Antibiotic Mixture Research Articles

CuNCs-MOFs with hydrogen bonding sites: H2O-induced emission-enhanced phosphorescence-fluorescence conversion and high photo-Fenton catalytic performance

Clusters-based metal–organic frameworks (CMOFs) obtained through supramolecular interactions between clusters are expected to be a promising class of materials with interesting properties and attractiveness. Herein, CuNCs protected by AMT (3-amino-1,2,4-triazole-5-thiol) ligands were synthesized, which coordinated with Zn2+ to form a nanosheet CuNCs-MOFs structure, resulting in AIE and enhanced photoluminescence (QY = 1.1 %). Upon aging in H2O, H2O molecules are inserted into S-CuNCs by the hydrogen bond to support 3D microflowers structures, and weak phosphorescence conver to strong fluorescence (28.9 %), simultaneously. After drying, H2O molecules are released by F-CuNCs, which is labled with V-CuNCs, and then easily combined with H2O2, which can be catalyzed to OH by Cu+. Under UV irradiation, CuNCs-MOFs generate photogenerated electrons and holes. As-obtained electrons react with H2O2 to generate more OH, and then catalyze dyes. The remaining holes will also receive electrons given by the dyes. Under the irradiation of Xe lamp, the common three dyes, MB, MO, RB and antibiotic, tetracycline, can be completely degraded within 30 min. Furthermore, under the sunlight, the mixture of dyes and antibiotics also can be completely degraded after 100 min. V-CuNCs show excellent photo-Fenton catalytic performance and have the bright photocatalytic prospects in waste water.

Wangshi Baochi Pills alleviate alcoholic liver disease by regulating the gut microbiota composition in a mouse model

IntroductionAlcoholic liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide. However, there are no currently available drugs for ALD. Wangshi Baochi Pill (WBP) is a is a national confidential formulary of China, commonly used in clinical pediatrics to treat dyspepsia. In this study, we measured the therapeutic effect of WBP on ALD. MethodsThe National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was used in our study. Experiments were performed to determine whether the hepatoprotective effect of WBP was associated with gut microbiota using a mixture of antibiotics (ABx). Gut flora was detected via full-length 16S rRNA sequencing on the Pacbio Sequel platform. Q-PCR and western blot were used to test lipid metabolism related genes. ResultsWBP significantly reduced AST and ALT levels and alleviated liver damage. It also elevated hepatic alcohol-metabolizing enzymes (alcohol dehydrogenase and cytochrome P4502E1) activity. WBP down-regulated the FASN, CPT1-α, and CD36 and up-regulated PPAR-α. Moreover, we found WBP could alleviate ethanol-induced intestinal injury and inflammation. Our results suggest WBP was effective in attenuating hepatic steatosis and injury via intestinal flora, likely by elevating probiotics (B. pseudolongum PV8–2) and decreasing harmful bacteria. DiscussionsOur study first suggested the therapeutic effect of WBP on ALD and provides a new approach for the treatment of ALD.

Efficient remediation of meropenem using Bacillus tropicus EMB20 β-lactamase immobilized on magnetic nanoparticles

Reducing antibiotic pollution in the environment in essential to preserve the effectiveness of the available antibiotics. In the present study, β-lactamase from Bacillus tropicus EMB20 was immobilized onto magnetic nanoparticles (Fe3O4) through covalent coupling method. The nanoconjugate was structurally characterized using SEM, FTIR, UV-spectrometry, and XRD diffraction analyses. The prepared enzyme nanoconjugate was thereafter used for remediation of meropenem (Mer) and showed complete removal of 10 mgL−1 Mer within 3 h of treatment. Moreover, the immobilized enzyme was successfully recovered and reused for up to 5 cycles with 57% removal efficiency. The immobilized preparation was also observed to be effective in the removal of higher Mer concentrations of 25 and 50 mgL−1 with 79% and 75% removal efficiency, respectively. The major hydrolyzed product of Mer was found to be opened-lactam ring structure with m/z 402.16. The hydrolyzed product(s) were observed to be non-toxic as revealed through microbial MTT, confocal microscopy, and growth studies. Under the mixed conditions of 50 mgL−1 ampicillin (Amp), 10 mgL−1 amoxicillin (Amox) and, Mer, the nanoconjugate showed simultaneous complete removal of Amp and Mer, while 49% Amox removal was detected after 3 h of treatment. Moreover, the nanoconjugates also showed concomitant complete removal of antibiotic mixture with in 2 h from aquaculture wastewater. Overall, the study comes out with an efficient approach for remediation of β-lactam antibiotics from contaminated systems.

