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Journal of Reproductive Immunology Jun 2024The roles of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 genes in the potential correlation between polycystic ovary syndrome (PCOS), inflammation, and cancer remain...
Comparison of serum levels of IL-10 and IL-11 and mRNA expression of IL-10, IL-11, COX-2, BCL6, and ZEB Family in peripheral blood mononuclear cells (PBMC) of women with polycystic ovary syndrome and healthy individuals.
BACKGROUND
The roles of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 genes in the potential correlation between polycystic ovary syndrome (PCOS), inflammation, and cancer remain controversial.
AIMS
This study aimed to compare serum levels of IL-10 and IL-11 and gene expression of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 in PBMCs of women with PCOS and healthy controls.
METHODS
A case-control study included 40 women with PCOS as the case group and 40 healthy women as controls. Group matching for age and BMI was performed. Serum levels of IL-10 and IL-11 were assessed using ELISA, while gene expression was measured using real-time PCR. Parameters were compared between groups, and correlations among gene expression and serum levels were explored.
RESULTS
In comparison to healthy women, women with PCOS exhibited a significant decrease in the expression of COX-2 and IL-10 genes (p<0.001), alongside a significant increase in ZEB2 gene expression (p<0.001). There were no significant differences observed in the expression of IL-11, BCL6, and ZEB1 genes. Furthermore, the serum level of IL-10 was significantly lower in women with PCOS compared to the control group (p<0.001), while no significant difference was found in IL-11 levels. Additionally, no significant correlations were identified between gene expression and serum levels.
CONCLUSION
In women with PCOS, reduced IL-10 gene expression may indicate inflammation and serve as a diagnostic biomarker. However, conflicting findings on COX-2 expression complicate understanding. Elevated ZEB2 expression in PCOS women may lead to infertility, epithelial-mesenchymal transition, and aggressive phenotypes.
PubMed: 38941927
DOI: 10.1016/j.jri.2024.104281 -
Colloids and Surfaces. B, Biointerfaces Jun 2024In cancer research, circulating tumor cells (CTCs) were identified as the main drivers of metastasis. They are vital for early detection and prevention of metastasis...
In cancer research, circulating tumor cells (CTCs) were identified as the main drivers of metastasis. They are vital for early detection and prevention of metastasis during cancer treatment. Even though continuous progress in research offers more and more tools to combat cancer, we still lack a proper arsenal of therapeutics. Especially in tumors with close to no targeting options, like triple-negative breast cancer, early detection is often the main difference between successful and failed therapy. When such tumors are detected too late, they may have already produced plenty of CTCs, likely causing metastasis, which is the primary reason for tumor-associated deaths. Detecting those CTCs early on could substantially impact therapy outcomes and the 5-year survival rate. In our study, we developed and evaluated a reliable and affordable CTC screening method based on flow cytometry and 5-aminolevulinic acid (5-ALA) staining. We successfully established a circulation model for 5-ALA and CTCs research and demonstrated that the method can detect an average of 11 ± 3.3 CTCs out of 10,000 peripheral blood mononuclear cells, representing as low as approximately 0.1 % with a reasonable number of false positive events. Additionally, we present initial results on a theranostic approach using 5-ALA converted to protoporphyrin IX. The outcomes of this study might contribute significantly to the further development of CTC detection and the overall detection and treatment of cancer.
PubMed: 38941652
DOI: 10.1016/j.colsurfb.2024.114059 -
Annual Review of Immunology Jun 2024The intestine is the largest peripheral lymphoid organ in animals, including humans, and interacts with a vast array of microorganisms called the gut microbiota.... (Review)
Review
The intestine is the largest peripheral lymphoid organ in animals, including humans, and interacts with a vast array of microorganisms called the gut microbiota. Comprehending the symbiotic relationship between the gut microbiota and our immune system is essential not only for the field of immunology but also for understanding the pathogenesis of various systemic diseases, including cancer, cardiometabolic disorders, and extraintestinal autoimmune conditions. Whereas microbe-derived antigens are crucial for activating the intestinal immune system, particularly T and B cells, as environmental cues, microbes and their metabolites play a critical role in directing the differentiation of these immune cells. Microbial metabolites are regarded as messengers from the gut microbiota, since bacteria have the ability to produce unique molecules that humans cannot, and many immune cells in the intestine express receptors for these molecules. This review highlights the distinct relationships between microbial metabolites and the differentiation and function of the immune system.
Topics: Humans; Animals; Gastrointestinal Microbiome; Cell Differentiation; B-Lymphocytes; T-Lymphocytes; Bacteria
PubMed: 38941602
DOI: 10.1146/annurev-immunol-090222-102035 -
Medicine Jun 2024Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic... (Observational Study)
Observational Study
Elevated neutrophil-to-lymphocyte ratio combined with decreased lymphocyte-to-monocyte ratio is associated with increased peripheral airway resistance in patients with hepatic steatosis.
Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic steatosis and increased peripheral airway resistance has not yet been explored. Hepatic steatosis and increased peripheral resistance are connected with immunity dysregulation. High neutrophil-to-lymphocyte ratio (NLR) and low lymphocyte-to-monocyte ratio (LMR) have been recognized as indicators of immunity dysregulation. In this study, the association between hepatic steatosis and increased peripheral airway resistance was evaluated, and the effect of immunity dysregulation (high NLR/low LMR) on the increased peripheral airway resistance among patients with hepatic steatosis was explored. In this retrospective study, chest or abdomen CT scans and spirometry/impulse oscillometry (IOS) from 2018 to 2019 were used to identify hepatic steatosis and increased central/peripheral airway resistance in patients. Among 1391 enrolled patients, 169 (12.1%) had hepatic steatosis. After 1:1 age and abnormal ALT matching was conducted, clinical data were compared between patients with and without hepatic steatosis. A higher proportion of patients with hepatic steatosis had increased peripheral airway resistance than those without hepatic steatosis (52.7% vs 40.2%, P = .025). Old age, high body mass index, history of diabetes, and high NLR/low LMR were significantly correlated with increased peripheral airway resistance. The presence of hepatic steatosis is associated with increased peripheral airway. High NLR/low LMR is an independent associated factor of increased peripheral airway resistance in patients with hepatic steatosis. It is advisable for patients with hepatic steatosis to regularly monitor their complete blood count/differential count and undergo pulmonary function tests including IOS.
Topics: Humans; Male; Female; Middle Aged; Retrospective Studies; Neutrophils; Lymphocytes; Monocytes; Airway Resistance; Fatty Liver; Adult; Aged; Leukocyte Count; Lymphocyte Count
PubMed: 38941417
DOI: 10.1097/MD.0000000000038530 -
Age and Ageing Jun 2024Epigenetic ageing is among the most promising ageing biomarkers and may be a useful marker of physical function decline, beyond chronological age. This study...
BACKGROUND
Epigenetic ageing is among the most promising ageing biomarkers and may be a useful marker of physical function decline, beyond chronological age. This study investigated whether epigenetic age acceleration (AA) is associated with the change in frailty scores over 7 years and the 7-year risk of incident frailty and persistent Activities of Daily Living (ADL) disability among 560 Australians (50.7% females) aged ≥70 years.
METHODS
Seven AA indices, including GrimAge, GrimAge2, FitAge and DunedinPACE, were estimated from baseline peripheral-blood DNA-methylation. Frailty was assessed using both the 67-item deficit-accumulation frailty index (FI) and Fried phenotype (Fried). Persistent ADL disability was defined as loss of ability to perform one or more basic ADLs for at least 6 months. Linear mixed models and Cox proportional-hazard regression models were used as appropriate.
RESULTS
Accelerated GrimAge, GrimAge2, FitAge and DunedinPACE at baseline were associated with increasing FI scores per year (adjusted-Beta ranged from 0.0015 to 0.0021, P < 0.05), and accelerated GrimAge and GrimAge2 were associated with an increased risk of incident FI-defined frailty (adjusted-HRs 1.43 and 1.39, respectively, P < 0.05). The association between DunedinPACE and the change in FI scores was stronger in females (adjusted-Beta 0.0029, P 0.001 than in males (adjusted-Beta 0.0002, P 0.81). DunedinPACE, but not the other AA measures, was also associated with worsening Fried scores (adjusted-Beta 0.0175, P 0.04). No associations were observed with persistent ADL disability.
CONCLUSION
Epigenetic AA in later life is associated with increasing frailty scores per year and the risk of incident FI-defined frailty.
Topics: Humans; Female; Activities of Daily Living; Male; Aged; Frailty; Frail Elderly; Epigenesis, Genetic; Geriatric Assessment; Aging; Risk Factors; Aged, 80 and over; Disability Evaluation; DNA Methylation; Age Factors; Risk Assessment; Time Factors; Functional Status
PubMed: 38941117
DOI: 10.1093/ageing/afae127 -
European Archives of... Jun 2024In Japan, two types of tests for diagnosing olfactory disorders, T and T (T&T) olfactometry and intravenous olfactory tests, are covered by insurance and performed on...
PURPOSE
In Japan, two types of tests for diagnosing olfactory disorders, T and T (T&T) olfactometry and intravenous olfactory tests, are covered by insurance and performed on patients with olfactory disorders. This study examined the validity of these olfactory tests and whether psychophysical or morphological tests are more helpful in evaluating olfactory disorders.
