Physiological Functions Research Articles

RNA granules in flux: dynamics to balance physiology and pathology.

The life cycle of an mRNA is a complex process that is tightly regulated by interactions between the mRNA and RNA-binding proteins, forming molecular machines known as RNA granules. Various types of these membrane-less organelles form inside cells, including neurons, and contributecritically to various physiological processes. RNA granules are constantly in flux, change dynamically and adapt to their local environment, depending on their intracellular localization. The discovery that RNA condensates can form by liquid-liquid phase separation expanded our understanding of how compartments may be generated in the cell. Since then, a plethora of new functions have been proposed for distinct condensates in cells that await their validation in vivo. The finding that dysregulation of RNA granules (for example, stress granules) islikely toaffect neurodevelopmental and neurodegenerative diseases further boosted interest in this topic. RNA granules have various physiological functions in neurons and in the brain that we would like to focus on. We outline examples of state-of-the-art experiments including timelapse microscopy in neurons to unravel the precise functions of various types ofRNA granule. Finally, we distinguish physiologically occurring RNA condensation from aberrant aggregation, induced by artificial RNA overexpression, and present visual examples to discriminate both forms in neurons.

Precision proteomics with TurboID: mapping the suborganelle landscape.

Recent research underscores the pivotal role of cellular organelles, such as mitochondria, the endoplasmic reticulum, and lysosomes, in maintaining cellular homeostasis. Their dynamic interactions are critical for metabolic regulation and stress response. Analysis of organelle proteomes offers valuable insights into their functions in both physiology and disease. Traditional proteomic approaches to studying isolated organelles are now complemented by innovative methodologies focusing on inter-organelle interactions. This review examines the integration of advanced proximity labeling technologies, including TurboID and split-TurboID, which address the inherent limitations of traditional techniques and enable precision proteomics of suborganelle compartments and inter-organellar contact sites. These innovations have led to discoveries regarding organelle interconnections, revealing mechanisms underlying metabolic processes such as cholesterol metabolism, glucose metabolism, and lysosomal repair. In addition to highlighting the advancements in TurboID applications, this review delineates the evolving trends in organelle research, underscoring the transformative potential of these techniques to significantly enhance organelle-specific proteomic investigations.

A newly identified secretory phospholipase A2 group XIIA homolog (LcPLA2XIIA) in Larimichthys crocea exhibits antimicrobial and antitumor activities

The phospholipase A2 (PLA2) superfamily has attracted increasing attention in recent years due to the multiple physiological and pathological functions exerted by its members. Up to date, the knowledge about the biological role of PLA2XIIA subfamily members remains limited. In this study, a new member of PLA2XIIA subfamily, LcPLA2XIIA, was characterized in large yellow croaker. Different from most members of the PLA2 superfamily with positive charge, LcPLA2XIIA encodes an anionic protein, which is similar to other members of PLA2XIIA subfamily. LcPLA2XIIA is highly expressed in the intestine, and afterwards, it is up-regulated after with Pseudomonas plecoglossicida or Staphylococcus aureus. LcPLA2XIIA exhibits strong inhibitory activity against these two bacteria. The results indicate that LcPLA2XIIA plays an important role in the antimicrobial immune responses of large yellow croaker. LcPLA2XIIA displays strong binding activity to all the tested bacteria. It specifically interacts with LTA, a unique component on the surface of Gram-positive bacteria. It also significantly promotes bacterial agglutination in the presence of Ca2+. These findings reveal that the binding and agglutinating abilities of LcPLA2XIIA to bacteria contribute greatly to its antibacterial activity. In addition, LcPLA2XIIA significantly inhibits the proliferation of infectious hematopoietic necrosis virus instead of recombinant human adenovirus type 5. It also suppresses the growth of human colorectal adenocarcinoma cells by inducing apoptosis, but it has no obvious inhibitory effect on the growth of epithelioma papulosum cyprinid cells. This study provides new insights into the antibacterial activity, and the mechanism of LcPLA2XIIA in large yellow croaker, and antiviral and antitumor functions of PLA2XIIA subfamily members.

Prolonged exposure to NaAsO2 induces thyroid dysfunction and inflammatory injury in Sprague‒Dawley rats, involvement of NLRP3 inflammasome‒mediated pyroptosis.

