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Current Microbiology Jun 2024Delftia has been separated from freshwater, sludge, and soil and has emerged as a novel opportunistic pathogen in the female vagina. However, the genomic...
Delftia has been separated from freshwater, sludge, and soil and has emerged as a novel opportunistic pathogen in the female vagina. However, the genomic characteristics, pathogenicity, and biotechnological properties still need to be comprehensively investigated. In this study, a Delftia strain was isolated from the vaginal discharge of a 43-year-old female with histologically confirmed cervical intraepithelial neoplasm (CIN III), followed by whole-genome sequencing. Phylogenetic analysis and average nucleotide identity (ANI) analysis demonstrated that it belongs to Delftia lacustris, named D. lacustris strain LzhVag01. LzhVag01 was sensitive to β-lactams, macrolides, and tetracyclines but exhibited resistance to lincoamines, nitroimidazoles, aminoglycosides, and fluoroquinolones. Its genome is a single, circular chromosome of 6,740,460 bp with an average GC content of 66.59%. Whole-genome analysis identified 16 antibiotic resistance-related genes, which match the antimicrobial susceptibility profile of this strain, and 11 potential virulence genes. These pathogenic factors may contribute to its colonization in the vaginal environment and its adaptation and accelerate the progression of cervical cancer. This study sequenced and characterized the whole-genome of Delftia lacustris isolated from vaginal discharge, which provides investigators and clinicians with valuable insights into this uncommon species.
Topics: Delftia; Genome, Bacterial; Vaginal Discharge; Humans; Female; Adult; Phylogeny; Anti-Bacterial Agents; Drug Resistance, Bacterial; Virulence Factors; Species Specificity
PubMed: 38898312
DOI: 10.1007/s00284-024-03758-x -
International Journal of Molecular... May 2024Amino acid permeases (AAPs) transporters are crucial for the long-distance transport of amino acids in plants, from source to sink. While and rice have been extensively...
Amino acid permeases (AAPs) transporters are crucial for the long-distance transport of amino acids in plants, from source to sink. While and rice have been extensively studied, research on foxtail millet is limited. This study identified two transcripts of , both of which were induced by NO and showed similar expression patterns. The overexpression of and in inhibited plant growth and seed size, although SiAAP9 was found to transport more amino acids into seeds. Furthermore, transgenic showed increased tolerance to high concentrations of glutamate (Glu) and histidine (His). The high overexpression level of suggested its protein was not only located on the plasma membrane but potentially on other organelles, as well. Interestingly, sequence deletion reduced SiAAP9's sensitivity to Brefeldin A (BFA), and SiAAP9 had ectopic localization on the endoplasmic reticulum (ER). Protoplast amino acid uptake experiments indicated that SiAAP9 enhanced Glu transport into foxtail millet cells. Overall, the two transcripts of have similar functions, but SiAAP9L shows a higher colocalization with BFA compartments compared to SiAAP9S. Our research identifies a potential candidate gene for enhancing the nutritional quality of foxtail millet through breeding.
Topics: Arabidopsis; Plants, Genetically Modified; Gene Expression Regulation, Plant; Plant Proteins; Endoplasmic Reticulum; Seeds; Setaria Plant; Amino Acid Transport Systems; Protein Transport; Brefeldin A; Amino Acids; Glutamic Acid
PubMed: 38892028
DOI: 10.3390/ijms25115840 -
International Journal of Molecular... May 2024(IIIb) is frequently isolated from reptiles and less frequently from birds and mammals. However, its isolation from invasive human infections has not been widely...
