Mortality Risk of Colistin vs. Non-Colistin Use in Cancer Patients with Multidrug-Resistant Gram-Negative Bacterial Infections: Stratified by Resistance Profile and Concomitant Medications.

Cancer patients are particularly susceptible to infections caused by multidrug-resistant Gram-negative bacteria (MDR GNB) due to chemotherapy- or radiation therapy-induced immunosuppression. Colistin is often prescribed as a last-resort agent for MDR GNB infection, but its clinical benefit in oncology patients remains unclear. This study aims to evaluate the mortality risk associated with colistin versus non-colistin regimens in cancer patient with MDR GNB infections, stratified by resistance profiles, infection sites, and concomitant medication use.

Investigation into Safety Profiles of Antiepileptic Drugs and Identification of Predictors for Serious Adverse Events: Insights from National Pharmacovigilance Data.

This study aims to comprehensively characterize the prevalence and severity of antiepileptic drug (AED)-induced adverse drug events (ADEs) and to identify predictors strongly associated with serious adverse events (SAEs) in both general and geriatric populations. This cross-sectional study investigated AED-related ADEs reported to the KIDS KAERS DB from January 2014 to December 2023. Disproportionality analysis was performed to detect the association between reported SAEs, and multiple logistic regression was conducted to identify predictors associated with SAEs.

Depletion of BRD9-mediated R-loop accumulation inhibits leukemia cell growth via transcription-replication conflict.

Bromodomain-containing protein 9 (BRD9) has emerged as a promising therapeutic target for blood cancers, including acute myeloid leukemia, acute lymphoblastic leukemia, and multiple myeloma. PROTAC-based BRD9 degraders effectively hamper the growth and survival of leukemia cells; however, the underlying mechanism of these BRD9 degraders remains unclear. In this study, we demonstrated that depletion of BRD9 triggers DNA damage via R-loop accumulation, leading to conflicts between transcription and replication processes.

Identifying Predictors of Serious Adverse Events in Antidepressant Treatment from a Decade-Long Nationwide Pharmacovigilance Study: Impact of Dementia and Parkinson's Disease Treatment.

This study aims to characterize the prevalence and severity of antidepressant-associated adverse drug events (ADEs) and to identify predictors strongly associated with serious adverse events (SAEs). Disproportionality analysis on antidepressant-related ADEs spontaneously reported to the Korea Adverse event Reporting System (KIDS KAERS DB) from 2014 to 2023 was performed. Multiple logistic regression was conducted to identify predictors associated with SAEs.

Modulatory effects of cinnamomi cortex and its components epicatechin and linalool on skin circadian rhythms.

Circadian rhythms, intrinsic 24-h cycles regulating physiological processes, are crucial for skin homeostasis. Disruptions in these rhythms are linked to various skin disorders and impaired barrier function. Circadian rhythms can be modulated by botanical compounds, which hold therapeutic potential.

A Comprehensive 10-Year Nationwide Pharmacovigilance Surveillance on Antibacterial Agents in Korea: Data Mining for Signal Detection of Trends and Seriousness of Adverse Events.

A comprehensive pharmacovigilance surveillance on antibacterials is lacking. This study aims to investigate safety signals of antibacterial-related adverse drug events (ADEs) with seriousness and to identify predictors of serious ADEs. This study investigated 52,503 antibacterial-induced ADEs reported to the Korea Adverse Event Reporting System Database from January 2013 to December 2022.

REXO5 promotes genomic integrity through regulating R-loop using its exonuclease activity.

Chronic myeloid leukemia (CML), caused by BCR::ABL1 fusion gene, is known to regulate disease progression by altering the expression of genes. However, the molecular mechanisms underlying these changes are largely unknown. In this study, we identified RNA Exonuclease 5 (REXO5/LOC81691) as a novel gene with elevated mRNA expression levels in chronic myeloid leukemia (CML) patients.

Synthesis and Evaluation of diaryl ether modulators of the leukotriene A hydrolase aminopeptidase activity.

