[Effect of ten-eleven translocation methylcytosine dioxygenase 2 gene mutations on the secondary myelofibrosis of JAK2 positive myeloproliferative neoplasms patients].

To investigate the effect of ten-eleven translocation methylcytosine dioxygenase 2 (TET2) gene mutations on the secondary myelofibrosis (SMF) of JAK2 myeloproliferative neoplasms (MPN) patients. A retrospective collection was conducted on MPN patients with JAK2 mutation detected by second-generation sequencing in the Department of Hematology, the Second Hospital of Tianjin Medical University. TET2JAK2 MPN patients were selected as the mutant group, and TET2JAK2 MPN patients matched for age and gender were selected as the non-mutant group.

Computer-Aided Design of Self-Assembled Nanoparticles to Enhance Cancer Chemoimmunotherapy via Dual-Modulation Strategy.

The rational design of self-assembled compounds is crucial for the highly efficient development of carrier-free nanomedicines. Herein, based on computer-aided strategies, important physicochemical properties are identified to guide the rational design of self-assembled compounds. Then, the pharmacophore hybridization strategy is used to design self-assemble nanoparticles by preparing new chemical structures by combining pharmacophore groups of different bioactive compounds.

Proposed resources required for a comprehensive program for CCT CHD imaging.

Background: Cardiac Computed Tomography (CCT) is increasingly used for evaluation of congenital heart disease (CHD) in patients of all ages. Pediatric and adult congenital heart disease (ACHD) surgical programs require high quality CCT imaging as part of the multimodality imaging support expected of comprehensive care centers. Despite these expectations, there are no benchmarks or defined programmatic elements specific to the performance of CCT in patients with CHD.

Interleukin-6 (IL-6)-associated tumor microenvironment remodelling and cancer immunotherapy.

Interleukin-6 (IL-6) is a pro-inflammatory cytokine playing a pivotal role during inflammation and immune responses. In the recent years, the function of IL-6 in the tumor microenvironment (TME) for affecting tumorigenesis and immunotherapy response has been investigated. The genetic mutations are mainly responsible for the development of cancer, while interactions in TME are also important, involving both cancers and non-cancerous cells.

Neratinib Efficacy in Patients With EGFR Exon 18-Mutant Non-Small-Cell Lung Cancer: Findings From the SUMMIT Basket Trial.

Background: Activating mutations in the epidermal growth factor receptor (EGFR) gene occur in 7% to 23% of patients with non-small-cell lung cancer (NSCLC). A small proportion of these (3-5%) are exon 18 mutations. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), had activity in the phase II SUMMIT basket study.

Inflammasome Activation and Neutrophil Extracellular Traps in Atherosclerosis.

The deposition of cholesterol containing cholesterol crystals and the infiltration of immune cells are features of atherosclerosis. Although the role of cholesterol crystals in the progression of atherosclerosis have long remained unclear, recent studies have clarified the involvement of cholesterol crystals in inflammatory responses. Cholesterol crystals activate the NLRP3 inflammasome, a molecular complex involved in the innate immune system.

Successful treatment of etanercept- and adalimumab-resistant pyoderma gangrenosum with spesolimab, moderate-dose corticosteroids, and minocycline.

Purpose: Pyoderma gangrenosum (PG) is a rare, neutrophilic dermatosis characterized by rapidly developing, painful ulcers. This study explores the potential of spesolimab, an anti-IL-36R antibody, as a therapeutic option for refractory PG.

Materials And Methods: We report a case of a 48-year-old male with refractory PG who failed to respond to etanercept and adalimumab.

Purification and characterization of recombinant human mitochondrial proton-pumping nicotinamide nucleotide transhydrogenase.

The human mitochondrial nicotinamide nucleotide transhydrogenase (NNT) uses the proton motive force to drive hydride transfer from NADH to NADP and is a major contributor to the generation of mitochondrial NADPH. NNT plays a critical role in maintaining cellular redox balance. NNT-deficiency results in oxidative damage and its absence results in familial glucocorticoid deficiency.

Immunological and protective evaluation of purE/purK gene-deletion mutant of Brucella melitensis M5 strain.

