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Lake Nansi, primarily dominated by macrophytes, faces threats from heavy metals and antibiotics due to human activity. This study investigated sediment dissolved organic matter (SDOM) characteristics and complexation of lead (Pb) and tetracycline (TC) in barren zone (BZ) and submerged macrophytes zone (PZ). Additionally, a microbial degradation experiment was conducted to examine its impact on the regional variations in complexation. SDOM abundance and protein-like materials in PZ was significantly greater than in BZ, indicating a probable contribution from the metabolism and decomposition of submerged macrophytes. Both zones exhibited a higher affinity of SDOM for Pb compared to TC, with all four components participating in Pb complexation. Protein-like materials in PZ had a higher binding ability (LogKPb=4.19 ± 1.07, LogKTC=3.89 ± 0.67) than in BZ (LogKPb=3.98 ± 0.61, LogKTC=3.69 ± 0.13), suggesting a potential presence of organically bound Pb and TC due to the higher abundance of protein-like materials in PZ. Although microbial communities differed noticeably, the degradation patterns of SDOM were similar in both zones, affecting the binding ability of SDOM in each. Notably, the fulvic-like component C4 emerged as the dominant binding material for both Pb and TC in both zones. Degradation might increase the amount of organically bound TC due to the increase in the LogKTC.
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Biodegradación Ambiental , Sedimentos Geológicos , Plomo , Tetraciclina , Contaminantes Químicos del Agua , Plomo/química , Plomo/metabolismo , Tetraciclina/química , Tetraciclina/metabolismo , Sedimentos Geológicos/microbiología , Sedimentos Geológicos/química , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Antibacterianos/química , Antibacterianos/metabolismoRESUMEN
Anisakis can cause Anisakiasis in humans if raw or undercooked fish is consumed. Symptoms of infection may include vomiting, acute abdominal symptoms, or allergies. In this study, we collected 187 commercially available marine fish from the Yellow Sea, East China Sea, and South China Sea. Among them, 79 were found positive containing 520 Anisakis worms. The average prevalence rate was found 42% in this investigation. Ninety-two worms from different sea areas were selected and analyzed for identification, revealing the presence of five different species, which are Anisakis pegreffii, Hysterothylacium aduncum, Hysterothylacium zhoushanense, Hysterothylacium amoyense, and Hysterothylacium sp. In the meta-analysis, three databases: PubMed, CNKI, and BaiduXueshu were searched for surveys on the prevalence of Anisakis in Chinese waters from January 2000 to December 2023. A total of 26 studies were included in this analysis of which 25 publications were retrieved from different databases and one being the present study. The pooled prevalence of Anisakis was 45% among commercially available marine fish. Variances in the prevalence of Anisakis were noted among the four seas, with the highest rates in the East China Sea and the Bohai Sea, reaching 53% [0.38; 0.68] and 49% [0.36; 0.62], respectively. The Prevalence of Anisakis infection was significantly higher in astern parts such as Liaoning, Shanghai, and Zhejiang. Analysis of the host fish subgroups revealed that the orders of Anguilliformes, Scombriformes, and Gadiformes had high rates of infection. These findings suggest a significant prevalence of Anisakis, posing an increasing risk of infection for individuals. This study provides impactful information for implementing preventative measures against Anisakis.
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Nanotechnology has emerged as a promising solution for tackling antibiotic resistance in monogastric animals, providing innovative methods to enhance animal health and well-being. This review explores the novel use of nanotechnology-based nanomaterials as substitutes for antibiotics in monogastric animals. With growing global concerns about antibiotic resistance and the need for sustainable practices in animal husbandry, nanotechnology offers a compelling avenue to address these challenges. The objectives of this review are to find out the potential of nanomaterials in improving animal health while reducing reliance on conventional antibiotics. We examine various forms of nanomaterials and their roles in promoting gut health and also emphasize fresh perspectives brought by integrating nanotechnology into animal healthcare. Additionally, we delve into the mechanisms underlying the antibacterial properties of nanomaterials and their effectiveness in combating microbial resistance. By shedding light on the transformative role of nanotechnology in animal production systems. This review contributes to our understanding of how nanotechnology can provide safer and more sustainable alternatives to antibiotics.
