Systems Biology

Adaptogens in Long-Lasting Brain Fatigue: An Insight from Systems Biology and Network Pharmacology

Wed, 2025-02-26 06:00

Pharmaceuticals (Basel). 2025 Feb 15;18(2):261. doi: 10.3390/ph18020261.

ABSTRACT

Long-lasting brain fatigue is a consequence of stroke or traumatic brain injury associated with emotional, psychological, and physical overload, distress in hypertension, atherosclerosis, viral infection, and aging-related chronic low-grade inflammatory disorders. The pathogenesis of brain fatigue is linked to disrupted neurotransmission, the glutamate-glutamine cycle imbalance, glucose metabolism, and ATP energy supply, which are associated with multiple molecular targets and signaling pathways in neuroendocrine-immune and blood circulation systems. Regeneration of damaged brain tissue is a long-lasting multistage process, including spontaneously regulating hypothalamus-pituitary (HPA) axis-controlled anabolic-catabolic homeostasis to recover harmonized sympathoadrenal system (SAS)-mediated function, brain energy supply, and deregulated gene expression in rehabilitation. The driving mechanism of spontaneous recovery and regeneration of brain tissue is a cross-talk of mediators of neuronal, microglia, immunocompetent, and endothelial cells collectively involved in neurogenesis and angiogenesis, which plant adaptogens can target. Adaptogens are small molecules of plant origin that increase the adaptability of cells and organisms to stress by interaction with the HPA axis and SAS of the stress system (neuroendocrine-immune and cardiovascular complex), targeting multiple mediators of adaptive GPCR signaling pathways. Two major groups of adaptogens comprise (i) phenolic phenethyl and phenylpropanoid derivatives and (ii) tetracyclic and pentacyclic glycosides, whose chemical structure can be distinguished as related correspondingly to (i) monoamine neurotransmitters of SAS (epinephrine, norepinephrine, and dopamine) and (ii) steroid hormones (cortisol, testosterone, and estradiol). In this narrative review, we discuss (i) the multitarget mechanism of integrated pharmacological activity of botanical adaptogens in stress overload, ischemic stroke, and long-lasting brain fatigue; (ii) the time-dependent dual response of physiological regulatory systems to adaptogens to support homeostasis in chronic stress and overload; and (iii) the dual dose-dependent reversal (hormetic) effect of botanical adaptogens. This narrative review shows that the adaptogenic concept cannot be reduced and rectified to the various effects of adaptogens on selected molecular targets or specific modes of action without estimating their interactions within the networks of mediators of the neuroendocrine-immune complex that, in turn, regulates other pharmacological systems (cardiovascular, gastrointestinal, reproductive systems) due to numerous intra- and extracellular communications and feedback regulations. These interactions result in polyvalent action and the pleiotropic pharmacological activity of adaptogens, which is essential for characterizing adaptogens as distinct types of botanicals. They trigger the defense adaptive stress response that leads to the extension of the limits of resilience to overload, inducing brain fatigue and mental disorders. For the first time, this review justifies the neurogenesis potential of adaptogens, particularly the botanical hybrid preparation (BHP) of Arctic Root and Ashwagandha, providing a rationale for potential use in individuals experiencing long-lasting brain fatigue. The review provided insight into future research on the network pharmacology of adaptogens in preventing and rehabilitating long-lasting brain fatigue following stroke, trauma, and viral infections.

PMID:40006074 | DOI:10.3390/ph18020261

Categories: Literature Watch

Mutational Analysis Supports Three-Hairpin Model of Attenuator for Transcription Regulation of <em>ilvBN</em>C Operon in <em>Corynebacterium glutamicum</em>

Wed, 2025-02-26 06:00

Microorganisms. 2025 Jan 28;13(2):291. doi: 10.3390/microorganisms13020291.