Kesesuaian Aseptik Dispensing Injeksi Antibiotik Pada Pasien Anak Rumah Sakit Umum Daerah dr. Soediran Mangun Sumarso Wonogiri

The use of injection preparations in hospitalized patients has a high prevalence rate so that dispensing injections needs attention because there are many risks that can arise during the mixing process. The purpose of the study was to determine the suitability of the aseptic procedure for dispensing antibiotics in pediatric patients with standard operating procedures applicable at the dr. Sudirman Mangun Sumarso Wonogiri. This study used a retrospective method with descriptive analysis of the data for August – October 2021. Conformity was measured using a checklist form and the percentage of conformity was calculated. The results showed that from 106 antibiotic mixtures consisting of Cefotaxim inj (46%), Ceftriaxon inj (12%), Chloramphenicol inj (3%), and Gentamicin inj (39%) obtained 85.71% according to standard operating procedures. Compliance that has met the standard includes reviewing prescriptions, doing 5 correct, calculating dosage suitability, choosing solvents, calculating solvent volumes, making delivery forms and those that are not appropriate, namely checking the condition of the drug when it is received. Examination of the condition of the drug when it is received should be carried out accompanied by a form so that there is a record that can be used for tracing when a medication error occurs.

Penicillin and amikacin mixture has bactericidal activity equivalent to gentamicin, tylosin, lincomycin and spectinomycin mixture in equine frozen semen.

Neat stallion semen can contain a variety of microorganisms, some of which may impair sperm quality and/or cause infection of the mares' reproductive tract. For this reason, antibiotics are commonly added to semen extenders. A combination of gentamicin, tylosin, lincomycin and spectinomycin (GTLS) has been recommended for use, but there are no reports on the use of this mixture in equine semen extender. Penicillin and amikacin (PA) are safe for preserving sperm quality while effectively controlling bacterial growth in equine cooled stored semen, but data on frozen semen are scarce. Therefore, a bioequivalence study was performed to assess the bactericidal activity of GTLS and PA in equine frozen semen. Nine mature, healthy stallions were used in the study. Split ejaculates were processed using media without antibiotics (Control) or with different antibiotics. For the GTLS group, centrifugation medium and freezing extender were prepared with gentamicin 250 μg/ml, tylosin 50 μg/ml, lincomycin 150 μg/ml and spectinomycin 300 μg/ml. For the PA group, the centrifugation medium was prepared with potassium penicillin G (PPG) 1200 units/ml and the freezing extender was prepared with PPG 1200 units/ml and amikacin 500 μg/ml. Semen processed in extenders without antibiotics had higher (p< .005) bacterial loads throughout all cryopreservation processing steps than semen samples processed using antibiotics. There were no differences in semen bacterial load after centrifugation, 15 and 30min after final extension, and after thawing between GTLS and PA groups, but PA had faster (p< .05) kill-time kinetics than GTLS. Only minor differences in sperm kinetic parameters were observed among groups. In conclusion, this study demonstrated bioequivalence between GTLS and PA in mitigating end-point bacterial loads. Prudent concentrations of the antibiotic mixtures evaluated in this study can be considered both effective and sperm-safe for equine frozen semen.

Synergy of R-(–)carvone and cyclohexenone-based carbasugar precursors with antibiotics to enhance antibiotic potency and inhibit biofilm formation

The widespread use of antibiotics in recent decades has been a major factor in the emergence of antibiotic resistances. Antibiotic-resistant pathogens pose increasing challenges to healthcare systems in both developing and developed countries. To counteract this, the development of new antibiotics or adjuvants to combat existing resistance to antibiotics is crucial. Glycomimetics, for example carbasugars, offer high potential as adjuvants, as they can inhibit metabolic pathways or biofilm formation due to their similarity to natural substrates. Here, we demonstrate the synthesis of carbasugar precursors (CSPs) and their application as biofilm inhibitors for E. coli and MRSA, as well as their synergistic effect in combination with antibiotics to circumvent biofilm-induced antibiotic resistances. This results in a biofilm reduction of up to 70% for the CSP rac-7 and a reduction in bacterial viability of MRSA by approximately 45% when combined with the otherwise ineffective antibiotic mixture of penicillin and streptomycin.

