaluated through batch and fixed-bed column experiments. The results revealed that NCE-Ni2+ monolith exhibited a relatively fast His-β2M adsorption rate with a maximum adsorption capacity of 329.2 mg/g. The fixed-bed column adsorption implied that NCE-Ni2+ monolith showed high efficiency for His-β2M adsorption. Finally, NCE-Ni2+ monolith was demonstrated to have an excellent His-β2M purification ability from E. coli lysate with exceptional reusability. Therefore, the resultant NCE-Ni2+ monolith had large potential to be used as an efficient adsorbent for recombinant protein purification in practical applications.

PMID:38616085 | DOI:10.1016/j.carbpol.2024.122046

J Sport Health Sci. 2024 Apr 12:S2095-2546(24)00056-5. doi: 10.1016/j.jshs.2024.04.007. Online ahead of print.

NO ABSTRACT

PMID:38615711 | DOI:10.1016/j.jshs.2024.04.007

Neuroimage. 2024 Apr 12:120605. doi: 10.1016/j.neuroimage.2024.120605. Online ahead of print.

ABSTRACT

Trust propensity (TP) relies more on social than economic rationality to transform the perceived probability of betrayal into positive reciprocity expectations in older adults with normal cognition. While deficits in social rationality have been observed in older adults with mild cognitive impairment (MCI), there is limited research on TP and its associated resting-state functional connectivity (RSFC) mechanisms in this population. To measure TP and related psychological functions (affect, motivation, executive cognition, and social cognition), MCI (n=42) and normal healthy control (NHC, n=115) groups completed a one-shot trust game and additional assessments of related psychological functions. RSFC associated with TP was analyzed using connectome-based predictive modeling (CPM) and lesion simulations. Our behavioral results showed that the MCI group trusted less (i.e., had lower TP) than the NHC group, with lower TP associated with higher sensitivity to the probability of betrayal in the MCI group. In the MCI group, only negative CPM models (RSFC negatively correlated with TP) significantly predicted TP, with a high salience network (SN) contribution. In contrast, in the NHC group, positive CPM models (RSFC positively correlated with TP) significantly predicted TP, with a high contribution from the default mode network (DMN). In addition, the total network strength of the NHC-specific positive network was lower in the MCI group than in the NHC group. Our findings demonstrated a decrease in TP in the MCI group compared to the NHC group, which is associated with deficits in social rationality (social cognition, associated with DMN) and increased sensitivity to betrayal (affect, associated with SN) in a trust dilemma. In conclusion, our study contributes to understanding MCI-related alterations in trust and their underlying neural mechanisms.

PMID:38615705 | DOI:10.1016/j.neuroimage.2024.120605

EBioMedicine. 2024 Apr 9:105102. doi: 10.1016/j.ebiom.2024.105102. Online ahead of print.

ABSTRACT

BACKGROUND: Cell-cell interaction factors that facilitate the progression of adenoma to sporadic colorectal cancer (CRC) remain unclear, thereby hindering patient survival.

METHODS: We performed spatial transcriptomics on five early CRC cases, which included adenoma and carcinoma, and one advanced CRC. To elucidate cell-cell interactions within the tumour microenvironment (TME), we investigated the colocalisation network at single-cell resolution using a deep generative model for colocalisation analysis, combined with a single-cell transcriptome, and assessed the clinical significance in CRC patients.

FINDINGS: CRC cells colocalised with regulatory T cells (Tregs) at the adenoma-carcinoma interface. At early-stage carcinogenesis, cell-cell interaction inference between colocalised adenoma and cancer epithelial cells and Tregs based on the spatial distribution of single cells highlighted midkine (MDK) as a prominent signalling molecule sent from tumour epithelial cells to Tregs. Interaction between MDK-high CRC cells and SPP1+ macrophages and stromal cells proved to be the mechanism underlying immunosuppression in the TME. Additionally, we identified syndecan4 (SDC4) as a receptor for MDK associated with Treg colocalisation. Finally, clinical analysis using CRC datasets indicated that increased MDK/SDC4 levels correlated with poor overall survival in CRC patients.

INTERPRETATION: MDK is involved in the immune tolerance shown by Tregs to tumour growth. MDK-mediated formation of the TME could be a potential target for early diagnosis and treatment of CRC.

FUNDING: Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Science Research; OITA Cancer Research Foundation; AMED under Grant Number; Japan Science and Technology Agency (JST); Takeda Science Foundation; The Princess Takamatsu Cancer Research Fund.

