Production Of Signaling Molecules Research Articles

Gas-producing potential of intestinal microbiota representatives in patients with post-infarction cardiosclerosis

Relevance. Analyzing the spectrum of gaseous signaling molecules (GSM) produced and consumed by the intestinal microbiota in patients with post-infarction cardiosclerosis (PICS) is essential for understanding their potential role in the pathogenesis of cardiovascular complications and for identifying strategies to address these conditions.Purpose. To investigate the prevalence and abundance of specific intestinal microbiota representatives isolated from patients with post-infarction cardiosclerosis (PICS) and to examine the species diversity and concentrations of microbial gaseous signaling molecules in this population.Materials and methods. This case-control study involved the analysis of stool samples from 35 healthy individuals (14 men and 21 women) aged 45–60 years (mean age: 51.8 ± 4.8 [49; 56] years) and 34 patients with PICS (19 men and 15 women) aged 40–84 years (mean age: 64.5 ± 8.1 [53; 72] years). Gaseous signaling molecules (CO, CH₄, NO, H₂S) were quantified using gas chromatography.Results. Patients with post-infarction cardiosclerosis exhibited a functional microbial imbalance marked by disrupted production of gaseous signaling molecules (GSM) compared to healthy individuals. In the PICS group, Lactobacillus spp. were observed to exclusively absorb NO, whereas in healthy individuals, Lactobacilli produced NO at a statistically significant higher mean concentration of 5.283 µg/mL (p < 0.001). Additionally, Staphylococcus aureus in the PICS group produced CO at levels 880 times higher than those observed in healthy individuals, a difference that was also statistically significant (p < 0.001).Conclusion. Restoring the functional activity of the intestinal normal microbiota in patients with PICS is essential. Through the production of gaseous signaling molecules (primarily NO and CO), the normal microbiota can support neuromodulatory, cardiomodulatory, immunomodulatory, and other beneficial functions that are critical for the rehabilitation process.

Biofilm as a supracellular organization of pathogenic bacteria

The high frequency of resistance to antibiotics among bacterial clinical isolates necessitates the discovery of new targets for suppressing the pathogenicity of microbes without stimulating their resistance. The studied sources suggest that this can be achieved by targeting the determinants of virulence. The search for new active substances with anti-biofilm activity based on the analysis of literature data on the structure of bacterial biofilms, mechanisms of their resistance to antimicrobial agents was the purpose of this work. An electronic search was conducted in Medline (PubMed interface), Scopus, and Web of Science between 2011 and July, 2024 using the keywords: biofilms, antibiotic resistance, Quorum sensing, persisters. 30 sources were selected, 85 were processed. The subject of the search was: microbial landscape of hospital strains of microorganisms, biofilm formation by microorganisms – pathogens of infectious diseases, regulation of virulence factors in bacterial biofilm. Studies of recent years have established that many pathogenic bacteria produce signal molecules for cellular communication. This signaling system is called Quorum sensing (QS) and it depends on the density of the bacterial population and is mediated by signaling molecules called pheromones or autoinducers (AI). Bacteria use QS to regulate activities and behavior including competence, conjugation, symbiosis, virulence, motility, sporulation, antibiotic production and biofilm formation. Researches aimed at bacterial communicative signals and suppressing QS demonstrate a fundamental approach to forming competitive microbial communication. The search, synthesis, and development of drugs based on modified autoinducers of various natures can lead to a breakthrough in the field of antibacterial therapy of infectious diseases, as well as surgical purulent postoperative complications. The pro­cessed literature describes a number of hypotheses regarding the participation of "toxin-antitoxin" systems that control the growth and metabolism of bacteria in the stimulation of the formation of persister cells. The simultaneous acquisition of resistance to many antibacterial factors, including physico-chemical ones, is suggested. Therefore, there is an increased attention of scientists to the study of the anti-biofilm effect of new compounds and drugs capable of influencing energy or metabolic processes in cells, as well as substances that do not require a metabolically active target. The review illustrates general modern approaches to the use of QS chains in pathogenic bacteria as new therapeutic targets.

