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PloS One 2024The role of reactive oxygen species (ROS) in the killing exerted by antibiotics on bacteria is debated. Evidence attributes part of toxicity of many antibiotics to their...
The role of reactive oxygen species (ROS) in the killing exerted by antibiotics on bacteria is debated. Evidence attributes part of toxicity of many antibiotics to their ability to generate ROS by interfering with cellular metabolism, but some studies dismiss the role of ROS. Bicyclomycin (BCM) is a broad-spectrum antibiotic that is the only known compound to inhibit E. coli transcription terminator factor Rho with no known other cellular targets. In the present study, we addressed this question by checking whether the induction of oxidative stress could explain the increased sensitivity to Bicyclomycin in the hns deleted strain even in Δkil background in E. coli. BCM evoked the generation of ROS in E. coli cells. BCM is known to cause the cell filamentation phenotype in E. coli. Performing fluorescence microscopic analysis, we show that bicyclomycin-dependent cell filamentation is associated with SOS response. RecA-GFP filaments were found to colocalize with the damaged DNA sites in the cell. Further analysis revealed that the genomic DNA was partitioned but the cell septum formation was severely affected under BCM treatment. Furthermore, we observed biofilm formation by E. coli after BCM treatment. We hypothesize that ROS production after BCM treatment could lead to cell filamentation in bacteria. A better understanding of the mode of toxicity of BCM will help us design better antibiotic treatment regimes for clinical practices, including combinatorial drug therapies. The cell filamentation phenotype observed after BCM treatment makes this antibiotic a promising drug for phage-antibiotic synergy (PAS) therapy.
Topics: Escherichia coli; Reactive Oxygen Species; Anti-Bacterial Agents; Bacteria; Cell Division; DNA; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 38551933
DOI: 10.1371/journal.pone.0293858 -
Molecules (Basel, Switzerland) Mar 2024This study concentrates on assessing the insecticidal attributes of the γ-AlO nanoparticles derived from the remnants of , which include essential oil, ethanolic...
This study concentrates on assessing the insecticidal attributes of the γ-AlO nanoparticles derived from the remnants of , which include essential oil, ethanolic extract, and plant waste. The synthesis of the γ-AlO nanoparticles was executed using a direct sol-gel procedure, affirming the crystal structure according to extensive physicochemical analyses such as UV-Vis, XRD, FTIR, and SEM. Evaluation of the insecticidal activity in vitro was conducted against , a pest that infests carob wood, utilizing strains from diverse forests in the Khenifra region, situated in the Moroccan Middle Atlas. The lethal doses 50 ranged from 40 mg/g to 68 mg/g, indicating moderate effectiveness compared to the commercial insecticide Permethrin. Optimization of the conditions for the efficiency of the γ-AlO nanoparticles was determined using experimental plans, revealing that time, humidity, and temperature were influential factors in the lethal dose 50 of these nanomaterials. Moreover, this study encompasses the establishment of correlations using Principal Component Analysis (PCA) and Ascending Hierarchical Classification (AHC) among various geographic, biological, and physical data, amalgamating geographic altitude and γ-AlO nanoparticle insecticide parameters, as well as the attributes of the mechanical tests conducted on the carob wood affected by insects. The correlations highlight the close connections between the effectiveness of the insecticide, mountain altitude, and the mechanical parameters that were examined. Ultimately, these nanoparticles demonstrate promising potential as alternative insecticides, thus opening up encouraging prospects for safeguarding against carob wood pests.
Topics: Animals; Coleoptera; Insecticides; Mentha pulegium; Weevils; Nanoparticles; Galactans; Mannans; Plant Gums
PubMed: 38542842
DOI: 10.3390/molecules29061205 -
Nutrients Mar 2024This multi-center prospective randomized controlled trial was a tolerance and safety study investigating the thickener locust bean gum (LBG) in infants with... (Randomized Controlled Trial)
Randomized Controlled Trial
Tolerance and Safety of an Anti-Regurgitation Formula Containing Locust Bean Gum, Pre-, and Postbiotics: A Multi-Country Multi-Center Prospective Randomized Controlled Study in Infants with Regurgitation.
