Mice with Infectious Colitis Exhibit Linear Growth Failure and Subsequent Catch-Up Growth Related to Systemic Inflammation and IGF-1

In developing communities, intestinal infection is associated with poor weight gain and linear-growth failure. Prior translational animal models have focused on weight gain investigations into key contributors to linear growth failure have been lacking. We hypothesized that murine intestinal infection with Citrobacter-rodentium would induce linear-growth failure associated with systemic inflammation and suppressed serum levels of insulin-like growth factor-1 (IGF-1). We evaluated 4 groups of mice infected or sham-infected on day-of-life 28: uninfected-controls, wild-type C.-rodentium-infected, partially-attenuated C. rodentium-infected (with deletion of 3 serine protease genes involved in colonization), and pair-fed (given the amount of daily food consumed by the wild-type C.-rodentium group). Relative to the uninfected group, mice infected with wild-type C.-rodentium exhibited temporal associations of lower food intake, weight loss, linear-growth failure, higher IL-6 and TNF-α and lower IGF-1. However, relative to the pair-fed group, the C.-rodentium-infected group only differed significantly by linear growth and systemic inflammatory cytokines. Between post-infection days 15–20, the infected group exhibited resolution of systemic inflammation. Between days 16–20, both wild-type C.-rodentium and pair-fed groups exhibited rapid linear-growth velocities exceeding the uninfected and mutant C.-rodentium groups; during this time levels of IGF-1 increased to match the uninfected group. We submit this as a model providing important opportunities to study mechanisms of catch-up growth related to intestinal inflammation. We conclude that in addition to known effects of weight loss, infection with C.-rodentium induces linear-growth failure potentially related to systemic inflammation and low levels of IGF-1, with catch-up of linear growth following resolution of inflammation

Biofabricated Aluminium Oxide Nanoparticles Derived from <i>Citrus aurantium</i> L.: Antimicrobial, Anti-Proliferation, and Photocatalytic Efficiencies

A current strategy in material science and nanotechnology is the creation of green metal oxide nanoparticles. Citrus aurantium peel extract was used to create aluminium oxide nanoparticles (Al2O3 NPs) in an efficient, affordable, environmentally friendly, and simple manner. Various characterisation methods such as UV-vis spectrophotometer (UV), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and field emission scanning electron microscopy (FE-SEM) were utilised to assess the morphology of Al2O3 NPs. The elemental composition was performed by EDX analysis. Using the well diffusion method, Al2O3 NPs’ antimicrobial properties were used against pathogenic organisms. The antiproliferation efficacy of a neuronal cell line was investigated using the MTT assay. The photocatalytic activities were studied against methylene blue dye. In this study, Al2O3 NPs were found to have an average crystallite size of 28 nm in the XRD, an absorption peak at 322 nm in the UV spectrum, and functional groups from 406 to 432 in the FT-IR spectrum, which were ascribed to the stretching of aluminium oxide. Antimicrobial efficiencies were observed against Pseudomonas aeruginosa [36 ± 2.12], Staphylococcus aureus [35 ± 1.23], Staphylococcus epidermis [27 ± 0.06], Klebsiella pneumonia [25 ± 1.65], Candida albicans [28 ± 1.06], and Aspergillus niger [27 ± 2.23], as well as the cell proliferation of a PC 12 cell line (54.09 at 31.2 μg/mL). Furthermore, photocatalytic degradation of methylene blue dye decreased up to 89.1 percent after 150 min. The current investigation concluded that biosynthesised Al2O3 NPs exhibit feasible antimicrobial, anti-proliferative, and photocatalytic behaviours

Bio-Mediated Zinc Oxide Nanoparticles through Tea Residue: Ecosynthesis, Characterizations, and Biological Efficiencies

Recent advances in nanotechnology have placed a major emphasis on environmentally friendly processes that encourage sustainable growth by using moderate reaction conditions and non-toxic precursors. In the present study, a simple, inventive, and affordable green technique was applied to generate bio-augmented ZnO nanoparticles using an aqueous extract of tea residue as a reducing and stabilizing component. Numerous methods, including UV-Vis, XRD, FT-IR, FE-SEM with EDAX and TEM were used to analyze ZnO nanoparticles that were generated. The antimicrobial capabilities of biomediated ZnO nanoparticles against pathogenic organisms were examined using an agar well method. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) and flow cytometry analysis was utilized to explore cytotoxic effects and apoptosis, and methylene blue dye was used to examine photocatalytic activity. The ZnO nanoparticles demonstrated considerable anticancer activity in human lung cancer cells (A549) as well as highly effective antibacterial activity against several different microbial pathogens. Furthermore, the greatest degradation percentage of methylene blue obtained was found to be 86% after 140 min. Therefore, it is concluded that the chosen nanoparticle combination enhanced antimicrobial, anticancer and photocatalytic activities. The combination may represent a useful tool for removing dye pollution from wastewater and, ideally, be used in the pharmaceutical sector to combat lung cancer