Arsenic, a well-known hazardous toxicant, has been found in recent years to act as an environmental endocrine disruptor that accumulates in various endocrine organs, impeding the normal physiological functions of these organs and altering hormone secretion levels. Moreover, some research has demonstrated a correlation between arsenic exposure and thyroid functions, suggesting that arsenic has a toxicological effect on the thyroid gland. However, the specific type of thyroid gland damage caused by arsenic exposure and its potential molecular mechanism remain poorly understood. In this study, the toxic effects of sodium arsenite (NaAsO2) exposure at different doses (0, 2.5, 5.0 and 10.0mg/kg bw) and over different durations (12, 24 and 36 weeks) on thyroid tissue and thyroid hormone levels in Sprague‒Dawley (SD) rats were investigated, and the specific mechanisms underlying the effects were also explored. Our results showed that NaAsO2 exposure can cause accumulation of this element in the thyroid tissue of rats. More importantly, chronic exposure to NaAsO2 significantly upregulated the expression of NLRP3 inflammasome-related proteins in thyroid tissue, leading to pyroptosis of thyroid cells and subsequent development of thyroid dysfunction, inflammatory injury, epithelial-mesenchymal transition (EMT), and even fibrotic changes in the thyroid glands of SD rats. These findings increase our understanding of the toxic effects of arsenic exposure on the thyroid gland and its functions.

Trivalent chromium stress trigger accumulation of secondary metabolites in rice plants: Integration of biochemical and transcriptomic analysis

Trivalent chromium [Cr (III)] is a frequently detected environmental contaminant that negatively affects plant metabolism, growth, and yield. Plant secondary metabolites are non-nutrient compounds involved in diverse physiological functions in response to abiotic stresses. This study performed biochemical and transcriptomic analyses to clarify the protective role and mechanism of secondary metabolites in rice seedlings under Cr(III) stress. The content of measured secondary metabolites i.e., total soluble phenolics, flavonoids, lignin, and anthocyanin in rice tissues was significantly enhanced under Cr(III) exposure. Additionally, the activities of several enzymes including chalcone synthase, phenylalanine ammonialyase, peroxidase, and anthocyanidin synthase, were positively activated. Transcriptomic analysis revealed a number of differentially expressed genes (DEGs) in Cr(III)-treated rice seedlings and their expression patterns are tissue-specific. Additionally, the DEGs involved in secondary metabolism pathways were evident after KEGG enrichment analysis. Cr(III) exposure resulted in distinct genetic regulation strategies in rice tissues, with different DEGs activating various sub-pathways in the secondary metabolism pathways to cope with Cr(III) stress. Furthermore, the integrated correlation analysis of the secondary metabolites and transcriptome data identified key genes involved in different steps of the sub-pathways of secondary metabolism pathway in rice plants under Cr(III) stress. This study indicates that the accumulation of secondary metabolites in rice plants is a survival and detoxification strategy to reduce the adverse effects of toxic compounds. Future research should explore how key genes in secondary metabolism pathways aid in Cr(III) detoxification and enhance crop stress tolerance.

Peptide Drugs: Current Status and it's Applications in the Treatment of Various Diseases.

Peptides represent a class of natural molecules with diverse physiological functions, including hormone regulation, neurotransmission, and immune modulation. In recent years, peptide- based therapeutics have gained significant attention in pharmaceutical research and development due to their high specificity, efficacy, and relatively low toxicity. This review provides an overview of the current landscape of peptide drug development, highlighting the challenges faced in their formulation and delivery and the innovative strategies employed to overcome these hurdles. The review explores the wide range of applications of peptide drugs in treating various diseases, including HIV, multiple sclerosis, osteoporosis, chronic pain, diabetes, and cancer. Examples of FDA-approved peptide drugs and ongoing clinical trials are presented, showcasing the continuous advancements in peptide-based therapeutics across different therapeutic areas. This review underscores the promising potential of peptide drugs as targeted and effective treatments for a multitude of medical conditions, offering improved therapeutic outcomes and enhanced patient care.

