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Infection and Drug Resistance 2024
PubMed: 38947370
DOI: 10.2147/IDR.S480068 -
Frontiers in Public Health 2024In recent years, the prevalence of obesity has continued to increase as a global health concern. Numerous epidemiological studies have confirmed the long-term effects of...
BACKGROUND
In recent years, the prevalence of obesity has continued to increase as a global health concern. Numerous epidemiological studies have confirmed the long-term effects of exposure to ambient air pollutant particulate matter 2.5 (PM) on obesity, but their relationship remains ambiguous.
METHODS
Utilizing large-scale publicly available genome-wide association studies (GWAS), we conducted univariate and multivariate Mendelian randomization (MR) analyses to assess the causal effect of PM exposure on obesity and its related indicators. The primary outcome given for both univariate MR (UVMR) and multivariate MR (MVMR) is the estimation utilizing the inverse variance weighted (IVW) method. The weighted median, MR-Egger, and maximum likelihood techniques were employed for UVMR, while the MVMR-Lasso method was applied for MVMR in the supplementary analyses. In addition, we conducted a series of thorough sensitivity studies to determine the accuracy of our MR findings.
RESULTS
The UVMR analysis demonstrated a significant association between PM exposure and an increased risk of obesity, as indicated by the IVW model (odds ratio [OR]: 6.427; 95% confidence interval [CI]: 1.881-21.968; = 0.005). Additionally, PM concentrations were positively associated with fat distribution metrics, including visceral adipose tissue (VAT) (OR: 1.861; 95% CI: 1.244-2.776; = 0.004), particularly pancreatic fat (OR: 3.499; 95% CI: 2.092-5.855; PFDR =1.28E-05), and abdominal subcutaneous adipose tissue (ASAT) volume (OR: 1.773; 95% CI: 1.106-2.841; = 0.019). Furthermore, PM exposure correlated positively with markers of glucose and lipid metabolism, specifically triglycerides (TG) (OR: 19.959; 95% CI: 1.269-3.022; = 0.004) and glycated hemoglobin (HbA1c) (OR: 2.462; 95% CI: 1.34-4.649; = 0.007). Finally, a significant negative association was observed between PM concentrations and levels of the novel obesity-related biomarker fibroblast growth factor 21 (FGF-21) (OR: 0.148; 95% CI: 0.025-0.89; = 0.037). After adjusting for confounding factors, including external smoke exposure, physical activity, educational attainment (EA), participation in sports clubs or gym leisure activities, and Townsend deprivation index at recruitment (TDI), the MVMR analysis revealed that PM levels maintained significant associations with pancreatic fat, HbA1c, and FGF-21.
CONCLUSION
Our MR study demonstrates conclusively that higher PM concentrations are associated with an increased risk of obesity-related indicators such as pancreatic fat content, HbA1c, and FGF-21. The potential mechanisms require additional investigation.
Topics: Humans; Particulate Matter; Obesity; Mendelian Randomization Analysis; Genome-Wide Association Study; White People; Air Pollutants; Environmental Exposure; Air Pollution
PubMed: 38947357
DOI: 10.3389/fpubh.2024.1366838 -
Frontiers in Public Health 2024Heavy metals, ubiquitous in the environment, pose a global public health concern. The correlation between these and diabetic kidney disease (DKD) remains unclear. Our...
BACKGROUND AND OBJECTIVE
Heavy metals, ubiquitous in the environment, pose a global public health concern. The correlation between these and diabetic kidney disease (DKD) remains unclear. Our objective was to explore the correlation between heavy metal exposures and the incidence of DKD.
METHODS
We analyzed data from the NHANES (2005-2020), using machine learning, and cross-sectional survey. Our study also involved a bidirectional two-sample Mendelian randomization (MR) analysis.