Investigation of Biofabricated Iron Oxide Nanoparticles for Antimicrobial and Anticancer Efficiencies

Capparis zeylanica leaf extract was employed in this work to create iron oxide nanoparticles (α-Fe2O3) using anhydrous ferric chloride. The UV spectrum, XRD, FT-IR, and FE-SEM with EDX methods were used to characterize the fabricated nanoparticles. The iron oxide nanoparticles obtained were spherical in form, with an average crystallite size of 28.17 nm determined by XRD. The agar well diffusion method was used to assess the antimicrobial activity of the α-Fe2O3 nanoparticles created in this study against pathogenic organisms, Gram-negative bacteria (Escherichia coli and Pseudomonas aeroginosa), Gram-positive bacteria (Staphylococcus aureus and Streptococcus pyogenes), and fungi (Candida albicans and Aspergillus niger). Among the pathogens tested, S. pyogenes had the highest zones of inhibition (25 ± 1.26 mm), followed by S. aureus (23 ± 0.8 mm), E. coli (23 ± 2.46 mm), P. aeroginosa (22 ± 1.86 mm), C. albicans (19 ± 2.34 mm) and A. niger (17 ± 3.2 mm). The substance was further tested for anticancer activity against A549 (lung cancer) cells using the MTT assay. The cytotoxic reaction was found to be concentration-dependent. The present study, therefore, came to the conclusion that the bio-effectiveness of the manufactured α-Fe2O3 nanoparticles may result in applications in biomedical domains

Microbial mediated synthesis of ZnO nanoparticles derived from Lactobacillus spp: Characterizations, antimicrobial and biocompatibility efficiencies

The present study reported that the green protocols for the synthesis of ZnO nanoparticles with Lactobacillus spp extract are cost-effective and eco-friendly and the reports say that green ZnO nanoparticles have better antimicrobial and biocompatibility analysis. X-ray diffraction (XRD), Ultraviolet absorption spectrum (UV–Vis), Fourier transform infrared spectroscopy (FTIR), Field emission scanning electron microscopy (FE-SEM), Energy dispersive X-ray analysis (EDX), and Atomic force microscopy (AFM) were used to characterize the ZnO nanoparticles. XRD and FTIR analysis confirmed the formation of a pure ZnO phase. The antimicrobial efficiencies have been conducted using ZnO nanoparticles against microbial strains such as Clostridium difficile, Clostridium perfringens, E. coli, Salmonella typhi, Candida albicans, and Aspergillus flavus using the agar well method. The biocompatibility of the human colon cancer cell line (HT-29) was performed by MTT assay. Results of this study, MTT test measurements on cell viability studies have demonstrated the excellent biocompatibility activity against HT 29 cancer cell line. The effective antimicrobial activity of ZnO nanoparticles against different Gram positive and Gram negative bacterial and fungal pathogens was demonstrated by the amazing inhibition zones (mm). In this research, we concluded that bio-mediated ZnO nanostructures proved to be an excellent new antimicrobial and anticancer material

Sustainable Environmental-Based ZnO Nanoparticles Derived from Pisonia grandis for Future Biological and Environmental Applications

