Protein Levels In Patients Research Articles

Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease.

We comprehensively evaluated the expression of therapeutically targetable immune checkpoint molecules involved in celiac disease (CD). We have focused on the alteration of the CD200/CD200R pathway and Elafin expression in celiac disease and discussed their roles in regulating the immune response. There are limited data related to the expression or function of these molecules in celiac disease. This finding could significantly contribute to the understanding of the clinical manifestation of CD. CD200, CD200R and Elafin distributions were determined by ELISA and immunohistochemistry analyses in serum and biopsies of CD patients. Analyses of Th1 and Th17 cytokines were determined. PCR amplification of a fragment of the PI3 gene was carried out using genomic DNA isolated from whole blood samples of the study subjects. Different aliquots of the PCR reaction product were subjected to RFLP analysis for SNP genotyping and detection. We characterized the expression and function of the CD200-CD200R axis and PI3 in celiac disease. A significantly higher level of soluble CD200 and CD200R and lower expression of PI3 in serum of CD patients was observed compared to healthy controls. Consistent with our results, CD200 expression is regulated by IFN-gamma. Interaction of CD200/CD200R leads to production of type-Th1 and -Th17 cytokines. Regarding the PI3 genotype, the CT genotype proportion SNP rs1733103 and the GG genotype SNP rs41282752 were predominant in CD patients. SNP rs1733103 showed a significant association between the SNP variables and CD. In celiac disease the immune checkpoint is compromised or dysregulated, which can contribute to inflammation and the autoimmunity process. The study of these checkpoint points will lead to the development of targeted therapies aimed at restoring immunological balance in CD. Specific coding regions of the PI3 gene-splice variants predispose the Elafin protein, both at the transcriptional and post-translational levels, to modify its expression and function, resulting in reduced differential functional protein levels in patients with active celiac disease.

Predicting Short- and Long-Term Functional Outcomes Based on Serum S100B Protein Levels in Patients with Ischemic Stroke.

Ischemic stroke is one of the leading causes of mortality and disability. The neuroimaging methods are the gold standard for diagnostics. Biomarkers of cerebral ischemia are considered to be potentially helpful in the determination of the etiology and prognosis of patients with ischemic stroke. This study aimed to investigate the usefulness of serum S100B protein levels as a short- and long-term prognostic factor in patients with ischemic stroke. The study group comprised 65 patients with ischemic stroke. S100B protein levels were measured by immunoenzymatic assay. Short-term functional outcome was determined by the NIHSS score on day 1 and the difference in the NIHSS scores between day 1 and day 9 (delta NIHSS). Long-term outcome was assessed by the modified Rankin Scale (MRS) at 3 months after the stroke. At the end of the study, patients were divided into groups based on the NIHSS score on day 9 (0-8 "good" and >8 "poor"), the delta NIHSS ("no improvement" ≤0 and >0 "improvement"), and the MRS ("good" 0-2 and >2 "poor"). Differences in S100B levels between groups were analyzed with the ROC curve to establish the optimal cut-off point for S100B. The odds ratio was calculated to determine the strength of association. Correlations between S100B levels at three time points and these variables were evaluated. We revealed a statistically significant correlation between S100B levels at each measurement point (<24 h, 24-48 H, 48-72 h) and the NIHSS score on day 9 (R Spearman 0.534, 0.631, and 0.517, respectively) and the MRS score after 3 months (R Spearman 0.620, 0.657, and 0.617, respectively). No statistically significant correlation was found between S100B levels and the delta NIHSS. Analysis of the ROC curve confirmed a high sensitivity and specificity for S100B. The calculated AUC for the NIHSS on day 9 were 90.2%, 95.0%, and 82.2%, respectively, and for the MRS, 83.5%, 83.4%, and 84.0%, respectively. After determining the S100B cut-off, the odds ratio for beneficial effect (NIHSS ≤ 8 at day 9 or MRS 0-2 after 3 months) was determined for each sampling point. S100B is a useful marker for predicting short- and long-term functional outcomes in patients with ischemic stroke.

Factors Influencing CRP levels in Laparoscopic and Robotic Total Hysterectomy.

Patients with high postoperative C-reactive protein levels are known to have a high risk of complications such as intestinal injuries than those with low levels. However, the factors that influence postoperative C-reactive protein levels in patients without complications are unknown. In this study, we aimed to determine the factors affecting postoperative C-reactive protein levels in patients undergoing laparoscopic and robotic total hysterectomy. We conducted a retrospective cohort study of patients who had undergone laparoscopic or robotic total hysterectomy for uterine fibroids, adenomyosis, or cervical neoplasia. The study was conducted between July 2016 and December 2022 at our hospital. In total, 185 patients underwent laparoscopic or robotic total hysterectomy during the relevant period. Of these, 180 patients were included, excluding 3 who underwent laparotomy, 1 who developed an abscess, and 1 who did not have a postoperative blood draw. The measured outcome was the C-reactive protein level on the first postoperative day. Patient age, body mass index, operative time, blood loss, and uterine weight were deemed the possible influencing factors. Multiple regression analysis was performed to evaluate the influence of these factors on the postoperative C-reactive protein values. Statistical significance was defined as a P value less than .05. The median value was 1.72 (interquartile range, 1.11-2.52). Body mass index and operative time were determined to be the most significant factors. Patients' body mass index and operative time were found to be associated with first postoperative day C-reactive protein levels in uncomplicated cases.