RESULTS
Machine learning reveals correlation coefficients of -0.5059 and - 0.6510 for urinary Ba and urinary Tl with DKD, respectively. Multifactorial logistic regression implicates urinary Ba, urinary Pb, blood Cd, and blood Pb as potential associates of DKD. When adjusted for all covariates, the odds ratios and 95% confidence intervals are 0.87 (0.78, 0.98) ( = 0.023), 0.70 (0.53, 0.92) ( = 0.012), 0.53 (0.34, 0.82) ( = 0.005), and 0.76 (0.64, 0.90) ( = 0.002) in order. Furthermore, multiplicative interactions between urinary Ba and urinary Sb, urinary Cd and urinary Co, urinary Cd and urinary Pb, and blood Cd and blood Hg might be present. Among the diabetic population, the OR of urinary Tl with DKD is a mere 0.10, with a 95%CI of (0.01, 0.74), urinary Co 0.73 (0.54, 0.98) in Model 3, and urinary Pb 0.72 (0.55, 0.95) in Model 2. Restricted Cubic Splines (RCS) indicate a linear linkage between blood Cd in the general population and urinary Co, urinary Pb, and urinary Tl with DKD among diabetics. An observable trend effect is present between urinary Pb and urinary Tl with DKD. MR analysis reveals odds ratios and 95% confidence intervals of 1.16 (1.03, 1.32) ( = 0.018) and 1.17 (1.00, 1.36) ( = 0.044) for blood Cd and blood Mn, respectively.
CONCLUSION
In the general population, urinary Ba demonstrates a nonlinear inverse association with DKD, whereas in the diabetic population, urinary Tl displays a linear inverse relationship with DKD.
Topics: Humans; Cross-Sectional Studies; Mendelian Randomization Analysis; Machine Learning; Metals, Heavy; Male; Female; Middle Aged; Diabetic Nephropathies; Adult; Environmental Exposure; Nutrition Surveys; Aged
PubMed: 38947355
DOI: 10.3389/fpubh.2024.1367061 -
Frontiers in Public Health 2024The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in...
Epidemiology and antimicrobial resistance of spp. in the United Arab Emirates: a retrospective analysis of 12 years of national antimicrobial resistance surveillance data.
INTRODUCTION
The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in the United Arab Emirates (UAE) to 204 per 100,000 in Djibouti. The national surveillance data from the Middle East and North Africa (MENA) region on the epidemiology and antimicrobial resistance trends of TB, including MDR-TB remains scarce.
METHODS
A retrospective 12-year analysis of = 8,086 non-duplicate diagnostic complex (MTB complex) isolates from the UAE was conducted. Data were generated through routine patient care during the 2010-2021 years, collected by trained personnel and reported by participating surveillance sites to the UAE National Antimicrobial Resistance (AMR) Surveillance program. Data analysis was conducted with WHONET, a windows-based microbiology laboratory database management software developed by the World Health Organization Collaborating Center for Surveillance of Antimicrobial Resistance, Boston, United States (https://whonet.org/).
RESULTS
A total of 8,086 MTB-complex isolates were analyzed. MTB-complex was primarily isolated from respiratory samples (sputum 80.1%, broncho-alveolar lavage 4.6%, pleural fluid 4.1%). Inpatients accounted for 63.2%, including 1.3% from ICU. Nationality was known for 84.3% of patients, including 3.8% Emiratis. Of UAE non-nationals, 80.5% were from 110 countries, most of which were Asian countries. India accounted for 20.8%, Pakistan 13.6%, Philippines 12.7%, and Bangladesh 7.8%. Rifampicin-resistant MTB-complex isolates (RR-TB) were found in 2.8% of the isolates, resistance to isoniazid, streptomycin, pyrazinamide, and ethambutol, was 8.9, 6.9, 3.4 and 0.4%, respectively. A slightly increasing trend of resistance among MTB-complex was observed for rifampicin from 2.5% (2010) to 2.8% (2021).
CONCLUSION
Infections due to MTB-complex are relatively uncommon in the United Arab Emirates compared to other countries in the MENA region. Most TB patients in the UAE are of Asian origin, mainly from countries with a high prevalence of TB. Resistance to first line anti-tuberculous drugs is generally low, however increasing trends for MDR-TB mainly rifampicin linked resistance is a major concern. MDR-TB was not associated with a higher mortality, admission to ICU, or increased length of hospitalization as compared to non-MDR-TB.