ABSTRACT

The ilvBNC operon in Corynebacterium glutamicum encodes key enzymes for the biosynthesis of branched-chain amino acids (L-isoleucine, L-leucine, and L-valine). This operon has been studied for quite a long time, and it is assumed that three hairpin mRNA structures can be formed in its regulatory region; however, their functionality and role in the attenuation mechanism of the ilvBNC operon are not completely clear. In the present work, we performed a mutational analysis of mRNA secondary structures in the regulatory region of the C. glutamicum ilvBNC operon, which allowed us to propose a model of the regulation of its transcription involving three mRNA hairpins that essentially act as a transcription terminator, an antiterminator, and an antiantiterminator. In this work, we proved the existence of a transcription terminator in this operon and experimentally confirmed the effectiveness of its influence on the expression of the ilvBNC operon, AHAS enzyme activity, and valine production. We demonstrated the unique functional features of this attenuator, which, due to the overlapping of the terminator and antiterminator hairpins, is capable of rapid low-energy transitions between them without the complete disruption of the hairpin structures.

PMID:40005659 | DOI:10.3390/microorganisms13020291

Categories: Literature Watch

Adaptive Laboratory Evolution and Carbon/Nitrogen Imbalance Promote High-Yield Ammonia Release in <em>Saccharomyces cerevisiae</em>

Wed, 2025-02-26 06:00

Microorganisms. 2025 Jan 25;13(2):268. doi: 10.3390/microorganisms13020268.

ABSTRACT

Ammonia, essential for fertilizers and energy storage, is mainly produced through the energy-demanding Haber-Bosch process. Microbial production offers a sustainable alternative, but natural yeast cells have not yet demonstrated success. This study aimed to enhance ammonia production in Saccharomyces cerevisiae by optimizing amino acid utilization through its deamination metabolism. Adaptive laboratory evolution is a method for rapidly generating desirable phenotypes through metabolic and transcriptional reorganization. We applied it to the efficiently fermenting S. cerevisiae strain CEN.PK113-7D using an unbalanced carbon/nitrogen medium to impose selective pressure. We selected several evolved strains with a 3-5-fold increase in amino acid utilization and ammonia secretion. The multi-step bioreactor strategy of the evolved strain AAV6, supplemented with concentrated nitrogen sources, resulted in the production of 1.36 g/L of ammonia, a value in line with levels produced by other microbial systems. This proof-of-concept study suggests that yeast-based processes can be adapted straightforwardly to ammonia production from high-protein waste derived from several sources.

PMID:40005635 | DOI:10.3390/microorganisms13020268

Categories: Literature Watch

Nutritional Intake and Sensory Processing in School-Aged Children with Autism Spectrum Disorder

Wed, 2025-02-26 06:00

Nutrients. 2025 Feb 7;17(4):604. doi: 10.3390/nu17040604.

ABSTRACT

Background: Individuals diagnosed with autism spectrum disorder (ASD) commonly experience sensory processing that differs from general-population norms, and the autistic lived experience of eating includes preferences for routine, and sensory processing difficulty related to scents, tastes, temperatures, and textures of food. Meanwhile, research indicates that nutrients involved in one-carbon metabolism (OCM) may be related to sensory processing. Methods: This study enrolled 33 school-aged children with autism to assess whether OCM nutrient intake is associated with sensory processing. Parents completed two parent-report assessments: the youth and adult food frequency questionnaire (YAFFQ), and a sensory processing tool, Sensory Profile 2 (SP2). Results: Participant data showed generally good nutritional profiles mirroring those of general-population U.S. children. A group-binarized linear regression model showed the following relationships (p < 0.05): vitamin B12 consumption had a negative association with the SP2 Oral and Sensor domain scores. Choline intake had a positive association with the SP2 Avoider domain score. Vitamin B1 showed a positive association with the SP2 Visual domain score. Conclusions: These results support the possible existence of a relationship between sensory symptoms and OCM nutrient consumption levels in school-aged children diagnosed with autism. Future research is needed to confirm and explore the potential for causality.

PMID:40004933 | DOI:10.3390/nu17040604

Categories: Literature Watch

Unveiling Racial Disparities in Localized Prostate Cancer: A Systems-Level Exploration of the lncRNA Landscape

Wed, 2025-02-26 06:00

Genes (Basel). 2025 Feb 17;16(2):229. doi: 10.3390/genes16020229.

