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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 2024Despite advances in surgical and therapeutic approaches, high-grade serous ovarian carcinoma (HGSOC) prognosis remains poor. Surgery is an indispensable component of...
Despite advances in surgical and therapeutic approaches, high-grade serous ovarian carcinoma (HGSOC) prognosis remains poor. Surgery is an indispensable component of therapeutic protocols, as removal of all visible tumor lesions (cytoreduction) profoundly improves the overall survival. Enhanced predictive tools for assessing cytoreduction are essential to optimize therapeutic precision. Patients' immune status broadly reflects the tumor cell biological behavior and the patient responses to disease and treatment. Serum cytokine profiling is a sensitive measure of immune adaption and deviation, yet its integration into treatment paradigms is underexplored. This study is part of the IMPACT trial (NCT03378297) and aimed to characterize immune responses before and during primary treatment for HGSOC to identify biomarkers for treatment selection and prognosis. Longitudinal serum samples from 22 patients were collected from diagnosis until response evaluation. Patients underwent primary cytoreductive surgery or neoadjuvant chemotherapy (NACT) based on laparoscopy scoring. Twenty-seven serum cytokines analyzed by Bio-Plex 200, revealed two immune phenotypes at diagnosis: Immune High with marked higher serum cytokine levels than Immune Low. The immune phenotypes reflected the laparoscopy scoring and allocation to surgical treatment. The five Immune High patients undergoing primary cytoreductive surgery exhibited immune mobilization and extended progression-free survival, compared to the Immune Low patients undergoing the same treatment. Both laparoscopy and cytoreductive surgery induced substantial and transient changes in serum cytokines, with upregulation of the inflammatory cytokine IL-6 and downregulation of the multifunctional cytokines IP-10, Eotaxin, IL-4, and IL-7. Over the study period, cytokine levels uniformly decreased in all patients, leading to the elimination of the initial immune phenotypes regardless of treatment choice. This study reveals distinct pre-treatment immune phenotypes in HGSOC patients that might be informative for treatment stratification and prognosis. This potential novel biomarker holds promise as a foundation for improved assessment of treatment responses in patients with HGSOC. ClinicalTrials.gov Identifier: NCT03378297.
Topics: Humans; Female; Ovarian Neoplasms; Cystadenocarcinoma, Serous; Cytokines; Middle Aged; Aged; Neoadjuvant Therapy; Phenotype; Cytoreduction Surgical Procedures; Biomarkers, Tumor; Neoplasm Grading; Prognosis; Treatment Outcome; Adult
PubMed: 38947323
DOI: 10.3389/fimmu.2024.1394497 -
Frontiers in Immunology 2024In spite of its high mortality rate and poor prognosis, the pathogenesis of sepsis is still incompletely understood. This study established a cuproptosis-based risk...
Identification and experimental validation of cuproptosis regulatory program in a sepsis immune microenvironment through a combination of single-cell and bulk RNA sequencing.
BACKGROUND
In spite of its high mortality rate and poor prognosis, the pathogenesis of sepsis is still incompletely understood. This study established a cuproptosis-based risk model to diagnose and predict the risk of sepsis. In addition, the cuproptosis-related genes were identified for targeted therapy.
METHODS
Single-cell sequencing analyses were used to characterize the cuproptosis activity score (CuAS) and intercellular communications in sepsis. Differential cuproptosis-related genes (CRGs) were identified in conjunction with single-cell and bulk RNA sequencing. LASSO and Cox regression analyses were employed to develop a risk model. Three external cohorts were conducted to assess the model's accuracy. Differences in immune infiltration, immune cell subtypes, pathway enrichment, and the expression of immunomodulators were further evaluated in distinct groups. Finally, various experiments, such as flow cytometry, Western blot, and ELISA, were used to explore the role of LST1 in sepsis.