Deciphering the code of temperature rise on aerobic granular sludge stability: a DSF-c-di-GMP mediated regulatory mechanism.

Diffusible signal factor (DSF)-c-di-GMP-mediated strategies have been proposed as an effective regulatory approach for signal molecules in aerobic granular sludge (AGS). The increase in temperature from low to normal levels had a significant impact on AGS stability. In this study, two reactors were established to investigate the effects of different temperature rise modes (abrupt or gradual) on AGS stability. Following the temperature rise, the DSF concentration in Reactor 1 (R1, abrupt) rose nearly fourfold by day 125, while LB-EPS levels decreased by 70%. In contrast, in Reactor 2 (R2, gradual), the DSF concentration increased by only twofold, and TB-EPS levels decreased by 25%. Flavobacterium (R1: 3.64%→0.41%, R2: 3.70%→1.97%) and Thauera (R1: 28.62%→4.01%, R2: 27.56%→13.10%), which are associated with EPS and signal molecule production, exhibited significantly different trends in response to the different temperature rise modes. Batch experiments exhibited that the exogenous addition of DSF and the DSF inhibitor, salicylic acid (SA), can regulate EPS content by altering the concentration of signaling molecules, particularly the LB-EPS, thereby reducing the risk of sludge collapse. These findings offer novel insights into the role of DSF in bacterial communication during AGS formation under temperature rise, providing a basis for regulating AGS formation and stability.

Dysbiosis-epigenetics-immune system interaction and ageing health problems.

Background. The growing interest in microbiota-epigenetics-immune system research stems from the understanding that microbiota, a group of micro-organisms colonized in the human body, can influence the gene expression through epigenetic mechanisms and interaction with the immune system. Epigenetics refers to changes in gene activity that are not caused by the alteration in the DNA sequence itself.Discussion. The clinical significance of this research lies in the potential to develop new therapies for diseases linked to the imbalance of these microbial species (dysbiosis), such as cancer and neurodegenerative diseases. The intricate interaction between microbiota and epigenetics involves the production of metabolites and signalling molecules that can impact our health by influencing immune responses, metabolism and inflammation. Understanding these interactions could lead to novel therapeutic strategies targeting microbiota-epigenetic pathways to improve health outcomes.Conclusion. In this context, we aim to review and emphasize the current knowledge and key concepts that link the microbiota to epigenetics and immune system function, exploring their relevance to the development and maintenance of homeostasis and susceptibility to different diseases later in life. We aim to elucidate key concepts concerning the interactions and potential effects among the human gut microbiota, epigenetics, the immune system and ageing diseases linked to dysbiosis.

Microbial Primer: what is the stringent response and how does it allow bacteria to survive stress?

The stringent response is a conserved bacterial stress response that allows bacteria to alter their activity and survive under nutrient-limiting conditions. Activation of the stringent response is characterized by the production of intracellular signalling molecules, collectively termed (p)ppGpp, which interact with multiple targets inside bacterial cells. Together, these interactions induce a slow growth phenotype to aid bacterial survival by altering the transcriptomic profile of the cell, inhibiting ribosome biosynthesis and targeting enzymes involved in other key metabolic processes.

The LuxO-OpaR quorum-sensing cascade differentially controls Vibriophage VP882 lysis-lysogeny decision making in liquid and on surfaces.