Brucellosis is listed by the World Health Organization as one of the seven most neglected global zoonotic diseases. A live-attenuated vaccine is still the main strategy used to prevent the spread of brucellosis. In this study, we constructed a two-gene (purE and purK)-deletion vaccine in Brucella melitensis vaccine strain M5 with homologous recombination.

Tracheal, bronchus, and lung cancer mortality and air pollution exposure in Tuscany, Italy: Bayesian Health Impact Assessment and Global Sensitivity Analysis on a sub-regional scale.

Outdoor air pollution is a significant risk factor for tracheal, bronchus, and lung (TBL) cancer. This study employs a Bayesian approach to evaluate TBL cancer mortality due to air pollution in Tuscany, Central Italy, in 2023. Using locally validated data, we assessed the impact of fine particulate matter (PM and PM) and nitrogen dioxide (NO) in terms of attributable deaths and years of life lost (YLL).

Toona sinensis fruit polyphenols alleviate cerebral ischemia-reperfusion injury in rats by inhibiting MAPK signaling pathways and NLRP3 inflammasome/pyroptosis.

Ethnopharmacological Relevance: Toona sinensis fruit polyphenols (TSFP) are polyphenols that have been separated and extracted from mature Toona sinensis fruits. TSFP anti-inflammatory and neuroprotective properties have demonstrated promise. However, the underlying mechanisms require more elucidation.

An engineered Palivizumab IgG2 subclass for synthetic gp130 and fas mediated signaling.

Recently, we phenocopied Interleukin (IL-)6 signaling using the dimerized single-chain variable fragment (scFv) derived from the respiratory syncytial virus (RSV) IgG1-antibody Palivizumab (PLHFc) to activate a Palivizumab anti-idiotypic nanobody (AIP)-gp130 receptor fusion protein. Palivizumab was unable to activate STAT3 signaling, so we aimed to create a similar ligand capable of triggering this pathway. Here, we created three variants of the ligand called PLH0Fc, PLH4Fc and PLH8Fc by shortening the spacer region connecting PLH and Fc from 23 amino acids in PLHFc to 0 amino acids or expanding it by rigid linkers of 4 or 8 alpha helical loops, respectively.

Trends and Epidemiology in Revision Total Hip Arthroplasty: A Large Database Study.

Background: The clinical and financial burden of revision total hip arthroplasty (rTHA) continues to grow. Therefore, further investigation is needed to characterize case volume, reason for failure, and postoperative complications. The purpose of this study was to characterize contemporary indications for and complications following rTHA.

Bacterial enteritis caused by Salmonella Kedougou after returning from Thailand: A case report.

Non-typhoid Salmonella (NTS) includes many serotypes that differ in host, geographic distribution, and virulence. We report the case of a 64-year-old man who developed enteritis caused by Salmonella Kedougou without bacteremia after returning from Thailand. The patient stayed in Chiang Mai, Thailand, for 10 days to play golf and was hospitalized with fever, chills, watery diarrhea, and vomiting on the day the patient returned to Japan.

Characterization and Targeting of the Main Drivers of Elective Imaging Utilization: A Cross-sectional Study Applying Conjoint Analysis.

Objective: To characterize patient and referring physician preferences when selecting where to have elective imaging performed METHODS: In this Institutional Research Board approved survey-based study, online surveys were completed by 393 patients who had recently had a non-contrast MRI of the shoulder, lumbar spine, or knee within the past 2 years and 168 physicians who had ordered at least 12 such MRIs in the past year. The survey data included explicit questions about preferences as well as a set of conjoint choice screens. Conjoint analysis utilized a logistic model estimated using maximum likelihood estimation.

Age- and cytokine-dependent modulation of GABAergic transmission within the basolateral amygdala of male Sprague Dawley rats.

Alcohol binge drinking has a multitude of effects on CNS function, including changes in inflammatory cytokines such as IL-6 and IL-1β that may contribute to mood fluctuations associated with the intoxication-withdrawal cycle. Widely throughout the brain, including the amygdala, IL-6 mRNA is enhanced during intoxication, whereas IL-1β is initially suppressed during alcohol intoxication, with increased expression seen shortly after ethanol clearance, during acute hangover. Furthermore, induction of neuroimmune genes appears to be muted during adolescence in the amygdala, suggesting a broader functional immaturity of the adolescent neuroimmune system in structures involved in negative affect associated with ethanol exposure.