(IIIb) is frequently isolated from reptiles and less frequently from birds and mammals. However, its isolation from invasive human infections has not been widely reported. Migratory mallard ducks are excellent bioindicators of pathogen presence and pathogen antibiotic resistance (AMR). We present the first isolation from a mallard duck in central Europe of the antibiotic-resistant subsp. with the unique antigenic pattern 58:r:z and report its whole-genome sequencing, serosequencing, and genotyping, which enabled the prediction of its pathogenicity and comparison with phenotypic AMR. The isolated strain was highly similar to isolated from humans and food. Twenty-four AMR genes were detected, including those encoding aminoglycoside, fluoroquinolone, macrolide, carbapenem, tetracycline, cephalosporin, nitroimidazole, peptide antibiotic, and disinfecting agent/antiseptic resistance. Six pathogenicity islands were found (SPI-1, SPI-2, SPI-3, SPI-5, SPI-9, and SPI-13). An iron transport system was detected in SPI-1 centisome C63PI. Plasmid profile analyses showed three to be present. Sequence mutations in the and genes were noted, which truncated and elongated the proteins, respectively. The strain also harbored genes encoding type-III secretion-system effector proteins and many virulence factors found in associated with human infections. This study aims to elucidate the AMR and virulence genes in subsp. that may most seriously threaten human health.
Topics: Animals; Ducks; Humans; Salmonella; Whole Genome Sequencing; Genomic Islands; Salmonella Infections, Animal; Anti-Bacterial Agents; Salmonella enterica; Drug Resistance, Multiple, Bacterial; Genome, Bacterial; Phylogeny; Drug Resistance, Bacterial; Plasmids
PubMed: 38891852
DOI: 10.3390/ijms25115664 -
Open Heart Jun 2024For high bleeding-risk patients (HBR) undergoing percutaneous coronary intervention (PCI), the LEADERS FREE (LF) and LEADERS FREE II (LF II) trials established the... (Comparative Study)
Comparative Study
BACKGROUND
For high bleeding-risk patients (HBR) undergoing percutaneous coronary intervention (PCI), the LEADERS FREE (LF) and LEADERS FREE II (LF II) trials established the safety and efficacy of a stainless steel polymer-free biolimus-coated stent (SS-BCS) with 30 days of dual antiplatelet treatment (DAPT). The LEADERS FREE III (LF III) trial investigated clinical outcomes after PCI with the next-generation cobalt-chromium thin-strut polymer-free biolimus-coated stent (CoCr-BCS) in HBR patients.
AIMS
To report the final 3-year results of the LF III trial and compare them to LF II.
METHODS
LF III was a prospective, multicentre, open-label single-arm study to evaluate the safety and efficacy of the CoCr-BCS stent. The primary safety endpoint was the composite of cardiac death (CD), myocardial infarction(MI) or definite/probable stent thrombosis (ST). The primary efficacy endpoint was clinically driven target lesion revascularisation (cd-TLR). We performed a propensity-matched comparison to the 3-year outcomes of LF II.
RESULTS
After 3 years, CD/MI/ST had occurred in 57 patients (15%, 95% CI 11.8% to 19%) and cd-TLR in 23 (6.2%, 95% CI 4.1% to 9.2%) patients. In a propensity-matched comparison of patients treated with the CoCr-BCS versus the SS-BCS, there were similar rates of CD (6.6% vs 7.8%, p=0.50), MI (7.1% vs 8.3%, p=0.47) and definite/probable ST (1.1% vs 2%, HR 0.56, 95% CI 0.16 to 1.93, p=0.35). The rates of cd-TLR were 5.3% with CoCr-BCS versus 9.8% with SS-BCS (HR 0.54, 95% CI 0.31 to 0.96, p=0.03).
CONCLUSION
LF III confirms the long-term safety and efficacy of the CoCr-BCS in HBR patients treated with 1 month of DAPT.
TRIAL REGISTRATION NUMBER
NCT02843633, NCT03118895.
Topics: Humans; Drug-Eluting Stents; Male; Prospective Studies; Female; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Treatment Outcome; Coronary Artery Disease; Aged; Time Factors; Middle Aged; Follow-Up Studies; Platelet Aggregation Inhibitors; Risk Factors
PubMed: 38890129
DOI: 10.1136/openhrt-2024-002679 -
Clinical Cardiology Jun 2024Long-term follow-up results of various trials comparing Zotarolimus eluting stents (ZES) with Everolimus eluting stents (EES) have been published recently. Additionally,... (Comparative Study)
Comparative Study Meta-Analysis
Temporal Trends in the Outcomes of Percutaneous Coronary Intervention With Zotarolimus Eluting Stents Versus Everolimus Eluting Stents: A Meta-Analysis of Randomized Controlled Trials.