Saga of Soggy Sauerkraut

The creation of undesirable (soggy) sauerkraut resulted in the loss of $1,000,000 worth of organic sauerkraut in 2022, which prompted a multistep investigation of the cause and potential solution. The cause of this condition has been previously reported as unique fermentation conditions and the lack of key trace nutrients essential for cabbage (Brassica oleracea var. capitata) cell wall integrity. Because the condition was limited to organic sauerkraut in 2022, this investigation initially focused on differences in fermentation conditions between organic and conventional sauerkraut. No differences in fermentation conditions accounted for the condition; therefore, attention was focused on analyzing the mineral content of cabbage grown for sauerkraut production that pinpointed a deficiency in critical micronutrients such as iron, copper, manganese, boron, and zinc. This deficiency was traced to the use of poultry manure that was contaminated with glyphosate residue from conventionally fed turkeys and chickens that consumed genetically engineered (GE) feed and used as the fertilizer for organic cabbage production. The presence of glyphosate, a potent mineral chelator and antibiotic, was identified as a significant factor that impairs the absorption and physiological function of essential minerals in the shikimate metabolic pathway whereby cell walls and lignin are produced, thus compromising the structural quality of the sauerkraut. After this discovery, the study progressed to evaluate various remediation strategies aimed at eliminating glyphosate from the soil and restoring nutrient uptake. Corn grain and silage were selected as the test crops for this phase. Among the tested remediation solutions were raw sauerkraut juice containing Lactobacillus plantarum, which is reported to degrade glyphosate in the rumen of dairy cows and two patented proprietary microbial mixtures, PB027 and PB027SK, that degrade glyphosate by all three of the known metabolic pathways. These treatments were specifically formulated to degrade residual glyphosate in the soil. The results showed that these interventions could reduce soil glyphosate levels by 80% to 90% within 6 to 7 months to significantly enhance both the yield and quality of corn grain and silage. The increase in corn grain yield from glyphosate degradation on the Shiocton silt loam soil was 907.89 kg·ha−1 (13.5 bushels/acre). The increase in yield on the irrigated Kidder sandy loam soil was quantified at 726.31 kg·ha−1 (10.8 bushels/acre) for corn grain and 6.62 t·ha−1 (2.68 t/acre) for silage, with an additional improvement in silage feed quality beneficial for milk production. The findings underscore the importance of addressing both micronutrient sufficiency and glyphosate residue in soil to ensure the optimal growth of cabbage and the quality of sauerkraut produced. By successfully identifying manure as a subtle source of nutrient immobilization and implementing effective soil remediation techniques, this research highlights a clear path forward for improving crop yield and quality to ultimately enhance the structural integrity and consumer acceptance of sauerkraut. This study has broader applications for the nutritional content and crop yields of many organic crops that use conventional poultry and animal manures that may contain glyphosate in desiccated plant tissues or GE feeding operations.

Taurocholic acid represents an earlier and more sensitive biomarker and promotes cholestatic hepatotoxicity in ANIT-treated rats.

Bile acid homeostasis is crucial for the normal physiological functioning of the liver. Disruptions in bile acid profiles are closely linked to the occurrence of cholestatic liver injury. As part of our diagnostic and therapeutic approach, we aimed to investigate the disturbance in bile acid profiles during cholestasis and its correlation with cholestatic liver injury. Before the occurrence of liver injury, alterations in bile acid profiles were detected in both plasma and liver between 8 and 16 h, persisting up to 96 h. TCA, TCDCA, and TUDCA in the plasma, as well as TCA, TUDCA, TCDCA, TDCA, TLCA, and THDCA in the liver, emerged as early sensitive and potential markers for diagnosing ANIT-induced cholestasis at 8-16 h. The distinguishing features of ANIT-induced liver injury were as follows: T-BAs exceeding G-BAs and serum biochemical indicators surpassing free bile acids. Notably, plasma T-BAs, particularly TCA, exhibited higher sensitivity to cholestatic hepatotoxicity compared with serum enzyme activity and liver histopathology. Further investigation revealed that TCA exacerbated ANIT-induced liver injury by elevating liver function enzyme activity, inflammation, and bile duct proliferation and promoting the migration of bile duct epithelial cell. Nevertheless, no morphological changes or alterations in transaminase activity indicative of liver damage were observed in the rats treated with TCA alone. Additionally, there were no changes in bile acid profiles or inflammatory responses under physiological conditions with maintained bile acid homeostasis. In summary, our findings suggest that taurine-conjugated bile acids in both plasma and liver, particularly TCA, can serve as early and sensitive markers for predicting intrahepatic cholestatic drugs and can act as potent exacerbators of cholestatic liver injury progression. However, exogenous TCA does not induce liver injury under physiological conditions where bile acid homeostasis is maintained.