Topics: United Arab Emirates; Humans; Retrospective Studies; Tuberculosis, Multidrug-Resistant; Male; Mycobacterium tuberculosis; Female; Adult; Antitubercular Agents; Middle Aged; Drug Resistance, Bacterial; Adolescent; Microbial Sensitivity Tests; Young Adult; Population Surveillance
PubMed: 38947352
DOI: 10.3389/fpubh.2024.1244353 -
Frontiers in Immunology 2024The interaction between pyroptosis-a form of programmed cell death-and tumor immunity represents a burgeoning field of interest. Pyroptosis exhibits a dual role in... (Review)
Review
BACKGROUND
The interaction between pyroptosis-a form of programmed cell death-and tumor immunity represents a burgeoning field of interest. Pyroptosis exhibits a dual role in cancer: it can both promote tumor development and counteract it by activating immune responses that inhibit tumor evasion and encourage cell death. Current tumor immunotherapy strategies, notably CAR-T cell therapy and immune checkpoint inhibitors (ICIs), alongside the potential of certain traditional Chinese medicinal compounds, highlight the intricate relationship between pyroptosis and cancer immunity. As research delves deeper into pyroptosis mechanisms within tumor therapy, its application in enhancing tumor immune responses emerges as a novel research avenue.
PURPOSE
This review aims to elucidate the mechanisms underlying pyroptosis, its impact on tumor biology, and the advancements in tumor immunotherapy research.
METHODS
A comprehensive literature review was conducted across PubMed, Embase, CNKI, and Wanfang Database from the inception of the study until August 22, 2023. The search employed keywords such as "pyroptosis", "cancer", "tumor", "mechanism", "immunity", "gasdermin", "ICB", "CAR-T", "PD-1", "PD-L1", "herbal medicine", "botanical medicine", "Chinese medicine", "traditional Chinese medicine", "immunotherapy", linked by AND/OR, to capture the latest findings in pyroptosis and tumor immunotherapy.
RESULTS
Pyroptosis is governed by a complex mechanism, with the Gasdermin family playing a pivotal role. While promising for tumor immunotherapy application, research into pyroptosis's effect on tumor immunity is still evolving. Notably, certain traditional Chinese medicine ingredients have been identified as potential pyroptosis inducers, meriting further exploration.
CONCLUSION
This review consolidates current knowledge on pyroptosis's role in tumor immunotherapy. It reveals pyroptosis as a beneficial factor in the immunotherapeutic landscape, suggesting that leveraging pyroptosis for developing novel cancer treatment strategies, including those involving traditional Chinese medicine, represents a forward-looking approach in oncology.
Topics: Pyroptosis; Humans; Neoplasms; Immunotherapy; Animals; Immune Checkpoint Inhibitors; Tumor Microenvironment
PubMed: 38947336
DOI: 10.3389/fimmu.2024.1381778 -
Frontiers in Immunology 2024The recent trend of global warming poses a significant threat to ecosystems worldwide. This global climate change has also impacted the pollution levels in aquatic...