Activation of the aminopeptidase (AP) activity of leukotriene A hydrolase (LTAH) presents a potential therapeutic strategy for resolving chronic inflammation. Previously, ARM1 and derivatives were found to activate the AP activity using the alanine-p-nitroanilide (Ala-pNA) as a reporter group in an enzyme kinetics assay. As an extension of this previous work, novel ARM1 derivatives were synthesized using a palladium-catalyzed Ullmann coupling reaction and screened using the same assay.

Unleashing the potential of CRISPR multiplexing: Harnessing Cas12 and Cas13 for precise gene modulation in eye diseases.

Gene therapy is a flourishing field with the potential to revolutionize the treatment of genetic diseases. The emergence of CRISPR-Cas9 has significantly advanced targeted and efficient genome editing. Although CRISPR-Cas9 has demonstrated promising potential applications in various genetic disorders, it faces limitations in simultaneously targeting multiple genes.

Curative resection of leiomyosarcoma of the descending colon with metachronous liver metastasis: A case report.

Background: Leiomyosarcoma (LMS) has a poor prognosis and rarely originates from the colon. If resection is possible, surgery is the first treatment most commonly considered. Unfortunately, no standard treatment exists for hepatic metastasis of LMS; although, several treatments, such as chemotherapy, radiotherapy, and surgery, have been used.

Substrate-dependent modulation of the leukotriene A hydrolase aminopeptidase activity and effect in a murine model of acute lung inflammation.

The aminopeptidase activity (AP) of the leukotriene A hydrolase (LTAH) enzyme has emerged as a therapeutic target to modulate host immunity. Initial reports focused on the benefits of augmenting the LTAH AP activity and clearing its putative pro-inflammatory substrate Pro-Gly-Pro (PGP). However, recent reports have introduced substantial complexity disconnecting the LTAH modulator 4-methoxydiphenylmethane (4MDM) from PGP as follows: (1) 4MDM inhibits PGP hydrolysis and subsequently inhibition of LTAH AP activity, and (2) 4MDM activates the same enzyme target in the presence of alternative substrates.

An intravitreal implant injection method for sustained drug delivery into mouse eyes.

Using small molecule drugs to treat eye diseases carries benefits of specificity, scalability, and transportability, but their efficacy is significantly limited by a fast intraocular clearance rate. Ocular drug implants (ODIs) present a compelling means for the slow and sustained release of small molecule drugs inside the eye. However, methods are needed to inject small molecule ODIs into animals with small eyes, such as mice, which are the primary genetic models for most human ocular diseases.

Peptidomimetics Therapeutics for Retinal Disease.

Ocular disorders originating in the retina can result in a partial or total loss of vision, making drug delivery to the retina of vital importance. However, effectively delivering drugs to the retina remains a challenge for ophthalmologists due to various anatomical and physicochemical barriers in the eye. This review introduces diverse administration routes and the accordant pharmacokinetic profiles of ocular drugs to aid in the development of safe and efficient drug delivery systems to the retina with a focus on peptidomimetics as a growing class of retinal drugs, which have great therapeutic potential and a high degree of specificity.

Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome.

To elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline.

Improved Diabetic Wound Healing by EGF Encapsulation in Gelatin-Alginate Coacervates.

Topical imageplication of epidermal growth fctor (EGF) has been used to accelerate diabetic foot ulcers but with limited efficacy. In this study, we selected a complex coacervate (EGF-Coa) composed of the low molecular weight gelatin type A and sodium alginate as a novel delivery system for EGF, based on encapsulation efficiency and protection of EGF from protease. EGF-Coa enhanced in vitro migration of keratinocytes and accelerated wound healing in streptozotocin-induced diabetic mice with increased granulation and re-epithelialization.

A Disintegrin and Metalloproteinase 9 (ADAM9) in Advanced Hepatocellular Carcinoma and Their Role as a Biomarker During Hepatocellular Carcinoma Immunotherapy.

The chemotherapeutics sorafenib and regorafenib inhibit shedding of MHC class I-related chain A (MICA) from hepatocellular carcinoma (HCC) cells by suppressing a disintegrin and metalloprotease 9 (ADAM9). MICA is a ligand for natural killer (NK) group 2 member D (NKG2D) and is expressed on tumor cells to elicit attack by NK cells. This study measured mRNA levels in blood samples of advanced HCC patients ( = 10).