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Photodegradation of a Broad-Spectrum Antibiotic Azithromycin Using HO under Ultraviolet Irradiation.International Journal of Molecular... Jun 2024The photodegradation of azithromycin present was carried out in water using HO under UV irradiation. The reaction variables considered in this study were the amount of...
The photodegradation of azithromycin present was carried out in water using HO under UV irradiation. The reaction variables considered in this study were the amount of HO solution and the initial concentration of azithromycin to evaluate the performance of the photodegradation process. The azithromycin degradation was not observed in the dark during stirring for 20 min. The study showed an efficient photodegradation of azithromycin using HO as an oxidant in the presence of UV irradiation. The azithromycin degradation was altered significantly by the pH of the irradiated solution. The degradation was low at an acidic pH and showed an increasing trend as the pH changed to basic. The azithromycin degradation increased with a higher amount (higher concentration) of HO. The degradation of azithromycin decreased with a higher concentration of azithromycin in the reacting solution. The highest degradation of AZT was achieved in 1 h using a 1.0 ppm AZT solution containing 3 mL of HO. The experimental data obtained were well-fitted to zero-order reaction kinetics. The results of this study were found quite excellent. They showed 100% degradation in 1 h when compared with those reported in the literature, both with photocatalysis using nanomaterials and photolysis using light irradiation and/or HO. The UV/HO system was found to be quite efficient for the photodegradation of azithromycin, and this system can be applied to degrade other organic pollutants present in industrial wastewater.
Topics: Azithromycin; Hydrogen Peroxide; Ultraviolet Rays; Photolysis; Anti-Bacterial Agents; Hydrogen-Ion Concentration; Water Pollutants, Chemical; Kinetics
PubMed: 38928406
DOI: 10.3390/ijms25126702 -
International Journal of Molecular... Jun 2024The FUT2 gene encodes an enzyme called α-1,2-fucosyltransferase, which is involved in the formation of blood group antigens AB0(H) and is also involved in the processes...
The FUT2 gene encodes an enzyme called α-1,2-fucosyltransferase, which is involved in the formation of blood group antigens AB0(H) and is also involved in the processes of vitamin B12 absorption and its transport between cells. FUT2 gene polymorphisms are associated with vitamin B12 levels in the body. Vitamin B12 deficiency associated with hyperhomocysteinemia is a major risk factor for cardiovascular diseases (CVDs), which are one of the main causes of death in patients after kidney transplantation. The aim of our study was to determine the impact of the rs602662 (G>A) polymorphism of the FUT2 gene on the functionality of transplanted kidneys and the risk of CVD in patients after kidney transplantation. The study included 402 patients treated with immunosuppression (183 patients taking cyclosporine (CsA) and 219 patients taking tacrolimus (TAC)). The analysis of the FUT2 rs602662 (G>A) polymorphism was performed using real-time PCR. Patients with CsA were more likely to be underweight (1.64% vs. 0.91%) and obese (27.87% vs. 15.98%), while those taking TAC were more likely to be of normal weight (39.27%) or overweight (43.84%). No statistically significant differences were observed comparing the mean blood pressure, both systolic and diastolic. The renal profile showed a higher median urea nitrogen concentration in patients with CsA (26.45 mg/dL (20.60-35.40) vs. 22.95 mg/dL (17.60-33.30), = 0.004). The observed frequency of rs602662 alleles of the FUT2 gene was similar in the analyzed groups. The A allele was present in 43.7% of patients with CsA and 41.1% of those taking TAC (OR = 0.898; 95% CI: 0.678-1.189; = 0.453). In the group with CsA, the GG genotype was present in 32.2% of patients, the GA in 48.1% and the AA in 19.7%. A similar distribution was obtained in the TAC group: GG-33.8%, GA-50.2%, and AA-16.0%. An association of genotypes containing the G allele with a higher incidence of hypertension was observed. The G allele was present in 65% of people with hypertension and in 56% of patients with normal blood pressure ( = 0.036). Moreover, the evaluation of the renal parameters showed no effect of the FUT2 polymorphism on the risk of organ rejection because the levels of creatinine, eGFR, potassium, and urea nitrogen were prognostic of successful transplantation. Our results suggest that the rs6022662 FUT2 polymorphism may influence the risk of cardiovascular diseases.