Efficacy and safety of polyethylene glycol loxenatide in treating mild-to-moderate diabetic kidney disease in type 2 diabetes patients: a randomized, open-label, clinical trial.

This study aimed to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEG-Loxe) compared to those of dapagliflozin in patients with mild-to-moderate diabetic kidney disease (DKD), a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). The study is set against the backdrop of increasing global diabetes incidence and the need for effective DKD management. This study constituted a single-center, randomized, open-label, clinical trial. The trial included patients with mild-to-moderate DKD and suboptimal glycemic control. Eligible participants were randomly allocated to one of the two groups for treatment with either PEG-Loxe or dapagliflozin. The primary endpoint was the change in UACR from baseline at 24 weeks. Overall, 106 patients were randomized and 80 patients completed the study. Following 24 weeks of treatment, the PEG-Loxe group exhibited a mean percent change in baseline UACR of -29.3% (95% confidence interval [CI]: -34.8, -23.7), compared to that of -31.8% in the dapagliflozin group (95% CI: -34.8, -23.7). Both PEG-Loxe and dapagliflozin showed similar efficacy in reducing UACR, with no significant difference between the groups (p = 0.336). The HbA1c levels decreased by -1.30% (95% CI: -1.43, -1.18) in the PEG-Loxe group and by -1.29% (95% CI: -1.42, -1.17) in the dapagliflozin group (p = 0.905). The TG levels decreased by -0.56 mmol/L (95% CI: -0.71, -0.42) in the PEG-Loxe group and -0.33 mmol/L (95% CI: -0.48, -0.19) in the dapagliflozin group (p = 0.023). Differences in TC, HDL-C, LDL-C, SBP, and DBP levels between the groups were not statistically significant (all p > 0.05). Safety profiles were consistent with previous findings, with gastrointestinal adverse events being more common in the PEG-Loxe group. PEG-Loxe is as effective as dapagliflozin in improving urine protein levels in patients with mild-to-moderate DKD and offers superior benefits in improving lipid profiles. These findings support the use of PEG-Loxe in DKD management, contributing to evidence-based treatment options. www.chictr.org.cn, identifier ChiCTR2300070919.

Determination of vWF, ADAMTS-13 and Thrombospondin-1 in Venous Thromboembolism and Relating Them to the Presence of Factor V Leiden Mutation.

Thrombophilia in venous thromboembolism (VTE) is multifactorial. Von Willebrand factor (vWF) plays a major role in primary hemostasis. While elevated vWF levels are well documented in VTE, findings related to its cleaving protease (ADAMTS-13) are contradicting. The aim of this study was to determine vWF, ADAMTS-13, and the multifactorial Thrombospondin-1 (TSP-1) protein levels in patients after 3-6 months following an unprovoked VTE episode. We also explored a possible association with factor V Leiden (FVL) mutation. vWF, ADAMTS-13 and TSP-1 were analyzed using ELISA kits in 60 VTE patients and 60 controls. Patients had higher levels of vWF antigen (P = .021), vWF collagen-binding activity (P = .008), and TSP-1 protein (P < .001) compared to controls. ADAMTS-13 antigen was lower in patients (P = .046) compared to controls but ADAMTS-13 activity was comparable between the two groups (P = .172). TSP-1 showed positive correlation with vWF antigen (rho = 0.303, P = .021) and negative correlation with ADAMTS-13 activity (rho = -0.244, P = .033) and ADAMTS-13 activity/vWF antigen ratio (rho = -0.348, P = .007). A significant association was found between the presence of FVL mutation and VTE (odds ratio (OR): 9.672 (95% confidence interval (CI) 2.074-45.091- P = .004), but no association was found between the mutation and the studied proteins (P > .05). There appears to be an imbalance between vWF and ADAMTS-13 in VTE patients even after 3-6 months following the onset of VTE. We report that the odds of developing VTE in carriers of FVL mutation are 9.672 times those without the mutation, but the presence of this mutation is not associated with the studied proteins.

