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BMC Cancer Jun 2024The role of hemoglobin (HGB) in common malignant tumors remains unclear.
BACKGROUND
The role of hemoglobin (HGB) in common malignant tumors remains unclear.
METHODS
A retrospective analysis was conducted to identify the correlation between HGB levels and risk of 15 malignant tumors using 50,085 samples from the National Health and Nutrition Examination Survey. Mendelian Randomization analyses (MRAs) were performed based on genome-wide association study data to assess the causal relationship between HGB levels and these malignant tumors using more than 700,000 samples. The robustness of the MRA results was confirmed through various analytical methods. Fifty-six in-house samples were used to investigate the correlation between HGB levels and the prognosis in prostate cancer (PRCA) using the Kaplan-Meier curve.
RESULTS
High HGB levels were associated with a higher risk for patients with cervix cancer, melanoma, and non-melanoma skin cancer (OR > 1.000, p < 0.05). It served as a protective factor for colon cancer, esophagus cancer, stomach cancer, bone cancer, lung cancer, renal cancer, and PRCA (OR < 1.000, p < 0.05). Furthermore, MRAs suggested that elevated HGB levels were correlated with a reduced risk of PRCA (OR = 0.869, p < 0.05), with no significant association observed between this marker and the remaining 14 malignant tumors. No pleiotropy or heterogeneity was found in the ultimate results for MRAs (p-values > 0.05), suggesting the robustness of the results. The results derived from the in-house data revealed a relationship between higher HGB values and a more favorable prognosis in PRCA (p < 0.05).
CONCLUSION
High circulating HGB levels may play a protective prognostic role for PRCA and serve as a protective factor against the occurrence of PRCA.
Topics: Humans; Retrospective Studies; Male; Female; Hemoglobins; Neoplasms; Genome-Wide Association Study; Prognosis; Middle Aged; Mendelian Randomization Analysis; Risk Factors; Nutrition Surveys; Adult; Aged; Biomarkers, Tumor
PubMed: 38907210
DOI: 10.1186/s12885-024-12495-0 -
Scientific Reports Jun 2024Cardiac ischemic preconditioning (Pre) reduces cardiac ischemia-reperfusion injury (IRI) by stimulating opioid receptors. Chronic use of opioids can alter the signaling...
Cardiac ischemic preconditioning (Pre) reduces cardiac ischemia-reperfusion injury (IRI) by stimulating opioid receptors. Chronic use of opioids can alter the signaling pathways. We investigated the effects of chronic methadone use on IRI and Pre. The experiments were performed on isolated hearts of male Wistar rats in four groups: IRI, Methadone + IRI (M-IRI), Pre + IRI (Pre-IRI), Methadone + Pre + IRI (M-Pre-IRI). The infarct size (IS) in the Pre-IRI group was smaller than the IRI group (26.8% vs. 47.8%, P < 0.05). In the M-IRI and M-Pre-IRI groups, the infarct size was similar to the IRI group. Akt (Ak strain transforming) phosphorylation in the Pre-IRI, M-IRI, and M-Pre-IRI groups was significantly higher than in the IRI group (0.56 ± 0.15, 0.63 ± 0.20, and 0.93 ± 0.18 vs 0.28 ± 0.17 respectively). STAT3 (signal transducer and activator of transcription 3) phosphorylation in the Pre-IRI and M-Pre-IRI groups (1.38 ± 0.14 and 1.46 ± 0.33) was significantly higher than the IRI and M-IRI groups (0.99 ± 0.1 and 0.98 ± 0.2). Thus, chronic use of methadone not only has no protective effect against IRI but also destroys the protective effects of ischemic preconditioning. This may be due to the hyperactivation of Akt and changes in signaling pathways.
Topics: Animals; Methadone; STAT3 Transcription Factor; Male; Proto-Oncogene Proteins c-akt; Phosphorylation; Rats; Rats, Wistar; Myocardial Reperfusion Injury; Ischemic Preconditioning, Myocardial; Signal Transduction; Reperfusion Injury
PubMed: 38906975
DOI: 10.1038/s41598-024-65349-x -
Journal of Vascular Surgery. Venous and... Jun 2024To study the risk factors influencing the occurrence of moderate-severe post-thrombotic syndrome (PTS) within 2 years in patients with subacute lower extremity deep vein...