This multi-center prospective randomized controlled trial was a tolerance and safety study investigating the thickener locust bean gum (LBG) in infants with regurgitation, to support the re-evaluation of the safety of LBG in infant formula. The primary objective was to demonstrate that after an 8-week intervention, stool consistency was not inferior (i.e., was not looser or more watery) in infants fed an anti-regurgitation (AR) formula containing LBG vs. the stool consistency of infants fed with an unthickened control formula. A total of 103 full-term infants with regurgitation were randomized to the test or control formula. The test formula contained LBG (0.4 g/100 mL), short-chain galacto-oligosaccharides, and long-chain fructo-oligosaccharides (scGOS/lcFOS; 9:1; 0.4 g/100 mL) and postbiotics and the control formula contained scGOS/lcFOS (0.8 g/100 mL), the same amount of postbiotics, and did not contain LBG. The average stool consistency score at the 8th intervention week was the primary outcome parameter. Secondary outcome parameters were stool consistency at other timepoints, stool frequency, Infant Gastrointestinal Symptom Questionnaire (IGSQ) score, growth, (serious) adverse events ([S]AEs), regurgitation severity, and infant well-being. Overall, the infants were 36.9 ± 12.9 [mean ± SD] days old, 62.7% girls in the test, and 50.0% girls in the control group. The primary analysis showed that the test group did not have looser or more watery stools than the control group. IGSQ sum scores decreased comparably in both groups. The frequency of regurgitation was significantly lower in the test group compared to the control group (mixed model repeated measurement, ≤ 0.028) and parent-reported well-being scores were favorable. Adequate growth was observed in both groups. Both products were well-tolerated and safe and the AR formula with LBG was efficacious in reducing regurgitation frequency. This study provides further evidence for the dietary management of regurgitation by LBG-containing formulae in infants who are not exclusively breastfed, and the reassurance it can bring to parents.
Topics: Infant; Female; Humans; Male; Prospective Studies; Galactans; Mannans; Vomiting; Feces; Oligosaccharides; Gastrointestinal Diseases; Infant Formula; Double-Blind Method; Plant Gums
PubMed: 38542810
DOI: 10.3390/nu16060899 -
Journal of Functional Biomaterials Mar 2024Montmorillonite has been refined to overcome uncertainties originating from different sources, which offers opportunities for addressing various health issues, e.g.,...
Montmorillonite has been refined to overcome uncertainties originating from different sources, which offers opportunities for addressing various health issues, e.g., cosmetics, wound dressings, and antidiarrheal medicines. Herein, three commercial montmorillonite samples were obtained from different sources and labeled M1, M2, and M3 for Ca-montmorillonite, magnesium-enriched Ca-montmorillonite, and silicon-enriched Na-montmorillonite, respectively. Commercial montmorillonite was refined via ultrasonic scission-differential centrifugation and labeled S, M, or L according to the particle sizes (small, medium, or large, respectively). The size distribution decreased from 2000 nm to 250 nm with increasing centrifugation rates from 3000 rpm to 12,000 rpm. Toxicological evaluations with human colon-associated cells and human skin-associated cells indicated that side effects were correlated with excess dosages and silica sand. These side effects were more obvious with human colon-associated cells. The microscopic interactions between micro/nanosized montmorillonite and human colon-associated cells or human skin-associated cells indicated that those interactions were correlated with the size distributions. The interactions of the M1 series with the human cells were attributed to size effects because montmorillonite with a broad size distribution was stored in the M1 series. The M2 series interactions with human cells did not seem to be correlated with size effects because large montmorillonite particles were retained after refining. The M3 series interactions with human cells were attributed to size effects because small montmorillonite particles were retained after refining. This illustrates that toxicological evaluations with refined montmorillonite must be performed in accordance with clinical medical practices.