Topics: Humans; Fucosyltransferases; Galactoside 2-alpha-L-fucosyltransferase; Kidney Transplantation; Male; Female; Cardiovascular Diseases; Middle Aged; Polymorphism, Single Nucleotide; Adult; Risk Factors; Genetic Predisposition to Disease; Genotype; Immunosuppressive Agents; Cyclosporine; Tacrolimus
PubMed: 38928269
DOI: 10.3390/ijms25126562 -
Antibiotics (Basel, Switzerland) May 2024The authors wish to make the following corrections to this paper [...].
Correction: Furugaito et al. Antimicrobial Susceptibility to 27 Drugs and the Molecular Mechanisms of Macrolide, Tetracycline, and Quinolone Resistance in sp. 2023, , 1538.
The authors wish to make the following corrections to this paper [...].
PubMed: 38927238
DOI: 10.3390/antibiotics13060515 -
Biomolecules Jun 2024Diabetes imposes a huge burden worldwide. Islet transplantation is an alternative therapy for diabetes. However, tacrolimus, a kind of immunosuppressant after organ...
Diabetes imposes a huge burden worldwide. Islet transplantation is an alternative therapy for diabetes. However, tacrolimus, a kind of immunosuppressant after organ transplantation, is closely related to post-transplant diabetes mellitus. Mesenchymal stem cells (MSCs) have attracted interest for their potential to alleviate diabetes. In vivo experiments revealed that human menstrual blood-derived stem cells (MenSCs) treatment improved tacrolimus-induced blood glucose, body weight, and glucose tolerance disorders in mice. RNA sequencing was used to analyze the potential therapeutic targets of MenSCs. In this study, we illustrated that cystathionine β-synthase (CBS) contributed to tacrolimus -induced islet dysfunction. Using β-cell lines (MIN6, β-TC-6), we demonstrated that MenSCs ameliorated tacrolimus-induced islet dysfunction in vitro. Moreover, MenSC reduced the tacrolimus-induced elevation of CBS levels and significantly enhanced the viability, anti-apoptotic ability, glucose-stimulated insulin secretion (GSIS), and glycolytic flux of β-cells. We further revealed that MenSCs exerted their therapeutic effects by inhibiting CBS expression to activate the IL6/JAK2/STAT3 pathway. In conclusion, we showed that MenSCs may be a potential strategy to improve tacrolimus-induced islet dysfunction.
Topics: Humans; STAT3 Transcription Factor; Tacrolimus; Interleukin-6; Animals; Mice; Female; Cystathionine beta-Synthase; Islets of Langerhans; Janus Kinase 2; Insulin-Secreting Cells; Menstruation; Mesenchymal Stem Cells; Signal Transduction; Insulin Secretion; Cell Line
PubMed: 38927074
DOI: 10.3390/biom14060671 -
BMC Cancer Jun 2024Accumulating evidence indicates that the use of antibiotics (ATBs) in cancer patients is potentially correlated with patient prognosis. Interestingly, the use of these...
AIMS
Accumulating evidence indicates that the use of antibiotics (ATBs) in cancer patients is potentially correlated with patient prognosis. Interestingly, the use of these agents is not uncommon in colorectal cancer (CRC) patients during surgery; however, their prognostic value in the clinic has never been addressed.
MATERIALS AND METHODS
Data on ATB use during surgery, including the cumulative defined daily dose (cDDD) and the number of categories, were collected. Differences in the clinical data between the low and high cDDD subgroups and between subgroups with ≤ 4 and >4 categories. Additionally, the disease-free survival (DFS) and overall survival (OS) among these subgroups and the specific categories were compared. Finally, a Cox proportional hazard model was used to validate the risk factors for the outcome.