OBJECTIVE
To study the risk factors influencing the occurrence of moderate-severe post-thrombotic syndrome (PTS) within 2 years in patients with subacute lower extremity deep vein thrombosis (DVT).
METHODS
Seventy patients who developed moderate-severe PTS within 2 years after subacute lower extremity DVT from June 2018 to June 2022 were retrospectively selected as the case group. They were matched 1:1 by sex and age (±5 years) with 70 patients who did not develop moderate- severe PTS during the same follow-up period as the control group. Multiple logistic regression, stratified analysis, and interaction analyses were used to explore the risk factors for moderate-severe PTS.
RESULTS
The multiple logistic regression model showed that patients with iliofemoral vein thrombosis had a significantly increased risk of developing moderate-severe PTS within 2 years. Patients who underwent intraluminal intervention treatment during hospitalization had a significantly reduced risk. The odds ratios (ORs) were 4.000 (95%CI 1.597∼10.016) for the femoral-popliteal vein thrombosis and 0.262 (95%CI 0.106∼0.647) for the anticoagulation treatment group. The stratified analysis showed that intraluminal intervention treatment was a protective factor against moderate-severe PTS within 2 years across different strata of hypertension, thrombus type, BMI, duration of anticoagulation, and wearing compression stockings. Additionally, there was an interaction between thrombus type and treatment method, with intraluminal intervention treatment having a more pronounced effect on preventing moderate-severe PTS in patients with iliofemoral vein thrombosis.
CONCLUSION
Iliofemoral vein thrombosis is a risk factor for the development of moderate-severe PTS within 2 years in patients with subacute lower extremity DVT. Intraluminal intervention treatment can reduce the risk of moderate-severe PTS, especially in patients with iliofemoral vein thrombosis.
PubMed: 38906457
DOI: 10.1016/j.jvsv.2024.101933 -
Polish Journal of Microbiology Jun 2024Serological testing can be a powerful complementary approach to achieve timely diagnosis of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection, along with... (Review)
Review Comparative Study
Serological testing can be a powerful complementary approach to achieve timely diagnosis of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection, along with nucleic acid detection. Immunoglobulin (Ig) A antibodies are less frequently utilized to detect SARS-CoV-2 infection than IgM and IgG antibodies, even though IgA antibodies play an important role in protective immunity against SARS-CoV-2. This review discusses the differences in kinetics and assay performance between IgA and IgM antibodies and the factors influencing antibody responses. It highlights the potential usefulness of analyzing IgA antibodies for the early detection of SARS-CoV-2 infection. The early appearance of IgA and the high sensitivity of IgA-based immunoassays can aid in diagnosing coronavirus disease 2019. However, because of cross-reactivity, it is important to recognize the only moderate specificity of the early detection of SARS-CoV-2 IgA antibodies against spike antigens. Either the analysis of antibodies targeting the nucleocapsid antigen or a combination of antibodies against the nucleocapsid and spike antigens may strengthen the accuracy of serological evaluation.
Topics: Humans; COVID-19; Immunoglobulin A; Immunoglobulin M; SARS-CoV-2; Antibodies, Viral; Early Diagnosis; COVID-19 Serological Testing; Sensitivity and Specificity
PubMed: 38905276
DOI: 10.33073/pjm-2024-019 -
Diabetes & Vascular Disease Research 2024A pharmacoepidemiological study to assess VTE risk factors in a diabetes-rich population.
A pharmacoepidemiological nested case-control study of risk factors for venous thromboembolism with the focus on diabetes, cancer, socioeconomic group, medications, and comorbidities.
OBJECTIVES
A pharmacoepidemiological study to assess VTE risk factors in a diabetes-rich population.
METHODS
The study comprised 299,590 individuals. We observed 3450 VTEs and matched them with 15,875 controls using a nested case-control approach and collected data on comorbidities and prescriptions. By multivariable conditional logistic regression, we calculated ORs with 95%CIs for comorbidities and medications to evaluate their associations with VTE.