INTRODUCTION
Long-term follow-up results of various trials comparing Zotarolimus eluting stents (ZES) with Everolimus eluting stents (EES) have been published recently. Additionally, over the last decade, there have been new trials comparing the ZES with various commercially available EES. We aim to conduct an updated meta-analysis in light of new evidence from randomized controlled trials (RCTs) to provide comprehensive evidence regarding the temporal trends in the clinical outcomes.
METHODS
A comprehensive literature search was conducted across PubMed, Cochrane, and Embase. RCTs comparing ZES with EES for short (<2 years), intermediate (2-3 years), and long-term follow-ups (3-5 years) were included. Relative risk was used to pool the dichotomous outcomes using the random effects model employing the inverse variance method. All statistical analysis was conducted using Revman 5.4.
RESULTS
A total of 18 studies reporting data at different follow-ups for nine trials (n = 14319) were included. At short-term follow-up (<2 years), there were no significant differences between the two types of stents (all-cause death, cardiac death, Major adverse cardiovascular events (MACE), target vessel myocardial infarction, definite or probable stent thrombosis or safety outcomes (target vessel revascularization, target lesion revascularization, target vessel failure, target lesion failure). At intermediate follow-up (2-3 years), EES was superior to ZES for reducing target lesion revascularization (RR = 1.28, 95% CI = 1.05-1.58, p < 0.05). At long-term follow-up (3-5 years), there were no significant differences between the two groups for any of the pooled outcomes (p > 0.05).
CONCLUSION
ZES and EES have similar safety and efficacy at short, intermediate, and long-term follow-ups.
Topics: Humans; Cardiovascular Agents; Coronary Artery Disease; Drug-Eluting Stents; Everolimus; Percutaneous Coronary Intervention; Prosthesis Design; Randomized Controlled Trials as Topic; Risk Factors; Sirolimus; Time Factors; Treatment Outcome
PubMed: 38888152
DOI: 10.1002/clc.24306 -
Journal of Environmental Health Science... Jun 2024Today, antibiotics are widely used for treatment and feed additives to enhance livestock growth. Antibiotic residues may be found in food of animal origin for various... (Review)
Review
BACKGROUND
Today, antibiotics are widely used for treatment and feed additives to enhance livestock growth. Antibiotic residues may be found in food of animal origin for various reasons, including ignoring the withdrawal period after treatment, overuse for animals, and contamination of feed with treated animals in animal products. Among animal products, dairy products have a special place in the human diet, and antibiotic residues in them have caused a great deal of concern among consumers.
OBJECTIVE
This systematic review and meta-analysis aimed to evaluate and compare studies conducted in Iran on antibiotic residues in dairy products during 2000-2022.
METHODS
In this review, 52 eligible studies were collected by searching the Scientific Information Database (SID), Magiran, Google Scholar, Science-Direct, Scopus, and PubMed using the English or Persian keywords such as an antibiotic or antimicrobial residue, Beta-lactam residue, Tetracycline residue, Sulfonamide residue, Chloramphenicol residue, Aminoglycosides residue, Macrolide residue, Quinolones residue, Milk, Raw milk, Pasteurized milk, UHT milk, Powder milk, Cheese, Yogurt, Butter, Cream, Doogh, Kashk, Ice cream, and Iran.
