Publications

Background/Objectives: Sodium glucose co-transporter 2 inhibitors (SGLT2is) have demonstrated a reduction in heart failure (HF) hospitalizations in HF patients and decreased recurrence of atrial fibrillation (AF), including in those who have undergone catheter ablation (CA). The effects of SGLT2i are likely due to suppression of the renin-angiotensin-aldosterone system, reduction in oxidative stress with subsequent improvement in myocardial efficiency, and attenuation of cardiac remodeling. We aim to present the effects of SGLT2i on AF recurrence in patients who have undergone CA for AF. Methods: This is a systematic review and meta-analysis of randomized controlled trials (RCTs) and retrospective studies evaluating the effect of SGLT2i on AF recurrence following CA compared with non-SGLT2i. The primary outcome was the recurrence of AF by the final follow-up reported in each study. Secondary outcomes include AF recurrence by the first follow-up within 12 to 24 months and follow-up intervals (6, 12, 18, 24, and 36 to 42 months) post-ablation, multivariate risk of AF recurrence, and the effect on left atrial diameter (LAD) (less than 45 mm vs. greater than or equal to 45 mm). For risk of bias (ROB) analysis, the NIH ROB and Cochrane ROB2 tool were used. All statistical, heterogeneity, and sensitivity analyses were conducted using Cochrane Review Manager. A random-effect model was employed for all pooled statistical analyses. Results: A total of nine studies, two RCTs and seven retrospective studies, were included (N = 6874) for the primary outcome. Compared to non-SGLT2i (N = 3693), SGLT2i (N = 3181) significantly decreased AF recurrence by the final follow-up (OR = 0.62; 95% CI: 0.45-0.85; p = 0.008). For secondary outcomes, SGLT2i significantly reduced AF recurrence by the first follow-up within 12 to 24 months post-ablation (OR = 0.58; p = 0.0001) and by the different follow-up periods, 6-month (OR = 0.53; p = 0.02), 12-month (OR = 0.56; p = 0.0001), 18-month (OR = 0.55; p = 0.01), and 24-month (OR = 0.60; p = 0.12) follow-up periods. On the other hand, by 36 to 42 months, SGLT2i was associated with increased risk of AF recurrence (OR = 1.41; p = 0.004). Conclusions: We conclude that SGLT2i demonstrated a reduction in AF recurrence following CA, particularly by 12 to 18 months post-ablation.

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of liver disease in the United States and frequently coexists with other liver diseases. Despite growing interest, the presence of MASLD in patients with primary sclerosing cholangitis (PSC) remains underexplored. This study aimed to assess the prevalence and characteristics of the MASLD-PSC overlap syndrome, with a specific focus on patient-reported outcomes such as pruritus and fatigue. Methods: A cross-sectional analysis was performed within a prospective cohort of patients with PSC enrolled in the Autoimmune Liver Diseases Registry at a United States tertiary medical center (2018-2024). MASLD overlap was established based on evidence of hepatic steatosis on liver imaging or biopsy, combined with at least one cardiometabolic risk factor. Fatigue and pruritus were assessed using the Chronic Liver Disease Questionnaire (CLDQ) and the 5D Itch Scale. Ordinal logistic regression models were used to explore the potential impact of MASLD overlap on fatigue and pruritus severity. Results: Among 103 PSC patients, 33% had MASLD overlap. These patients were older (55 vs. 46 years, p = 0.006), had a higher BMI (30 vs. 25 kg/m2, p < 0.001), and were more likely to have small bile duct involvement (43% vs. 12%, p = 0.002). A history of liver transplantation (LT) was noted in 18% of PSC-only patients, compared to 3% of those with PSC/MASLD (p = 0.055). MASLD overlap was significantly associated with higher pruritus intensity (OR 3.09, 95% CI 1.02-9.28, p = 0.044), but was paradoxically linked to lower fatigue levels (OR 0.37, 95% CI 0.16-0.85, p = 0.020). Conclusions: Patients with PSC/MASLD exhibit distinct clinical features. MASLD overlap was found to significantly impact patient-reported outcomes, with lower fatigue intensity but increased pruritus severity, suggesting a role for metabolic or inflammatory pathways, warranting further investigation.

Plants inhabiting arid regions often harbor microbial communities that contribute to their resilience under extreme conditions. Yet, the genomic diversity and functional potential of bacterial endophytes associated with desert-adapted plants, particularly in Africa, remain largely unexplored. In this study, we investigated Microbacterium endophytes from the xerophytic cucurbit Citrullus colocynthis L. (Cucurbitaceae), collected in a semi-arid environment in central Morocco. Using culture-based isolation, phenotypic characterization, and whole-genome sequencing, we analyzed three representative isolates from leaf and root tissues. Genome-based taxonomy combined with polyphasic analyses identified two novel species, Microbacterium xerophyticum sp. nov. and Microbacterium umsixpiens sp. nov., with genome sizes of approximately 4.0 Mb and 3.9 Mb, respectively. Functional annotation revealed traits consistent with endophytism in water-limited ecosystems, including oxidative and osmotic stress responses, metal homeostasis, and high-affinity phosphate uptake. Differences in siderophore acquisition and nitrogen metabolism suggest niche partitioning between the two species. These findings document two novel bacterial species from a medicinal plant native to arid ecosystems, broaden the known diversity of plant-associated Microbacterium, and provide region-specific genomic references with adaptive traits relevant to host resilience under arid conditions.

RATIONALE: The lung is uniquely positioned for chemical inhalation exposures considering its direct communication with the environment. Childhood interstitial lung diseases (chILD) syndrome is a rare and heterogeneous group of pediatric lung diseases. Despite common inhalation exposures, few studies have associated chemical inhalation exposures with chILD. The purpose of this review was to assess for chILD syndromes following toxic chemical inhalation exposures.

METHODS: PubMed and Embase databases were searched with the following inclusion criteria: (1) toxic chemical inhalation exposure, (2) pediatric subjects, and (3) chILD syndrome. Studies were excluded due to incorrect (1) study design, (2) patient population, and/or (3) outcome.

RESULTS: Two hundred and one studies were identified, of which 142 articles were retrieved, with 74 articles included after inclusion/exclusion criteria were applied by two independent reviewers. Most of the evidence stemmed from two pandemics: humidifier disinfectant associated lung disease (HD-ILD; n = 27) and e-cigarette, or vaping product associated, lung injury (EVALI; n = 45). Common signs and symptoms included cough, shortness of breath, hypoxemia, and inspiratory crackles. Common radiographic findings included centrilobular nodules and ground-glass opacities with subpleural sparing. Histopathologic features included airway-centric injury/inflammation with foamy macrophages, as well as subpleural sparing. Oxidized lipids were common plasma biomarkers associated with both HD-ILD and EVALI. Long-term pulmonary function testing suggests a restrictive phenotype in HD-ILD but variable phenotypes in EVALI.

CONCLUSIONS: ChILD syndromes secondary to toxic chemical inhalation exposures manifest with common radiographic and histopathologic findings of airway-centric disease with subpleural sparing. Long-term monitoring is under-reported in toxic chemical inhalation chILD syndromes but suggests persistent lung function impairment, especially after high-dose, repeated exposures. Additional monitoring, evaluation, and reporting of chILD syndromes secondary to chemical inhalation exposure are needed to better understand its complex pathogenesis and long-term lung function implications.

PURPOSE: This study describes the establishment of the first electronic cystic fibrosis (CF) registry, analyzing the demographic and clinical data of Jordanian patients registered with CF.

METHODS: The CF registry steering committee, a collaborative group of stakeholders across Jordan interested in CF, defined the objectives and multi-step process. They identified data sources from hospitals and healthcare facilities, and developed a standardized data collection tool tailored to the Jordanian health system. Ethical approval and patient consent were secured, and data collectors were trained. Data collection began with compiling records from all health sectors, identifying and removing duplicates, and excluding deceased patients. Medical record reviews and patient interviews further refined the data set. A validation process ensured data accuracy, and statistical analysis was performed using Stata software.

RESULTS: The 385 documented and confirmed cases of CF in Jordan were mainly concentrated in Amman (35.3%), Irbid (26%), and Zarqa (8.6%). The data showed that 63.6% of patients were under the age of 20, and 56.6% were males. A reported sweat chloride level was available for 52.7% of the patients, while genotyping results were available for 15.1%. Pulmonary function test (PFT) results were available for (9.0%). Treatments predominantly included inhaled bronchodilators (59%), macrolide antibiotics (55.6%), inhaled antibiotics (36.4%), and enzyme replacement (75.3%).

CONCLUSION: The establishment of Jordan's CF registry offers insights into the CF population, though challenges in data standardization and completeness persist. Enhanced efforts in data collection accuracy and comprehensive documentation are essential for the registry's continued development and monitoring changes in outcomes.

Coxiella burnetii, the causative agent of human Q fever, subverts macrophage antimicrobial functions to establish an intracellular replicative niche. To better understand host-pathogen interactions, we investigated the transcriptional responses of human alveolar macrophages (hAMs) infected with virulent [NMI, G (Q212)], attenuated (NMII), and avirulent (Dugway) strains of C. burnetii. RNA sequencing indicated that all strains activated proinflammatory pathways, particularly IL-17 signaling, though the magnitude and nature of the response varied by strain. Infections with NMI, NMII or G (Q212) resulted in differential expression of roughly the same number of genes, while Dugway infection induced a stronger transcriptional response. Dugway and G (Q212) tended to polarize macrophages toward M1-like states, whereas responses to NMI and NMII were variable. Cytokine assays of NMII-infected THP-1 macrophages suggested the activation of IL-17 signaling, but only at later stages of infection, and single-cell RNA sequencing of NMII-infected THP-1 macrophages indicated heterogeneity in host response to infection, with distinct subpopulations exhibiting M1-like and M2-like inflammatory profiles. These findings highlight the complexity of macrophage response to C. burnetii and underscore the importance of strain-specific and cell-specific factors in shaping host immunity. Understanding these dynamics may inform the development of targeted therapies for Q fever.

Background/Objectives: A non-toxic nano-platform which can increase drug-loading rate and synergistically increase antitumor effect is very ideal. This study provides the concept that a combination of photothermal therapy with chemotherapy and anti-inflammatory therapy will be achieved by ablation of the local tumor, robust strategies for the suppression of distant tumors with enhanced antitumor therapy outcomes. Methods: In this study, the chemotherapeutic drug cisplatin (DDP) and the anti-inflammatory drug Aspirin-DL-Lysine (ADL) were loaded into a hollow porous nanomaterial zeolitic imidazolate framework-8 (ZIF-8), which was then coated with polydopamine, in order to form near-infrared absorption organic nanoparticles DDP-ADL@ZIF-8@PDA with excellent photothermal conversion efficiency. The antitumor efficacy of the nanodrug was evaluated through physicochemical characterization, cell biology studies, and animal experiments. Results: Photothermal therapy (PTT) of polydopamine combined with DDP and ADL can reduce inflammation and the immunosuppressive tumor microenvironment, and enhance antitumor effect. The results showed that the combined therapy could effectively eliminate the primary tumor, shrink the distant tumor, and inhibit the metastasis of the tumor. PTT in combination with chemotherapy and anti-inflammatory therapy can inhibit the expression of inflammatory factors, significantly reducing tumor immunosuppression by eliminating bone marrow-derived suppressor cells and increasing levels of cytotoxic T lymphocyte. Conclusions: This study successfully developed a DDP-ADL@ZIF-8@PDA nanomedicine for effective drug delivery, synergistic photothermal therapy, and anti-inflammatory attenuated immunotherapy to enhance treatment of human cervical cancer xenografts in mice. Overall, the combination of photothermal therapy with chemotherapy and anti-inflammatory therapy on a nano-platform has great potential for antitumor therapy applications.