PubMed: 38535268
DOI: 10.3390/jfb15030075 -
Scientific Reports Mar 2024Constipation is a major health problem worldwide that requires effective and safe treatment options. Increasing evidence indicates that disturbances in gut microbiota...
Constipation is a major health problem worldwide that requires effective and safe treatment options. Increasing evidence indicates that disturbances in gut microbiota may be a risk factor for constipation. Administration of lacidophilin tablets shows promising therapeutic potential in the treatment of inflammatory bowel disease owing to their immunomodulatory properties and regulation of the gut microbiota. The focus of this study was on investigating the ability of lacidophilin tablets to relieve constipation by modulating the gut microbiome. Rats with loperamide hydrochloride induced constipation were treated with lacidophilin tablets via intragastric administration for ten days. The laxative effect of lacidophilin tablets was then evaluated by investigating the regulation of intestinal microflora and the possible underlying molecular mechanism. Our results reveal that treatment with lacidophilin tablets increased the intestinal advancement rate, fecal moisture content, and colonic AQP3 protein expression. It also improved colonic microflora structure in the colonic contents of model rats mainly by increasing Akkermansia muciniphila and decreasing Clostridium_sensu_stricto_1. Transcriptome analysis indicated that treatment with lacidophilin tablets maintains the immune response in the intestine and promotes recovery of the intestinal mechanical barrier in the constipation model. Our study shows that lacidophilin tablets improve constipation, possibly by promoting Akkermansia colonization and by modulating the intestinal immune response.
Topics: Rats; Animals; Gastrointestinal Microbiome; Akkermansia; Constipation; Intestines; Loperamide
PubMed: 38531966
DOI: 10.1038/s41598-024-57732-5 -
Frontiers in Pharmacology 2024Plants and their extracts have been integral to the development of medicinal treatments throughout history, offering a vast array of compounds for innovative therapies....
Plants and their extracts have been integral to the development of medicinal treatments throughout history, offering a vast array of compounds for innovative therapies. Müll. Arg., commonly known as Rambai, is an evergreen tree with economic importance in the Old-World Tropics. The study investigates its phytochemical composition through Gas Chromatography-Mass Spectrometry (GC-MS) and evaluates its pharmacological properties, including antidiabetic, antidiarrheal, antimicrobial, and antidepressant effects. The GC-MS analysis revealed 15 bioactive compounds in the methanol extract, with Phenol, 3,5-bis(1,1-dimethylethyl)-, Methyl stearate, and Hexadecanoic acid, methyl ester being the predominant ones. The cytotoxicity assay demonstrated significant activity in the ethyl acetate fraction. Antimicrobial assays indicated mild to moderate antibacterial activity. studies on mice revealed significant hypoglycemic, antidiarrheal, and antidepressant properties. Molecular docking studies against EGFR, DHFR, GLUT-3, KOR, and MOA identified promising compounds with potential therapeutic effects. The identified compounds exhibited favorable ADME/T properties, emphasizing their potential for drug development. The study underscores the promising therapeutic potential of , showcasing its diverse bioactive compounds with significant medicinal properties. These findings lay the groundwork for future research, emphasizing the exploration of as a source of natural remedies for addressing prevalent health conditions.