Quorum sensing (QS) is a process of cell-to-cell communication that bacteria use to synchronize collective behaviors. QS relies on the production, release, and group-wide detection of extracellular signaling molecules called autoinducers. Vibrios use two QS systems: the LuxO-OpaR circuit and the VqmA-VqmR circuit. Both QS circuits control group behaviors including biofilm formation and surface motility. The Vibrio parahaemolyticus temperate phage φVP882 encodes a VqmA homolog (called VqmAφ). When VqmAφ is produced by φVP882 lysogens, it binds to the host-produced autoinducer called DPO and launches the φVP882 lytic cascade. This activity times induction of lysis with high host cell density and presumably promotes maximal phage transmission to new cells. Here, we explore whether, in addition to induction from lysogeny, QS controls the initial establishment of lysogeny by φVP882 in naïve host cells. Using mutagenesis, phage infection assays, and phenotypic analyses, we show that φVP882 connects its initial lysis-lysogeny decision to both host cell density and whether the host resides in liquid or on a surface. Host cells in the low-cell-density QS state primarily undergo lysogenic conversion. The QS regulator LuxO~P promotes φVP882 lysogenic conversion of low-cell-density planktonic host cells. By contrast, the ScrABC surface-sensing system regulates lysogenic conversion of low-cell-density surface-associated host cells. ScrABC controls the abundance of the second messenger molecule cyclic diguanylate, which in turn, modulates motility. The scrABC operon is only expressed when its QS repressor, OpaR, is absent. Thus, at low cell density, QS-dependent derepression of scrABC drives lysogenic conversion in surface-associated host cells. These results demonstrate that φVP882 integrates cues from multiple sensory pathways into its lifestyle decision making upon infection of a new host cell.

Effects of chlorogenic acid-grafted-chitosan on biofilms, oxidative stress, quorum sensing and c-di-GMP in Pseudomonas fluorescens

This study determined the inhibitory mechanism as well as anti-biofilm activity of chlorogenic acid-grafted-chitosan (CS-g-CA) against Pseudomonas fluorescens (P. fluorescens) in terms of biofilm content, oxidative stress, quorum sensing and cyclic diguanosine monophosphate (c-di-GMP) concentration, and detected the changes in the expression levels of related genes by quantitative real-time PCR (qRT-PCR). Results indicated that treatment with sub-concentrations of CS-g-CA for P. fluorescens led to reduce the biofilm size of large colonies, decrease the content of biofilm and extracellular polymers, weaken the motility and adhesion of P. fluorescens. Moreover, CS-g-CA resulted in higher ROS levels, diminished catalase activity (CAT), and increased superoxide dismutase (SOD) in P. fluorescens. CS-g-CA reduced the production of quorum-sensing signaling molecules (AHLs) and the concentration of c-di-GMP in bacteria. Genes for flagellar synthesis (flgA), the resistance to stress (rpoS and hfq), and pde (phosphodiesterases that degrade c-di-GMP) were significantly down-regulated as determined by RT-PCR. Overall, CS-g-CA leads to the accumulation of ROS in bacteria via P. fluorescens environmental resistance genes and decreases the activity of enzymes in the bacterial antioxidant system, and interferes with the production and reception of quorum-sensing signaling molecules and the synthesis of c-di-GMP in P. fluorescens, which regulates the generation of biofilms.

Effects of exogenous autoinducer-2 precursor on the ability of Lactiplantibacillus plantarum SH7 to degrade biogenic amines: In vitro and in a dry-sausage model

The effects of the exogenous autoinducer-2 (AI-2) precursor, 4,5-dihydroxy-2,3-pentanedione (DPD; 0, 300, 600, and 900 nmol/L), on the degradation capacity of Lactiplantibacillus plantarum SH7 toward biogenic amines (BA) were investigated both in vitro and in a dry-sausage model. L. plantarum SH7 exhibited a significant increase in BA-degradation capacity (putrescine, cadaverine, and histamine) under DPD treatments compared to the absence of DPD treatment in vitro. Additionally, a significant increase in the production of AI-2 signal molecule and diamine oxidase in L. plantarum SH7 was observed with the addition of exogenous DPD (p < 0.05). In the dry-sausage model, the contents of BAs (tryptamine, 2-phenethylamine, putrescine, cadaverine, and histamine) significantly decreased with the addition of DPD (p < 0.05). Meanwhile, the sausage with 600-nM DPD exhibited the lowest cadaverine content (11.13 mg/kg), while the sausage with 900-nM DPD exhibited the lowest tryptamine, putrescine, and histamine contents (12.44, 11.15, and 13.21 mg/kg, respectively). Results suggest that an optimal concentration of exogenous DPD can enhance the capacity of L. plantarum SH7 to degrade BAs and that the degradation of BAs by L. plantarum SH7 may be dependent on the LuxS/AI-2 quorum sensing (QS) system. This study provides the theoretical basis for the development of functional starter cultures of lactic acid bacteria with BA-degradation ability based on targeted LuxS/AI-2 QS system regulation and reducing the accumulation of BAs in fermented meat products.

Different reactions of wheat, maize, and rice plants to putrescine treatment

Polyamines play an important role in growth and differentiation by regulating numerous physiological and biochemical processes at the cellular level. In addition to their roborative effect, their essential role in plant stress responses has been also reported. However, the positive effect may depend on the fine-tuning of polyamine metabolism, which influences the production of free radicals and/or signalling molecules. In the present study, 0.3 mM hydroponic putrescine treatment was tested in wheat, maize, and rice in order to reveal differences in their answers and highlight the relation of these with polyamine metabolism. In the case of wheat, the chlorophyll content and the actual quantum yield increased after putrescine treatment, and no remarkable changes were detected in the stress markers, polyamine contents, or polyamine metabolism-related gene expression. Although, in maize, the actual quantum yield decreased, and the root hydrogen peroxide content increased, no other negative effect was observed after putrescine treatment due to activation of polyamine oxidases at enzyme and gene expression levels. The results also demonstrated that after putrescine treatment, rice with a higher initial polyamine content, the balance of polyamine metabolism was disrupted and a significant amount of putrescine was accumulated, accompanied by a detrimental decrease in the level of higher polyamines. These initial differences and the putrescine-induced shift in polyamine metabolism together with the terminal catabolism or back-conversion-induced release of a substantial quantity of hydrogen peroxide could contribute to oxidative stress observed in rice.

A new approach to understanding the role of gasotransmitters in the development of chronic generalized periodontitis

Relevance. Recent studies investigating the role of the microbial gaseous substances (O2, N2, CO2, CH4, NO, CO, H2S) indicate not only in the regulation of the host's metabolic activity and the functioning of its nervous system, in particular but also their participation the pathogenesis of some diseases. However, there is scarce data in the national and international literature on the production of gas signaling molecules by the oral microbiota (Streptococcus spp. and Staphylococcus spp.) and the changes in the gas composition during the development of chronic inflammatory periodontal diseases.Material and methods. The study included 69 people. The main group included 36 patients aged 35 to 67 years with clinically confirmed moderate chronic generalized periodontitis. The control group included 33 patients aged 27 to 55 without periodontal disease. The samples from the back of the tongue were the study material. The gas chromatography determined the production of gas signaling molecules using the Khromatek-crystal 5000.2 device. The measurement of the amount of released gases was in % (for O2, N2) and ppm (0.001 mg/mL) for other gas molecules (CO2, CH4, NO, CO, H2S).Results. The metabolic activity of streptococci only for the production of NO (p = 0.002) and CO (p = 0.008) appeared to have a statistically significant difference. In periodontal inflammation, there was practically no NO emission by Streptococci spp., and the concentration of CO was ten times higher than in the group of healthy individuals. The difference in the number of other signaling gas molecules was not statistically significant (p &gt; 0.05) in healthy people and patients with chronic generalized periodontitis.In the production of gasotransmitters among Staphylococcus spp., N2 production (p = 0.007, increasing in the comparison group) was statistically significantly different. As in the streptococcal sampling, the amount of CO significantly increased in periodontal inflammation. Certain species of staphylococci showed a significant decrease in the production of the entire gas molecule range in the main group. At the same time, unlike Streptococcus spp., Staphylococcus spp. absorbed a much higher amount of nitric oxide in chronic periodontitis.Conclusion. In patients with chronic generalized periodontitis and inflammation, the oral microbiota is poorly active and produces a low concentration of gasotransmitters, so they cannot participate in inflammatory process reduc-tion, thereby contributing to the progression of the disease.