METHODS
We evaluated patients who visited our department and underwent two types of olfaction tests and sinus computed tomography (CT). Data regarding the age, sex, peripheral blood eosinophil percentage, presence of bronchial asthma, diagnoses, olfactory symptom score, results of the two olfactory tests, and CT findings in eligible patients were extracted from medical records and retrospectively reviewed.
RESULTS
One hundred and sixty-three patients underwent all tests during the study period. The results of the T&T olfactometry and intravenous olfactory tests were significantly correlated. However, only the results of T&T olfactometry and olfactory cleft opacification on CT were statistically significant predictors of the olfactory symptom scores.
CONCLUSION
T&T olfactometry and CT evaluations of olfactory cleft opacification helped evaluate olfactory dysfunction. It is important to note that intravenous olfactory tests are best performed with careful control and not blindly to assess olfactory disorders.
PubMed: 38940928
DOI: 10.1007/s00405-024-08803-w -
Journal of Imaging Informatics in... Jun 2024To assess the effectiveness of the vViT model for predicting postoperative renal function decline by leveraging clinical data, medical images, and image-derived...
Predicting EGFR Status After Radical Nephrectomy or Partial Nephrectomy for Renal Cell Carcinoma on CT Using a Self-attention-based Model: Variable Vision Transformer (vViT).
OBJECTIVE
To assess the effectiveness of the vViT model for predicting postoperative renal function decline by leveraging clinical data, medical images, and image-derived features; and to identify the most dominant factor influencing this prediction.
MATERIALS AND METHODS
We developed two models, eGFR10 and eGFR20, to identify patients with a postoperative reduction in eGFR of more than 10 and more than 20, respectively, among renal cell carcinoma patients. The eGFR10 model was trained on 75 patients and tested on 27, while the eGFR20 model was trained on 77 patients and tested on 24. The vViT model inputs included class token, patient characteristics (age, sex, BMI), comorbidities (peripheral vascular disease, diabetes, liver disease), habits (smoking, alcohol), surgical details (ischemia time, blood loss, type and procedure of surgery, approach, operative time), radiomics, and tumor and kidney imaging. We used permutation feature importance to evaluate each sector's contribution. The performance of vViT was compared with CNN models, including VGG16, ResNet50, and DenseNet121, using McNemar and DeLong tests.
RESULTS
The eGFR10 model achieved an accuracy of 0.741 and an AUC-ROC of 0.692, while the eGFR20 model attained an accuracy of 0.792 and an AUC-ROC of 0.812. The surgical and radiomics sectors were the most influential in both models. The vViT had higher accuracy and AUC-ROC than VGG16 and ResNet50, and higher AUC-ROC than DenseNet121 (p < 0.05). Specifically, the vViT did not have a statistically different AUC-ROC compared to VGG16 (p = 1.0) and ResNet50 (p = 0.7) but had a statistically different AUC-ROC compared to DenseNet121 (p = 0.87) for the eGFR10 model. For the eGFR20 model, the vViT did not have a statistically different AUC-ROC compared to VGG16 (p = 0.72), ResNet50 (p = 0.88), and DenseNet121 (p = 0.64).
CONCLUSION
The vViT model, a transformer-based approach for multimodal data, shows promise for preoperative CT-based prediction of eGFR status in patients with renal cell carcinoma.
PubMed: 38940889
DOI: 10.1007/s10278-024-01180-0 -
International Microbiology : the... Jun 2024Candida auris (C. auris) is an emerging aggressive pathogen that causes severe infections in critically ill patients. Therefore, the assessment of this pathogen,...
BACKGROUND
Candida auris (C. auris) is an emerging aggressive pathogen that causes severe infections in critically ill patients. Therefore, the assessment of this pathogen, characterized by inclination for biofilm formation, elevated colonization rate, and resistance to multiple drugs, holds a paramount importance. There is no data regarding the isolation of C. auris in our tertiary care hospitals' intensive care units (ICUs). The current case study was arranged to assess the incidence of C. auris central line-associated bloodstream infection (CLABSI) problem in our (ICUs).
METHODS
Specimens of central venous catheter blood, peripheral blood, and catheter tips were collected from 301 critically ill patients with suspected (CLABSI). Microbiological cultures were utilized to diagnose bacterial and fungal superinfections. The fungal species identification and antifungal susceptibility testing were conducted using the Brilliance Chrome agar, VITEK® 2 compact system, and MALDI-TOF MS.
RESULTS
All included specimens (100%) yielded significant growth. Only 14 specimens (4.7%) showed fungal growth in the form of different Candida species. When comparing the identification of C. auris, MALDI-TOF MS is considered the most reliable method. Brilliance CHROMagar demonstrated a sensitivity of 100%, whereas VITEK only showed a sensitivity of approximately 33%. All recovered isolates of C. auris were fluconazole resistant.