The bio-synthesis of zinc oxide nanoparticles (ZnO NPs) using aqueous leaf extract of Pisonia grandis is discussed in this work as an effective ecologically beneficial and straightforward method. This strategy intends to increase ZnO nanoparticle usage in the biomedical and environmental sectors, while reducing the particle of hazardous chemicals in nanoparticle synthesis. In the current study, bio-augmented zinc oxide nanomaterials (ZnO-NPs) were fabricated from Pisonia grandis aqueous leaf extracts. Different methods were used to analyze the ZnO-nanoparticles including X-ray diffraction (XRD), Fourier Transforms Infrared (FT-IR), Ultraviolet (UV) spectroscopy, and Field Emission Scanning Electron Microscopy (FE-SEM) with EDX. The synthesized nanoparticles as spheres were verified by FE-SEM analysis; XRD measurements showed that the particle flakes had an average size of 30.32 nm and were very pure. FT-IR analysis was used to validate the functional moieties in charge of capping and stabilizing ZnO nanoparticles. The antimicrobial, cytotoxic, and photodegradation properties of synthesized nanoparticles were assessed using well diffusion, MTT, and UV visible irradiation techniques. The bio-fabricated nanoparticles were proven to be outstanding cytotoxic and antimicrobial nanomaterials. As a result of the employment of biosynthesized ZnO nanoparticles as photocatalytic agents, 89.2% of the methylene blue dye was degraded in 140 min. ZnO nanoparticles produced from P. grandis can serve as promising substrates in biomedicine and applications of environmental relevance due to their eco-friendliness, nontoxic behavior, and cytocompatibility

Sustainable Environmental-Based ZnO Nanoparticles Derived from <i>Pisonia grandis</i> for Future Biological and Environmental Applications

The bio-synthesis of zinc oxide nanoparticles (ZnO NPs) using aqueous leaf extract of Pisonia grandis is discussed in this work as an effective ecologically beneficial and straightforward method. This strategy intends to increase ZnO nanoparticle usage in the biomedical and environmental sectors, while reducing the particle of hazardous chemicals in nanoparticle synthesis. In the current study, bio-augmented zinc oxide nanomaterials (ZnO-NPs) were fabricated from Pisonia grandis aqueous leaf extracts. Different methods were used to analyze the ZnO-nanoparticles including X-ray diffraction (XRD), Fourier Transforms Infrared (FT-IR), Ultraviolet (UV) spectroscopy, and Field Emission Scanning Electron Microscopy (FE-SEM) with EDX. The synthesized nanoparticles as spheres were verified by FE-SEM analysis; XRD measurements showed that the particle flakes had an average size of 30.32 nm and were very pure. FT-IR analysis was used to validate the functional moieties in charge of capping and stabilizing ZnO nanoparticles. The antimicrobial, cytotoxic, and photodegradation properties of synthesized nanoparticles were assessed using well diffusion, MTT, and UV visible irradiation techniques. The bio-fabricated nanoparticles were proven to be outstanding cytotoxic and antimicrobial nanomaterials. As a result of the employment of biosynthesized ZnO nanoparticles as photocatalytic agents, 89.2% of the methylene blue dye was degraded in 140 min. ZnO nanoparticles produced from P. grandis can serve as promising substrates in biomedicine and applications of environmental relevance due to their eco-friendliness, nontoxic behavior, and cytocompatibility

Removal of a Membrane Anchor Reveals the Opposing Regulatory Functions of Vibrio cholerae Glucose-Specific Enzyme IIA in Biofilms and the Mammalian Intestine

The V. cholerae phosphoenolpyruvate phosphotransferase system (PTS) is a well-conserved, multicomponent phosphotransfer cascade that regulates cellular physiology and virulence in response to nutritional signals. Glucose-specific enzyme IIA (EIIAGlc), a component of the PTS, is a master regulator that coordinates bacterial metabolism, nutrient uptake, and behavior by direct interactions with protein partners. We show that an amphipathic helix (AH) at the N terminus of V. cholerae EIIAGlc serves as a membrane association domain that is dispensable for interactions with cytoplasmic partners but essential for regulation of integral membrane protein partners. By removing this amphipathic helix, hidden, opposing roles for cytoplasmic partners of EIIAGlc in both biofilm formation and metabolism within the mammalian intestine are revealed. This study defines a novel paradigm for AH function in integrating opposing regulatory functions in the cytoplasm and at the bacterial cell membrane and highlights the PTS as a target for metabolic modulation of the intestinal environment.The Vibrio cholerae phosphoenolpyruvate phosphotransferase system (PTS) is a well-conserved, multicomponent phosphotransfer cascade that coordinates the bacterial response to carbohydrate availability through direct interactions of its components with protein targets. One such component, glucose-specific enzyme IIA (EIIAGlc), is a master regulator that coordinates bacterial metabolism, nutrient uptake, and behavior by direct interactions with cytoplasmic and membrane-associated protein partners. Here, we show that an amphipathic helix (AH) at the N terminus of V. cholerae EIIAGlc serves as a membrane association domain that is dispensable for interactions with cytoplasmic partners but essential for regulation of integral membrane protein partners. By deleting this AH, we reveal previously unappreciated opposing regulatory functions for EIIAGlc at the membrane and in the cytoplasm and show that these opposing functions are active in the laboratory biofilm and the mammalian intestine. Phosphotransfer through the PTS proceeds in the absence of the EIIAGlc AH, while PTS-dependent sugar transport is blocked. This demonstrates that the AH couples phosphotransfer to sugar transport and refutes the paradigm of EIIAGlc as a simple phosphotransfer component in PTS-dependent transport. Our findings show that Vibrio cholerae EIIAGlc, a central regulator of pathogen metabolism, contributes to optimization of bacterial physiology by integrating metabolic cues arising from the cytoplasm with nutritional cues arising from the environment. Because pathogen carbon metabolism alters the intestinal environment, we propose that it may be manipulated to minimize the metabolic cost of intestinal infection