Co-Cultures of Lactobacillus acidophilus and Bacillus subtilis Enhance Mucosal Barrier by Modulating Gut Microbiota-Derived Short-Chain Fatty Acids.

Weaning stress induces intestinal barrier dysfunction and immune dysregulation in mammals. Various interventions based on the modulation of intestinal microbiota have been proposed. Our study aims to explore the effects of co-cultures from Lactobacillus acidophilus and Bacillus subtilis (FAM®) on intestinal mucosal barrier from the perspective of metabolic function of gut microbiota. A total of 180 piglets were allocated to three groups, i.e., a control group (C, basal diet), a FAM group (F, basal diet supplemented with 0.1% FAM), and an antibiotic group (A, basal diet supplemented with antibiotic mixtures). Here, we showed FAM supplementation significantly increased body weight and reduced diarrhea incidence, accompanied by attenuated mucosal damage, increased levels of tight junction proteins, serum diamine oxidase (DAO) and antimicrobial peptides. In addition, 16S rRNA sequencing and metabolomic analysis revealed an increase in relative abundance of Clostridiales, Ruminococcaceae, Firmicutes and Muribaculaceae and a significant increase in the total short-chain fatty acids (SCFAs) and butyric acid in FAM-treated piglets. FAM also increased CD4+ T cells and SIgA+ cells in intestinal mucosa and SIgA production in colon contents. Furthermore, FAM upregulated the expression of IL-22, short-chain fatty acid receptors GPR43 and GPR41, aryl hydrocarbon receptor (AhR), and hypoxia-inducible factor 1α (HIF-1α). FAM shows great application prospect in gut health and provides a reference for infant weaning.

Cardiac-derived extracellular matrix: A decellularization protocol for heart regeneration.

Extracellular matrix (ECM) is a fundamental component of the heart, guiding vital cellular processes during organ homeostasis. Most cardiovascular diseases lead to a remarkable remodeling of the ECM, accompanied by the formation of a fibrotic tissue that heavily compromises the heart function. Effective therapies for managing fibrosis and promoting physiological ECM repair are not yet available. The production of a decellularized extracellular matrix (d-ECM) serving as a three-dimensional and bioactive scaffold able to modulate cellular behavior and activities is considered crucial to achieve a successful regeneration. The protocol represents a step-by-step method to obtain a decellularized cardiac matrix through the combination of sodium dodecyl sulphate (SDS) and Triton X-100. Briefly, cardiac samples obtained from left ventricles of explanted, pathological human hearts were dissected and washed to remove residual body fluids. Samples were then snap-frozen and sliced by a cryostat into 350 μm thick sections. The sections obtained were decellularized using a solution containing 1% Triton X-100 and 1% SDS in combination, for 24 hours, until observing the color change from brownish-red to translucent-white. As a result, the protocol shows efficiency in preserving ECM architecture and protein composition during the whole process, suggesting that it is worthwhile, highly reproducible and produces a well- preserved decellularized extracellular matrix from cardiac samples. Notwithstanding, some limitations need to be addressed, such as the risk for microbial contamination and the unpredictable trend of the protocol when applied to decellularize samples other than myocardium, vessels, or skin. These issues require antibiotics mixture supplement during the procedure followed by UV sterilization, and appropriate adjustments for a tissue-specific utilization, respectively. The protocol is intended to produce a cardiac d-ECM for cell settlement, representing the ideal scaffold for tissue engineering purposes.

Occurrence and Risk Assessment of Antibiotic Residues in Sewage Sludge of Two Nigerian Hospital Wastewater Treatment Plants

Antibiotic residues in sewage sludge can present detrimental environmental effects due to sewage sludge application onto soils for agricultural purposes. Reports on the occurrence of antibiotics in sewage sludge and risk assessment due to the application of sewage sludge onto soils are still limited in Africa. The occurrence of fourteen antibiotic residues in sewage sludge from two Nigerian hospital wastewater treatment plants was investigated. For the first time, the potential environmental risk of target antibiotics associated with the use of sewage sludge for application onto soils in Nigeria was assessed. Risk assessment was carried out using both terrestrial and aquatic toxicity data. All target antibiotics were detected in at least one sludge sample. Ciprofloxacin and ofloxacin (fluoroquinolones) had the highest concentrations, up to 674 ng g−1 dry weight for ciprofloxacin. All ten antibiotics evaluated for terrestrial ecological risk in sludge-amended soils presented low risk. Only three out of thirteen antibiotics assessed for aquatic ecological risk in sludge-amended soils posed medium risk, while the remaining antibiotics presented low risk. Antibiotic mixtures presented low risk in sludge-amended soils. A more holistic evaluation of the potential risks due to a mixture of a wider scope of chemicals in Nigerian sewage sludge is recommended prior to application onto soils as fertilizers for agricultural purposes.