PubMed: 38487168
DOI: 10.3389/fphar.2024.1359815 -
Revista de Gastroenterologia de Mexico... 2024New oncologic treatments, particularly immunotherapy (IT), have revolutionized the treatment of advanced-stage malignant tumors. Immune checkpoint inhibitors are the... (Review)
Review
New oncologic treatments, particularly immunotherapy (IT), have revolutionized the treatment of advanced-stage malignant tumors. Immune checkpoint inhibitors are the main form of IT and act by increasing T cell activity and the organism's immune response against neoplastic cells. Targeted therapy is another form of IT that acts by inhibiting oncogenes or inflammation signaling and tumor angiogenesis pathways. However, these mechanisms of tumor destruction can interfere with the host's immune self-tolerance or with the mechanisms of epithelial tissue repair and predispose to immune system-mediated adverse events that can affect multiple organs, including the digestive tract. The gastrointestinal manifestations of damage caused by IT can range from low-grade mucositis to ulceration, and in some cases, necrosis and perforation. Any part of the gastrointestinal tract can be affected, but there is greater involvement of the small bowel and colon, with a pattern similar to that seen in inflammatory bowel disease. The most common clinical manifestation is chronic diarrhea. The differential diagnosis includes enteropathogenic infections, especially those caused by opportunistic microorganisms; adverse drug reactions; and other inflammatory and malabsorption disorders. Treatment is guided by damage severity. Mild cases can be treated with antidiarrheals and rehydration in the outpatient setting; moderate cases with hospitalization, systemic steroids, and temporary suspension of IT; and severe cases with immunosuppressants or biologic agents and definitive suspension of IT.
Topics: Humans; Gastroenterologists; Neoplasms; Immunotherapy; Enterocolitis
PubMed: 38485558
DOI: 10.1016/j.rgmxen.2023.11.001 -
Physiological Reports Mar 2024Opium abuse and exposure to heavy metals elevate the risk of coronary artery disease (CAD). Therefore, we aimed to determine the association between opium abuse and...
Opium abuse and exposure to heavy metals elevate the risk of coronary artery disease (CAD). Therefore, we aimed to determine the association between opium abuse and blood lead levels (BLLs) and the CAD complexity. We evaluated patients with acute coronary symptoms who underwent coronary angiography, and those with >50% stenosis in at least one of the coronary arteries were included. Furthermore, Synergy between PCI with Taxus and Cardiac Surgery I (SYNTAX I) score and BLLs were measured. Based on the opium abuse, 95 patients were subdivided into opium (45) and control (50) groups. Differences in demographics and CAD risk factors were insignificant between the two groups. The median BLLs were remarkably higher in the opium group than in controls (36 (35.7) and 20.5 μg/dL (11.45), respectively, p = 0.003). We also revealed no significant differences in SYNTAX score between the two groups (15.0 (9.0) and 17.5 (14.0), respectively, p = 0.28). Additionally, we found no significant correlation between BLLs and the SYNTAX scores (p = 0.277 and r = -0.113). Opium abuse was associated with high BLLs. Neither opium abuse nor high BLLs were correlated with the complexity of CAD. Further studies are warranted to establish better the relationship between opium abuse, BLLs, and CAD.
Topics: Humans; Coronary Artery Disease; Lead; Percutaneous Coronary Intervention; Opium Dependence; Opium; Severity of Illness Index
PubMed: 38480374
DOI: 10.14814/phy2.15975 -
Cureus Feb 2024Background The curry leaf tree, , is a tropical to subtropical tree in the family Rutaceae that is native to Asia. The plant parts are shown to have potential...
Background The curry leaf tree, , is a tropical to subtropical tree in the family Rutaceae that is native to Asia. The plant parts are shown to have potential antimicrobial, antioxidant, antifungal, antidiarrheal, antidiabetic, anticancer, and anti-inflammatory properties. is a facultative anaerobic, Gram-positive cocci, a common inhabitant of the human oral cavity that forms biofilms, contributing to dental caries. Aim The study aimed to analyze the inhibitory potential of phytocompounds in against the oral pathogen . Materials and methods The protein and ligand were prepared, and molecular docking was carried out using the Hex protein docking server. The PyMOL program was used to view, analyze, and annotate the docked complex. The interaction of the drug, including the mechanism of action, and predicted adverse effects were predicted using the Way2Drug PASS Online server. The absorption, distribution, metabolism, excretion, and toxicity properties of the drug candidates were analyzed using the SwissADME online server. Results The study identified O-methyl murrayamine, koenigine, koenigicine, and murrayone as having inhibitory potential against the glycosyltransferase protein of Among the four compounds analyzed for docking, koenigicine had the lowest E-score, indicating a strong interaction with the receptor. Among the four compounds analyzed, murrayone had a high topological polar surface area score, while all four compounds had similar bioavailability scores. Conclusion This study concluded that O-methyl murrayamine, koenigine, koenigicine, and murrayone exhibit potent inhibitory potential against . leaf extract can be used in toothpaste as an antibacterial agent to protect teeth against dental caries. These findings are important for the potential use of the above compound to act as an anticariogenic agent in oral health applications.