ABSTRACT

BACKGROUND/OBJECTIVES: Prostate cancer (PC) is the most common non-cutaneous cancer in men globally, and one which displays significant racial disparities. Men of African descent (AF) are more likely to develop PC and face higher mortality compared to men of European descent (EU). The biological mechanisms underlying these differences remain unclear. Long non-coding RNAs (lncRNAs), recognized as key regulators of gene expression and immune processes, have emerged as potential contributors to these disparities. This study aimed to investigate the regulatory role of lncRNAs in localized PC in AF men relative to those of EU and assess their involvement in immune response and inflammation.

METHODS: A systems biology approach was employed to analyze differentially expressed (DE) lncRNAs and their roles in prostate cancer (PC). Immune-related pathways were investigated through over-representation analysis of lncRNA-mRNA networks. The study also examined the effects of vitamin D supplementation on lncRNA expression in African descent (AF) PC patients, highlighting their potential regulatory roles in immune response and inflammation.

RESULTS: Key lncRNAs specific to AF men were identified, with several being implicated for immune response and inflammatory processes. Notably, 10 out of the top 11 ranked lncRNAs demonstrated strong interactions with immune-related genes. Pathway analysis revealed their regulatory influence on antigen processing and presentation, chemokine signaling, and ribosome pathways, suggesting their critical roles in immune regulation.

CONCLUSIONS: These findings highlight the pivotal role of lncRNAs in PC racial disparities, particularly through immune modulation. The identified lncRNAs may serve as potential biomarkers or therapeutic targets to address racial disparities in PC outcomes.

PMID:40004558 | DOI:10.3390/genes16020229

Categories: Literature Watch

From Local to Systemic: The Journey of Tick Bite Biomarkers in Australian Patients

Wed, 2025-02-26 06:00

Int J Mol Sci. 2025 Feb 11;26(4):1520. doi: 10.3390/ijms26041520.

ABSTRACT

Tick bites and tick-related diseases are on the rise. Diagnostic tests that identify well-characterised tick-borne pathogens (TBPs) possess limited capacity to address the causation of symptoms associated with poorly characterised tick-related illnesses, such as debilitating symptom complexes attributed to ticks (DSCATT) in Australia. Identification of local signals in tick-bitten skin that can be detected systemically in blood would have both clinical (diagnostic or prognostic) and research (mechanistic insight) utility, as a blood sample is more readily obtainable than tissue biopsies. We hypothesised that blood samples may reveal signals which reflect relevant local (tissue) events and that the time course of these signals may align with local pathophysiology. As a first step towards testing this hypothesis, we compared molecular signatures in skin biopsies taken from the tick-bite location of human participants, as published in our previous study, together with peripheral blood signatures obtained concurrently. This approach captures differentially expressed molecules across multiple omics datasets derived from peripheral blood (including cellular and cell-free transcriptomics, proteomics, metabolomics, and DNA methylation), and skin biopsies (spatial transcriptomics). Our original data revealed that extracellular matrix organisation and platelet degranulation pathways were upregulated in the skin within 72 h of a tick bite. The same signals appeared in blood, where they then remained elevated for three months, displaying longitudinally consistent alterations of biological functions. Despite the limited sample size, these data represent proof-of-concept that molecular events in the skin following a tick bite can be detectable systemically. This underscores the potential value of blood samples, akin to a liquid biopsy, to capture biomarkers reflecting local tissue processes.

PMID:40003986 | DOI:10.3390/ijms26041520

Categories: Literature Watch

Bridging the Gap Between Platforms: Comparing Grape Phylloxera <em>Daktulosphaira vitifoliae</em> (Fitch) Microsatellite Allele Size and DNA Sequence Variation

Wed, 2025-02-26 06:00

Insects. 2025 Feb 19;16(2):230. doi: 10.3390/insects16020230.