The recent trend of global warming poses a significant threat to ecosystems worldwide. This global climate change has also impacted the pollution levels in aquatic ecosystems, subsequently affecting human health. To address these issues, an experiment was conducted to investigate the mitigating effects of iron nanoparticles (Fe-NPs) on arsenic and ammonia toxicity as well as high temperature stress (As+NH+T). Fe-NPs were biologically synthesized using fish waste and incorporated into feed formulations at 10, 15, and 20 mg kg diet. A total of 12 treatments were designed in triplicate following a completely randomized design involving 540 fish. Fe-NPs at 15 mg kg diet notably reduced the cortisol levels in fish exposed to multiple stressors. The gene expressions of , damage-inducible protein (), and DNA damage were upregulated by stressors (As+NH+T) and downregulated by Fe-NPs. Apoptotic genes ( and ) and detoxifying genes (), metallothionein (), and inducible nitric oxide synthase () were downregulated by Fe-NPs at 15 mg kg diet in fish subjected to As+NH+T stress. Immune-related genes such as tumor necrosis factor (), immunoglobulin (), and interleukin () were upregulated by Fe-NPs, indicating enhanced immunity in fish under As+NH+T stress. Conversely, Toll-like receptor () expression was notably downregulated by Fe-NPs at 15 mg kg diet in fish under As+NH+T stress. Immunological attributes such as nitro blue tetrazolium chloride, total protein, albumin, globulin, A:G ratio, and myeloperoxidase (MPO) were improved by dietary Fe-NPs at 15 mg kg diet in fish, regardless of stressors. The antioxidant genes (, , and ) were also strengthened by Fe-NPs in fish. Genes associated with growth performance, such as growth hormone regulator ( and ), growth hormone (), and insulin-like growth factor ( and ), were upregulated, enhancing fish growth under stress, while and were downregulated by Fe-NPs in the diet. Various growth performance indicators were improved by dietary Fe-NPs at 15 mg kg diet. Notably, Fe-NPs also enhanced arsenic detoxification and reduced the cumulative mortality after a bacterial infection. In conclusion, this study highlights that dietary Fe-NPs can effectively mitigate arsenic and ammonia toxicity as well as high temperature stress by modulating gene expression in fish.
Topics: Animals; Gene Expression Regulation; Iron; Fishes; Stress, Physiological; Metal Nanoparticles; Arsenic
PubMed: 38947331
DOI: 10.3389/fimmu.2024.1410150 -
Frontiers in Immunology 2024Epithelioid hemangioendothelioma is a rare vascular malignancy, and currently, there is no standard treatment regimen for this disease and existing treatment options...
Epithelioid hemangioendothelioma is a rare vascular malignancy, and currently, there is no standard treatment regimen for this disease and existing treatment options have limited efficacy. In this case report, we present a patient with lung and lymph node metastases from prostate epithelioid hemangioendothelioma who achieved a significant partial response. This was accomplished through alternating nivolumab therapy with ipilimumab and liposomal doxorubicin, resulting in a progression-free-survival more than 6 months to date. The treatment was well-tolerated throughout. Our report suggests that dual immunotherapy alternating with anti-PD-1antibody plus doxorubicin may be a potential treatment modality for epithelioid hemangioendothelioma. However, larger sample studies are necessary to ascertain the effectiveness of this treatment strategy and it is essential to continue monitoring this patient to sustain progression-free survival and overall survival.
Topics: Humans; Male; Doxorubicin; Hemangioendothelioma, Epithelioid; Nivolumab; Prostatic Neoplasms; Programmed Cell Death 1 Receptor; Antineoplastic Combined Chemotherapy Protocols; Immunotherapy; Immune Checkpoint Inhibitors; Ipilimumab; Treatment Outcome; Polyethylene Glycols; Middle Aged
PubMed: 38947327
DOI: 10.3389/fimmu.2024.1384111 -
Frontiers in Immunology 2024Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC... (Comparative Study)
Comparative Study
INTRODUCTION
Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency.
METHODS
We retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m and cyclophosphamide 500 mg/m for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m and cyclophosphamide 500 mg/m for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity.
RESULTS
From June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026).
DISCUSSION
As the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.
