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La demanda de la sociedad respecto al cuidado de la salud y del ambiente es cada vez mayor, requiriéndose la evaluación de potenciales impactos negativos producidos por las prácticas agropecuarias, entre ellos la contaminación de los recursos naturales por el uso de agroquímicos. El objetivo de este trabajo fue evaluarla vulnerabilidad general a la contaminación de un acuífero libre localizado en la cuenca agrícola del Arroyo Las Conchas (Entre Ríos), que posee una superficie de 2.156,6 Km2 y alta densidad poblacional. Se utilizó el índice DRASTIC que se basa en la aplicación de siete parámetros hidrogeológicos, desarrollándose mapas para cada uno de ellos a partir del análisis de 82 fuentes de agua existentes en la cuenca y de la selección de 39 ubicadas en el acuífero libre. El acuífero libre se localiza superficialmente entre los 0,39 m y los 12 m y en presencia de suelos con buena capacidad de drenaje. La vulnerabilidad general a la contaminación fue moderada y presenta homogeneidad en la totalidad de la cuenca. La zona más vulnerable está situada en el extremo NE (próximo a María Grande), coincidente con zonas planas en el paisaje y de acumulación de agua, mientras que el área centro–sur presenta menor vulnerabilidad, coincidiendo con una zona de mayor profundidad del acuífero y de baja recarga. La información generada constituye una base para la gestión ambientaly el desarrollo de buenas prácticas agropecuarias.

Abstract Methotrexate (MTX), an efficient chemotherapy medication is used in treating various malignancies. However, the breast cancer cell line MDA-MB-231 has developed resistance to it due to low levels of the MTX transport protein, and reduced folate carrier (RFC), making it less effective against these cancer cells. Here we designed a very simple, biocompatible, and non-toxic amine-capped ZnO quantum dots to overcome the MTX resistance on the MDA-MB-231 breast cancer cell line. The QD was characterized by HRTEM, DLS EDX, FT-IR, UV–Vis, and Fluorescence spectroscopy. MTX loading onto the QD was confirmed through fluorescence and UV–Vis spectroscopy. Additionally, extensive confocal microscopic investigations were carried out to determine whether the MTX was successfully released on the MDA-MB-231 cell line. It was discovered that QD is a better pH-responsive delivery system than the previous ones because it successfully delivers MTX to the MDA-MB-231 at a higher rate on an acidic pH than it does at a physiological pH. QD also has anticancer activity and can eradicate cancer cells on its own. These factors make the QD to be an effective pH-responsive delivery system that can improve the efficacy of the medication in therapeutic diagnosis.

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.

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.

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.

[This corrects the article DOI: 10.1371/journal.pgen.1004749.].

The vast surface area of the respiratory system acts as an initial site of contact for microbes and foreign particles. The whole respiratory epithelium is covered with a thin layer of the airway and alveolar secretions. Respiratory secretions contain host defense peptides (HDPs), such as defensins and cathelicidins, which are the best-studied antimicrobial components expressed in the respiratory tract. HDPs have an important role in the human body’s initial line of defense against pathogenic microbes. Epithelial and immunological cells produce HDPs in the surface fluids of the lungs, which act as endogenous antibiotics in the respiratory tract. The production and action of these antimicrobial peptides (AMPs) are critical in the host’s defense against respiratory infections. In this study, we have described all the HDPs secreted in the respiratory tract as well as how their expression is regulated during respiratory disorders. We focused on the transcriptional expression and regulation mechanisms of respiratory tract HDPs. Understanding how HDPs are controlled throughout infections might provide an alternative to relying on the host’s innate immunity to combat respiratory viral infections.

Due to huge diversity and dynamic competition, the human gut microbiome produces a diverse array of antimicrobial peptides (AMPs) that play an important role in human health. The gut microbiome has an important role in maintaining gut homeostasis by the AMPs and by interacting with other human organs via established connections such as the gut–lung, and gut–brain axis. Additionally, gut AMPs play a synergistic role with other gut microbiota and antimicrobials to maintain gut homeostasis by fighting against multi-antibiotic resistance (MAR) bacteria. Further, conventional antibiotics intake creates a synergistic evolutionary pressure for gut AMPs, where antibiotics and gut AMPs fight synergistically against MAR. Overall, gut AMPs are evolving under a complex and highly synergistic co-evolutionary pressure created by the various interactions between gut microbiota, gut AMPs, and antibiotics; however, the complete mechanism is not well understood. The current review explores the synergistic action of gut AMPs and antibiotics along with possibilities to fight against MAR bacteria.

Pilocytic astrocytomas are typically grade I astrocytomas, only rarely progressing to anaplastic counterparts [1]. In the case of anaplastic pilocytic astrocytomas, some are associated with neurofibromatosis type 1 (NF1) [2], others are associated with radiation treatment [2], and the remainder appear de novo. These de novo tumours can be particularly challenging to distinguish from glioblastomas, which are grade IV and carry a worse prognosis. Here we report an unusual case of malignant transformation of a pilocytic astrocytoma in the absence of NF1 alterations or radiation treatment.

The Omicron variant of SARS-CoV-2 bears peptide sequence alterations that correlate with a higher infectivity than was observed in the original SARS-CoV-2 isolated from Wuhan, China. We analyzed the CendR motif of spike protein and performed in silico molecular docking with neuropilin-1 (Nrp1), a receptor–ligand interaction known to support infection by the original variant. Our analysis predicts conserved and slightly increased energetic favorability of binding for Omicron CendR:Nrp1. We propose that the viral spike:Nrp1 coreceptor pathway may contribute to the infectivity of the Omicron variant of SARS-CoV-2.

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]

In the lungs of infected individuals, the downstream molecular signaling pathways induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are incompletely understood. Here, we describe and examine predictions of a model in which NOTCH may represent a central signaling axis in lung infection in Coronavirus Disease 2019 (COVID-19). A pathway involving NOTCH signaling, furin, ADAM17, and ACE2 may be capable of increasing SARS-CoV-2 viral entry and infection. NOTCH signaling can also upregulate IL-6 and pro-inflammatory mediators induced to hyperactivation in COVID-19. Furthermore, if NOTCH signaling fails to turn down properly and stays elevated, airway regeneration during lung healing can be inhibited—a process that may be at play in COVID-19. With specific NOTCH inhibitor drugs in development and clinical trials for other diseases being conducted, the roles of NOTCH in all of these processes central to both infection and healing merit contemplation if such drugs might be applied to COVID-19 patients.

We explore the design of a smart inhaler with electrostatic sterilizer and propose the utilization of cationic amphiphilic peptides, independently or in conjunction with a bronchodilator, for COVID-19 patients to quickly improve wellbeing while maintaining a strategic distance to protect healthcare personnel from virus-containing aerosol or droplets during the process of inhalation.