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Background: Anisakis are globally distributed, marine parasitic nematodes that can cause human health problems, including symptoms such as vomiting, acute diarrhea, and allergic reactions. As parasitic nematodes that primarily affect the patient's digestive tract, intestinal helminths can interact directly with the host microbiota through physical contact, chemicals, or nutrient competition. It is widely accepted that the host microbiota plays a crucial role in the regulation of immunity. Materials and methods: Nematodes collected from the abdominal cavity of marine fish were identified by molecular biology and live worms were artificially infected in rats. Infection was determined by indirect ELISA based on rat serum and worm extraction. Feces were collected for 16S rDNA-based analysis of microbiota diversity. Results: Molecular biology identification based on ITS sequences identified the collected nematodes as A. pegreffii. The success of the artificial infection was determined by indirect ELISA based on serum and worm extraction from artificially infected rats. Microbiota diversity analysis showed that a total of 773 ASVs were generated, and PCoA showed that the infected group was differentiated from the control group. The control group contained five characterized genera (Prevotellaceae NK3B31 group, Turicibacter, Clostridium sensu stricto 1, Candidatus Stoquefichus, Lachnospira) and the infected group contained nine characterized genera (Rodentibacter, Christensenella, Dubosiella, Streptococcus, Anaeroplasma, Lactococcus, Papillibacter, Desulfovibrio, Roseburia). Based on the Wilcoxon test, four processes were found to be significant: bacterial secretion system, bacterial invasion of epithelial cells, bacterial chemotaxis, and ABC transporters. Conclusion: This study is the first to analyze the diversity of the intestinal microbiota of rats infected with A. pegreffii and to determine the damage and regulation of metabolism and immunity caused by the infection in the rat gut. The findings provide a basis for further research on host-helminth-microbe correlationships.
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An essential research area for scientists is the development of high-performing, inexpensive, non-toxic antibacterial materials that prevent the transfer of bacteria. In this study, pure Bi2WO6 and Bi2WO6/MWCNTs nanocomposite were prepared by hydrothermal method. A series of characterization results by using XRD FTIR, Raman, FESEM, TEM, and EDS analyses, reveal the formation of orthorhombic nanoflakes Bi2WO6 by the addition of NaOH and pH adjustment to 7. Compared to pure Bi2WO6, the Bi2WO6/MWCNTs nanocomposite exhibited that CNTs are efficiently embedded into the structure of Bi2WO6 which results in charge transfer between metal ion electrons and the conduction or valence band of Bi2WO6 and MWCNTs and result in shifting to longer wavelength as shown in UV-visible and PL. The results confirmed that MWCNTs are stuck to the surface of the microflowers, and some of them embedded inside the Bi2WO6 nanoflakes without affecting the structure of Bi2WO6 nanoflakes as demonstrated by TEM. In addition, Pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite were tested against P. mirabilis and S. mutans., confirming the effect of addition MWCNTs materials had better antibacterial activity in opposition to both bacterial strains than pure Bi2WO6. Besides, pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite tested for cytotoxicity against lung MTT test on Hep-G2 liver cancer cells, and flow-cytometry. Results indicated that pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite have significant anti-cancer efficacy against Hep-G2 cells in vitro. In addition, the findings demonstrated that Bi2WO6 and Bi2WO6/MWCNTs triggered cell death via increasing ROS. Based on these findings, it appears that pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite have the potential to be developed as nanotherapeutics for the treatment of bacterial infections, and liver cancer.
