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The Science of the Total Environment Jun 2024We investigated the potential accumulation of tetracyclines (TCs) such as chlortetracycline (CTC), oxytetracycline (OTC) and doxycycline (DC), and fluoroquinolones (FQs)...
We investigated the potential accumulation of tetracyclines (TCs) such as chlortetracycline (CTC), oxytetracycline (OTC) and doxycycline (DC), and fluoroquinolones (FQs) like enrofloxacin (ENR) and ciprofloxacin (CIP) in chicken litter and agricultural soils fertilized over short-term to long-term (<1-30 yrs) with chicken litter in a poultry hub for the first time from Tamil Nadu, India. CTC, OTC, DC, CIP, and ENR were detected in 46-92 % of the selected chicken litter samples, with mean levels ranging from 2.90 to 23.30 μg kg. Higher concentrations of TCs and FQs were observed in freshly collected chicken litter from poultry sheds than in those stockpiled in cultivated lands. CTC was the prevalent antibiotic in chicken litter. The overall occurrence, as well as the ecological risks of TCs and FQs, changed over a 30-yr period. The accumulation of veterinary antibiotics (VAs) (in μg kg) in short-term (>1 yr) to medium-term (1-3 yrs) chicken litter-fertilized soils reached a maximum of 11.60 for CTC, 6.50 for OTC, 0.80 for DC, 3.70 for CIP, and 3.60 for ENR, but decreased in long-term (10-30 yrs) fertilized soils. Ecological risk assessment revealed a Risk Quotient (RQ) of ≤0.10 for CTC, OTC, and DC in all soils, while an average risk (RQ >0.10-<1.0) was evident with CIP and ENR in short-term and medium-term fertilized soils. Antibiotic resistance genes (ARGs), including tetA, tetB, qnrA, qnrB and qnrS were detected in most of the chicken litter samples and litter-fertilized soils. Thus, it is critical to develop and adopt effective mitigation strategies before applying chicken litter in farmlands to decrease VAs and ARGs, reducing their associated risks to public health and ecosystems in India considering 'One Health' approach. Future investigations on the occurrence of other VAs and ARGs in soils fertilized with poultry litter at regional scale are required for effective risk mitigation of the widely used VAs.
PubMed: 38942301
DOI: 10.1016/j.scitotenv.2024.174286 -
Poultry Science Jun 2024The black soldier fly (BSF, Hermetia illucens) is a resource insect that can utilize livestock and poultry feces. However, BSFs may also increase the risk of...
The black soldier fly (BSF, Hermetia illucens) is a resource insect that can utilize livestock and poultry feces. However, BSFs may also increase the risk of transmission of antibiotic resistance genes (AGRs) that are widespread in livestock and poultry farm environments. Therefore, we aimed to evaluate the biosecurity risks of different BSF treatments in the laying chicken food chain using the "chicken manure-BSF-laying hens" model. Our results indicated that different BSF treatments significantly affected antibiotic residue, ARGs, MGEs, bacterial antibiotic resistance, and bacterial microbial community composition in the food chain of laying hens fed BSFs. These risks can be effectively reduced through starvation treatment and high-temperature grinding treatment. Comprehensive risk assessment analysis revealed that starvation combined with high-temperature milling (Group H) had the greatest effect.
PubMed: 38941787
DOI: 10.1016/j.psj.2024.103965 -
JAMA Jun 2024
PubMed: 38941084
DOI: 10.1001/jama.2024.11024 -
Cancer Medicine Jul 2024Nucleoporin 98 (NUP98) fusion proteins are recurrently found in leukemia and are associated with unfavorable clinical outcomes. They are distributed to the nucleus and...
INTRODUCTION
Nucleoporin 98 (NUP98) fusion proteins are recurrently found in leukemia and are associated with unfavorable clinical outcomes. They are distributed to the nucleus and contribute to leukemogenesis via aberrant transcriptional regulation. We previously identified NUP98-BPTF (NB) fusion in patients with T-cell acute lymphoblastic leukemia (T-ALL) using next-generation sequencing. The FG-repeat of NUP98 and the PHD finger and bromodomain of bromodomain PHD finger transcription factor (BPTF) are retained in the fusion. Like other NUP98 fusion proteins, NB is considered to regulate genes that are essential for leukemogenesis. However, its target genes or pathways remain unknown.
MATERIALS AND METHODS
To investigate the potential oncogenic properties of the NB fusion protein, we lentivirally transduced a doxycycline-inducible NB expression vector into mouse NIH3T3 fibroblasts and human Jurkat T-ALL cells.
RESULTS
NB promoted the transformation of mouse NIH3T3 fibroblasts by upregulating the proto-oncogene Pim1, which encodes a serine/threonine kinase. NB transcriptionally regulated Pim1 expression by binding to its promoter and activated MYC and mTORC1 signaling. PIM1 knockdown or pharmacological inhibition of mTORC1 signaling suppressed NB-induced NIH3T3 cell transformation. Furthermore, NB enhanced the survival of human Jurkat T-ALL cells by inactivating the pro-apoptotic protein BCL2-associated agonist of cell death (BAD).