RESULTS
According to the reviewed studies, the total prevalence of antibiotic residues in dairy products was 29% (95% CI: 15-43%). Among the seven evaluated antibiotic groups, most studies have been conducted on tetracycline, beta-lactam, and sulfonamide groups, with 16, 10, and 7 respectively, and the highest level of contamination with 663 ± 1540 μg/l is related to tetracycline. Most studies on antibiotic dairy product residues in Iran with 12, 11, and 8 studies are associated with East Azarbaijan province, then Tehran and Khorasan Razavi respectively, and no study has been conducted in 11 provinces of the country. According to the studies, Gilan, Qazvin and Razavi Khorasan provinces had the highest amount of antibiotic residue in milk with an average value of 56.415 ± 33.354, 45.955 ± 4.179 and 45.928 ± 33.027, respectively. Most of the methods used in the studies to measure antibiotic residues in milk were the Copan test kit and the HPLC method, which were used in 19 and 14 studies, respectively.
CONCLUSIONS
Studies have shown that the prevalence of antibiotic residue in dairy products in Iran is high, so applying an effective strategy and developing the necessary standards in this field to control milk quality is a public health necessity. The findings of this study show that further evaluation of fermented dairy products, especially non-fermented ones such as butter and cream, is needed to prevent adverse health reactions.
PubMed: 38887764
DOI: 10.1007/s40201-023-00889-4 -
BMC Pulmonary Medicine Jun 2024Rapamycin has been extensively utilized for coating coronary artery stents to reduce the occurrence of restenosis, yet there has been limited research on the potential...
BACKGROUND
Rapamycin has been extensively utilized for coating coronary artery stents to reduce the occurrence of restenosis, yet there has been limited research on the potential harms of rapamycin-eluting stents. Herein, We report a case of eosinophilia and interstitial pneumonia caused by a cobalt-based alloy stent eluted with rapamycin.
CASE PRESENTATION
The patient was admitted due to fever, cough, and expectoration symptoms. Previously, the patient had undergone a procedure of percutaneous coronary stent implantation in our hospital's cardiology department, which led to a gradual rise in blood eosinophil count. This time, the eosinophil count was higher than the previous admission. A chest CT scan revealed multiple flocculent density increases in both lungs and bronchiectasis. The rapamycin-eluting stents may have caused eosinophilia and interstitial pneumonia, which improved after administering corticosteroids. A systematic review of relevant literature was conducted to summarize the characteristics of interstitial pneumonia caused by drug-eluting stents.
CONCLUSION
Paclitaxel, everolimus, zotarolimus, and rapamycin are the types of drugs that can lead to drug-eluting stents, and because of the rarity of their onset, clinical doctors must be precise and prompt in diagnosing suspected cases to avoid misdiagnosis and delayed treatment.
Topics: Humans; Lung Diseases, Interstitial; Drug-Eluting Stents; Sirolimus; Eosinophilia; Male; Tomography, X-Ray Computed; Percutaneous Coronary Intervention; Aged
PubMed: 38886703
DOI: 10.1186/s12890-024-03101-x -
Vascular Health and Risk Management 2024Kaposiform hemangioendothelioma(KHE) without Kasabach-Merritt phenomenon is a rare tumor primarily observed in pediatric patients; however, its documentation in the... (Review)
Review
Kaposiform hemangioendothelioma(KHE) without Kasabach-Merritt phenomenon is a rare tumor primarily observed in pediatric patients; however, its documentation in the literature remains limited. We reported about a 1-year-old boy diagnosed with superficial KHE who received oral propranolol in combination with topical sirolimus and reviewed relevant reports and treatment of superficial KHE.
Topics: Humans; Infant; Male; Administration, Oral; Biopsy; Hemangioendothelioma; Propranolol; Sarcoma, Kaposi; Sirolimus; Treatment Outcome
PubMed: 38883398
DOI: 10.2147/VHRM.S461505 -
Signal Transduction and Targeted Therapy Jun 2024Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK, an endothelial transmembrane receptor...
Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK, an endothelial transmembrane receptor signaling through PIK3CA. Venous malformations are associated with pain, bleedings, thrombosis, pulmonary embolism, esthetic deformities and, in severe cases, life-threatening situations. No authorized medical treatment exists for patients with venous malformations. Here, we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient phenotypes. We showed that these malformations only partially signal through AKT proteins. We compared the efficacy of different drugs, including rapamycin, a mTORC1 inhibitor, miransertib, an AKT inhibitor and alpelisib, a PI3Kα inhibitor at improving the lesions seen in the mouse model. We demonstrated the effectiveness of alpelisib in preventing vascular malformations' occurrence, improving the already established ones, and prolonging survival. Considering these findings, we were authorized to treat 25 patients with alpelisib, including 7 children displaying PIK3CA (n = 16) or TEK (n = 9)-related capillary venous malformations resistant to usual therapies including sirolimus, debulking surgical procedures or percutaneous sclerotherapies. We assessed the volume of vascular malformations using magnetic resonance imaging (MRI) for each patient. Alpelisib demonstrated improvement in all 25 patients. Vascular malformations previously considered intractable were reduced and clinical symptoms were attenuated. MRI showed a decrease of 33.4% and 27.8% in the median volume of PIK3CA and TEK malformations respectively, over 6 months on alpelisib. In conclusion, this study supports PI3Kα inhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.
Topics: Class I Phosphatidylinositol 3-Kinases; Animals; Mice; Humans; Vascular Malformations; Capillaries; Female; Male; Sirolimus; Child; Disease Models, Animal; Molecular Targeted Therapy; Thiazoles
PubMed: 38880808
DOI: 10.1038/s41392-024-01862-9 -
Biomedicine & Pharmacotherapy =... Jul 2024The unresectable or postoperative recurrence of advanced metastatic colorectal cancer (CRC) is the difficulty of its clinical management, and pharmacological therapy is...
The unresectable or postoperative recurrence of advanced metastatic colorectal cancer (CRC) is the difficulty of its clinical management, and pharmacological therapy is the main source of benefit. Immune checkpoint inhibitors are therapeutic options but are effective in approximately 5 % of patients with deficient mismatch repair (MMR)/microsatellite instability CRC and are ineffective in patients with MMR-proficient (pMMR)/microsatellite stable (MSS) CRCs, which may be associated with the tumor microenvironment (TME). Here, we propose a new combination strategy and evaluate the efficacy of rapamycin (Rapa) combined with anti-PD-1 (αPD-1) in CT26 tumor-bearing mice, azoxymethane (AOM)/dextran sodium sulfate (DSS) inflammation-associated CRC mice, CT26-Luc tumor-bearing mice with postoperative recurrence, and CT26 liver metastasis mice. The results revealed that Rapa improved the therapeutic effect of αPD-1 and effectively inhibited colorectal carcinogenesis, postoperative recurrence, and liver metastasis. Mechanistically, Rapa improved the anticancer effect of αPD-1, associated with Rapa reprograming of the immunosuppressive TME. Rapa effectively depleted α-SMA cancer-associated fibroblasts and degraded collagen in the tumor tissue, increasing T lymphocyte infiltration into the tumor tissue. Rapa induced the downregulation of programed cell death 1 ligand 1 (PD-L1) protein and transcript levels in CT26 cells, which may be associated with the inhibition of the mTOR/P70S6K signaling axis. Furthermore, co-culture of tumor cells and CD8 T lymphocytes demonstrated that Rapa-induced PD-L1 downregulation in tumor cells increased spleen-derived CD8 T lymphocyte activation. Therefore, Rapa improves the anti-tumor effect of αPD-1 in CRCs, providing new ideas for its use to improve combinatorial strategies for anti-PD-1 immunotherapy.
Topics: Animals; Tumor Microenvironment; Colorectal Neoplasms; Sirolimus; B7-H1 Antigen; Mice; Cell Line, Tumor; Immune Checkpoint Inhibitors; Mice, Inbred BALB C; Drug Resistance, Neoplasm; Programmed Cell Death 1 Receptor; Male; Humans; Liver Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38876047
DOI: 10.1016/j.biopha.2024.116883