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Antibacterianos , Antineoplásicos , Bismuto , Nanocompuestos , Compuestos de Tungsteno , Nanocompuestos/química , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Bismuto/química , Bismuto/farmacología , Compuestos de Tungsteno/química , Compuestos de Tungsteno/farmacología , Nanotubos de Carbono/química , Pruebas de Sensibilidad Microbiana , Supervivencia Celular/efectos de los fármacos , Células Hep G2RESUMEN
Protozoa exert a serious global threat of growing concern to human, and animal, and there is a need for the advancement of novel therapeutic strategies to effectively treat or mitigate the impact of associated diseases. Omega polyunsaturated fatty acids (ω-PUFAs), including Omega-3 (ω-3) and omega-6 (ω-6), are constituents derived from various natural sources, have gained significant attention for their therapeutic role in parasitic infections and a variety of essential structural and regulatory functions in animals and humans. Both ω-3 and ω-6 decrease the growth and survival rate of parasites through metabolized anti-inflammatory mediators, such as lipoxins, resolvins, and protectins, and have both in vivo and in vitro protective effects against various protozoan infections. The ω-PUFAs have been shown to modulate the host immune response by a commonly known mechanism such as (inhibition of arachidonic acid (AA) metabolic process, production of anti-inflammatory mediators, modification of intracellular lipids, and activation of the nuclear receptor), and promotion of a shift towards a more effective immune defense against parasitic invaders by regulation the inflammation like prostaglandins, leukotrienes, thromboxane, are involved in controlling the inflammatory reaction. The immune modulation may involve reducing inflammation, enhancing phagocytosis, and suppressing parasitic virulence factors. The unique properties of ω-PUFAs could prevent protozoan infections, representing an important area of study. This review explores the clinical impact of ω-PUFAs against some protozoan infections, elucidating possible mechanisms of action and supportive therapy for preventing various parasitic infections in humans and animals, such as toxoplasmosis, malaria, coccidiosis, and chagas disease. ω-PUFAs show promise as a therapeutic approach for parasitic infections due to their direct anti-parasitic effects and their ability to modulate the host immune response. Additionally, we discuss current treatment options and suggest perspectives for future studies. This could potentially provide an alternative or supplementary treatment option for these complex global health problems.
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Ácidos Grasos Omega-3 , Enfermedades Parasitarias , Infecciones por Protozoos , Animales , Humanos , Ácidos Grasos Omega-3/uso terapéutico , Ácidos Grasos Insaturados , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Infecciones por Protozoos/tratamiento farmacológico , Enfermedades Parasitarias/tratamiento farmacológicoRESUMEN
The objective of the study was to evaluate the performance of Pistia stratiotes for treatment of domestic wastewater in a free surface water flow constructed wetland. The objective of the study was to evaluate contaminants removal efficiency of the constructed wetland vegetated with P. stratiotes in treatment of domestic wastewater against Hydraulic retention time (HRT) of 10, 20 and 30 days was investigated. This asks for newer and efficient low-cost nature-based water treatment system which along with cost takes into consideration the sustainability of the ecosystem. Five constructed wetland setups improved the wastewater quality and purify it significantly by reducing the TDS by 83%, TSS by 82%, BOD by 82%, COD by 81%, Chloride by 80%, Sulfate by 77%, NH3 by 84% and Total Oil and Grease by 74%. There was an increase in pH of about 11.9%. Color and odor of wastewater was also improved significantly and effectively. It was observed that 30 days' HRT was optimum for the treatment of domestic wastewater. The final effluent was found to be suitable as per national environmental quality standards and recycled for watering plants and crop irrigation but not for drinking purposes. The treatment in constructed wetland system was found to be economical, as the cost of construction only was involved and operational and maintenance cost very minimal. Even this research was conducted on the sole purpose of commuting the efficiency of pollutant removal in short span time.
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Araceae , Purificación del Agua , Aguas Residuales , Humedales , Ecosistema , Eliminación de Residuos LíquidosRESUMEN
Poultry production occupies an important place in the economy of any country. High broiler production in recent years has badly affected its profitability due to bad feed quality, excessive use of chemotherapeutic agents, emergence of diverse pathogens, and the deficiencies in management practices during rearing cycle. Microbiological improvement of the meat quality using potential probiotics can be beneficial for broiler farming. Present study was initiated to isolate chicken gastrointestinal tract (GIT) bacteria with probiotic potential. To isolate probiotics from chicken gut, alimentary canal of chickens of known sizes and ages was suspended in ringers soln. Under shaking conditions for overnight followed by serial dilutions of ringers soln. Bacterial isolates were analyzed via growth curve analysis, biochemical testing using RapID™ NF Plus Panel kit, molecular characterization, antimicrobial activity assay, antibiotic sensitivity assay, GIT adherence assay, bile salt and gastric acid resistant assay, and cholesterol assimilation assay. Four bacteria isolated in present study were identified as Limosilactobacillus antri strain PUPro1, Lactobacillus delbrueckii strain PUPro2, Lacticaseibacillus casei strain PUPro3, and Ligilactobacillus salivarius strain PUPro4. L. delbrueckii strain PUPro2 grew extremely fast. All isolates exhibited exceptional resistance to increasing concentrations of NaCl and bile salts with value of p >0.5. L. delbrueckii strain PUPro2 adhered to chicken ileum epithelial cells and demonstrated the highest viable counts of 320 colony forming units (CFUs). Antagonistic action was found in all isolates against P. aeruginosa, B. subtilis, B. proteus, and S. aureus, with value of p >0.5. Antibiotic susceptibility testing showed sensitivity to all the antibiotics used. Cholesterol assimilation was detected in all bacteria, with values ranging from 216.12 to 192.2 mg/dL. All isolates exhibited γ-hemolysis. In future, these bacteria might be tested for their impact on broilers meat quality and growth and can be recommended for their use as supplements for broilers diet with positive impact on poultry production.