Infection decreases short chain phospholipids in the intestines of <i>V</i>. <i>cholerae</i>-infected flies.

<p><b>Lysophospholipids are more abundant in the intestines of Δ<i>gcvT</i> mutant infected flies.</b> (A) Schematic representation of the lipid species discussed in the text. Grey circles represent the polar headgroups, lines represent the fatty acid chains, and surrounding shaded shapes represent the relative space filled by the head group and fatty acid chains of each lipid species. The larger the area of the head group relative to the area filled by fatty acid chains, the greater the propensity to form a highly-curved structure such as a small lipid droplet. (B) Two mechanisms by which small lipid droplets may form a larger lipid droplet are illustrated. Enlargement, shown on the left, results when a large influx of triglycerides must be accommodated. Coalescence results when the supply of phospholipids is inadequate to coat the triglyceride core, and smaller lipid droplets join to minimize exposed surface area. (C-K) LC-MS/MS-based lipidomic analysis of the intestines of flies fed LB alone or inoculated with wild-type <i>V</i>. <i>cholerae</i> (WT) or a Δ<i>gcvT</i> mutant. (C) Triglycerides (TG), (D) Total phosphatidylcholine species with a total of 30 carbons or less in the two fatty acid chains (PC≤30), (E) Individual phosphatidylcholine species with the total number of fatty acid carbons indicated below. (F) Total phosphatidylethanolamine species with a total of 30 carbons or less in the two fatty acid chains (PE≤30) (G) Individual phosphatidylethanolamine species with the total number of fatty acid carbons indicated below. (H) Total lysophosphatidylcholine species. (I) Individual lysophosphatidylcholine species with the total number of fatty acid carbons indicated below. (J) Total lysophosphatidylethanolamine species. (K) Individual lysophosphatidylethanolamine species with the total number of fatty acid carbons indicated below. (L) Putative phospholipase cascade. (M-P) Lipidomic analysis of the intestines of flies infected with wild-type <i>V</i>. <i>cholerae</i> (WT) or a <i>Δacs1</i> mutant. (M) Total phosphatidylcholine species with fatty acid carbons less than or equal to 30 (PC≤30). (N) Total phosphatidylethanolamine species with fatty acid carbons less than or equal to 30 (PE≤30). (O) Total lysophosphatidylcholine species. (P) Total lysophosphatidylethanolamine species. For pooled data, the mean and SD are shown. Pairwise statistical significance was calculated using a student’s t-test (*p<0.05, **p<0.01, ***p<0.001).</p

<i>Vibrio cholerae</i> ensures function of host proteins required for virulence through consumption of luminal methionine sulfoxide

<div><p><i>Vibrio cholerae</i> is a diarrheal pathogen that induces accumulation of lipid droplets in enterocytes, leading to lethal infection of the model host <i>Drosophila melanogaster</i>. Through untargeted lipidomics, we provide evidence that this process is the product of a host phospholipid degradation cascade that induces lipid droplet coalescence in enterocytes. This infection-induced cascade is inhibited by mutation of the <i>V</i>. <i>cholerae</i> glycine cleavage system due to intestinal accumulation of methionine sulfoxide (MetO), and both dietary supplementation with MetO and enterocyte knock-down of host methionine sulfoxide reductase A (MsrA) yield increased resistance to infection. MsrA converts both free and protein-associated MetO to methionine. These findings support a model in which dietary MetO competitively inhibits repair of host proteins by MsrA. Bacterial virulence strategies depend on functional host proteins. We propose a novel virulence paradigm in which an intestinal pathogen ensures the repair of host proteins essential for pathogenesis through consumption of dietary MetO.</p></div