PMID:38614865 | DOI:10.1016/j.ebiom.2024.105102

Dev Biol. 2024 Apr 11:S0012-1606(24)00098-8. doi: 10.1016/j.ydbio.2024.04.003. Online ahead of print.

ABSTRACT

This paper introduces a single-cell atlas for pivotal developmental stages in Xenopus, encompassing gastrulation, neurulation, and early tailbud. Notably surpassing its predecessors, the new atlas enhances gene mapping, read counts, and gene/cell type nomenclature. Leveraging the latest Xenopus tropicalis genome version, alongside advanced alignment pipelines and machine learning for cell type assignment, this release maintains consistency with previous cell type annotations while rectifying nomenclature issues. Employing an unbiased approach for cell type assignment proves especially apt for embryonic contexts, given the considerable number of non-terminally differentiated cell types. An alternative cell type attribution here adopts a fuzzy, non-deterministic stance, capturing the transient nature of early embryo progenitor cells by presenting an ensemble of types in superposition. The value of the new resource is emphasized through numerous examples, with a focus on previously unexplored germ cell populations where we uncover novel transcription onset features. Offering interactive exploration via a user-friendly web portal and facilitating complete data downloads, this atlas serves as a comprehensive and accessible reference.

PMID:38614285 | DOI:10.1016/j.ydbio.2024.04.003

Drug Discov Today. 2024 Apr 11:103981. doi: 10.1016/j.drudis.2024.103981. Online ahead of print.

ABSTRACT

The combination of peptides and nanoparticles in cancer therapy has shown synergistic results. Nanoparticle functionalization with peptides can increase their targeting ability towards tumor cells. In some cases, the peptides can develop self-assembled nanoparticles, in combination with drugs, for targeted cancer therapy. The peptides can be loaded into nanoparticles and can be delivered by other drugs for synergistic cancer removal. Multifunctional types of peptide-based nanoparticles, including pH- and redox-sensitive classes, have been introduced in cancer therapy. The tumor microenvironment remolds, and the acceleration of immunotherapy and vaccines can be provided by peptide nanoparticles. Moreover, the bioimaging and labeling of cancers can be mediated by peptide nanoparticles. Therefore, peptides can functionalize nanoparticles in targeted cancer therapy.

PMID:38614161 | DOI:10.1016/j.drudis.2024.103981

Cell Metab. 2024 Apr 5:S1550-4131(24)00091-3. doi: 10.1016/j.cmet.2024.03.012. Online ahead of print.

ABSTRACT

On average, aging is associated with unfavorable changes in cellular metabolism, which are the processes involved in the storage and expenditure of energy. However, metabolic dysregulation may not occur to the same extent in all older individuals as people age at different rates. Those who are aging rapidly are at increased risk of adverse health outcomes and are said to be "frail." Here, we explore the links between frailty and metabolism, including metabolic contributors and consequences of frailty. We examine how metabolic diseases may modify the degree of frailty in old age and suggest that frailty may predispose toward metabolic disease. Metabolic interventions that can mitigate the degree of frailty in people are reviewed. New treatment strategies developed in animal models that are poised for translation to humans are also considered. We suggest that maintaining a youthful metabolism into older age may be protective against frailty.

PMID:38614092 | DOI:10.1016/j.cmet.2024.03.012

Immunity. 2024 Apr 5:S1074-7613(24)00139-0. doi: 10.1016/j.immuni.2024.03.018. Online ahead of print.

ABSTRACT

The development and function of the immune system are controlled by temporospatial gene expression programs, which are regulated by cis-regulatory elements, chromatin structure, and trans-acting factors. In this study, we cataloged the dynamic histone modifications and chromatin interactions at regulatory regions during T helper (Th) cell differentiation. Our data revealed that the H3K4me1 landscape established by MLL4 in naive CD4+ T cells is critical for restructuring the regulatory interaction network and orchestrating gene expression during the early phase of Th differentiation. GATA3 plays a crucial role in further configuring H3K4me1 modification and the chromatin interaction network during Th2 differentiation. Furthermore, we demonstrated that HSS3-anchored chromatin loops function to restrict the activity of the Th2 locus control region (LCR), thus coordinating the expression of Th2 cytokines. Our results provide insights into the mechanisms of how the interplay between histone modifications, chromatin looping, and trans-acting factors contributes to the differentiation of Th cells.

PMID:38614090 | DOI:10.1016/j.immuni.2024.03.018