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Eukaryotic translation initiation factors have long been recognized for their critical roles in governing the translation of coding RNAs into peptides/proteins. However, whether they harbor functional activities at the post-translational level remains poorly understood. Here, we demonstrate that eIF3f1 (eukaryotic translation initiation factor 3 subunit f1), which encodes an archetypal deubiquitinase, is essential for the antimicrobial innate immune defense of Drosophila melanogaster. Our in vitro and in vivo evidence indicate that the immunological function of eIF3f1 is dependent on the N-terminal JAMM (JAB1/MPN/Mov34 metalloenzymes) domain. Mechanistically, eIF3f1 physically associates with dTak1 (Drosophila TGF-beta activating kinase 1), a key regulator of the IMD (immune deficiency) signaling pathway, and mediates the turnover of dTak1 by specifically restricting its K48-linked ubiquitination. Collectively, these results provide compelling insight into a noncanonical molecular function of a translation initiation factor that controls the post-translational modification of a target protein.
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Proteínas de Drosophila , Drosophila , Animales , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Inmunidad Innata , Factores de Iniciación de Péptidos , Transducción de SeñalRESUMEN
Personalized medicine has witnessed remarkable progress with the emergence of RNA therapy, offering new possibilities for the treatment of various diseases, and in particular in the context of cardiovascular disease (CVD). The ability to target the human genome through RNA manipulation offers great potential not only in the treatment of cardiac pathologies but also in their diagnosis and prevention, notably in cases of hyperlipidemia and myocardial infarctions. While only a few RNA-based treatments have entered clinical trials or obtained approval from the US Food and Drug Administration, the growing body of research on this subject is promising. However, the development of RNA therapies faces several challenges that must be overcome. These include the efficient delivery of drugs into cells, the potential for immunogenic responses, and safety. Resolving these obstacles is crucial to advance the development of RNA therapies. This review explores the newest developments in medical studies, treatment plans, and results related to RNA therapies for heart disease. Furthermore, it discusses the exciting possibilities and difficulties in this innovative area of research.
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The prevalence of organophosphate esters (OPEs) in the global environment is increasing, which aligns with the decline in the usage of polybrominated diphenyl ethers (PBDEs). PBDEs, a category of flame retardants, were banned and classified as persistent organic pollutants (POPs) through the Stockholm Convention due to their toxic and persistent properties. Despite a lack of comprehensive understanding of their ecological and health consequences, OPEs were adopted as replacements for PBDEs. This research aims to offer a comparative assessment of PBDEs and OPEs in various domains, specifically focusing on their persistence, bioaccumulation, and toxicity (PBT) properties. This study explored physicochemical properties (such as molecular weight, octanol-water partition coefficient, octanol-air partition coefficient, Henry's law constant, and vapor pressures), environmental behaviors, global concentrations in environmental matrices (air, water, and soil), toxicities, bioaccumulation, and trophic transfer mechanisms of both groups of compounds. Based on the comparison and analysis of environmental and toxicological data, we evaluate whether OPEs represent another instance of regrettable substitution and global contamination as much as PBDEs. Our findings indicate that the physical and chemical characteristics, environmental behaviors, and global concentrations of PBDEs and OPEs, are similar and overlap in many instances. Notably, OPE concentrations have even surged by orders of several magnitude compared to PBDEs in certain pristine regions like the Arctic and Antarctic, implying long-range transport. In many instances, air and water concentrations of OPEs have been increased than PBDEs. While the bioaccumulation factors (BAFs) of PBDEs (ranging from 4.8 to 7.5) are slightly elevated compared to OPEs (-0.5 to 5.36) in aquatic environments, both groups of compounds exhibit BAF values beyond the threshold of 5000 L/kg (log10 BAF > 3.7). Similarly, the trophic magnification factors (TMFs) for PBDEs (ranging from 0.39 to 4.44) slightly surpass those for OPEs (ranging from 1.06 to 3.5) in all cases. Metabolic biotransformation rates (LogKM) and hydrophobicity are potentially major factors deciding their trophic magnification potential. However, many compounds of PBDEs and OPEs show TMF values higher than 1, indicating biomagnification potential. Collectively, all data suggest that PBDEs and OPEs have the potential to bioaccumulate and transfer through the food chain. OPEs and PBDEs present a myriad of toxicity endpoints, with notable overlaps encompassing reproductive issues, oxidative stress, developmental defects, liver dysfunction, DNA damage, neurological toxicity, reproductive anomalies, carcinogenic effects, and behavior changes. Based on our investigation and comparative analysis, we conclude that substituting PBDEs with OPEs is regrettable based on PBT properties, underscoring the urgency for policy reforms and effective management strategies. Addressing this predicament before an exacerbation of global contamination is imperative.