RESULTS
The number of categories, rather than the cDDD, was a significant predictor of both DFS (P = 0.043) and OS (P = 0.039). Patients with obstruction are more likely to have a high cDDD, whereas older patients are more likely to have multiple categories. There were no significant differences in the DFS (log rank = 1.36, P = 0.244) or OS (log rank = 0.40, P = 0.528) between patients in the low- and high-cDDD subgroups, whereas patients with ≤ 4 categories had superior DFS (log rank = 9.92, P = 0.002) and OS (log rank = 8.30, P = 0.004) compared with those with >4 categories. Specifically, the use of quinolones was harmful to survival (DFS: log rank = 3.67, P = 0.055; OS: log rank = 5.10, P = 0.024), whereas the use of macrolides was beneficial to survival (DFS: log rank = 12.26, P < 0.001; OS: log rank = 9.77, P = 0.002). Finally, the number of categories was identified as an independent risk factor for both DFS (HR = 2.05, 95% CI: 1.35-3.11, P = 0.001) and OS (HR = 1.82, 95% CI: 1.14-2.90, P = 0.012).
CONCLUSIONS
The cDDD of ATBs during surgery in stage I-III CRC patients did not correlate with outcome; however, patients in multiple categories or a specific category are likely to have inferior survival. These results suggest that particular caution should be taken when selecting ATBs for these patients in the clinic.
Topics: Humans; Colorectal Neoplasms; Male; Female; Anti-Bacterial Agents; Aged; Middle Aged; Neoplasm Staging; Prognosis; Disease-Free Survival; Risk Factors; Retrospective Studies; Adult; Aged, 80 and over; Treatment Outcome; Proportional Hazards Models
PubMed: 38926655
DOI: 10.1186/s12885-024-12550-w -
The Science of the Total Environment Jun 2024In response to the rapid emergence and dissemination of antimicrobial resistant bacteria (ARB) and genes (ARGs), integrated surveillance systems are needed to address...
In response to the rapid emergence and dissemination of antimicrobial resistant bacteria (ARB) and genes (ARGs), integrated surveillance systems are needed to address antimicrobial resistance (AMR) within the One Health Era. Wastewater analyses enable biomarker monitoring at the sewershed level, offering timely insights into pathogen circulation and ARB/ARGs trends originating from different compartments. During two consecutive epidemic waves of the COVID-19 pandemic in Portugal, taxonomic and functional composition of raw urban wastewater from two wastewater treatment plants (WWTPs) representing one million in equivalent population, located in the main urban areas of the country, were profiled by shotgun metagenomics. Hospital wastewater from two central hospitals located in the WWTPs catchment areas were also sequenced. The resistome and virulome were profiled using metagenomic assemblies without taxonomic constraint, and then specifically characterized for ESKAPE pathogens. Urban and hospital wastewater exhibited specific microbiota signatures, Pseudomonadota dominated in the first and Bacteroidota in the latter. Correlation network analyses highlighted 85 (out of top 100) genera co-occurring across samples. The most frequent ARGs were classified in the multidrug, tetracyclines, and Macrolides, Lincosamides, Streptogramins (MLS) classes. Links established between AMR determinants and bacterial hosts evidenced that the diversity and abundance of ARGs is not restricted to ESKAPE, being also highly predominant among emergent enteropathogens, like Aeromonas and Aliarcobacter, or in the iron (II) oxidizer Acidovorax. The Aliarcobacter genus accumulated high abundance of sulphonamides and polymyxins ARGs, while Acinetobacter and Aeromonas hosted the highest abundance of ARGs against beta-lactams. Other bacteria (e.g. Clostridioides, Francisella, Vibrio cholerae) and genes (e.g. vanA-type vancomycin resistance) of public health interest were detected, with targeted monitoring efforts being needed to establish informative baseline data. Altogether, results highlight that wastewater monitoring is a valuable component of pathogen and AMR surveillance in healthy populations, providing a community-representative snapshot of public health trends beyond priority pathogens.