Anti-Obesity Effect of Theabrownin from Dark Tea in C57BL/6J Mice Fed a High-Fat Diet by Metabolic Profiles through Gut Microbiota Using Untargeted Metabolomics.

The epidemic of obesity is a serious public health problem. In this study, the effect of theabrownin from dark tea on obesity was evaluated by biochemical tests and nuclear magnetic resonance in C57BL/6J mice fed a high-fat diet. A mixture of antibiotics was used to deplete gut microbiota and then fecal microbiota transplant was used to restore gut microbiota. Untargeted metabolomics was used to reveal the effects of theabrownin on metabolic profiles through gut microbiota. The results showed that theabrownin significantly reduced body weight gain (83.0%) and body fat accumulation (30.29%) without affecting appetite. Also, theabrownin promoted lipid clearance with a hepatoprotective effect. The extra antibiotics disrupted the regulation of theabrownin on weight control while fecal microbiota transplant restored the beneficial regulation. That is, gut microbiota was important for theabrownin to reduce body weight gain. The untargeted metabolomics indicated that 18 metabolites were related to the anti-obesity effect of theabrownin mediated by gut microbiota. Furthermore, phenylalanine metabolism, histidine metabolism, as well as protein digestion and absorption pathway played a role in the anti-obesity of theabrownin. Our findings suggested that theabrownin significantly alleviated obesity via gut microbiota-related metabolic pathways, and theabrownin could be used for the prevention and treatment of obesity.

Selection of Mass Transfer Models for Competitive Adsorption of Antibiotics Mixture from Aqueous Solution on Delonix regia Pod Activated Carbon

The selection of suitable mass transfer models that fit the adsorption of a mixture of antibiotics in aqueous solution onto activated carbon derived from Delonix Regia Pods (DRPs) was examined in this study. The ripe DRPs were cleaned, activated with KOH and then carbonised at 350 °C. The surface chemistry of the raw and the modified DRPs were characterised using Fourier Transform Infrared (FTIR), before being subjected to batch adsorption of a mixture of Amoxicillin (AMO), Tetracycline (TETRA) and Ampicillin (AMP) under the effect of time (0-240 mins), and concentration (20-100 mg/l). The adsorption diffusion mechanisms of the process were analyzed. The spectra of the raw and modified DRP indicate the existence of hydroxyl groups alkanes, unconjugated ketone, carbonyl, and ester groups. McKay has the highest (0.9445) for the mass transfer diffusion model. This indicates that the adsorption rate of the selected antibiotics in the wastewater is regulated and monitored by the internal mass transport processes in accordance with a pore diffusion mechanism.

Antibiotics-induced depression in mice via the microbiota-gut-brain axis

BackgroundIntestinal dysbacteriosis is associated with depression. This study aimed to establish an antibiotics-induced depression mouse model and explore the mechanism of antibiotic-induced depression. MethodsC57BL/6 J mice were treated with antibiotics to prepare the antibiotic-induced depression mouse model. Behavioral tests and depression-related bio-markers were examined. To understand the abundance of different bacteria in intestinal flora and screen out the predominant bacterial species, metagenomic analysis of feces was carried out. Finally, we detected the expression of NF-κB-p65 and p-NF-κB-p65 in PFC and the hippocampus using Western blot. ResultsMixtures A and B caused depression-like behavior in mice. Norepinephrine, 5-hydroxytryptamine, and brain-derived neurotrophic factor in hippocampus and PFC of antibiotic-induced depression mice significantly decreased. The serum adrenocorticotropic hormone and corticosterone concentrations increased. The abundance values of Bacteroides thetaiotaomicron, Klebsiella oxytoca, and Klebsiella aerogenes in antibiotic-induced depression mice significantly increased, and the characteristic KO genes and metabolic pathways in antibiotic-induced depression mice were significantly different with in CUMS depression mice (the positive control) and normal mice. The relative levels of p-NF-κB-p65 in antibiotics-induced depression mice were significantly higher than in normal mice. LimitationsHow dysbacteriosis induces inflammation in the central nervous system is unclear. ConclusionsSpecific antibiotic mixture can cause depression-like behavior and changes of depression-related bio-markers in mice. The antibiotic-induced depression mice display changes in the species and metabolism of intestinal bacterial flora. The activation of NF-κB inflammatory signaling pathway in the central nervous system may act as one of the mechanisms in the development of antibiotic-induced depression.

An improved protocol for protoplast production, culture, and whole plant regeneration of the commercial brown seaweed Undaria pinnatifida

Protoplasts (i.e., living plant cells devoid of cell wall) represent an important biotechnological tool with utility for the conduction of in vitro studies and crop improvement in economic cultivars. Undaria pinnatifida is an annual brown kelp commonly used in Asian cuisine and several industries because of its biological properties. It is one of the major seaweed cultivars used worldwide. This study establishes a simple and effective protocol for protoplast isolation, culture, and whole plant regeneration of U. pinnatifida . The results showed that high protoplast yields (2–4 × 10 7 protoplast g −1 of fresh weight) were obtained using the commercially available enzymes cellulase “Onozuka” RS (1 %) and alginate lyase (4 U mL −1 ) without any pre-treatment and with a short incubation time (2–4 h). The isolation protocol described herein presented with more effective results with meristematic explants and was superior to the protocols reported for U. pinnatifida and other brown algae. Additionally, the enzymatic mixture could be reused up to six times. Whole plant regeneration was accomplished after 3 months in culture at 20 °C using two culture media, and a mixture of antibiotics (penicillin G, streptomycin, and chloramphenicol) was added once at the beginning of the culture. Our regeneration protocol was less laborious and more cost-effective, exhibiting final plating efficiency higher than previously reported and demonstrating the potential to be used to produce up to 3 × 10 4 sporophytes g −1 of explant. The established protocol can be easily used for genetic manipulation, protoplast fusion, or micropropagation, thus enabling the expansion of the use of protoplasts in algae. • Single-step production of protoplasts from the edible seaweed Undaria pinnatifida using commercial enzymes • The reusability of the enzyme shows that the process is economically viable. • Antibiotics and temperature are key factors for protoplast survival, division and normal regeneration. • Regeneration protocol is simpler and more effective than previously reported.

Impact of MyD88, Microbiota, and Location on Type 1 and Type 3 Innate Lymphoid Cells during Toxoplasma gondii Infection.

Toxoplasma gondii induces strong IFN-γ-based immunity. Innate lymphoid cells (ILC), in particular ILC1, are an important innate source of this protective cytokine during infection. Our objective was to determine how MyD88-dependent signaling influences ILC function during peroral compared with i.p. infection with T. gondii. MyD88 +/+ and MyD88 -/- mice were orally inoculated with ME49 cysts, and small intestinal lamina propria ILC were assessed using flow cytometry. We observed T-bet+ ILC1, retinoic acid-related orphan receptor γt+ ILC3, and a population of T-bet+retinoic acid-related orphan receptor γt+ double-positive ILC. In MyD88 -/- mice, IFN-γ-producing T-bet+ ILC1 frequencies were reduced compared with wild-type. Treatment of MyD88 -/- mice with an antibiotic mixture to deplete microflora reduced IFN-γ+ ILC1 frequencies. To examine ILC responses outside of the mucosal immune system, peritoneal exudate cells were collected from wild-type and knockout mice after i.p. inoculation with ME49 cysts. In this compartment, ILC were highly polarized to the ILC1 subset that increased significantly and became highly positive for IFN-γ over the course of infection. Increased ILC1 was associated with expression of the Ki67 cell proliferation marker, and the response was driven by IL-12p40. In the absence of MyD88, IFN-γ expression by ILC1 was not maintained, but proliferation remained normal. Collectively, these data reveal new aspects of ILC function that are influenced by location of infection and shaped further by MyD88-dependent signaling.