RESULTS
Diabetes (aOR 2.16; 95%CI 1.99-2.34), inflammatory bowel disease (1.84; 1.27-2.66), and severe psychiatric disorders (1.72; 1.43-2.05) had the strongest associations among the non-cancer comorbidities. Pancreatic (12.32; 7.11-21.36), stomach (8.57; 4.07-18.03), lung and bronchus (6.26; 4.16-9.43), and ovarian (6.72; 2.95-15.10) cancers were ranked as high-risk for VTE. Corticosteroids, gabapentinoids, psychotropic drugs, risedronic acid, and pramipexole were most strongly associated (aOR exceeding 1.5) with VTE. Insulin (3.86; 3.33-4.47) and sulphonylureas (2.62; 2.18-3.16) had stronger associations than metformin (1.65; 1.49-1.83). Statins and lercanidipine (0.78; 0.62-0.98) were associated with a lowered risk of VTE.
CONCLUSIONS
In this cohort, with 50% diabetes prevalence, pancreatic, stomach, lung and bronchus, and ovarian cancers were strongly associated with VTE. Corticosteroids, gabapentinoids, and psychotropic medications had the strongest associations with VTE among medications. This may be valuable for generating hypotheses for the further research. Lercanidipine may be a novel protective medication against VTE.
Topics: Humans; Female; Risk Factors; Male; Case-Control Studies; Neoplasms; Middle Aged; Aged; Comorbidity; Venous Thromboembolism; Pharmacoepidemiology; Risk Assessment; Diabetes Mellitus; Adult; Socioeconomic Factors; Social Determinants of Health
PubMed: 38904171
DOI: 10.1177/14791641241236894 -
Frontiers in Endocrinology 2024Evidence has been increasingly pointing towards a potential link between phenotypes related to obesity and the incidence of colorectal cancer. However, confirming this...
OBJECTIVE
Evidence has been increasingly pointing towards a potential link between phenotypes related to obesity and the incidence of colorectal cancer. However, confirming this as a direct causal connection remains elusive. This investigation aims to elucidate the causative links between obesity-associated phenotypes and the incidence of colorectal cancer.
METHODS
Employing the Two Sample Mendelian Randomization (TwoSampleMR) R package, analyses were conducted using Mendelian randomization (MR) to discern potential causative links between obesity categories sourced from both the Institute for Education and University (IEU) Open GWAS Project and Zenodo, and colorectal tumors (data obtained from IEU Open GWAS and FinnGen). For primary evaluations, the study utilized the Wald ratio and the Inverse Variance Weighting (IVW) methods, while the MR-Egger approach was integrated for sensitivity assessment. Bidirectional Mendelian Randomization (Bidirectional MR), as well as Linkage Disequilibrium (LD) Score Regression with well-imputed HapMap3 single nucleotide polymorphisms (SNPs), were additionally executed. Sensitivity assessments entailed IVW, MR-Egger methodologies to assess heterogeneity and pleiotropy, along with a leave-one-out strategy. Instrumental variables were chosen judiciously based on predetermined P-value thresholds and F-statistics.
RESULTS
Results from MR evaluations did not identify a clear causative link between BMI and colorectal malignancy. Conversely, both measures of obesity, the Waist-Hip Ratio (WHR) and its adjusted form for BMI (WHRadjBMI), displayed a connection to increased risk of colorectal cancer, especially prominent among female subjects. Reverse MR analyses dismissed potential reverse causality between colorectal malignancies and obesity. A significant genetic interplay was observed between WHR, WHRadjBMI, and colorectal cancer instances. Ensuing MR probes spotlighted inflammatory bowel ailment as a protective factor, while salad intake was indicated as a potential risk concerning colorectal malignancies. Sensitivity reviews, which included tests for both pleiotropy and heterogeneity, validated the robustness of the MR findings.
CONCLUSION
Findings from this research indicate that specific obesity-related parameters, notably WHR and WHRadjBMI, carry a causal relationship with an elevated colorectal cancer risk. The impact is distinctly more evident among females. Such insights might be pivotal for public health deliberations, hinting that individuals boasting a high WHR might necessitate intensified colorectal cancer screenings.