Barriers and Facilitators in Lactation Support for the Preterm Mother-Infant Dyad: An Integrated Approach.

Breastfeeding offers significant health benefits for both mothers and infants, particularly preterm infants, where it serves as a therapeutic strategy to reduce mortality and morbidities. However, breastfeeding practices are threatened globally by societal norms and systemic barriers at both micro and macro levels. This paper explores the complex interplay of these barriers and facilitators, focusing on the Neonatal Intensive Care Unit (NICU) setting. Preterm infants face specific feeding challenges due to immature physiological functions, yet evidence supports that strategies like cue-based feeding and individualized care can enhance feeding success and health outcomes. For mothers, initiating and maintaining lactation after preterm birth is critical but challenging, with early lactation support and achieving sufficient milk volume being key predictors of success. Partner support significantly influences lactation outcomes, although more inclusive research is needed for diverse family structures. In the NICU, a multidisciplinary approach to lactation care is vital, emphasizing the need for experienced staff and family-centered practices. NICU design, policies promoting parental presence, and adherence to Baby-friendly Hospital Initiative guidelines further support breastfeeding. This paper aims to provide directives for local breastfeeding policies through an integrated approach, considering societal attitudes and healthcare practices. The findings advocate for improved lactation support in NICUs, inclusive language and policies, and further research into diverse familial and gender roles in breastfeeding.

Deep quantification of substrate turnover defines protease subsite cooperativity.

Substrate specificity determines protease functions in physiology and in clinical and biotechnological applications, yet quantitative cleavage information is often unavailable, biased, or limited to a small number of events. Here, we develop qPISA (quantitative Protease specificity Inference from Substrate Analysis) to study Dipeptidyl Peptidase Four (DPP4), a key regulator of blood glucose levels. We use mass spectrometry to quantify >40,000 peptides from a complex, commercially available peptide mixture. By analyzing changes in substrate levels quantitatively instead of focusing on qualitative product identification through a binary classifier, we can reveal cooperative interactions within DPP4's active pocket and derive a sequence motif that predicts activity quantitatively. qPISA distinguishes DPP4 from the related C. elegans DPF-3 (a DPP8/9-orthologue), and we relate the differences to the structural features of the two enzymes. We demonstrate that qPISA can direct protein engineering efforts like the stabilization of GLP-1, a key DPP4 substrate used in the treatment of diabetes and obesity. Thus, qPISA offers a versatile approach for profiling protease and especially exopeptidase specificity, facilitating insight into enzyme mechanisms and biotechnological and clinical applications.

The Relationship between Diet and Stress with Gastritis Symptoms in Adolescents at Integrated Agricultural Vocational Schools

Adolescence is a productive age that can experience lifestyle changes that don't pay attention to health, making them susceptible to gastritis symptoms. Common causes of gastritis include improper eating patterns, such as inappropriate frequency or timing of meals, eating excessively and quickly, or consuming foods that are stimulating (too spiced and spicy). Gastritis can easily attack individuals who have irregular eating patterns. Stress affects changes in physiological functions in the body's systems, one of which is the digestive system. Stress can cause decreased appetite, stomach emptying, increased stomach acid, resulting in pain in the stomach. This study aims to determine the relationship between diet and stress and symptoms of gastritis in adolescents. This research is a cross sectional study conducted on 271 teenagers at the Integrated Agricultural Vocational School, Riau Province. The data collection tool is a questionnaire that is valid and has high reliability. The results of the analysis carried out using the chi square test showed that there was a significant relationship between diet and stress and symptoms of gastritis in adolescents as evidenced by a correlation value of 0.000 α 0.05. After conducting research, the results showed that poor eating patterns and high levels of stress can result in symptoms of gastritis.

Exploring the Vital Role of Vitamins in Disease Prevention and Health Maintenance