Diagnostic Value of Serum Galectin-3 Binding Protein Level in Patients with Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) still lacks effective biomarkers to assist in its diagnosis and prognosis. Galectin-3 binding protein (Gal-3BP) plays a role in immune and inflammatory diseases. This study aimed to evaluate Gal-3BP as a prognostic and predictive factor in patients with PAH. From January 2017 to December 2019, we enrolled 167 consecutive PAH patients and 58 healthy controls. Right heart catheterization (RHC) was used to diagnose PAH. Serum Gal-3BP levels were measured by high-sensitivity human enzyme-linked immunosorbent assay (ELISA). Serum Gal-3BP levels in the PAH group were significantly higher compared with the control group (4.87±2.09 vs 2.22±0.86 μg/mL, p<0.001). Gal-3BP level was correlated with several hemodynamic parameters obtained from RHC (p<0.001). Multivariate linear regression analysis showed that Gal-3BP was a risk factor for PAH (odds ratio (OR)=2.947, 95% CI: 1.821-4.767, p<0.001). The optimal cut-off value of serum Gal-3BP level for predicting PAH was 2.89 μg/mL (area under the curve (AUC)=0.860, 95 % CI: 0.811-0.910, p<0.001). Kaplan-Meier analysis showed that Gal-3BP levels above the median (4.87 μg/mL) were associated with an increased risk of death in patients with PAH (hazard ratio (HR)=8.868, 95 % CI: 3.631-21.65, p<0.0001). Cox multivariate risk regression analysis showed that Gal-3BP was a risk factor for death in PAH patients (HR=2.779, 95 % CI: 1.823-4.237, p<0.001). Serum Gal-3BP levels were increased in patients with PAH, and levels of Gal-3BP were associated with the severity of PAH. Gal-3BP might have predictive value for the diagnosis and prognosis of PAH.

Osteonectin (SPARC) prognostic value in prostate cancer

BackgroundProstate cancer (PCa) is common malignancy among men worldwide. To date only few molecular markers are available to predict its course and outcome. SPARC is considered to be promising prognostic marker of PCa due to its involvement in various cancer processes. Materials and methodsstudy was conducted on PCa surgical primary tumor samples, obtained from 84 patients. Level of SPARC mRNA expression was estimated using RT-qPCR. To identify SPARC protein (osteonectin) in prostate tissue, immunohistochemical analysis was conducted. Bioinformatical analysis was performed on UALCAN and TNMplot resources. Resultsbioinformatical analysis demonstrated that SPARC mRNA levels are decreased in PCa samples, in comparison to normal tissue. In patients with lymph node metastases its levels are 1.26 times higher; p = 4.66E-02, than in N0 category. Ex vivo study demonstrated that SPARC expression was elevated on both mRNA and protein levels in PCa patients with lymph node metastases (by 2.34 and 1.91, respectively, p < 0.05). We established higher levels of SPARC mRNA and protein in PCa patients with T3 tumors, as well as high Gleason score. Estimation of survival rates demonstrated that PCa patients with a high level of SPARC mRNA and protein have decreased overall 2-year survival. ConclusionsSPARC protein was overexpressed on mRNA and protein levels in patients with presence of lymph node metastases and higher Gleason score of tumors. Also, both mRNA and protein upregulation were associated with worse survival rates. The current study has therefore provided further evidence that SPARC is indeed linked to the prognosis and aggressiveness of human PCa.

C-reactive Protein Levels in Patients With Autoimmune Hypothyroidism Before and After Levothyroxine Treatment.

Hypothyroidism is one of the most common endocrine disorders. Most patients with hypothyroidism have autoimmune thyroiditis (Hashimoto's), characterized by elevated concentrations of anti-thyroperoxidase (ATPO) antibodies. Both overt hypothyroidism (OH) and subclinical hypothyroidism (SH) have been associated with cardiovascular risk factors, including markers of inflammation. High-sensitivity C-reactive protein (hs-CRP) is a veridical marker of systemic inflammation. Even a minor increase in hs-CRP is considered a cardiovascular risk; therefore, evidence of a beneficial effect of levothyroxine treatment on hs-CRP could be an argument in favor of therapy for SH. To assess hs-CRP levels in patients with hypothyroidism and evaluate levothyroxine treatment's effect on hs-CRP. This is a cohort study in which patients with hypothyroidism were evaluated before and after treatment with levothyroxine. 37 patients (17 with OH and 20 with SH) and 38 healthy controls were included in the study. hs-CRP was measured at the baseline visit, then after 2 and 4 months of levothyroxine therapy at a dose necessary to achieve euthyroidism as evidenced by a normal level of thyroid-stimulating hormone (TSH). hs-CRP was significantly increased in OH (p < 0.001) and SH (p = 0.001) at baseline as compared to controls. hs-CRP significantly decreased in SH (2.2±1.6 mg/L at baseline visit, 1.4±1.1 mg/L after 2 months of levothyroxine treatment, P = 0.017) and tended to decrease in OH (2.3±1.6 mg/L at baseline visit, 1.6±1.1 mg/L after 4 months of levothyroxine treatment, P = 0.067*). