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γ-Aminobutyric acid (GABA) is one of the primary inhibitory neurotransmitters and encompasses 10–30% of the neurons in the CNS. Fundamentally, GABA is responsible for decreasing the nervous system activity by inhibiting the action potential and hence excitotoxicity of neurons. Owing to these neuroregulatory features, GABA has been known to be involved in numerous diseases such as schizophrenia, epilepsy, and other psychiatric conditions. Therefore, from a neuroanatomical as well as a pathological perspective, the visual localization and relative abundance research of neurotransmitters is of great importance. The intricacies of GABA release from neurons are still largely unknown; hence, it will be necessary to analyze endogenous GABA concentrations. Here, we synthesized nitrogen-doped carbon quantum dots (N-CQDs), which employ a turn-off mechanism to detect GABA in vivo. High-resolution transmission electron microscopy (HRTEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and energy-dispersive X-ray spectroscopy (EDX) have been used to verify the structural characteristics and size of the N-CQDs. Using the Stern–Volmer equation, UV–vis and fluorescence spectroscopies, and time-correlated single-photon counting (TCSPC), the mechanism of fluorescence quenching was thoroughly explained. Moreover, 0.16 μM was determined to be the N-CQD detection limit. Furthermore, exogenous GABA in human cell lines and endogenous GABA in the zebrafish forebrain (telencephalon) and midbrain (optic tectum) were both successfully detected by our sensor. Thus, this probe may be used as a competent nanosensor to detect comparative GABA levels among healthy and diseased animal models with GABA neurotransmitter imbalance and neurodegeneration. [ABSTRACT FROM AUTHOR]

The involvement of multiple antibiotic‐resistant gastrointestinal pathogens in diarrhea aggravates the disease condition uncontrollably. The current study aimed to find and develop a suitable formulation utilizing multiple natural components from known plant sources to augment the current therapeutic outcomes. The hydroethanolic extraction method was applied through boiling and fermentation on ancient observation‐based efficacious plant parts for developing the antidiarrheal polyherbal formulation AP‐01. An animal study model of diarrhea was used to evaluate the safety and efficacy of the formulation. The formulation was tested in vitro on four different multiple antibiotic‐resistant gastrointestinal pathogens collected from the national repository. The formulation depicted no cytotoxicity on normal gut cells and was efficacious at 10 ml/kg single dose in relieving symptoms of diarrhea by 79.71%, compared with the standard drug showing a reduction of symptoms by 83.01%. AP‐01 exhibited delayed gastric motility. The symptoms of diarrhea ceased to occur within 320.66 ± 5.05 minutes with AP‐01, whereas the standard drug took 308 ± 6.63 minutes. AP‐01 was found successful at a viable dosage regimen of 75 μl/ml v/v to 100 μl/ml v/v in inhibiting the growth of different pathogens from the Enterobacteriaceae family possessing resistance against several classes of antibiotics in culture media. Chemical analysis revealed different alkaloids, flavonoids, and polyphenols that probably work in unison through multiple modes of action to arrest diarrhea and inhibit pathogens simultaneously. These promising results shown by AP‐01 should evoke an effort to dive deep into research and development for better therapeutic formulations for infectious diarrhea by harvesting nature's arsenal. [ABSTRACT FROM AUTHOR]

The rapid evolution of drug resistance is one of the greatest health issues of the 21st century. There is an alarming situation to find new therapeutic strategies or candidate drugs to tackle ongoing multi-drug resistance development. The marine environment is one of the prime natural ecosystems on Earth, the majority of which is still unexplored, especially when it comes to the microbes. A wide variety of bioactive compounds have been obtained from a varied range of marine organisms; however, marine bacteria-produced bacteriocins are still undermined. Owing to the distinct environmental stresses that marine bacterial communities encounter, their bioactive compounds frequently undergo distinct adaptations that confer on them a variety of shapes and functions, setting them apart from their terrestrial counterparts. Bacterially produced ribosomally synthesized and posttranslationally modified peptides (RiPPs), known as bacteriocins, are one of the special interests to be considered as an alternative to conventional antibiotics because of their variety in structure and diverse potential biological activities. Additionally, the gut microbiome of marine creatures are a largely unexplored source of new bacteriocins with promising activities. There is a huge possibility of novel bacteriocins from marine bacterial communities that might come out as efficient candidates to fight against antibiotic resistance, especially in light of the growing pressure from antibiotic-resistant diseases and industrial desire for innovative treatments. The present review summarizes known and fully characterized marine bacteriocins, their evolutionary aspects, challenges, and the huge possibilities of unexplored novel bacteriocins from marine bacterial communities present in diverse marine ecosystems. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are considered a promising alternative to conventional antibiotics to fight against the rapid evolution of antibiotic resistance. Other than their potent antimicrobial properties, AMP-based vesicles can be used as efficient drug-delivery vehicles. In the present study, we synthesized and characterized a new cyclic AMP, consisting of all-hydrophobic cores with antimicrobial activity against S. aureus. Interestingly, CycP undergoes supramolecular self-assembly, and self-assembled CycP (sCycP) vesicles are characterized under an electron microscope; however, these vesicles do not display antimicrobial activity. Next, sCycP vesicles are used in combination with SXT (sulfamethoxazole–trimethoprim) vesicles to check the drug loading and delivery capacity of sCycP vesicles to bacterial cell membranes. Interestingly, sCycP vesicles showed synergistic action with SXT vesicles and resulted in a significant reduction in MIC against S. aureus. Further, electron microscopy confirmed the membrane-specific killing mechanism of SXT-loaded sCycP vesicles. Additionally, CycP showed high binding affinities with the β-lactamase of S. aureus, which was one of its possible antimicrobial mechanisms of action. Overall, the results suggested that CycP is a novel self-assembled dual-action cyclic AMP with non-cytotoxic properties that can be used alone as an AMP or a self-assembled drug delivery vehicle for antibiotics to combat S. aureus infections. [ABSTRACT FROM AUTHOR]

Hospital-acquired antibiotic-resistant pneumonia is one of the major causes of mortality around the world that pose a catastrophic threat. Pseudomonas aeruginosa is one of the most significant opportunistic pathogens responsible for hospital-acquired pneumonia and gained resistance to the majority of conventional antibiotics. There is an urgent need for antibiotic alternatives to control drug-resistant pneumonia and other related respiratory infections. In the present study, we explored the antibacterial potential of cineole in combination with homeopathic medicines against biofilm-forming drug-resistant P. aeruginosa. Out of 26 selected and screened homeopathic medicines, Hypericum Perforatum (HyPer) was found to eradicate biofilm-forming drug-resistant P. aeruginosa most effectively when used in combination with cineole. Interestingly, the synergistic action of HyPer and cineole was also found to be similarly effective against planktonic cells of P. aeruginosa. Further, the potential synergistic killing mechanisms of cineole and HyPer were determined by analyzing zeta membrane potential, outer membrane permeability, and DNA release from P. aeruginosa cells upon treatment with cineole and HyPer. Additionally, molecular docking analysis revealed strong binding affinities of hypericin (an active ingredient of HyPer) with the PqsA (a quorum sensing protein) of P. aeruginosa. Overall, our findings revealed the potential synergistic action of cineole and HyPer against biofilm-forming drug-resistant P. aeruginosa. Cineole and HyPer could be used in combination with other bronchodilators as inhalers to control the biofilm-forming drug-resistant P. aeruginosa. [ABSTRACT FROM AUTHOR]

This document explores the relationship between the gut microbiome, infection, and inflammation. It discusses the impact of respiratory infections like COVID-19 and tuberculosis on gut dysbiosis and the gut-lung axis. The document also examines the role of gut dysbiosis in chronic conditions such as cancer, diabetes, obesity, and inflammatory bowel disease. It further explores the involvement of the gut microbiota in biliary system diseases, liver inflammation, and Clostridioides difficile infection. The document concludes by discussing the potential of the gut microbiome as a biomarker in sepsis and its protective effect in children during COVID-19, as well as its role in disease progression in Type 2 diabetes patients. The document suggests that maintaining a healthy gut microbiome through probiotic enrichment may help reduce the incidence of these diseases. However, it is important to note that the claims made in the document are solely those of the authors and do not represent the views of the publisher or affiliated organizations. [Extracted from the article]