The human body relies on vitamins to carry out fundamental functions, yet it is unable to produce them on its own. Certain nutrients, like phytochemicals, are considered essential as the body cannot produce them in sufficient quantities. While ideally vitamins are obtained through a healthy diet, supplements are often necessary. Vitamins are crucial for growth, metabolism, and overall health, with vitamin D being the only one the body can produce. Vitamers, related molecules with similar vitamin activity, make up the bulk of vitamins. Vitamin C is a potent antioxidant drug used in dermatology to treat photoageing and hyperpigmentation. L-ascorbic acid is the active form, with limited oral absorption, making topical application more effective. Its electron-donating ability is crucial for various physiological processes, and its deficiency can lead to scurvy. Vitamin E (tocopherols and tocotrienols) has demonstrated significant biological effects on enhancing human health and play a promising role in food systems Supplementation of α-tocopherol up to 0.2% in oils provides higher oxidative stability, making vitamin E a valuable functional ingredient for food preservation and nutritional quality enhancement.This study investigates the roles of vitamins C and E in disease prevention and management, highlighting their antioxidant properties and physiological functions. Both vitamins are crucial for neutralizing free radicals, thereby reducing oxidative stress linked to various diseases, including cardiovascular conditions, cancer, and neurodegenerative disorders. Vitamin C supports immune function and collagen synthesis, while Vitamin E contributes to cellular integrity and skin health. The research underscores the synergistic effects of these vitamins, which enhance each other's antioxidant capabilities and may improve overall health outcomes. By addressing their roles in disease processes, the study emphasizes the importance of adequate vitamin intake for promoting health and preventing illness

Extraction of RNA from the fungus Moniliophthora Perniciosa (Stahel) Aime and Phillips-Mora cultivated in induction medium for characterization of chitininases

Chitin is considered the second most important biopolymer in nature, both for its physiological functions in different organisms and for its high availability in the biosphere. However, its natural accumulation does not occur in the environment, this demonstrates that there are natural mechanisms responsible for its degradation. The chitinolytic enzymes found in living beings are targets of great biotechnological interest because they degrade chitin into useful derivatives for various sectors of the economy. Given this, this study aimed to extract RNA for subsequent molecular characterization of chitinases from the fungus Moniliophthora perniciosa. To this end, the fungus was cultivated in WY medium, remaining in the greenhouse for 10-14 days. After growth, RNA was extracted using the traditional Trizol method and the Direct-zol commercial kit. The resulting samples were analyzed using the spectrophotometric technique and verified by photodocumentation after agarose electrophoresis. It was observed that the culture medium was considered satisfactory for RNA extraction and the ideal growth time was 8-10 days for the strain to present sufficient mycelial mass for extraction. Furthermore, the commercial kit used was more favorable than the traditional Trizol method, the product had a low level of contaminants and electrophoresis demonstrated high RNA quality due to the presence of intact rRNA bands. Therefore, as it was extracted from cultivation in a medium that induces chitinase production, the RNA extraction described becomes the most suitable method for the molecular characterization of chitinase production.

The mechanism of paclitaxel induced damage on placental trophoblast cells

ObjectiveChemotherapy during pregnancy has a certain risk of causing a series of complications, such as miscarriage, premature birth, or fetal growth restriction, although the relationship between these complications and chemotherapy is currently unclear. This experiment focuses on the possible damage mechanism of the chemotherapeutic drug paclitaxel on placental trophoblast cells, and explores whether chemotherapy can affect pregnancy outcomes by directly damaging placental tissue.MethodsThis study explored the mechanism of paclitaxel induced damage on placental trophoblast cell lines JEG-3 and BEWO through immunofluorescence staining, Western blot experiments, cell flow cytometry, Seahorese cell metabolism experiments, and mouse modeling verification.ResultsThe experiment found that paclitaxel could induce JEG-3 and BEWO cells to produce reactive oxygen species (ROS), and elevate the ratio of Bax/Bcl-2 expression. Besides, paclitaxel mediated the reduction of mitochondrial membrane potential in JEG-3 and BEWO cells, causing damage and leading to mitochondrial autophagy and the occurrence of unfolded protein response. Paclitaxel inhibited the glycolysis rate of JEG-3 and BEWO cells, and leaded to impaired mitochondrial function, including decreased basal respiratory values, decreased respiratory reserve capacity, and proton leakage. In pregnant mice with tumor modeling, paclitaxel could cause DNA damage in placental tissue cells, and might lead to apoptosis of chemotherapy mice placental tissue cells and impairment of normal physiological functions.ConclusionPaclitaxel may directly or indirectly affect the normal physiological functions of placental trophoblast cells, including energy metabolism and protein synthesis dysfunction, which may be related to the adverse pregnancy outcomes caused by paclitaxel chemotherapy.