RESULTS
ScRNA-seq analysis demonstrated that CuAS was highly enriched in monocytes and was closely related to the poor prognosis of sepsis patients. Patients with higher CuAS exhibited prominent strength and numbers of cell-cell interactions. A total of five CRGs were identified based on the LASSO and Cox regression analyses, and a CRG-based risk model was established. The lower riskScore cohort exhibited enhanced immune cell infiltration, elevated immune scores, and increased expression of immune modulators, indicating the activation of an antibacterial response. Ultimately, experiments demonstrated that LST1, a key gene in the risk model, was enhanced in the macrophage in response to LPS, which was closely related to the decrease of macrophage survival rate, the enhancement of apoptosis and oxidative stress injury, and the imbalance of the M1/M2 phenotype.
CONCLUSIONS
This study constructed a cuproptosis-related risk model to accurately predict the prognosis of sepsis. We further characterized the cuproptosis-related gene LST1 to provide a theoretical framework for sepsis therapy.
Topics: Sepsis; Humans; Single-Cell Analysis; Male; Female; Middle Aged; Prognosis; Sequence Analysis, RNA; Cellular Microenvironment; Aged
PubMed: 38947313
DOI: 10.3389/fimmu.2024.1336839 -
Frontiers in Immunology 2024Traumatic and thermal injuries result in a state of systemic immune suppression, yet the mechanisms that underlie its development are poorly understood. Released from...
Severe thermal and major traumatic injury results in elevated plasma concentrations of total heme that are associated with poor clinical outcomes and systemic immune suppression.
BACKGROUND
Traumatic and thermal injuries result in a state of systemic immune suppression, yet the mechanisms that underlie its development are poorly understood. Released from injured muscle and lysed red blood cells, heme is a damage associated molecular pattern with potent immune modulatory properties. Here, we measured plasma concentrations of total heme in over 200 traumatic and thermally-injured patients in order to examine its relationship with clinical outcomes and post-injury immune suppression.
METHODS
Blood samples were collected from 98 burns (≥15% total body surface area) and 147 traumatically-injured (injury severity score ≥8) patients across the ultra-early (≤1 hour) and acute (4-72 hours) post-injury settings. Pro-inflammatory cytokine production by lipopolysaccharide (LPS) challenged whole blood leukocytes was studied, and plasma concentrations of total heme, and its scavengers haptoglobin, hemopexin and albumin measured, alongside the expression of heme-oxygenase-1 (HO-1) in peripheral blood mononuclear cells (PBMCs). LPS-induced tumour necrosis factor-alpha (TNF-α) production by THP-1 cells and monocytes following heme treatment was also examined.
RESULTS
Burns and traumatic injury resulted in significantly elevated plasma concentrations of heme, which coincided with reduced levels of hemopexin and albumin, and correlated positively with circulating levels of pro and anti-inflammatory cytokines. PBMCs isolated from trauma patients 4-12 and 48-72 hours post-injury exhibited increased HO-1 gene expression. Non-survivors of burn injury and patients who developed sepsis, presented on day 1 with significantly elevated heme levels, with a difference of 6.5 µM in heme concentrations corresponding to a relative 52% increase in the odds of post-burn mortality. On day 1 post-burn, heme levels were negatively associated with LPS-induced TNF-α and interleukin-6 production by whole blood leukocytes. THP-1 cells and monocytes pre-treated with heme exhibited significantly reduced TNF-α production following LPS stimulation. This impairment was associated with decreased gene transcription, reduced activation of extracellular signal-regulated kinase 1/2 and an impaired glycolytic response.
CONCLUSIONS
Major injury results in elevated plasma concentrations of total heme that may contribute to the development of endotoxin tolerance and increase the risk of poor clinical outcomes. Restoration of the heme scavenging system could be a therapeutic approach by which to improve immune function post-injury.
Topics: Humans; Heme; Burns; Male; Adult; Female; Middle Aged; Cytokines; Wounds and Injuries; Young Adult; Aged; THP-1 Cells; Leukocytes, Mononuclear; Biomarkers; Lipopolysaccharides; Heme Oxygenase-1
PubMed: 38947312
DOI: 10.3389/fimmu.2024.1416820 -
World Journal of Gastroenterology Jun 2024Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver...
BACKGROUND
Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver function through a number of mechanisms, and thus, prevent liver failure.