A brainstem–hypothalamus neuronal circuit reduces feeding upon heat exposure

Empirical evidence suggests that heat exposure reduces food intake. However, the neurocircuit architecture and the signalling mechanisms that form an associative interface between sensory and metabolic modalities remain unknown, despite primary thermoceptive neurons in the pontine parabrachial nucleus becoming well characterized1. Tanycytes are a specialized cell type along the wall of the third ventricle2 that bidirectionally transport hormones and signalling molecules between the brain’s parenchyma and ventricular system3–8. Here we show that tanycytes are activated upon acute thermal challenge and are necessary to reduce food intake afterwards. Virus-mediated gene manipulation and circuit mapping showed that thermosensing glutamatergic neurons of the parabrachial nucleus innervate tanycytes either directly or through second-order hypothalamic neurons. Heat-dependent Fos expression in tanycytes suggested their ability to produce signalling molecules, including vascular endothelial growth factor A (VEGFA). Instead of discharging VEGFA into the cerebrospinal fluid for a systemic effect, VEGFA was released along the parenchymal processes of tanycytes in the arcuate nucleus. VEGFA then increased the spike threshold of Flt1-expressing dopamine and agouti-related peptide (Agrp)-containing neurons, thus priming net anorexigenic output. Indeed, both acute heat and the chemogenetic activation of glutamatergic parabrachial neurons at thermoneutrality reduced food intake for hours, in a manner that is sensitive to both Vegfa loss-of-function and blockage of vesicle-associated membrane protein 2 (VAMP2)-dependent exocytosis from tanycytes. Overall, we define a multimodal neurocircuit in which tanycytes link parabrachial sensory relay to the long-term enforcement of a metabolic code.

Review of quorum-quenching probiotics: A promising non-antibiotic-based strategy for sustainable aquaculture.

The emergence of antibiotic-resistant bacteria (ARBs) and genes (ARGs) in aquaculture underscores the urgent need for alternative veterinary strategies to combat antimicrobial resistance (AMR). These measures are vital to reduce the likelihood of entering a post-antibiotic era. Identifying environmentally friendly biotechnological solutions to prevent and treat bacterial diseases is crucial for the sustainability of aquaculture and for minimizing the use of antimicrobials, especially antibiotics. The development of probiotics with quorum-quenching (QQ) capabilities presents a promising non-antibiotic strategy for sustainable aquaculture. Recent research has demonstrated the effectiveness of QQ probiotics (QQPs) against a range of significant fish pathogens in aquaculture. QQ disrupts microbial communication (quorum sensing, QS) by inhibiting the production, replication, and detection of signalling molecules, thereby reducing bacterial virulence factors. With their targeted anti-virulence approach, QQPs have substantial promise as a potential alternative to antibiotics. The application of QQPs in aquaculture, however, is still in its early stages and requires additional research. Key challenges include determining the optimal dosage and treatment regimens, understanding the long-term effects, and integrating QQPs with other disease control methods in diverse aquaculture systems. This review scrutinizes the current literature on antibiotic usage, AMR prevalence in aquaculture, QQ mechanisms and the application of QQPs as a sustainable alternative to antibiotics.

N- acyl homoserine lactones (AHLs) type signal molecules produced by rhizobacteria associated with plants that growing in a metal(oids) contaminated soil: A catalyst for plant growth

The present study explores the potential of rhizobacteria isolated from Baccharis linearis and Solidago chilensis in metal(loid)-contaminated soil for producing N-acyl-homoserine lactones (AHLs)-type signal molecules and promoting plant growth. A total of 42 strains were isolated, four demonstrating the production of AHL-type signal molecules. Based on 16S rRNA gene sequencing analyses and MALDI-TOF analyses, these four isolates were identified as belonging to the Pseudomonas genus, specifically P. brassicacearum, P. frederickberguensis, P. koreensis, and P. orientalis. The four AHL-producing strains were evaluated for metal(loid)s tolerance, their plant growth promotion traits, AHL quantification, and their impact on in vitro Lactuca sativa plant growth.The study found that four strains exhibited high tolerance to metal(loid)s, particularly As, Cu, and Zn. Additionally, plant growth-promoting traits were detected in AHL-producing bacteria, such as siderophore production, ammonia production, ACC deaminase activity, and P solubilization. Notably, AHL production varied among strains isolated from B. linearis, where C7-HSL and C9-HSL signal molecules were detected, and S. chilensis, where only C7-HSL signal molecules were observed. In the presence of copper, the production of C7-HSL and C9-HSL significantly decreased in B. linearis isolates, while in S. chilensis isolates, C7-HSL production was inhibited. Further, when these strains were inoculated on lettuce seeds and in vitro plants, a significant increase in germination and plant growth was observed. Mainly, the inoculation of P. brassicacearum and P. frederickberguensis led to extensive root hair development, significantly increasing length and root dry weight.Our results demonstrate that rhizospheric strains produce AHL molecules and stimulate plant growth, primarily through root development. However, the presence of copper reduces the production of these molecules, potentially affecting the root development of non-metalloid tolerant plants such as S. chilensis, which would explain its low population in this hostile environment.

Phenolic Compounds from Ocimum basilicum Revealed as Antibacterial by Experimental and Computational Screening‐Based Studies against Oral Infections

Dental infections are initiated by Streptococcus sanguinis and Streptococcus mutans through the biofilm formation. In streptococcal, the ComA enzyme catalyzes the first step to produce signalling molecules in quorum sensing that influence biofilm formation. Ocimum basilicum is one of the natural sources which is potential for antibacterial agent. This study is aimed to isolate phenolic compounds from O. basilicum leaves with antibacterial activity against oral pathogens by experimental and computational screening studies. Isolation of phenolic compounds 1–4 was carried out by bioactivity guided using column chromatography. Methylparaben (1), methyl protocatechuate (2), caffeic acid (3), and methyl caffeate (4) were characterized by 1D and 2D‐NMR. The antibacterial activity was tested by disk diffusion, microdilution methods. 1 (625 μg·mL−1) provided moderate activity, and 2 (156.3 μg·mL−1) provided strong activity against S. mutans. 3 (125 μg·mL−1) and 4 (312.5 μg·mL−1) provided strong activity against S. sanguinis. In addition, phenolic compounds and their derivatives were predicted against ComA using Autodock 4.0 tools. The activity correlated positively with in silico tests against ComA where 2 (−7.69 kcal·mol−1) had a stronger binding affinity than 1 (−6.64 kcal·mol−1). 3 (−6.86 kcal·mol−1) provided a slightly stronger bond strength than 4 (−6.65 kcal·mol−1). The strongest binding affinity of hydroxybenzoic acid derivatives is 3,5‐dihydroxybenzoic acid (−8.10 kcal·mol−1). In addition, the strongest binding affinity of hydroxycinnamic acid derivatives is chlorogenic acid (−9.16 kcal·mol−1). The pharmacokinetics were predicted by ADMET analysis, and methyl caffeate (4) showed the best potential as a drug compound. The conclusion is that phenolic compounds isolated from O. basilicum have potential as natural antibacterials. In silico tests also showed the relationship between the structure and activity by the presence of the hydroxyl group in hydroxybenzoic acid derivatives and the presence of an alkyl group in the unsaturated side chain in hydroxycinnamic acid derivatives.

Fatty Acid Metabolism: A New Perspective in Breast Cancer Precision Therapy.

Breast cancer has a special tumor microenvironment compared to other solid tumors, which is usually surrounded by a large number of adipocytes that can produce and secrete fatty acids and adipokines. Adipocytes have a remodeling effect on breast cancer lipid metabolism, while fatty acids and lipid droplets can make breast cancer cells more aggressive. Lipid metabolism, especially the synthesis of fatty acids, is an important cellular process for membrane biosynthesis, energy storage, and signal molecule production. Therefore, blocking the lipid supply to cancer cells or changing the lipid composition has an important impact on the signal transmission and cell proliferation of cancer cells. Alterations in lipid availability can also affect cancer cell migration, induction of angiogenesis, metabolic symbiosis, evasion of immune surveillance, and cancer drug resistance. Fatty acid synthesis and metabolism have received extensive attention as potential targets for cancer therapy, and studies on modulating the tumor lipid microenvironment to improve the sensitivity of antitumor drugs have also been discussed; however, strategies to target these processes have not been translated into clinical practice.

Modeling downstream impact of a quorum sensing system of Pseudomonas aeruginosa in colony spreading

A single bacterial colony typically consists of two or more individual cells. To further growth, the cells within the colony need to coordinate through Quorum Sensing (QS), which serves as a communication mechanism between cells. The Quorum Sensing signalling system in Pseudomonas aeruginosa is known to involve multiple control components, notably the las and rhl systems. The las system controls the rhl system in a hierarchical signalling cascade, and the rhl system regulates certain gene expressions, including the rhlA and rhlB genes. Transcription of rhlA and rhlB results in the production of the enzyme rhamnosyltransferase, which leads to the biosurfactant production identified as rhamnolipids. In this paper, we investigate how the las system controls the rhl system to influence rhamnolipids production. We illustrate how the pulsed production of signal molecules in the las system affects the rhl system, leading to an increase in rhamnolipids concentration. Rhamnolipids play a crucial role in bacterial spreading. We employ a simple symmetric diffusion model to simulate colony spreading and demonstrate how bacteria spread from the centre of the colony. Our findings shed light on the interaction between the las and rhl systems, which may enable cells to trigger rhamnolipids production at the edge of the bacterial colony.

From Pain Relief to Cancer Defense: The Promise of NSAIDs

NSAIDs (Non-Steroidal Anti-inflammatory Drugs) are commonly used to treat various types of pain and inflammation. In recent decades, extensive scientific research has been conducted to examine the use of NSAIDs in the treatment and prevention of cancer. Chronic inflammation has been linked to various cancer types, suggesting that prolonged inflammation can promote genetic mutations and accelerate their accumulation within cells. The COX pathway, short for Cyclooxygenase pathway, is a critical biochemical pathway in the human body involved in the production of important signaling molecules called prostaglandins. Key factors like COX enzymes and cytokines are important in the development and progression of inflammation-induced cancer. Angiogenesis occurs during inflammation, and it plays a major role in cancer development and metastasis. NSAIDs inhibit this process, which may also contribute to their anticancer effects. This review highlights the potential of NSAIDs, particularly aspirin, ibuprofen, and celecoxib, to influence various aspects of tumor behavior. Although promising, further rigorous studies are needed to establish their clinical efficacy and safety in diverse cancer scenarios. The use of NSAIDs as adjunctive therapies along with conventional treatments presents a promising avenue for enhancing cancer management strategies.