Sugar alcohol degradation in Archaea: uptake and degradation of mannitol and sorbitol in Haloarcula hispanica

The halophilic archaeon Haloarcula hispanica utilizes the sugar alcohols mannitol and sorbitol as carbon and energy sources. Genes, enzymes, and transcriptional regulators involved in uptake and degradation of these sugar alcohols were identified by growth experiments with deletion mutants and enzyme characterization. It is shown that both mannitol and sorbitol are taken up via a single ABC transporter of the CUT1 transporter family. Then, mannitol and sorbitol are oxidized to fructose by two distinct dehydrogenases. Fructose is further phosphorylated to fructose-1-phosphate by a haloarchaeal ketohexokinase, providing the first evidence for a physiological function of ketohexokinase in prokaryotes. Finally, fructose-1-phosphate is phosphorylated via fructose-1-phosphate kinase to fructose-1,6-bisphosphate, which is cleaved to triosephosphates by a Class I fructose-1,6-bisphosphate aldolase. Two distinct transcriptional regulators, acting as activators, have been identified: an IclR-like regulator involved in activating genes for sugar alcohol uptake and oxidation to fructose, and a GfcR-like regulator that likely activates genes involved in the degradation of fructose to pyruvate. This is the first comprehensive analysis of a sugar alcohol degradation pathway in Archaea.

Development of a cardiotoxicity evaluation system using a Heart-on-a-Chip Microdevice with aligned fiber device

Abstract Background and Purpose Cardiovascular cells differentiated from human induced pluripotent stem (iPS) cells, such as cardiomyocytes, are expected to be useful for evaluating cardiac pharmacology and toxicity in humans. In recent years, myocardial damage caused by anticancer drugs has begun to attract attention. Being able to evaluate human cardiotoxicity early in the development of novel drugs like anticancer agents confers advantages in terms of cost and development speed. The aim of this study was to develop a highly sensitive bioassay system that can evaluate the physiological function of the human heart, and to validate the efficacy of the system toward detection of cardiotoxicity of drugs. Methods We differentiated human iPS cells into cardiovascular cells (cardiomyocytes, endothelial cells and mural cells) and applied dynamic culture training to generate vascularized microtissues (VCM) with vascular network structures. By integrating this VCM with a microfluidic chip containing microchannels, we developed a heart-on-a-chip microdevice (HMD) specialized for evaluating cardiac function (Figure 1). Furthermore, through a collaborative study with the Stem Cell & Device Laboratory (SCAD), application of their aligned fiber device improved throughput and stability, allowing development of a SCAD-HMD capable of evaluating longer-term cardiotoxicity. Results SCAD-HMD can quantify physiological parameters of VCM such as ejection volume and force based on displacement of particles within the microchannels. Our results showed that SCAD-HMD not only exhibited pharmacological responses to representative circulatory stimulants, but also reproduced clinical events occurring in actual practice, demonstrating that the anticancer drug trastuzumab, commonly used for breast cancer treatment, causes myocardial disfunction when combined with doxorubicin. Conclusions This study demonstrated that SCAD-HMD can stably evaluate the toxicity of drugs on the human heart. In the future, establishing SCAD-HMD using iPS cells derived from individual patients and assessing responses to specific drugs may enable "individualized cardiotoxicity assessment systems" that can preemptively avoid cardiac complications associated with anticancer drugs and other pharmacological agents.

From structure to therapy: the critical influence of cartilaginous endplates and microvascular network on intervertebral disc degeneration

The intervertebral disc (IVD) is the largest avascular structure in the human body. The cartilaginous endplate (CEP) is a layer of translucent cartilage located at the upper and lower edges of the vertebral bodies. On one hand, CEPs endure pressure from within the IVD and the tensile and shear forces of the annulus fibrosus, promoting uniform distribution of compressive loads on the vertebral bodies. On the other hand, microvascular diffusion channels within the CEP serve as the primary routes for nutrient supply to the IVD and the transport of metabolic waste. Degenerated CEP, characterized by increased stiffness, decreased permeability, and reduced water content, impairs substance transport and mechanical response within the IVD, ultimately leading to intervertebral disc degeneration (IDD). Insufficient nutrition of the IVD has long been considered the initiating factor of IDD, with CEP degeneration regarded as an early contributing factor. Additionally, CEP degeneration is frequently accompanied by Modic changes, which are common manifestations in the progression of IDD. Therefore, this paper comprehensively reviews the structure and physiological functions of CEP and its role in the cascade of IDD, exploring the intrinsic relationship between CEP degeneration and Modic changes from various perspectives. Furthermore, we summarize recent potential therapeutic approaches targeting CEP to delay IDD, offering new insights into the pathological mechanisms and regenerative repair strategies for IDD.