PubMed: 38925382
DOI: 10.1016/j.scitotenv.2024.174272 -
Clinical and Translational Science Jun 2024The recommended immunosuppressive treatment after kidney transplantation consists of tacrolimus, mycophenolate mofetil, and low-dose corticosteroids. Drug concentrations...
Immune responsiveness in stable kidney transplantation patients: Complete inhibition of T-cell proliferation but residual T-cell activity during maintenance immunosuppressive treatment.
The recommended immunosuppressive treatment after kidney transplantation consists of tacrolimus, mycophenolate mofetil, and low-dose corticosteroids. Drug concentrations are monitored using therapeutic drug monitoring (TDM), which does not necessarily correlate with pharmacodynamic activity. To find the balance between optimal efficacy and minimal toxicity, it might be more informative to monitor patients' immunological status rather than drug concentrations. We selected a panel of T-cell-based immune assays, which were used for immunomonitoring of 14 stable kidney transplantation patients. Whole blood was incubated with a T-cell stimulus, after which T-cell proliferation, T-cell activation marker expression and cytokine production were measured to study residual immune activity in vitro (before drug intake; drug added to the incubation) and ex vivo (after drug intake). T-cell proliferation was completely suppressed in all patients over the full day, while IL-2, IFN-γ, CD71, and CD154 showed fluctuations over the day with a strong inhibition (75%-25%) at 2 h post-dose. The level of inhibition was variable between patients and could not be related to pharmacokinetic parameters or the presence of regulatory or senescence immune cells. Moreover, the level of inhibition did not correlate with the in vitro tacrolimus drug effect as studied by incubating pre-dose blood samples with additional tacrolimus. Overall, IL-2, IFN-γ, CD71, and CD154 seem to be good markers to monitor residual immune activity of transplantation patients. To evaluate the correlation between these pharmacodynamic biomarkers and clinical outcome, prospective observational studies are needed.
Topics: Humans; Kidney Transplantation; Male; Immunosuppressive Agents; Middle Aged; Female; T-Lymphocytes; Cell Proliferation; Adult; Tacrolimus; Lymphocyte Activation; Drug Monitoring; Aged; Mycophenolic Acid; Interferon-gamma
PubMed: 38923308
DOI: 10.1111/cts.13860 -
Toxics Jun 2024The occurrence, distribution, and ecological risk assessment of 36 antibiotics from five groups, including macrolides (MLs), fluoroquinolones (FQs), tetracyclines (TCs),...
The occurrence, distribution, and ecological risk assessment of 36 antibiotics from five groups, including macrolides (MLs), fluoroquinolones (FQs), tetracyclines (TCs), amphenicols (APs), and sulfonamides (SAs), were investigated for the first time in the Anning River, Sichuan Province, China. The results show that antibiotics were widely present in the sediments of the Anning River, with a total of 22 antibiotics detected. FQs were among the most abundant antibiotics, followed by TCs, MLs, APs, and SAs. The total concentrations of antibiotics in surface sediments varied from 0.05 to 53.35 ng/g, with an average of 8.09 ng/g. Among these groups, MLs, FQs, and TCs emerged as the predominant classes of antibiotics. The midstream sediments showed the highest residual levels of antibiotics, with lower levels observed in the downstream and upstream sediments. Anthropogenic activities, such as human clinical practices and animal breeding, might be sources of antibiotics released into the river. An ecological risk assessment revealed that trimethoprim from the SA group exhibited high risks, and MLs showed medium risks in the Anning River, whereas most antibiotics presented minimal to low risks. This study provides valuable information on antibiotic pollution in the upstream region of the Yangtze River, and future management measures are needed for the Anning River.
PubMed: 38922091
DOI: 10.3390/toxics12060411 -
BioRxiv : the Preprint Server For... Jun 2024HflX is known to rescue stalled ribosomes and is implicated in antibiotic resistance in several bacteria. Here we present several high-resolution cryo-EM structures of...