ABSTRACT

Grape phylloxera, Daktulosphaira vitifoliae (Fitch), is an economically significant pest of grapevines. Identification of phylloxera genotypes is an important aspect of management as genotypes differ in virulence and susceptibility to control using resistant rootstocks. Microsatellite markers developed on polyacrylamide gel systems have been the most widely used molecular method for phylloxera genotype identification, but this approach has been superseded by fluorescent capillary-based genotyping. The current study presents new laboratory methods for amplifying a standard set of eight phylloxera microsatellite markers using PCR-incorporated fluorescently labelled primers, genotyped on an ABI capillary platform. Comparison of allele size data scored on (i) polyacrylamide, (ii) capillary, and (iii) high-throughput sequencing (HTS) platforms revealed that the capillary genotyping most closely matched the HTS allele sizes, while alleles of loci originally scored on a polyacrylamide platform differ in size by up to three base pairs, mostly due to the presence of previously uncharacterised DNA sequence indels. Seven common clonal lineages of phylloxera known from Australia are proposed as reference samples for use in calibrating genotyping systems between platforms and laboratories to ensure universal scoring of allele sizes, providing a critical link for accurately matching previous phylloxera genotype studies with current research.

PMID:40003859 | DOI:10.3390/insects16020230

Categories: Literature Watch

Thermodynamics of Morphogenesis: Beading and Branching Pattern Formation in Diffusion-Driven Salt Finger Plumes

Wed, 2025-02-26 06:00

Entropy (Basel). 2025 Jan 22;27(2):106. doi: 10.3390/e27020106.

ABSTRACT

Spontaneous pattern formation is a universal phenomenon that occurs in purely physical systems, biology, and human societies. Salt fingering due to differential diffusion of heat and salt in seawater is a typical example, although the general principle that governs pattern formation remains unknown. We show through simple experiments injecting a salt solution into a sucrose solution of equal density that a salt finger exhibits characteristic pattern transitions depending on the injection flow rate. When the rate increases, a linear finger starts meandering, branching, and multiple branching, whereas when the rate is decreased, it produces a beading pattern. These morphological instabilities and associated pattern formation are caused by a local accumulation of kinetic energy that minimizes the flow resistance and maximizes the energy dissipation in the final steady state. We suggest that this energy accumulation mechanism governs a wide variety of pattern formation phenomena in non-equilibrium systems, including morphogenesis of abiotic protocells.

PMID:40003103 | DOI:10.3390/e27020106

Categories: Literature Watch

Comprehensive Analysis of Granzymes and Perforin Family Genes in Multiple Cancers

Wed, 2025-02-26 06:00

Biomedicines. 2025 Feb 7;13(2):408. doi: 10.3390/biomedicines13020408.

ABSTRACT

Background/Objectives: Cancer remains a significant global health concern, with immunotherapies emerging as promising treatments. This study explored the role of perforin-1 (PRF1) and granzymes A, B and K (GZMA, GZMB and GZMK) in cancer biology, focusing on their impact on tumor cell death and immune response modulation. Methods: Through a comprehensive genomic analysis across various cancer types, we explored the differential expression, mutation profiles and methylation patterns of these genes, providing insights into their potential as therapeutic targets. Furthermore, we investigated their association with immune cell infiltration and pathway activation within the tumor microenvironment in each tumor type. Results: Our findings revealed distinct expression patterns and prognostic implications for PRF1, GZMA, GZMB and GZMK across different cancers, highlighting their multifaceted roles in tumor immunity. We found increased immune infiltration across all tumor types and significant correlations between the genes of interest and cytotoxic T cells, as well as the most significant survival outcomes in breast cancer. We also show that granzymes and perforin-1 are significantly associated with indicators of immunosuppression and T cell dysfunction within patient cohorts. In skin melanoma, glioblastoma, kidney and bladder cancers, we found significant correlations between the genes of interest and patient survival after receiving immune-checkpoint inhibition therapy. Additionally, we identified potential associations between the mRNA expression levels of these genes and drug sensitivity. Conclusions: Overall, this study enhances our understanding of the molecular mechanisms underlying tumor immunity and provides valuable insights into the potential therapeutic implications of PRF1, GZMA, GZMB and GZMK in cancer treatment.