Transcutaneous electrical stimulation enhances episodic memory encoding via a noradrenaline-attention network, with associated neuroinflammatory changes.

Background: Attention plays a central role in learning and memory processes. Prior research has demonstrated how goal-directed attention influences successful performance on both attention and working memory tasks. However, an important question remains about whether long-term memory outcomes can be reliably enhanced by targeting attention processes.

The Double Disparity: Vitamin D Deficiency and Lethal Prostate Cancer in Black Men.

Epidemiological data from as early as the 1930s documented a dramatic racial disparity in prostate cancer incidence, survival, and mortality rates among Black men-a trend that persists to this day. Black men are disproportionately burdened by prostate cancer, developing the disease at younger ages, facing more aggressive and lethal forms, and ultimately experiencing double the mortality rate of men of European descent. Investigating the multifactorial contributors to this racial disparity has been extensive, but results have often been inconsistent or inconclusive, making it difficult to pinpoint clear correlations.

Combating inflammation and oxidative stress: Exploring the cellular effects of Lonicera caerulea var. kamtschatica extract.

Lonicera caerulea var. kamtschatica (LCK), known as blue honeysuckle or haskap berry, is rich in bioactive compounds such as polyphenols, flavonoids, and anthocyanins, which are linked to various health benefits, including anti-inflammatory and antioxidant properties. The research specifically investigates the effects of an LCK extract that has been standardized to contain a minimum of 15% anthocyanins on inflammation and oxidative stress at the cellular level.

Identifying novel inflammatory protein biomarkers and drug targets of inflammatory bowel disease by integrating Mendelian randomization, bioinformatics, and druggability analysis.

Introduction: Inflammatory proteins have the potential to be used as therapeutic targets for inflammatory bowel disease (IBD).

Methods: We conducted Mendelian randomization (MR) analysis to probe causal associations between 91 circulating inflammatory proteins and IBD in the discovery and replication cohorts. Subsequently, we conducted meta-analysis of results from two cohorts.

Puerarin mitigates cognitive decline and white matter injury via CD36-Mediated microglial phagocytosis in chronic cerebral hypoperfusion.

Background: Chronic cerebral hypoperfusion (CCH) contributes significantly to white matter injury (WMI) and cognitive impairment, often leading to vascular dementia (VaD). Inefficient clearance of myelin debris by microglia impedes white matter repair, making microglia-mediated myelin clearance a promising therapeutic strategy for WMI. Puerarin (Pu), an isoflavonoid monomer from Pueraria lobata, is known for its neuroprotective, anti-inflammatory, and immunoregulatory properties.

Cisplatin-eugenol Pt(IV) prodrugs target colon cancer stem cells: A novel strategy for enhanced anticancer efficacy.

Platinum(IV) compounds possess distinct properties that set them apart from platinum(II) compounds. Often designed as prodrugs, they are reduced within cancer cells to their active platinum(II) form, enabling their cytotoxic effects. Their versatility also lies in their ability to be functionalized and conjugated with bioactive molecules to enhance cancer cell targeting.

The interplay of edentulism, smoking, microbiota, oral rehabilitation on cytokineprofile and different conditions of hypertension.

Objective: To evaluate the influence of edentulism, smoking, microbiota, and oral rehabilitation on the cytokine profile in healthy and hypertensive edentulous individuals using complete dentures.

Design: This case-control study was divided into four groups: normotensives (control group - NH), controlled hypertensives (case group 1 - CH), unreported hypertensives (case group 2 - UnrH), and uncontrolled hypertensives (case group 3 - UncH). The participants were characterized by sociodemographic data, clinical and behavioral information, and systolic and diastolic blood pressure.

Bromoxynil induced hepatic toxicity via dysregulating TLR4/MyD88, JAK1/STAT3 and NF-κB signaling pathways: A dose-dependent investigation.

Bromoxynil (BML) is a toxic herbicide that is reported to cause various organ toxicities. However, there is not a single investigation conducted to elucidate the adverse impacts of BML on hepatic tissues at different dose concentrations. Therefore, the current investigation was planned to assess the deleterious effects of BML on liver against different dose concentrations.