Topics: Humans; Immunotherapy, Adoptive; Male; Middle Aged; Female; Antigens, CD19; Vidarabine; Retrospective Studies; Lymphoma, Non-Hodgkin; Aged; Cyclophosphamide; Adult; Lymphocyte Depletion; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Biological Products; Receptors, Antigen, T-Cell
PubMed: 38947326
DOI: 10.3389/fimmu.2024.1403145 -
Frontiers in Immunology 2024The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with... (Meta-Analysis)
Meta-Analysis
UNLABELLED
The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis of studies investigating the circulating concentrations of bilirubin, the end product of heme metabolism and a potent endogenous antioxidant with anti-inflammatory properties, in patients with RDs and healthy controls. The electronic databases PubMed, Scopus, and Web of Science were searched from inception to 31 December 2023 for relevant articles. We evaluated the risk of bias and the certainty of evidence using the Joanna Briggs Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation Working Group system, respectively. In 17 eligible studies, all with low risk of bias, compared to controls, patients with RDs had significantly lower concentrations of total bilirubin (standard mean difference, SMD=-0.68, 95% CI -0.91 to -0.44, p<0.001; I = 92.5%, p<0.001; low certainty of evidence), direct (conjugated) bilirubin (SMD=-0.67, 95% CI -0.92 to -0.41, p<0.001; I = 81.7%, p<0.001; very low certainty of evidence), and the active antioxidant and anti-inflammatory indirect (unconjugated) form of bilirubin (SMD=-0.71, 95% CI -1.18 to -0.24, p=0.003; I = 95.1%, p<0.001; very low certainty of evidence). The results of the meta-analysis were stable in sensitivity analysis. In meta-regression, there were no significant associations between the SMD of total bilirubin and several clinical and demographic characteristics, including age, male to female ratio, number of participants, liver enzymes and erythrocyte sedimentation rate. In subgroup analysis, the SMD of total bilirubin was significant across a range of RDs, including rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren syndrome, and myositis. Therefore, the results of our systematic review and meta-analysis suggests that the reductions in bilirubin concentrations observed in patients with RDs reflect a state of impaired antioxidant and anti-inflammatory defence due to bilirubin consumption and highlight the promising role of this endogenous product as a biomarker of RDs.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023500649.
Topics: Female; Humans; Bilirubin; Biomarkers; Oxidative Stress; Rheumatic Diseases; Male
PubMed: 38947324
DOI: 10.3389/fimmu.2024.1369284 -
Frontiers in Immunology 2024Chronic obstructive pulmonary disease (COPD) is currently listed as the 3 leading cause of death in the United States. Accumulating data shows the association between...
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is currently listed as the 3 leading cause of death in the United States. Accumulating data shows the association between COPD occurrence and the usage of electronic nicotine delivery systems (ENDS) in patients. However, the underlying pathogenesis mechanisms of COPD have not been fully understood.
METHODS
In the current study, bENaC-overexpressing mice (bENaC mice) were subjected to whole-body ENDS exposure. COPD related features including emphysema, mucus accumulation, inflammation and fibrosis are examined by tissue staining, FACS analysis, cytokine measurement. Cell death and ferroptosis of alveolar epithelial cells were further evaluated by multiple assays including staining, FACS analysis and lipidomics.
RESULTS
ENDS-exposed mice displayed enhanced emphysema and mucus accumulation, suggesting that ENDS exposure promotes COPD features. ENDS exposure also increased immune cell number infiltration in bronchoalveolar lavage and levels of multiple COPD-related cytokines in the lungs, including CCL2, IL-4, IL-13, IL-10, M-CSF, and TNF-α. Moreover, we observed increased fibrosis in ENDS-exposed mice, as evidenced by elevated collagen deposition and a-SMA+ myofibroblast accumulation. By investigating possible mechanisms for how ENDS promoted COPD, we demonstrated that ENDS exposure induced cell death of alveolar epithelial cells, evidenced by TUNEL staining and Annexin V/PI FACS analysis. Furthermore, we identified that ENDS exposure caused lipid dysregulations, including TAGs (9 species) and phospholipids (34 species). As most of these lipid species are highly associated with ferroptosis, we confirmed ENDS also enhanced ferroptosis marker CD71 in both type I and type II alveolar epithelial cells.
DISCUSSION
Overall, our data revealed that ENDS exposure exacerbates features of COPD in bENaC mice including emphysema, mucus accumulation, abnormal lung inflammation, and fibrosis, which involves the effect of COPD development by inducing ferroptosis in the lung.
Topics: Animals; Ferroptosis; Pulmonary Disease, Chronic Obstructive; Mice; Nicotine; E-Cigarette Vapor; Disease Models, Animal; Cytokines; Mice, Inbred C57BL; Electronic Nicotine Delivery Systems; Male; Mice, Transgenic
PubMed: 38947318
DOI: 10.3389/fimmu.2024.1429946