PMID:40002821 | DOI:10.3390/biomedicines13020408

Categories: Literature Watch

Chronic Wound Initiation: Single-Cell RNAseq of Cutaneous Wound Tissue and Contributions of Oxidative Stress to Initiation of Chronicity

Wed, 2025-02-26 06:00

Antioxidants (Basel). 2025 Feb 13;14(2):214. doi: 10.3390/antiox14020214.

ABSTRACT

Chronic wounds (CWs) in humans affect millions of people in the US alone, cost billions of dollars, cause much suffering, and still there are no effective treatments. Patients seek medical care when wound chronicity is already established, making it impossible to investigate factors that initiate chronicity. In this study, we used a diabetic mouse model of CWs that mimics many aspects of chronicity in humans. We performed scRNAseq to compare the cell composition and function during the first 72 h post-injury and profiled 102,737 cells into clusters of all major cell types involved in healing. We found two types of fibroblasts. Fib 1 (pro-healing) was enriched in non-CWs (NCWs) whereas Fib 2 (non-healing) was in CWs. Both showed disrupted proliferation and migration, and extracellular matrix (ECM) deposition in CWs. We identified several subtypes of keratinocytes, all of which were more abundant in NCWs, except for Channel-related keratinocytes, and showed altered migration, apoptosis, and response to oxidative stress (OS) in CWs. Vascular and lymphatic endothelial cells were both less abundant in CWs and both had impaired migration affecting the development of endothelial and lymphatic microvessels. Study of immune cells showed that neutrophils and mast cells are less abundant in CWs and that NCWs contained more proinflammatory macrophages (M1) whereas CWs were enriched in anti-inflammatory macrophages (M2). Also, several genes involved in mitochondrial function were abnormally expressed in CWs, suggesting impaired mitochondrial function and/or higher OS. Heat shock proteins needed for response to OS were downregulated in CWs, potentially leading to higher cellular damage. In conclusion, the initiation of chronicity is multifactorial and involves various cell types and cellular functions, indicating that one type of treatment will not fix all problems, unless the root cause is fundamental to the cell and molecular mechanisms of healing. We propose that such a fundamental process is high OS and its association with wound infection/biofilm.

PMID:40002400 | DOI:10.3390/antiox14020214

Categories: Literature Watch

Oxidative Score and Microvesicle Profile Suggest Cardiovascular Risk in Chronic Kidney Disease

Wed, 2025-02-26 06:00

Antioxidants (Basel). 2025 Feb 3;14(2):178. doi: 10.3390/antiox14020178.

ABSTRACT

Chronic kidney disease (CKD) is associated with a high incidence of cardiovascular disease (CVD) due to the accumulation of uremic toxins, altered redox state, and chronic systemic inflammation. This study aimed to analyze the relationship between the redox status of patients with CKD and the phenotype of microvesicles (MVs) subtypes, and cardiovascular events. The oxidative stress level of each participant was determined using an individualized OXY-SCORE. The relationship between pro-oxidant and antioxidant parameters and the expression of membrane markers in endothelial-derived microvesicles (EMVs) and platelet-derived microvesicles (PMVs) was established. Patients with advanced CKD (ACKD) and hemodialysis (HD) had a higher OXY-SCORE than healthy subjects (HS), whereas peritoneal dialysis (PD) patients had similar scores to HS. PD patients showed elevated PMVs and CD41 expression, whereas HD patients had higher EMVs and CD31 expression. Patients with ACKD had higher tissue factor (TF) expression in the PMVs and EMVs. TF expression was correlated with xanthine oxidase (XO) activity and was negatively correlated with antioxidant parameters. Patients with cardiovascular events show elevated TF. In conclusion, microvesicles and oxidative stress may serve as markers of cardiovascular risk in CKD, with TF expression in PMVs and EMVs being potential predictive and prognostic biomarkers of CVD.

PMID:40002365 | DOI:10.3390/antiox14020178

Categories: Literature Watch

Biosynthesis of Edible Terpenoids: Hosts and Applications

Wed, 2025-02-26 06:00

Foods. 2025 Feb 17;14(4):673. doi: 10.3390/foods14040673.