Paradigm shift: Bacterial quorum sensing and possible control targets

QS Designates a cell-to-cell communication process that enables bacteria to collectively modify their behaviour in response to changes in the cell density and species composition of the surrounding microbial community. These processes involve the production, release and group-wide detection of extracellular signalling molecules, which are generically called Autoinducers (AIs). It controls various genes which are responsible for various phenotypes like bioluminescence, the secretion of virulence factors, and the formation of biofilms in bacteria. Quorum quenching inhibits QS and the substances that inhibit it are called quorum sensing inhibitors. Several chemical compounds and enzymes mediate inhibition of QS, such as, lactonases, acylases and oxidoreductases. Other than these, there are some non-enzymatic methods for quorum quenching and also some plant phytochemicals have been found to inhibit it. Blocking of QS by QS Inhibition (QSI) may play an important role to disrupt biofilm formation in a device associated infection and chronic drug resistant infection. More researches are required in this area related with QS and QSI. However, some chemicals have been found to be mimicking the quorum sensing AIs activities like serotonin and rosmaric acid.

Ultrabright organic fluorescent probe for quantifying the dynamics of cytosolic/nuclear lipid droplets

Lipid droplets (LDs) are extremely active organelles that play a crucial role in energy metabolism, membrane formation, and the production of lipid-derived signaling molecules by regulating lipid storage and release. Nevertheless, directly limited by the lack of superior fluorescent probes, studies of LDs dynamic motion velocity have been rarely reported, especially for nuclear LDs. Herein, a novel organic fluorescent probe Lipi-Bright has been rationally developed based on bridged cyclization of distyrylbenzene. The fully ring-fused molecule structure endows the probe with high photostability. Moreover, this new fluorescent probe displays the features of excellent LDs staining specificity as well as ultrahigh fluorescence brightness. Lipi-Bright labeled LDs was dozens of times brighter than representative probes BODIPY 493/503 or Nile Red. Consequently, by in-situ time-lapse fluorescence imaging, the dynamics of LDs have been quantitatively studied. For instance, the velocities of cytosolic LDs (37 ± 15 nm/s) are found to be obviously faster than those of nuclear LDs (24 ± 4 nm/s), and both the cytosolic LDs and the nuclear LDs would be moved faster or slower depend on the various stimulations. Overall, this work providing plentiful information on LDs dynamics will greatly facilitate the in-depth investigation of lipid metabolism.

Natural silencing of quorum-sensing activity protects Vibrio parahaemolyticus from lysis by an autoinducer-detecting phage.

Quorum sensing (QS) is a chemical communication process that bacteria use to track population density and orchestrate collective behaviors. QS relies on the production, accumulation, and group-wide detection of extracellular signal molecules called autoinducers. Vibriophage 882 (phage VP882), a bacterial virus, encodes a homolog of the Vibrio QS receptor-transcription factor, called VqmA, that monitors the Vibrio QS autoinducer DPO. Phage VqmA binds DPO at high host-cell density and activates transcription of the phage gene qtip. Qtip, an antirepressor, launches the phage lysis program. Phage-encoded VqmA when bound to DPO also manipulates host QS by activating transcription of the host gene vqmR. VqmR is a small RNA that controls downstream QS target genes. Here, we sequence Vibrio parahaemolyticus strain O3:K6 882, the strain from which phage VP882 was initially isolated. The chromosomal region normally encoding vqmR and vqmA harbors a deletion encompassing vqmR and a portion of the vqmA promoter, inactivating that QS system. We discover that V. parahaemolyticus strain O3:K6 882 is also defective in its other QS systems, due to a mutation in luxO, encoding the central QS transcriptional regulator LuxO. Both the vqmR-vqmA and luxO mutations lock V. parahaemolyticus strain O3:K6 882 into the low-cell density QS state. Reparation of the QS defects in V. parahaemolyticus strain O3:K6 882 promotes activation of phage VP882 lytic gene expression and LuxO is primarily responsible for this effect. Phage VP882-infected QS-competent V. parahaemolyticus strain O3:K6 882 cells lyse more rapidly and produce more viral particles than the QS-deficient parent strain. We propose that, in V. parahaemolyticus strain O3:K6 882, constitutive maintenance of the low-cell density QS state suppresses the launch of the phage VP882 lytic cascade, thereby protecting the bacterial host from phage-mediated lysis.