O IMPACTO DA REGULAÇÃO DO SISTEMA ENDOCANABINOIDE NA FARMACOTERAPIA DA ANSIEDADE E DO ESTRESSE

This article addresses the impact of regulation of the endocannabinoid system on the pharmacotherapy of anxiety and stress, topics of increasing relevance in neuroscience and pharmacology. The endocannabinoid system, composed of receptors, endocannabinoids and enzymes responsible for their synthesis and degradation, plays a fundamental role in modulating several physiological functions, including the regulation of stress and anxiety. Cannabidiol (CBD), a phytocannabinoid, has stood out for its anxiolytic and modulating effects on the endocannabinoid system, presenting itself as a promising therapeutic alternative for anxiety disorders. The objective of the study was to analyze the therapeutic effects of regulating the endocannabinoid system in the treatment of anxiety and stress, focusing on the benefits and limitations of using CBD. To this end, a bibliographic review of studies published between 2010 and 2024 was carried out, using databases such as PubMed, SciELO and Google Scholar. Inclusion criteria involved peer-reviewed studies that addressed the relationship between the endocannabinoid system and anxiety disorders. The results showed that CBD can significantly reduce symptoms of anxiety and stress, with few side effects. However, there are still gaps regarding optimal dosage and drug interactions, which limits its widespread clinical adoption. Regulation of the medicinal use of cannabis has also proven to be an obstacle in several countries. It is concluded that, despite the challenges, the use of cannabinoids such as CBD represents a promising approach, requiring greater investment in clinical research and adequate regulation.

The structure of the IL-11 signalling complex provides insight into receptor variants associated with craniosynostosis.

Interleukin 11 (IL-11), a member of the IL-6 family of cytokines, has roles in haematopoiesis, inflammation, bone metabolism, and craniofacial development. IL-11 also has pathological roles in chronic inflammatory diseases, fibrosis, and cancer. In this structural snapshot, we explore our recently published cryo-EM structure of the human IL-11 signalling complex to understand the molecular mechanisms of complex formation and disease-associated mutations. IL-11 signals by binding to its cell surface receptors, the IL-11 receptor α subunit (IL-11Rα) and glycoprotein 130 (gp130), to form a hexameric signalling complex. We examine the locations within the complex of receptor sequence variants that are associated with craniosynostosis and craniosynostosis-like phenotypes and speculate on potential molecular mechanisms leading to defects in signalling function. While these causative amino acid sequence changes in IL-11Rα are generally distal to interfaces between components of the complex, important structural residues are highly represented, including proline residues, cysteine residues involved in disulfide bonds, and residues within or surrounding the tryptophan-arginine ladder. We also note the locations and potential effects of amino acid substitutions within the extracellular domains of gp130 that are associated with craniosynostosis. As focus on the physiological and pathological functions of IL-11 grows, the importance of high-resolution structural knowledge of IL-11 signalling to understand disease-associated mutations and to inform therapeutic strategies will only increase.

Phosphonates of Pectobacterium atrosepticum: Discovery and Role in Plant–Pathogen Interactions

Many phytopathogens’ gene products that contribute to plant–pathogen interactions remain unexplored. In one of the most harmful phytopathogenic bacterium Pectobacterium atrosepticum (Pba), phosphonate-related genes have been previously shown to be among the most upregulated following host plant colonization. However, phosphonates, compounds characterized by a carbon–phosphorus bond in their composition, have not been described in Pectobacterium species and other phytopathogenic bacteria, with the exception of Pseudomonas syringae and Pantoea ananatis. Our study aimed to determine whether Pba synthesizes extracellular phosphonates and, if so, to analyze their physiological functions. We demonstrated that Pba produces two types of extracellular phosphonates: 2-diethoxyphosphorylethanamine and phenylphosphonic acid. Notably, such structures have not been previously described among natural phosphonates. The production of Pba phosphonates was shown to be positively regulated by quorum sensing and in the presence of pectic compounds. Pba phosphonates were found to have a positive effect on Pba stress resistance and a negative effect on Pba virulence. The discovered Pba phosphonates are discussed as metabolites that enable Pba to control its “harmful properties”, thereby maintaining its ecological niche (the host plant) in a relatively functional state for an extended period.