AIM
To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy.
METHODS
The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) v1. 4 pinpointed patients who had undergone hepatectomy for liver cancer, subdividing them into two cohorts: Those who were injected with heparin and those who were not. The statistical evaluations used were unpaired -tests, Mann-Whitney tests, chi-square tests, and Fisher's exact tests to assess the effect of heparin administration on PHLF, duration of intensive care unit (ICU) stay, need for mechanical ventilation, use of continuous renal replacement therapy (CRRT), incidence of hypoxemia, development of acute kidney injury, and ICU mortality. Logistic regression was utilized to analyze the factors related to PHLF, with propensity score matching (PSM) aiming to balance the preoperative disparities between the two groups.
RESULTS
In this study, 1388 patients who underwent liver cancer hepatectomy were analyzed. PSM yielded 213 matched pairs from the heparin-treated and control groups. Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples. Further analysis in the matched cohorts confirmed a significant association, with heparin reducing the risk of PHLF (odds ratio: 0.518; 95% confidence interval: 0.295-0.910; = 0.022). Additionally, heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations, diminished requirements for respiratory support and CRRT, and lower incidences of hypoxemia and ICU mortality.
CONCLUSION
Liver failure is an important hazard following hepatic surgery. During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure. This indicates that heparin may provide a hopeful option for controlling PHLF.
Topics: Humans; Hepatectomy; Heparin; Male; Female; Middle Aged; Liver Failure; Liver Neoplasms; Aged; Anticoagulants; Treatment Outcome; Postoperative Complications; Retrospective Studies; Length of Stay; Risk Factors; Intensive Care Units; Propensity Score
PubMed: 38947296
DOI: 10.3748/wjg.v30.i22.2881 -
World Journal of Gastroenterology Jun 2024In this editorial we comment on the article by Agatsuma published in the . They suggest policies for more effective colorectal screening. Screening is the main policy...
In this editorial we comment on the article by Agatsuma published in the . They suggest policies for more effective colorectal screening. Screening is the main policy that has led to lower mortality rates in later years among the population that was eligible for screening. Colonoscopy is the gold standard tool for screening and has preventive effects by removing precancerous or early malignant polyps. However, colonoscopy is an invasive process, and fecal tests such as the current hemoglobin immunodetection were developed, followed by endoscopy, as the general tool for population screening, avoiding logistical and economic problems. Even so, participation and adherence rates are low. Different screening options are being developed with the idea that if people could choose between the ones that best suit them, participation in population-based screening programs would increase. Blood tests, such as a recent one that detects cell-free DNA shed by tumors called circulating tumor DNA, showed a similar accuracy rate to stool tests for cancer, but were less sensitive for advanced precancerous lesions. At the time when the crosstalk between the immune system and cancer was being established as a new hallmark of cancer, novel immune system-related biomarkers and information on patients' immune parameters, such as cell counts of different immune populations, were studied for the early detection of colorectal cancer, since they could be effective in asymptomatic people, appearing earlier in the adenoma-carcinoma development compared to the presence of fecal blood. sCD26, for example, detected 80.37% of advanced adenomas. To reach as many eligible people as possible, starting at an earlier age than current programs, the direction could be to apply tests based on blood, urine or salivary fluid to samples taken during routine visits to the primary health system.
Topics: Humans; Colorectal Neoplasms; Early Detection of Cancer; Colonoscopy; Mass Screening; Biomarkers, Tumor; Occult Blood; Feces; Adenoma
PubMed: 38947291
DOI: 10.3748/wjg.v30.i22.2849 -
World Journal of Orthopedics Jun 2024The differences in complication rates between the direct anterior and posterior approaches for hemiarthroplasty in elderly patients with femoral neck fractures are not...
The differences in complication rates between the direct anterior and posterior approaches for hemiarthroplasty in elderly patients with femoral neck fractures are not yet fully understood. Dislocation, a severe complication associated with increased mortality and often requiring additional surgery, may occur less frequently with the direct anterior approach compared to the posterior approach. Careful consideration of patient demographics is essential when planning the surgical approach. Future research in this area should focus on robust randomized controlled trials involving elderly patients recovering from femoral neck fractures.