PubMed: 38455815
DOI: 10.7759/cureus.53679 -
Metabolism Open Mar 2024Liver disease is any disease that negatively affects the normal function of the liver, and it is a major health problem that challenges not only healthcare...
BACKGROUND
Liver disease is any disease that negatively affects the normal function of the liver, and it is a major health problem that challenges not only healthcare professionals, but also the pharmaceutical industry and drug regulatory agencies. Similarly, diarrhea is the second leading cause of death among children under five globally next to pneumonia. The available synthetic drugs for the treatment of liver disorders and diarrhoea have limited safety and efficacy.
OBJECTIVE
To evaluate the hepatoprotective and antidiarrheal activities of hydroalcoholic leaf and fruit extracts of L. (Anacardiaceae) in mice.
METHODS
Hepatoprotective activity of the extracts was evaluated by using CCl induced hepatotoxicity in mice model. In this model, mice were divided into groups and treated as follows. The normal control and toxicant control groups were treated with the vehicle used for reconstitution, the positive control was treated with the standard drug (silymarin), and the test groups were treated with different doses of plant extracts daily in the morning for seven days. Additionally, all groups except the normal control were treated with CCl (2 mg/kg, IP) on the 4th day of treatment, 30 min post-dose. On the 7th day, blood was collected from each mouse via a cardiac puncture. The collected blood was centrifuged, and serum levels of ALT, AST, and ALP were determined using an automated chemistry analyser. Data were analysed using one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test.The antidiarrheal activity of the extract was investigated using castor oil-induced diarrhoea, enteropooling, and small intestine transit. The test groups received various doses (100, 200, and 400 mg/kg) of the extract, whereas the positive control received loperamide (3 mg/kg), and the negative control received the vehicle (distilled water, 10 ml/kg).
RESULT
Hepatoprotective activity: The leaf and fruit crude extracts showed significant improvement in the body weight and liver weight of mice compared to the untreated toxicant control. Additionally, treatment with hydromethanol leaf and fruit extracts caused a significant (P < 0.05) improvement in liver biomarkers compared to the toxicant control. Similarly, the n-butanol and chloroform fractions of the fruit extract caused a significant reduction (P < 0.01) in serum AST, ALT, ALP and Bilirubin levels and a significant (P < 0.001) increase in total protein compared to the toxicant control. However, none of the three solvent fractions (n-butanol, chloroform, and aqueous) of the fruit extract significantly affected (P > 0.05) the level of albumin compared with the toxicant control.Antidiarrheal activity: In the castor oil-induced diarrheal model, the 80 % methanol extract delayed the onset of defaecation and significantly reduced the number and weight of faeces at all tested doses compared to the negative control. In the enteropooling test, 80 ME significantly (P < 0.001) reduced the weight and volume of intestinal fluid at all tested doses compared with the negative control. Results from the charcoal meal test revealed that the extracts produced a significant anti-motility effect at all tested doses compared with the negative control.
CONCLUSION
This study confirmed the hepatoprotective and antidiarrheal activities of hydroalcoholic extracts. The highest test dose produced the maximum hepatoprotective and antidiarrheal activities in all models.
PubMed: 38455232
DOI: 10.1016/j.metop.2024.100272