Topics: Humans; Colorectal Neoplasms; Mendelian Randomization Analysis; Obesity; Female; Male; Phenotype; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Sex Factors; Risk Factors
PubMed: 38904048
DOI: 10.3389/fendo.2024.1322253 -
Frontiers in Endocrinology 2024Gastric cancer (GC) is the third leading cause of cancer death worldwide, and hypothyroidism has been identified as a potential influencing factor. Despite known...
BACKGROUND
Gastric cancer (GC) is the third leading cause of cancer death worldwide, and hypothyroidism has been identified as a potential influencing factor. Despite known associations between hypothyroidism and various cancers, the causal link between hypothyroidism and GC and potential mediators of this relationship remains unclear. This study aimed to clarify these relationships using Mendelian randomization (MR).
METHODS
Utilizing genetic variant information from the FinnGen and MRC Integrative Epidemiology Unit open genome-wide association studies (GWAS) databases, we conducted univariable and multivariable MR analyses to explore the causal relationship between hypothyroidism and GC risk. The analysis was adjusted for confounders such as BMI, smoking status, and alcohol intake, and included mediator MR analysis to examine the role of high cholesterol.
RESULTS
We identified a significant inverse association between hypothyroidism and GC risk (OR = 0.93, 95% CI= 0.89-0.98, P = 0.003), with no evidence of reverse causation or pleiotropy. Adjustments for infection weakened this association. Mediator analysis highlighted high cholesterol levels, chronic hepatitis B infection, and diabetes/endocrine disease status as significant mediators of the protective effect of hypothyroidism on GC risk.
CONCLUSION
Our findings suggest that hypothyroidism may confer a protective effect against GC, mediated in part by high cholesterol and other factors. These results underscore the importance of thyroid function and metabolic health in GC risk, offering new insights for preventive strategies and highlighting the need for further research into these complex associations.
Topics: Humans; Mendelian Randomization Analysis; Stomach Neoplasms; Hypothyroidism; Genome-Wide Association Study; Mediation Analysis; Risk Factors; Female; Male; Polymorphism, Single Nucleotide
PubMed: 38904039
DOI: 10.3389/fendo.2024.1388608 -
International Journal of Medical... 2024Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against...
Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against mouse abdominal aortic aneurysm (AAA) induced by both angiotensin II (AngII) and calcium phosphate (Ca(PO)) , which was characterized with lower incidence of mouse AAA. Moreover, histomorphological staining visually presented more intact elastic fiber and less collagen deposition in abdominal aortas of mice treated by glutamine. Further, we found glutamine inhibited the excessive production of reactive oxide species (ROS), activity of matrix metalloproteinase (MMP), M1 macrophage activation, and apoptosis of vascular smooth muscle cells (VSMCs) in suprarenal abdominal aortas of mice, what's more, the high expressions of MMP-2 protein, MMP-9 protein, pro-apoptotic proteins, and IL-6 as well as TNF-α in protein and mRNA levels in cells treated by AngII were down-regulated by glutamine. Collectively, these results revealed that glutamine protected against mouse AAA through inhibiting apoptosis of VSMCs, M1 macrophage activation, oxidative stress, and extracellular matrix degradation.
Topics: Animals; Aortic Aneurysm, Abdominal; Apoptosis; Mice; Glutamine; Angiotensin II; Macrophage Activation; Muscle, Smooth, Vascular; Humans; Myocytes, Smooth Muscle; Oxidative Stress; Reactive Oxygen Species; Disease Models, Animal; Male; Macrophages; Aorta, Abdominal; Matrix Metalloproteinase 9; Matrix Metalloproteinase 2; Tumor Necrosis Factor-alpha; Interleukin-6; Calcium Phosphates
PubMed: 38903916
DOI: 10.7150/ijms.96395 -
Frontiers in Aging Neuroscience 2024Alzheimer's disease (AD) is the most widespread neurodegenerative disease in the world. Previous studies have shown that peripheral immune dysregulation plays a...
INTRODUCTION
Alzheimer's disease (AD) is the most widespread neurodegenerative disease in the world. Previous studies have shown that peripheral immune dysregulation plays a paramount role in AD, but whether there is a protective causal relationship between peripheral immunophenotypes and AD risk remains ambiguous.