Anaerobic Digestion in the Presence of Antimicrobials—Characteristics of Its Parameters and the Structure of Methanogens

Antibiotics are widely used in human and veterinary medicine, and they are accumulated in various types of waste, including sewage sludge (SS) and cattle slurry (CS), processed by anaerobic digestion (AD). Anaerobic treatment is a method enabling the stabilization of these substrates before transferring to the environment. The presence of contaminants, such as antimicrobials, in organic substrates processed by AD is not regulated by law. The accumulation of antimicrobials in SS and CS is a crucial issue because it may reduce the effectiveness of their stabilization. This study aimed to evaluate the long-term impact of growing concentrations of a mixture of antibiotics on the AD of SS and CS. Methane (CH4) yield, which is the main indicator of the efficiency of AD, was determined. Antibiotic exposure significantly decreased CH4 production only in SS (by 5–8% relative to control; p &lt; 0.05). The copy numbers of the mcrA gene, a functional marker of methanogenesis, were not reliable indicators of CH4 yields in either substrate. During long-term AD, the average concentrations of the mcrA gene were determined at 108 in 1 g of SS digestate and from 108 to 109 in 1 g of CS digestate samples. At the end of long-term AD, methanogens belonging to the family Methanosarcinaceae were more prevalent than methanogens of the family Methanosaetaceae both in SS and CS samples (107 and 108–109 gene copies in 1 g of digestate, respectively).

Effects of Ciprofloxacin Alone or in Mixture with Sulfamethoxazole on the Efficiency of Anaerobic Digestion and Its Microbial Community.

Some livestock farms rely on anaerobic digestion (AD) technology for manure disposal, thus obtaining energy (biogas) and fertilizer (digestate). Mixtures of antibiotics used for animal health often occur in organic waste and their possible synergistic/antagonistic effects on microorganisms involved in AD are still poorly studied. This work focuses on the effects of adding ciprofloxacin, alone (5 mg L−1) and in combination with sulfamethoxazole (2.5–5–10 mg L−1), on AD efficiency and microbial community structure. The experiment consisted of 90-day cattle manure batch tests and antibiotic removal percentages were assessed. Adding antibiotics always promoted CH4 and H2 production compared to untreated controls; however, CH4 production was lowered with the highest ciprofloxacin (CIP) concentrations. The overall results show antibiotic degradation caused by acidogenic Bacteria, and CH4 was mainly produced through the hydrogenotrophic-pathway by methanogenic Archaea. Shifts in microbial community abundance (DAPI counts) and composition (Illumina-MiSeq and FISH analyses) were observed.

Waktu Henti Antibotik Chloramphenicol Terhadap Perubahan Kadar Residu Pada Ikan Bandeng (Chanos Chanos)

Milkfish is one of the fishery commodities that are in great demand by the Indonesian people, where the obstacle to production decline is disease. Therefore, to prevent disease and treat diseases that attack fish, farmers use the antibiotic Chloramphenicol. However, the use of high doses of antibiotics will cause resistance to pathogenic bacteria and the residue left in the fish's body will have a negative impact on human health who consume them such as allergies, toxicity and even cause death in anemia sufferers which can progress to leukemia. This study aims to determine the length of downtime of the antibiotic Chloramphenicol on changes in residual levels in milkfish (Chanos chanos) aged 30 days decreased to a safe limit for consumption. Residual content test using ELISA at 450 nm wave . Based on the results of the study, milkfish fed with a mixture of chloramphenicol antibiotics at a dose of 1 ppm resulted in the highest residual value of 4.6375 ppb in the first week and a decrease in residue to 0.2363 ppb for 5 weeks. The stopping time of chloramphenicol antibiotics on changes in residual levels in milkfish (Chanos chanos) aged 30 days in treatment F (Milkfish fed with a mixture of chloramphenicol at a dose of 1g/kg of feed for a week, then fed without a mixture of chloramphenicol for 5 weeks) resulted in a safe limit for consumption .

Benign regulation of the gut microbiota: The possible mechanism through which the beneficial effects of manual acupuncture on cognitive ability and intestinal mucosal barrier function occur in APP/PS1 mice.

