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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 -
Antibiotics (Basel, Switzerland) May 2024Street food may be a vehicle of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) to humans. Foods contaminated with ARB entail serious problems... (Review)
Review
Street food may be a vehicle of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) to humans. Foods contaminated with ARB entail serious problems or challenges in the fields of medical care, animal husbandry, food industry, and public health worldwide. The objectives of this systematic review were to identify and evaluate scientific reports associated with ARB isolated from various street foods. "Preferred reporting items for systematic reviews and meta-analysis" (PRISMA) guidelines were followed. The bibliographic material covers a period from January 2015 to April 2024. Six electronic scientific databases were searched individually for full-text articles; only those papers that met the inclusion and exclusion criteria were selected. Seventeen papers were included in this systematic review. This study highlighted the wide distribution of ARB resistant to β-lactams and other antibiotics, posing significant health risks to consumers. High resistance levels were observed for antibiotics such as ampicillin, ceftriaxone, and tetracycline, while some antibiotics, such as ceftazidime, clavulanic acid, cefoperazone, cotrimoxazole, doxycycline, doripenem, fosfomycin, vancomycin, and piperacillin-tazobactam, demonstrated 100% susceptibility. The prevalence of ARB in street foods varied between 5.2% and 70.8% among different countries. The multiple resistance of various bacteria, including , , , and , to multiple classes of antibiotics, as well as environmental factors contributing to the spread of antibiotic resistance (AR), emphasize the urgent need for comprehensive approaches and coordinated efforts to confront antimicrobial resistance (AMR) under the "One Health" paradigm.
PubMed: 38927148
DOI: 10.3390/antibiotics13060481 -
Infectious Disease Reports Jun 2024We report the case of a 28-year-old male with uncontrolled human immunodeficiency virus (HIV) infection who presented with extensive ulcerated lesions with dark...
We report the case of a 28-year-old male with uncontrolled human immunodeficiency virus (HIV) infection who presented with extensive ulcerated lesions with dark lamellated crusting on his face, torso, and limbs. The patient had a rapid plasma reagin (RPR) titer of 1:512, indicative of syphilis. A skin biopsy revealed granulomata surrounded by lymphocytes, histiocytes, and plasma cells, with spirochetes visible on immunohistochemical staining. The patient's rash resolved with hyperpigmented scarring after penicillin and doxycycline treatment. This severe form of secondary syphilis has been termed malignant syphilis, lues maligna, ulceronodular syphilis, or rupioid syphilis. We propose a single descriptive name for this entity, ulceronodular-rupioid syphilis. In 1969, Fisher proposed criteria for malignant syphilis based on lesion appearance, histopathologic findings, high RPR values, and rapid response to treatment. We found that the Fisher criteria were imprecise with respect to specific histopathologic findings, the quantitation of RPR values, and what constitutes rapid response to treatment. Thus, we examined an additional 74 cases from the literature and propose new diagnostic criteria based on rash appearance, histopathologic characteristics, non-treponemal and treponemal test positivity, and response to therapy. We also found that uncontrolled viremia, and not a low CD4 count, is a major risk factor for ulceronodular-rupioid syphilis in HIV patients.
PubMed: 38920894
DOI: 10.3390/idr16030038