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Retardadores de Llama , Éteres Difenilos Halogenados , Éteres Difenilos Halogenados/toxicidad , Éteres Difenilos Halogenados/análisis , Monitoreo del Ambiente , Organofosfatos/análisis , Agua/análisis , Retardadores de Llama/toxicidad , Retardadores de Llama/análisis , Octanoles , Ésteres/toxicidadRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0293477.].
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Vitamin A imbalance during pregnancy and lactation is a global public health concern with potentially negative consequences for fetuses and neonates. Inadequate vitamin A intake during this critical period can lead to anemia, weakened immune function, night blindness, and increased susceptibility to infections. Conversely, excessive intake of vitamin A can result in birth defects, hypercalcemia, and psychiatric symptoms. This review aims to identify risk factors contributing to vitamin A deficiency in pregnant women and its impact on maternal, fetal, and neonatal outcomes. It also examines the effects of high-dose vitamin A supplementation during pregnancy on offspring health. By analyzing existing literature and recommendations, the review emphasizes the significance of vitamin A in the development of various body systems and organs. It provides a comprehensive overview of the effects of vitamin A during pregnancy and lactation, encompassing deficiencies, excessive intake, and supplementation guidelines. The need for further research in this field is highlighted. In conclusion, maintaining a balanced vitamin A status is crucial during pregnancy to promote better outcomes for fetuses and newborns. Effective monitoring and intervention strategies are essential to address vitamin A deficiency and excess in pregnant women, thereby improving fetal and neonatal health.
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Complicaciones del Embarazo , Deficiencia de Vitamina A , Deficiencia de Vitamina D , Recién Nacido , Femenino , Embarazo , Humanos , Vitamina A/uso terapéutico , Vitaminas/uso terapéutico , Deficiencia de Vitamina A/tratamiento farmacológico , Deficiencia de Vitamina A/epidemiología , Complicaciones del Embarazo/epidemiología , Lactancia , Suplementos DietéticosRESUMEN
Nicotinamide adenine dinucleotide (NAD+) has recently attracted much attention due to its role in aging and lifespan extension. NAD+ directly and indirectly affects many cellular processes, including metabolic pathways, DNA repair, and immune cell activities. These mechanisms are critical for maintaining cellular homeostasis. However, the decline in NAD+ levels with aging impairs tissue function, which has been associated with several age-related diseases. In fact, the aging population has been steadily increasing worldwide, and it is important to restore NAD+ levels and reverse or delay these age-related disorders. Therefore, there is an increasing demand for healthy products that can mitigate aging, extend lifespan, and halt age-related consequences. In this case, several studies in humans and animals have targeted NAD+ metabolism with NAD+ intermediates. Among them, nicotinamide mononucleotide (NMN), a precursor in the biosynthesis of NAD+, has recently received much attention from the scientific community for its anti-aging properties. In model organisms, ingestion of NMN has been shown to improve age-related diseases and probably delay death. Here, we review aspects of NMN biosynthesis and the mechanism of its absorption, as well as potential anti-aging mechanisms of NMN, including recent preclinical and clinical tests, adverse effects, limitations, and perceived challenges.