ABSTRACT

Microbial foods include microbial biomass, naturally fermented foods, and heterologously synthesized food ingredients derived from microbial fermentation. Terpenoids, using isoprene as the basic structure, possess various skeletons and functional groups. They exhibit diverse physicochemical properties and physiological activities, such as unique flavor, anti-bacterial, anti-oxidant, anti-cancer, and hypolipemic, making them extensively used in the food industry, such as flavor, fragrance, preservatives, dietary supplements, and medicinal health food. Compared to traditional strategies like direct extraction from natural species and chemical synthesis, microbial cell factories for edible terpenoids have higher titers and yields. They can utilize low-cost raw materials and are easily scaling-up, representing a novel green and sustainable production mode. In this review, we briefly introduce the synthetic pathway of terpenoids and the applications of microbial cell factories producing edible terpenoids. Secondly, we highlight several typical and non-typical microbial chassis in edible terpenoid-producing cell factories. In addition, we reviewed the recent advances of representative terpenoid microbial cell factories with a gram-scale titer in food flavor, food preservation, nutritional enhancers, and medicinal health foods. Finally, we predict the future directions of microbial cell factories for edible terpenoids and their commercialization process.

PMID:40002116 | DOI:10.3390/foods14040673

Categories: Literature Watch

The Curse of the Red Pearl: A Fibroblast-Specific Pearl-Necklace Mitochondrial Phenotype Caused by Phototoxicity

Wed, 2025-02-26 06:00

Biomolecules. 2025 Feb 19;15(2):304. doi: 10.3390/biom15020304.

ABSTRACT

The dynamic nature of mitochondria makes live cell imaging an important tool in mitochondrial research. Although imaging using fluorescent probes is the golden standard in studying mitochondrial morphology, these probes might introduce aspecific features. In this study, live cell fluorescent imaging was applied to investigate a pearl-necklace-shaped mitochondrial phenotype that arises when mitochondrial fission is restricted. In this fibroblast-specific pearl-necklace phenotype, constricted and expanded mitochondrial regions alternate. Imaging studies revealed that the formation time of this pearl-necklace phenotype differs between laser scanning confocal, widefield and spinning disk confocal microscopy. We found that the phenotype formation correlates with the excitation of the fluorescent probe and is the result of phototoxicity. Interestingly, the phenotype only arises in cells stained with red mitochondrial dyes. Serial section electron tomography of the pearl-necklace mitochondria revealed that the mitochondrial membranes remained intact, while the cristae structure was altered. Furthermore, filaments and ER were present at the constricted sites. This study illustrates the importance of considering experimental conditions for live cell imaging to prevent imaging artifacts that can have a major impact on the obtained results.

PMID:40001607 | DOI:10.3390/biom15020304

Categories: Literature Watch

The Matrix of Mitochondrial Imaging: Exploring Spatial Dimensions

Wed, 2025-02-26 06:00

Biomolecules. 2025 Feb 5;15(2):229. doi: 10.3390/biom15020229.

ABSTRACT

Mitochondria play a crucial role in human biology, affecting cellular processes at the smallest spatial scale as well as those involved in the functionality of the whole system. Imaging is the most important research tool for studying the fundamental role of mitochondria across these diverse spatial scales. A wide array of available imaging techniques have enabled us to visualize mitochondrial structure and behavior, as well as their effect on cells and tissues in a range from micrometers to centimeters. Each of the various imaging techniques that are available offers unique advantages tailored to specific research needs. Selecting an appropriate technique suitable for the scale and application of interest is therefore crucial, but can be challenging due to the large range of possibilities. The aim of this review is two-fold. First, we provide an overview of the available imaging techniques and discuss their strengths and limitations for applications across the sub-mitochondrial, cellular, tissue and organ levels for the imaging of mitochondria. Second, we identify opportunities for novel applications and advancement in the field. We emphasize the importance of integration across scales in mitochondrial imaging studies, particularly to bridge the gap between microscopic and non-invasive techniques. While integrating these diverse scales is challenging, primarily because such multi-scale approaches require expertise that spans different imaging modalities, we argue that integration has the potential to provide groundbreaking insights into mitochondrial biology. By providing a comprehensive overview of imaging techniques, this review paves the way for multi-scale imaging initiatives in mitochondrial research.