CONCLUSION
C. auris is a highly resistant emerging pathogen in our ICUs that is often overlooked in identification using conventional methods.
PubMed: 38940863
DOI: 10.1007/s10123-024-00545-3 -
Alternative Therapies in Health and... Jun 2024This study evaluated the effectiveness of nalbuphine combined with propofol in reducing visceral pain and preserving cognitive function during laparoscopic ovarian tumor...
OBJECTIVE
This study evaluated the effectiveness of nalbuphine combined with propofol in reducing visceral pain and preserving cognitive function during laparoscopic ovarian tumor resection.
METHODS
A total of 100 patients undergoing laparoscopic ovarian tumor resection from January 2019 to January 2022 were randomly assigned to either the control group or the research group (50 patients each). The control group received fentanyl combined with propofol for anesthesia, while the research group received nalbuphine combined with propofol. Various anesthetic parameters, hemodynamics, visceral pain(Visual analog scale was used to evaluate the degree of pain at rest and during movement at 2h, 6h, and 12h after the operation), cognitive function (Mini-Mental State Examination (MMSE) scale was used to assess the cognitive function before the operation and 1 day, 3 days, and 5 days after the operation, including time and place, language, orientation, calculation, delayed memory and useability), and incidence of adverse reactions were assessed and compared between the two groups.
RESULTS
The research group exhibited significantly lower propofol dosage and anesthesia recovery time compared to the control group (P < .05). Hemodynamic stability, as indicated by SBP (Systolic Blood Pressure), DBP (Diastolic Blood Pressure), and SpO2 (Peripheral Capillary Oxygen Saturation)levels, was better maintained in the research group, especially at the beginning of the operation (P < .05). VAS (Visual Analog Scale) scores for pain at rest and during exercise were significantly lower in the research group at 2h and 6h post-operation (P < .05). MMSE (Mini-Mental State Examination) scores were higher in the research group compared to the control group at 1and3 days post-operation (P < .05). Additionally, the incidence of adverse reactions was significantly lower in the research group (8.00%) compared to the control group (20.00%, P < .05).The above results were subjected to t test and χ2 test.
CONCLUSIONS
Nalbuphine combined with propofol effectively alleviates visceral pain during laparoscopic ovarian tumor resection, stabilizes hemodynamics, and preserves cognitive function. This combination demonstrates promising analgesic and sedative effects with high safety, suggesting its potential for widespread clinical use.
PubMed: 38940805
DOI: No ID Found -
The Journal of Clinical Endocrinology... Jun 2024Atypical parathyroid tumor (APT) represents a neoplasm characterized by histological features typical of parathyroid carcinoma (PC) but lacking local infiltration and/or...
CONTEXT
Atypical parathyroid tumor (APT) represents a neoplasm characterized by histological features typical of parathyroid carcinoma (PC) but lacking local infiltration and/or distant metastasis, leading to uncertainty regarding its malignant potential.
OBJECTIVE
To characterize the molecular landscape and deregulated pathways in APT.
METHODS
Whole exome sequencing (WES) was conducted on 16 APTs. DNA from tumors and matched peripheral blood underwent WES using Illumina HiSeq3000.
RESULTS
A total of 192 nonsynonymous variants were identified. The median number of protein-altering mutations was 9. The most frequently mutated genes included BCOR, CLMN, EZH1, JAM2, KRTAP13-3, MUC16, MUC19, and OR1S1. Seventeen mutated genes belong to the Cancer Gene Census list. The most consistent hub genes identified through STRING network analysis were ATM, COL4A5, EZH2, MED12, MEN1, MTOR, PI3, PIK3CA, PIK3CB, and UBR5. Deregulated pathways included the PI3 K/AKT/mTOR pathway, Wnt signaling, and extracellular matrix organization. Variants in genes such as MEN1, CDC73, EZH2, PIK3CA, and MTOR, previously reported as established or putative/candidate driver genes in benign adenoma (PA) and/or PC, were also identified in APT.
CONCLUSIONS
APT does not appear to have a specific molecular signature but shares genomic alterations with both PA and PC. The incidence of CDC73 mutations is low, and it remains unclear whether these mutations are associated with a higher risk of recurrence. Our study confirms that PI3 K/AKT/mTOR and Wnt signaling represents the pivotal pathways in parathyroid tumorigenesis and also revealed mutations in key epigenetic modifier genes (BCOR, KDM2A, MBD4, and EZH2) involved in chromatin remodeling, DNA, and histone methylation.
PubMed: 38940486
DOI: 10.1210/clinem/dgae441