PubMed: 38947271
DOI: 10.5312/wjo.v15.i6.605 -
Global Heart 2024The objective of this study is to conduct a temporal analysis of rheumatic heart disease (RHD) disease burden trends over a 30-year period (1991 to 2021), focusing on...
BACKGROUND
The objective of this study is to conduct a temporal analysis of rheumatic heart disease (RHD) disease burden trends over a 30-year period (1991 to 2021), focusing on prevalence, deaths, and disability-adjusted life years (DALYs) in the South Asia (SA).
METHODS
In this ecological study, we analyzed data regarding burden of RHD from the Global Burden of Diseases (GBD) study spanning the years 1991 to 2021 for the SA Region. Estimates of the number RHD-related prevalence, deaths, and DALYs along with age-standardized rates (ASR) per 100,000 population and 95% uncertainty intervals (UI) were evaluated.
RESULTS
The overall prevalent cases of RHD in the 2021 were 54785.1 × 10 (43328.4 × 10 to 67605.5 × 10), out of which 14378.8 × 10 (11206.9 × 10 to 18056.9 × 10) were from SA. The ASR of point prevalence showed upward trend between 1991 and 2021, at global level and for SA with an average annual percentage change (AAPC) of 0.40 (0.39 to 0.40) and 0.12 (0.11 to 0.13), respectively. The overall number of RHD-related deaths in the 2021 were 373.3 × 10 (324.1 × 10 to 444.8 × 10), out of which 215 × 10 (176.9 × 10 to 287.8 × 10) were from SA, representing 57.6% of the global deaths. The ASR of deaths also showed downward trend between 1991 and 2021, at global level and for SA with an AAPC of -2.66 (-2.70 to -2.63) and -2.07 (-2.14 to -2.00), respectively. The ASR of DALYs showed downward trend between 1990 and 2019, at global level and for South Asian region with an AAPC of -2.47 (-2.49 to -2.44) and -2.22 (-2.27 to -2.17), respectively.
CONCLUSION
The rising age-standardized prevalence of RHD remains a global concern, especially in South Asia which contribute to over 50% of global RHD-related deaths. Encouragingly, declining trends in RHD-related deaths and DALYs hint at progress in RHD management and treatment on both a global and regional scale.
Topics: Humans; Rheumatic Heart Disease; Global Burden of Disease; Male; Female; Prevalence; Adult; Middle Aged; Asia; Cost of Illness; Disability-Adjusted Life Years; Quality-Adjusted Life Years; Retrospective Studies; Asia, Southern
PubMed: 38947253
DOI: 10.5334/gh.1336 -
Frontiers in Medicine 2024Necrotizing fasciitis is an aggressive bacterial infection that causes necrosis of the fascia and subcutaneous tissues with rapid progression and high mortality. Early...
Necrotizing fasciitis is an aggressive bacterial infection that causes necrosis of the fascia and subcutaneous tissues with rapid progression and high mortality. Early stages often lead to misdiagnosis, resulting in improper treatment and severe implications. This case study presents a patient with diabetes mellitus combined with hepatitis B who rapidly developed necrotizing fasciitis of the left forearm and left breast after trauma and controlled the infection with early surgical treatment. It is worth noting that early surgical exploration is the gold standard for the diagnosis of necrotizing fasciitis and is the most effective means of reducing mortality and amputation rates in necrotizing fasciitis.
PubMed: 38947243
DOI: 10.3389/fmed.2024.1413593 -
BJA Open Jun 2024Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery...
Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery-a multicentre observational study.
BACKGROUND
Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment.
METHODS
Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses.
RESULTS
Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; <0.001) and Clavien-Dindo ≥3a (<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; =0.024, relative to ideal body weight; =0.001, body surface area; =0.009) and V/VCO at anaerobic threshold (=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival.
CONCLUSIONS
VO peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision.
CLINICAL TRIAL REGISTRATION
NCT03637647.
PubMed: 38947220
DOI: 10.1016/j.bjao.2024.100289