PMID:40001532 | DOI:10.3390/biom15020229

Categories: Literature Watch

Structural Characterization of the Dimers and Selective Synthesis of the Cyclic Analogues of the Antimicrobial Peptide Cm-p5

Wed, 2025-02-26 06:00

Antibiotics (Basel). 2025 Feb 13;14(2):194. doi: 10.3390/antibiotics14020194.

ABSTRACT

Background/Objectives: Cm-p5 and its cyclic monomeric and dimeric analogues are known for their antifungal, antibacterial, antiviral, and antibiofilm activities. Previously, our cyclization method produced a mixture of peptides that were difficult to separate, which was then improved by a selective synthesis of the parallel dimer and its differentiation from the antiparallel by comparison of the retention times in RP-HPLC. Methods: Here, we developed a more reliable identification method for the Cm-p5 dimer identification, which included chymotrypsin proteolytic digestion and sequencing of the different fragments by ESI-MSMS. We also improved our cyclization methods to specifically produce higher amounts of the desired cyclic variant, either cyclic monomer or dimer. Results: We show that liquid phase oxidation with 20% DMSO or iodine oxidation yields only the cyclic analogue. However, the on-resin oxidation with iodine showed greater efficacy and efficiency. Additionally, liquid phase cyclization yields the antiparallel dimer in high EtOH or peptide concentration, indicating a kinetic control. On the other hand, the parallel dimer was preferentially produced in 5% of TFE and low peptide concentration without the formation of the cyclic analogue indicating a thermodynamic control. Conclusions: In conclusion, we report that chymotryptic digestion combined with ESI-MS and MS/MS allows an unambiguous differentiation of Cm-p5 dimers. Here, we develop more selective and efficient methods for the synthesis of cyclic and dimeric analogues of Cm-p5.

PMID:40001437 | DOI:10.3390/antibiotics14020194

Categories: Literature Watch

Phage Therapy for Orthopaedic Infections: The First Three Cases from the United Kingdom

Wed, 2025-02-26 06:00

Antibiotics (Basel). 2025 Jan 22;14(2):114. doi: 10.3390/antibiotics14020114.

ABSTRACT

Background: Bacteriophages (phages) are viruses that infect and kill bacteria. The antimicrobial resistance crisis has driven renewed interest in phage therapy, including the use of phages to treat chronic orthopaedic infections. Methods: Here, we present the results of the first three orthopaedic patients treated with phage therapy in the United Kingdom. Results: The first patient was treated in May 2023 and received phages active against Staphylococcus aureus. At nine months follow-up, the patient's wound remained healed, the C-reactive protein normal and the patient was walking independently. The second patient received phages active against Klebsiella pneumoniae and S. aureus; the infection remained unresolved. The third patient received phages active against Staphylococcus epidermidis; at six months follow-up, the patient was free of infection. Endotoxin was considered at least partially responsible for mild self-limiting adverse effects in two cases. Conclusions: These promising results hint at the potential for phage therapy to transform the care of chronic orthopaedic infections.

PMID:40001358 | DOI:10.3390/antibiotics14020114

Categories: Literature Watch

Causal effects of education, intelligence, and income on COVID-19: evidence from a Mendelian randomization study

Wed, 2025-02-26 06:00

Hum Genomics. 2025 Feb 25;19(1):18. doi: 10.1186/s40246-025-00731-y.

ABSTRACT

BACKGROUND: The protective effects of higher educational attainment (EA) and intelligence on COVID-19 outcomes are not yet understood with regard to their dependency on income. The objective of our study was to examine the overall as well as independent effects of the three psychosocial factors on the susceptibility to and severity of COVID-19. To accomplish this, we utilized genetic correlation, Mendelian randomization (MR), and multivariable MR (MVMR) analyses to evaluate genetic associations between EA, intelligence, household income, and three specific COVID-19 outcomes: SARS-CoV-2 infection, hospitalized COVID-19, and critical COVID-19.