METHODS
Two-sample Mendelian randomization (MR) was performed using large genome-wide association study (GWAS) genetic data to assess causal effects between peripheral immunophenotypes and AD risk. Utilizing the genetic associations of 731 immune cell traits as exposures. We adopted the inverse variance weighted method as the primary approach. The Weighted median and MR-Egger regression methods were employed as supplements. Various sensitivity analyses were performed to assess the robustness of the outcomes.
RESULTS
Based on the IVW method, we identified 14 immune cell traits that significantly reduced the risk of AD, of which six demonstrated statistical significance in both IVW and Weighted median methods. Among the seven immune traits, four were related to regulatory T (Treg) cells : (1) CD25++ CD45RA- CD4 not regulatory T cell % T cell (odds ratio (OR) [95% confidence interval (CI)] = 0.96 [0.95, 0.98], adjusted = 1.17E-02), (2) CD25++ CD45RA- CD4 not regulatory T cell % CD4+ T cell (OR [95% CI] = 0.97 [0.96, 0.99], adjusted = 3.77E-02), (3) Secreting CD4 regulatory T cell % CD4 regulatory T cell (OR [95% CI] = 0.98 [0.97, 0.99], adjusted = 7.10E-03), (4) Activated & secreting CD4 regulatory T cell % CD4 regulatory T cell(OR [95% CI] = 0.98 [0.97, 0.99], adjusted = 7.10E-03). In addition, HLA DR++ monocyte % monocyte (OR [95% CI] = 0.93 [0.89, 0.98], adjusted = 4.87E-02) was associated with monocytes, and HLA DR on myeloid Dendritic Cell (OR [95% CI] = 0.93 [0.89, 0.97], adjusted = 1.17E-02) was related to dendritic cells (DCs).
CONCLUSION
These findings enhance the comprehension of the protective role of peripheral immunity in AD and provide further support for Treg and monocyte as potential targets for immunotherapy in AD.
PubMed: 38903900
DOI: 10.3389/fnagi.2024.1403077 -
Journal of Inflammation Research 2024Intervertebral disc degeneration (IDD) underlies the pathogenesis of degenerative diseases of the spine; however, its exact molecular mechanism is unclear.
BACKGROUND
Intervertebral disc degeneration (IDD) underlies the pathogenesis of degenerative diseases of the spine; however, its exact molecular mechanism is unclear.
PURPOSE
To explore the molecular mechanism of mechanical pressure (MP)-induced IDD and to assess the role and mechanism of Rosuvastatin (RSV) inhibits MP-induced IDD.
METHODS
SD rat nucleus pulposus cells (NPCs) were cultured in vitro and an apoptosis model of NPCs was constructed using MP. Proliferative activity, reactive oxygen species content, apoptosis, and wound healing were detected in each group of NPCs, respectively. The expression of relevant proteins was detected by qPCR and Western Blot techniques. 18 SD rats were randomly divided into control, pressure and RSV groups. Elisa, qPCR, Western Blot and immunohistochemical staining techniques were used to detect changes in the content of related proteins in the intervertebral discs of each group. HE staining and Modified Saffron-O and Fast Green Stain Kit were used to assess IDD in each group.
RESULTS
MP treatment at 1.0 MPa could significantly induce apoptosis of NPCs after 24 h. MP could significantly inhibit the proliferative activity and wound healing ability of NPCs, and increase the intracellular reactive oxygen species content and apoptosis rate; pretreatment with RSV could significantly activate the Nrf2/HO-1 signaling pathway and reverse the cellular damage caused by MP; when inhibit the Nrf2/HO-1 signaling pathway activation, the protective effect of RSV was reversed. In vivo MP could significantly increase the content of inflammatory factors within the IVD and promote the degradation of extracellular matrix, leading to IDD. When the intervention of RSV was employed, it could significantly activate the Nrf2/HO-1 signaling pathway and improve the above results.
CONCLUSION
RSV may inhibit MP-induced NPCs damage and IDD by activating the Nrf2/HO-1 signaling pathway.
PubMed: 38903877
DOI: 10.2147/JIR.S461348