Background: Current disease-modifying therapies (DMTs) for multiple sclerosis (MS) attenuate pathogenic immune responses but are limited by safety and tolerability concerns. Antigen-specific tolerance approaches provide targeted immunomodulation yet remain constrained by their dependence on known autoantigens. LPX-TI641, an orally bioavailable, clinical-stage small-molecule agonist of Tim-3/4, represents an antigen-independent strategy to restore immune tolerance by expanding regulatory T cells (Tregs). Methods: LPX-TI641 was evaluated in vitro for its ability to induce Treg populations in murine splenocytes. Therapeutic efficacy was assessed in vivo using MOG35-55- and PLP139-151-induced experimental autoimmune encephalomyelitis (EAE) mouse models. Ex vivo, peripheral blood mononuclear cells (PBMCs) from people with MS (PwMS) were analyzed for Treg phenotype and function in response to LPX-TI641. Results: LPX-TI641 induced dose-dependent expansion of CD4+Foxp3+ and CD4+Foxp3+Tim-3+ Tregs in vitro. In EAE models, treatment significantly reduced disease severity, prevented relapses, and maintained clinical benefit after discontinuation. In PBMCs from patients with MS, LPX-TI641 restored diminished Tim-3+ Treg populations and reversed Treg dysfunction in recall assays. Efficacy in animal models was comparable to or exceeded that of high-efficacy DMTs, including natalizumab. Conclusions: LPX-TI641 promotes antigen-independent immune tolerance through Tim receptor agonism and Treg expansion. These findings support its potential as a novel therapeutic candidate for MS, addressing the limitations of current DMTs.

Few studies have prospectively examined the joint effect of mercury (Hg) and omega-3 long-chain polyunsaturated fatty acids on gestational weight gain (GWG). This exploratory study included 120 women from the Environment and Reproductive Health (EARTH) study with preconception measurements of hair Hg and serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), followed through pregnancy. Linear regression was used to examine associations between hair Hg and GWG, while logistic regression estimated the odds of inadequate GWG based on National Academy of Medicine recommendations. In unadjusted models, higher hair Hg (≥1 vs. <1 ppm) was associated with lower GWG (β = -1.89; 95% CI: -3.70, -0.08) and increased odds of insufficient GWG (OR = 2.27; 95% CI: 1.00, 5.18). However, after multivariable adjustment including serum EPA + DHA, these associations were attenuated and became non-significant. A negative, though not statistically significant, association between hair Hg and GWG was observed among women in the lowest tertile of serum EPA + DHA (≥1 vs. <1 ppm: β = -3.26; 95% CI: -7.69, 1.17), whereas no such association was observed among those in higher tertiles (β [95% CI] = 0.44 [-4.21, 5.09] and -1.05 [-4.13, 2.02], respectively). Our findings suggest that the association between preconception Hg exposure and insufficient GWG may differ by serum EPA + DHA, but results require confirmation in cohorts with larger sample sizes.

Acute myocardial infarction is the most common form of coronary artery disease, and myocardial ischemia-reperfusion injury remains a major challenge despite advances in reperfusion therapy. Endotoxin preconditioning has been linked to reduced ischemia-reperfusion injury, but mechanisms remain unclear, and prior studies have used varied assessment methods with inconsistent results. In this study, we confirmed the protective effect of endotoxin preconditioning and assessed its role in preserving mitochondrial respiration using a multi-model approach of in vivo ischemia-reperfusion rat model, ex vivo normothermic rat heart perfusion, and in vitro hypoxia-reoxygenation in neonatal rat cardiomyocytes. Hemodynamic and cell-based analyses were performed in control (n = 5), ischemia-reperfusion/hypoxia-reoxygenation (n = 4/3), and endotoxin-pretreated (n = 5/3) groups. Low-dose endotoxin pretreatment significantly preserved left ventricular function, myocardial oxygen consumption, and mitochondrial respiration (p < 0.001). Preservation of function was associated with reduced hypoxia-inducible factor 1-alpha (HIF-1α) expression and decreased mitochondrial superoxide production, indicating reduced oxidative stress. Nonlethal endotoxin pretreatment protects the myocardium from ischemia-reperfusion injury by sustaining mitochondrial respiration and limiting oxidative damage. These findings support further investigation in large animal models to better replicate human myocardial infarction and evaluate translational potential.