BackgroundGut microbiota dysbiosis and intestinal barrier injury play vital roles in Alzheimer’s disease (AD) onset and development. Our previous studies have demonstrated that manual acupuncture (MA) could improve the cognitive abilities of APP/PS1 mice. However, the effect of MA on the intestinal mucosal barrier and the gut microbiota mechanism through which this effect occurs remain to be clarified.MethodsIn the APP/PS1 manual acupuncture (Am) group, MA was applied in Baihui (GV20), Yintang (GV29), and Zusanli (ST36). Mice in the APP/PS1 antibiotic + manual acupuncture (Aa) group were treated with an antibiotic mixture and MA at the same time. Probiotics were delivered to the APP/PS1 probiotics (Ap) group. Alterations in spatial learning and memory, the gut microbiota, the intestinal barrier function, and the expression of glial fibrillary acidic protein (GFAP), lipopolysaccharide (LPS), and TNF-α were evaluated in each group.ResultsCompared with the C57BL/6 control (Cc) group, cognitive ability was significantly decreased, the gut microbiota structure was obviously disrupted, intestinal barrier integrity was drastically impaired, and the intestinal inflammatory response was enhanced in the APP/PS1 control (Ac) group (P < 0.01). These changes were reversed by MA and probiotics (P < 0.01 or P < 0.05), whereas antibiotics inhibited the benign regulation by MA (P < 0.01 or P < 0.05).ConclusionManual acupuncture can benignly modulate gut microbiota dysbiosis, significantly reduce intestinal inflammation, and effectively alleviate the destruction of the intestinal mucosal barrier in APP/PS1 mice, and the effects are comparable to those of probiotics. The gut microbiota may play an important role in the improvement of the cognitive function and intestinal barrier function by MA.

Parental transfer of an antibiotic mixture induces cardiotoxicity in early life-stage zebrafish: A cross-generational study

Antibiotic residues in the aquatic environment have been shown to induce significant adverse effects on the early-life stage development of aquatic organisms, though the underlying molecular mechanisms of these effects have not been well characterized. In this study, we performed global mRNA-miRNA sequencing, canonical pathway analyses, morphological, physiological, immunohistochemical, and behavioral analyses to comprehensively assess the cross-generational cardiotoxicity and mechanisms of antibiotic mixtures in zebrafish. Following parental treatment to 1 and 100 μg/L antibiotic mixtures (15 of the most commonly detected antibiotics) for 150 days, all 15 assessed antibiotics were detected in the F1 eggs, indicating the cross-generational transfer of antibiotics. Global mRNA-miRNA sequencing functional analysis predicted cardiotoxicity in the F1 generation by using the F1 whole fish. Consistent with canonical pathway analyses, significant cardiotoxicity was observed in F1 larvae, as well as the apoptosis of cardiac cells. Furthermore, let-7a-5p regulated the cardiac hypertrophy signaling pathway, suggesting mechanisms of miRNA of let-7 family mediating cross-generational cardiotoxicity of antibiotics in zebrafish. This study lays some groundwork for developing interventions to prevent parental exposure to environmental pollutants such as antibiotics from adversely affecting offspring development.

Artificial microbial consortium producing oxidases enhanced the biotransformation efficiencies of multi-antibiotics

Antibiotic mixtures in the environment result in the development of bacterial strains with resistance against multiple antibiotics. Oxidases are versatile that can bio-remove antibiotics. Various laccases (LACs), manganese peroxidases (MNPs), and versatile peroxidase (VP) were reconstructed in Pichia pastoris. For the single antibiotics, over 95.0% sulfamethoxazole within 48 h, tetracycline, oxytetracycline, and norfloxacin within 96 h were bio-removed by recombinant VP with α-signal peptide, respectively. In a mixture of the four antibiotics, 80.2% tetracycline and 95.6% oxytetracycline were bio-removed by recombinant MNP2 with native signal peptide (NSP) within 8 h, whereas < 80.0% sulfamethoxazole was bio-removed within 72 h, indicating that signal peptides significantly impacted removal efficiencies of antibiotic mixtures. Regarding mediators for LACs, 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) resulted in better removal efficiencies of multi-antibiotic mixtures than 1-hydroxybenzotriazole or syringaldehyde. Furthermore, artificial microbial consortia (AMC) producing LAC2 and MNP2 with NSP significantly improved bio-removal efficiency of sulfamethoxazole (95.5%) in four-antibiotic mixtures within 48 h. Tetracycline and oxytetracycline were completely bio-removed by AMC within 48 and 72 h, respectively, indicating that AMC accelerated sulfamethoxazole, tetracycline, and oxytetracycline bio-removals. Additionally, transformation pathways of each antibiotic by recombinant oxidases were proposed. Taken together, this work provides a new strategy to simultaneously remove antibiotic mixtures by AMC.