CONCLUSION
We demonstrated the pivotal role of NB in cell transformation and survival and identified PIM1as a key downstream target of NB. These findings propose a promising therapeutic strategy for patients with NB fusion-positive leukemia.
Topics: Humans; Proto-Oncogene Proteins c-pim-1; Animals; Mice; Cell Transformation, Neoplastic; Nuclear Pore Complex Proteins; Oncogene Proteins, Fusion; Jurkat Cells; Up-Regulation; NIH 3T3 Cells; Proto-Oncogene Mas; Transcription Factors; Apoptosis; Cell Proliferation
PubMed: 38940430
DOI: 10.1002/cam4.7445 -
BioMedicine 2024Metastasis of breast cancer cells to distant sites including lungs, liver, lymph node, brain and many more have substantially affected the overall survival outcome and...
BACKGROUND
Metastasis of breast cancer cells to distant sites including lungs, liver, lymph node, brain and many more have substantially affected the overall survival outcome and distant metastasis free survival rate amongst the diseased individuals. Several pre-clinical and clinical studies were carried out to determine the potency of vigorous inhibitors but they extensively deteriorated the patient's quality of life. Hence, there exists an urgent need to explore potent natural remedy to fight against metastatic breast cancer.
METHODS
Ayurvedic medicinal plants documented in literature for their ability to fight against breast cancer was screened and their respective active moieties were evaluated to exert inhibitory effect against MMP9. Drug like efficacy of phytochemicals were determined using Molecular docking, MD Simulation, ADMET and MM-PBSA and were further compared with synthetic analogs i.e. Doxycycline.
RESULTS
Out of 1000 phytochemicals, 12 exerted highest binding affinity (BA) even more than -9.0 kcal/mol that was significantly higher in comparison to Doxycycline which exhibited BA of -7.3 kcal/mol. In comparison to 37 × 30 × 37 Å, 53 × 45 × 66 Å offered best binding site and the highest BA was exhibited by Viscosalactone at LYS104, ASP185, MET338, LEU39, ASN38. During MD Simulation, Viscosalactone-MMP9 complex remained stable for 20 ns and the kinetic, electrostatic and potential energies were observed to be better than Doxycycline. Furthermore, Viscosalactone obtained from justified the Lipinski's Rule of 5.
CONCLUSION
Viscosalactone obtained from may act as promising drug candidate to fight against metastatic breast cancer.
PubMed: 38939099
DOI: 10.37796/2211-8039.1448 -
Journal of Dentistry Jun 2024To investigate the effectiveness of different adjunctive local treatments combined with non-surgical periodontal therapy (NSPT) to reduce pocket depth (PD), gain... (Review)
Review
OBJECTIVES
To investigate the effectiveness of different adjunctive local treatments combined with non-surgical periodontal therapy (NSPT) to reduce pocket depth (PD), gain clinical attachment level (CAL), and/or reduce glycated hemoglobin (HbA1c) in individuals with both type 2 diabetes mellitus (T2DM) and periodontitis in a systematic review and network meta-analysis.
DATA SOURCES
Publications were searched in Cochrane databases, EMBASE, Google Scholar, MEDLINE, PubMed, opengrey.eu, and www.
CLINICALTRIALS
gov up to May 29, 2024 with no language restriction.
STUDY SELECTION
Only randomized controlled trials (RCTs) were included. Network meta-analysis utilized frequentist models.
DATA
The network meta-analysis of 30 RCTs involving 1224 patients revealed that, in short-term (2-3 months) and medium-term (4-6 months), adjunctive local treatment involving statins or metformin significantly outperformed scaling and root planning (SRP) with/without additional interventions such as photodynamic and laser therapies (PDT/LT), phytotherapy, doxycycline, bisphosphonates, antibiotics, antiseptics, or placebo for reducing PD and/or gaining CAL. In the long-term (>6 months), statins yielded the most significant additional PD reduction and CAL gain, followed by antibiotics, compared to SRP with antiseptics or placebo. Only PDT/LT demonstrated significantly greater HbA1c reduction in the short term compared to SRP with/without statins, antiseptics, or placebo.
CONCLUSION
This study moderately supports that adding metformin or statins locally to NSPT may enhance PD reduction and CAL gain compared to SRP with/without placebo.
CLINICAL SIGNIFICANCE
Clinicians are guided to optimize adjunctive therapies, enhancing the health of patients with type 2 diabetes and periodontitis. A strategic approach is proposed to tackle systemic and oral health challenges simultaneously.
PubMed: 38936456
DOI: 10.1016/j.jdent.2024.105212 -
Dermatologie (Heidelberg, Germany) Jun 2024Prurigo pigmentosa is an inflammatory dermatosis that rarely occurs in Europe and mostly affects young women. Here, we describe the typical clinical and dermoscopic...