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NAD , Mononucleótido de Nicotinamida , Humanos , Animales , Anciano , Mononucleótido de Nicotinamida/metabolismo , Envejecimiento , Longevidad , HomeostasisRESUMEN
BACKGROUND: Drosophila ubiquitin carboxy-terminal hydrolase L5 (Uch-L5) functions as a critical component of the 26S proteasome to mediate degradation of polyubiquitinated proteins. It was recently shown to modulate tissue/organ development by targeting the Smoothened protein in the hedgehog pathway. However, whether it plays a role in controlling organismal immune response remains largely unknown. METHODS: Reverse transcription plus quantitative polymerase chain reaction (RT-qPCR), dual-luciferase, and Western blot assays were used to explore the potential function of Uch-L5 in the innate immune regulation in cultured Drosophila S2 cells. Further genetic manipulations and bacterial infections were conducted to confirm the findings in vivo. RESULTS: Silencing of Uch-L5 antagonizes the immune deficiency (IMD) but not the Toll innate immune signaling both in vitro and in vivo. Moreover, Uch-L5 positively contributes to the Drosophila innate immune response via its N-terminal Uch domain, which is the catalytical triad executing its deubiquitinase activity. CONCLUSIONS: Our studies shed light on a novel function of the deubiquitinase Uch-L5 in governing the anti-microbial defense in Drosophila.
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Infecciones Bacterianas , Ubiquitina Tiolesterasa , Animales , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/metabolismo , Proteínas Hedgehog , Drosophila , Inmunidad Innata/genéticaRESUMEN
The current study was designed to analyze nutritional parameters and to characterize carbapenemase producing-Klebsiella pneumoniae isolates from bovine mastitic cow's milk. Out of 700 milk samples K. pneumoniae was identified by phenotypic and molecular techniques along with their antibiogram analysis and nutritional analysis was performed using the procedure of Association of Official Analytical Chemists. Carbapenemase-producing K. pneumoniae was detected by phenotypic CarbaNP test followed by molecular characterization of their associated resistant genes blaVIM, blaKPC, blaOXA-48, blaNDM, and blaIMP along with insertion sequence common region 1 (ISCR1) and integrons (Int1, Int2, and Int3) genes. Among nutritional parameters, fat content was observed (2.99%) followed by protein (2.78%), lactose (4.32%), and total solid (11.34%), respectively. The prevalence of K. pneumoniae among bovine mastitis was found 25.71%. Antibiogram analysis revealed that more effective antibiotics was ceftazidime (80%) followed by amikacin (72%), while highly resistant antibiotics was Fusidic acid (100%). Distribution of carbapenemase producer K. pneumoniae was found 44.4%. Among carbapenem resistant genes blaKPC was found 11.25%, blaVIM 2.75%, blaNDM 17.5%, and blaOXA-48 7.5%, while blaIMP gene was not detected. Furthermore, distribution of ISCR1 was found 40%, while integron 1 was found 61.2% followed by integron 2 (20%), and integron 3 (5%). In conclusion, the recent scenario of carbapenemase resistant K. pneumoniae isolates responsible for mastitis may affect not only the current treatment regime but also possess a serious threat to public health due to its food borne transmission and zoonotic potential.