HflX is known to rescue stalled ribosomes and is implicated in antibiotic resistance in several bacteria. Here we present several high-resolution cryo-EM structures of mycobacterial HflX in complex with the ribosome and its 50S subunit, with and without antibiotics. These structures reveal a distinct mechanism for HflX-mediated ribosome splitting and antibiotic resistance in mycobacteria. In addition to dissociating ribosome into two subunits, mycobacterial HflX mediates persistent disordering of multiple 23S rRNA helices to generate an inactive pool of 50S subunits. Mycobacterial HflX also acts as an anti-association factor by binding to pre-dissociated 50S subunits. A mycobacteria-specific insertion in HflX reaches further into the peptidyl transferase center. The position of this insertion overlaps with ribosome-bound macrolides or lincosamide class of antibiotics. The extended conformation of insertion seen in the absence of these antibiotics retracts and adjusts around the bound antibiotics instead of physically displacing them. It therefore likely imparts antibiotic resistance by sequestration of the antibiotic-bound inactive 50S subunits.
PubMed: 38915643
DOI: 10.1101/2024.06.13.598844 -
Journal of Korean Medical Science Jun 2024Antimicrobial resistance (AMR) is an important global public health concern in adults and children. Laryngotracheobronchitis (croup) is a common acute respiratory...
BACKGROUND
Antimicrobial resistance (AMR) is an important global public health concern in adults and children. Laryngotracheobronchitis (croup) is a common acute respiratory infection (ARI) among children, most often caused by a virus, and should not be treated with antibiotics. Reducing the usage of unnecessary antibiotics in ARI using an antimicrobial stewardship program (ASP) is an effective measure against AMR in children. This study investigates the antibiotic prescription pattern in pediatric patients with laryngotracheobronchitis in Korea. Our results will be useful to improve the ASP.
METHODS
The data were obtained from the government agency Health Insurance Review and Assessment Service. We analyzed outpatient prescriptions issued to children ≤ 5 years of age with a first-listed diagnosis code for laryngotracheobronchitis, i.e., International Classification of Disease, 10th Revision, code J050 (croup), J040 (laryngitis), or J041 (tracheitis), during 2017-2020. For each prescription, demographic information and information about medical facilities visited (type of hospital, specialty of physician, location of hospital) were extracted. The overall antibiotic prescription rate was subsequently estimated, and multivariable analysis was conducted to determine the associated factors of antibiotic prescription. Prescribed antibiotics were described and classified into extended-spectrum penicillins, cephalosporin, and macrolides.
RESULTS
Of 2,358,194 prescriptions reviewed, 829,172 (35.2%) contained antibiotics. In the multivariable analysis, management in a hospital was the strongest factor associated with antibiotic prescription (adjusted odds ratio [aOR], 22.33; 95% confidence interval [CI], 20.87-23.89; < 0.001), followed by management in a clinic (aOR, 12.66; 95% CI, 11.83-13.54; < 0.001) and management in a general hospital (aOR, 8.96; 95% CI, 8.37-9.59; < 0.001). Antibiotic prescription was also significantly associated with patients who were ≤ 2 years of age, managed by a pediatric specialist, and treated at a hospital located in a non-metropolitan region. Overall, extended-spectrum penicillins were the most frequently prescribed (18.6%) antibiotics, followed by cephalosporins (9.4%) and macrolides (8.5%).
CONCLUSION
The results of our study suggest that ASPs need to focus on physicians in hospitals, clinics, general hospitals, and pediatric specialties. Providing education programs to these groups to increase awareness of AMR and appropriate antibiotics use could be effective ASP policy and may help to reduce unnecessary prescriptions of antibiotics for laryngotracheobronchitis among pediatric patients and therefore potentially AMR in children in Korea.
Topics: Humans; Anti-Bacterial Agents; Republic of Korea; Child, Preschool; Infant; Male; Female; Tracheitis; Antimicrobial Stewardship; Laryngitis; Practice Patterns, Physicians'; Bronchitis; Infant, Newborn; Drug Prescriptions; Croup
PubMed: 38915281
DOI: 10.3346/jkms.2024.39.e189