RESULTS: The genetic correlation analysis revealed that COVID-19 outcomes were negatively correlated with the three psychosocial factors (rg: -0.19‒-0.36). The MR analysis indicated that genetic liability to EA, intelligence, and income exerted overall protective effects against SARS-CoV-2 infection (OR: 0.86‒0.92), hospitalized COVID-19 (OR: 0.70‒0.80), and critical COVID-19 (OR: 0.65‒0.85). MVMR analysis revealed that elevated levels of EA conferred independent protective effects against SARS-CoV-2 infection (OR: 0.85), hospitalization due to COVID-19 (OR: 0.79), and critical COVID-19 (OR: 0.63). Furthermore, intelligence exhibited a negative association with the risk of SARS-CoV-2 infection (OR: 0.91), whereas a higher income was linked to an elevated risk of SARS-CoV-2 infection (OR: 1.13).

CONCLUSIONS: Our findings indicated that EA could significantly reduce the risk and severity of COVID-19, regardless of intelligence and income. However, the impact of intelligence or income on COVID-19 severity was not supported by our research.

PMID:40001252 | DOI:10.1186/s40246-025-00731-y

Categories: Literature Watch

Th1-poised naive CD4 T cell subpopulation reflects anti-tumor immunity and autoimmune disease

Tue, 2025-02-25 06:00

Nat Commun. 2025 Feb 25;16(1):1962. doi: 10.1038/s41467-025-57237-3.

ABSTRACT

Naïve CD4 T cells are traditionally viewed as a quiescent, homogeneous, resting population, but emerging evidence reveals their heterogeneity, which can be crucial for understanding disease contexts and therapeutic outcomes. In this study, we identify distinct subpopulations within both murine and human naïve CD4 T cells by single cell-RNA-sequencing (scRNA-seq), particularly focusing on a subpopulation that expresses super-high levels of interleukin-7 receptor (IL-7Rsup-hi), along with CD97, IL-18R, and Ly6C. This subpopulation, absent in the thymus and peripherally induced, exhibits type 1 helper T cell (Th1)-poised characteristics and contributes to the inhibition of cancer progression in B16F10 tumor-bearing mice. In humans, this IL-7Rsup-hi subpopulation expressing CD97 correlates with the responsiveness to anti-PD-1 therapy in cancer patients and the disease state of multiple sclerosis. By elucidating the heterogeneity of naive CD4 T cells and identifying a Th1-poised subpopulation capable of robust type 1 responses, we highlight the importance of this heterogeneity in inflammatory conditions for defining the disease states and predicting drug responsiveness.

PMID:40000667 | DOI:10.1038/s41467-025-57237-3

Categories: Literature Watch

The Great Reset: A "Tuft" Journey Towards Tumorigenesis

Tue, 2025-02-25 06:00

Cell Mol Gastroenterol Hepatol. 2025 Feb 22:101476. doi: 10.1016/j.jcmgh.2025.101476. Online ahead of print.

NO ABSTRACT

PMID:39999952 | DOI:10.1016/j.jcmgh.2025.101476

Categories: Literature Watch

Biomolecular condensates at the plasma membrane: Insights into plant cell signaling

Tue, 2025-02-25 06:00

Curr Opin Plant Biol. 2025 Feb 24;84:102697. doi: 10.1016/j.pbi.2025.102697. Online ahead of print.

ABSTRACT

Biomolecular condensates, often formed through liquid-liquid phase separation (LLPS), are increasingly recognized as a critical mechanism for cellular compartmentalization across diverse biological systems. Although traditionally considered membrane-less entities, recent discoveries highlight their dynamic interactions with membranes, where they regulate various processes, including signal transduction. Signaling lipids are observed in condensates. Despite these advancements, our understanding of such condensates in plant biology remains limited. This review highlights recent studies involving membrane-associated condensates in plants, focusing particularly on their interactions with the plasma membrane (PM) and their potential roles in PM-based signaling.

PMID:39999604 | DOI:10.1016/j.pbi.2025.102697

Categories: Literature Watch

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