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Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Klebsiella , Mastitis Bovina , Femenino , Animales , Bovinos , Klebsiella pneumoniae , Leche/metabolismo , Mastitis Bovina/genética , Proteínas Bacterianas/genética , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Antibacterianos/farmacología , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Elementos Transponibles de ADN , Pruebas de Sensibilidad Microbiana , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/genética , Infecciones por Klebsiella/veterinariaRESUMEN
Background: Urease belongs to the family of amid hydrolases with two nickel atoms in their core structure. On the basis of literature survey, this research work is mainly focused on the study of bis-Schiff base derivatives of benzyl phenyl ketone nucleus. Objective: Synthesis of benzyl phenyl ketone based bis-Schiff bases in search of potent urease inhibitors. Method: In the current work, bis-Schiff bases were synthesized through two steps reaction by reacting benzyl phenyl ketone with excess of hydrazine hydrate in ethanol solvent in the first step to get the desired hydrazone. In last, different substituted aromatic aldehydes were refluxed in catalytic amount of acetic acid with the desired hydrazone to obtain bis-Schiff base derivatives in tremendous yields. Using various spectroscopic techniques including FTIR, HR-ESI-MS, and 1H NMR spectroscopy were used to clarify the structures of the created bis-Schiff base derivatives. Results: The prepared compounds were finally screened for their in-vitro urease inhibition activity. All the synthesized derivatives (3-9) showed excellent to less inhibitory activity when compared with standard thiourea (IC50 = 21.15 ± 0.32 µM). Compounds 3 (IC50 = 22.21 ± 0.42 µM), 4 (IC50 = 26.11 ± 0.22 µM) and 6 (IC50 = 28.11 ± 0.22 µM) were found the most active urease inhibitors near to standard thiourea among the synthesized series. Similarly, compound 5 having IC50 value of 34.32 ± 0.65 µM showed significant inhibitory activity against urease enzyme. Furthermore, three compounds 7, 8, and 9 exhibited less activity with IC50 values of 45.91 ± 0.14, 47.91 ± 0.14, and 48.33 ± 0.72 µM respectively. DFT used to calculate frontier molecular orbitals including; HOMO and LUMO to indicate the charge transfer from molecule to biological transfer, and MEP map to indicate the chemically reactive zone suitable for drug action. The electron localization function (ELF), non-bonding orbitals, AIM charges are also calculated. The docking study contributed to the analysis of urease protein binding.
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Aspirin, also known as acetylsalicylic acid, is widely consumed as a pain reliever and an anti-inflammatory as well as anti-platelet agent. Recently, our studies using the animal model of Drosophila demonstrated that the dietary supplementation of aspirin renovates age-onset intestinal dysfunction and delays organismal aging. Nevertheless, it remains probable that aspirin plays functional roles in other biological activities, for instance antiviral defense reactions. Intriguingly, we observed that the replications of several types of viruses were drastically antagonized in Drosophila macrophage-like S2 cells with the addition of aspirin. Further in vivo experimental approaches illustrate that adult flies consuming aspirin harbor higher resistances to viral infections with respect to flies without aspirin treatment. Mechanistically, aspirin positively contributes to the Drosophila antiviral defense largely through mediating the STING (stimulator of interferon genes) but not the IMD (immune deficiency) signaling pathway. Collectively, our studies uncover a novel biological function of aspirin in modulating Drosophila antiviral immunity and provide theoretical bases for exploring new antiviral treatments in clinical trials.
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Drosophila , Virosis , Animales , Aspirina/farmacología , Aspirina/metabolismo , Inmunidad Innata , Antivirales/metabolismo , Suplementos Dietéticos , Drosophila melanogaster/metabolismoRESUMEN
SARS-CoV-2 vaccination promises to improve outcomes for patients with COVID-19 pneumonia (most notably those with advanced age and at high risk for severe disease). Here, we examine serum 25-Hydroxyvitamin D (25(OH)D) status and outcomes in both old (>70 years) and young vaccinated (n = 80) and unvaccinated (n = 91) subjects, who were hospitalized due to COVID-19 pneumonia in a single center (Connolly Hospital Dublin). Outcomes included ICU admission and mortality. Serum 25(OH)D levels were categorized as D30 (<30 nmol/L), D40 (30-49.99 nmol/L) and D50 (≥50 nmol/L). In multivariate analyses, D30 was independently associated with ICU admission (OR: 6.87 (95% CI: 1.13-41.85) (p = 0.036)) and mortality (OR: 24.81 (95% CI: 1.57-392.1) (p = 0.023)) in unvaccinated patients, even after adjustment for major confounders including age, sex, obesity and pre-existing diabetes mellitus. While mortality was consistently higher in all categories of patients over 70 years of age, the highest observed mortality rate of 50%, seen in patients over 70 years with a low vitamin D state (D30), appeared to be almost completely corrected by either vaccination, or having a higher vitamin D state, i.e., mortality was 14% for vaccinated patients over 70 years with D30 and 16% for unvaccinated patients over 70 years with a 25(OH)D level greater than 30 nmol/L. We observe that high mortality from COVID-19 pneumonia occurs in older patients, especially those who are unvaccinated or have a low vitamin D state. Recent vaccination or having a high vitamin D status are both associated with reduced mortality, although these effects do not fully mitigate the mortality risk associated with advanced age.