Prurigo pigmentosa is an inflammatory dermatosis that rarely occurs in Europe and mostly affects young women. Here, we describe the typical clinical and dermoscopic criteria so that therapy can be initiated as early as possible. The 17-year-old patient presented here shows that this disease can also be observed in Western Europe and in men, and that doxycycline is a very effective treatment option.
PubMed: 38935290
DOI: 10.1007/s00105-024-05383-y -
Journal of Clinical Medicine Jun 2024: () infections can progress to severe respiratory complications, necessitating intensive care treatment. Recent post COVID-19 pandemic surges underscore the need for...
: () infections can progress to severe respiratory complications, necessitating intensive care treatment. Recent post COVID-19 pandemic surges underscore the need for timely diagnosis, given potential diagnostic method limitations. A retrospective case series analysis was conducted on PCR-positive patients admitted to two Dutch secondary hospitals' ICUs between January 2023 and February 2024. Clinical presentations, treatments, outcomes, and mechanical ventilation data were assessed. : Seventeen ICU-admitted patients were identified, with a median age of 44 years, primarily due to hypoxia. Non-invasive ventilation was effective for most, while five required invasive mechanical ventilation. None of the patients required extracorporeal membrane oxygenation. No fatalities occurred. Post-PCR, treatment was adjusted to doxycycline or azithromycin; seven received steroid treatment. : Increased ICU admissions for infection were observed. Diverse clinical and radiological findings emphasize heightened clinical awareness. Early molecular diagnostics and tailored antibiotic regimens are crucial since beta-lactam antibiotics are ineffective. : This study highlights the escalating challenge of severe infections in ICUs, necessitating a multifaceted approach involving accurate diagnostics, vigilant monitoring, and adaptable treatment strategies for optimal patient outcomes.
PubMed: 38929972
DOI: 10.3390/jcm13123443 -
Antibiotics (Basel, Switzerland) May 2024Bacterial urinary tract infections (UTIs) occur frequently in companion animals and are often treated with antibiotics. However, antimicrobial resistance can severely...
Antimicrobial Susceptibility of Canine and Feline Urinary Tract Infection Pathogens Isolated from Animals with Clinical Signs in European Veterinary Practices during the Period 2013-2018.
Bacterial urinary tract infections (UTIs) occur frequently in companion animals and are often treated with antibiotics. However, antimicrobial resistance can severely hamper treatment success. Therefore, antimicrobial susceptibility monitoring is key. UTI isolates were obtained from dogs and cats in two collection periods (ComPath II: 2013-2014 and ComPath III: 2017-2018) as part of CEESA's ComPath programme. Susceptibility testing of the UTI isolates (2021 in total) was carried out at one central laboratory using agar and broth dilution methodology as recommended by the Clinical and Laboratory Standards Institute. was the most frequently isolated bacterium in UTI in both dogs (46.9%, 43.1%) and cats (61.2%, 48.3%) across ComPath II and ComPath III, respectively. The percentage of resistance in was low (<10%) across both programmes in both dogs and cats except for trimethoprim-sulfamethoxazole (dogs ComPath III: 12.9%; cats ComPath II: 13.0%) and enrofloxacin (10.5%), marbofloxacin (11.4%), and doxycycline (98.8%) for dogs in ComPath III. Three (7.5%) of the 40 isolated bacteria in total were MRSA and harboured . The level of multidrug resistance (MDR) was generally low and ranged from 0.0% for feline coagulase-negative spp. to 11.7% for canine spp., except for a peak of MDR observed in canine isolates from ComPath II (36.7%). Overall, antimicrobial resistance for most canine and feline UTI pathogens isolated during the ComPath II and ComPath III programmes was low (1-10%) to moderate (10-20%).
PubMed: 38927167
DOI: 10.3390/antibiotics13060500 -
Antibiotics (Basel, Switzerland) May 2024The impact of soil fertilization with animal manure on the spread and persistence of antibiotic resistance in the environment is far from being fully understood. To add...
The impact of soil fertilization with animal manure on the spread and persistence of antibiotic resistance in the environment is far from being fully understood. To add knowledge about persistence and correlations between antibiotic residues and antibiotic resistance genes (ARGs) in fertilized soil, a longitudinal soil mesocosm study was conducted. Soil samples were collected from the mesocosms immediately before spreading and then afterward at fifteen time points during a 320-day observation period. Eight ARGs (, , A, G, M, , A, and A) and the class 1 integron-integrase gene, , were determined in both pig slurry and soil, as well as residues of 36 antibiotics. Soil chemical and biochemical parameters were also measured. Twelve antibiotics were detected in the slurry in the range of 3 µg kg-3605 µg kg, with doxycycline, lincomycin, and tiamulin being the most abundant, whereas , , and were the predominant ARGs. Before spreading, neither antibiotic residues nor ARGs were detectable in the soil; afterwards, their concentrations mirrored those in the slurry, with a gradual decline over the duration of the experiment. After about three months, the effect of the amendment was almost over, and no further evolution was observed.
PubMed: 38927154
DOI: 10.3390/antibiotics13060486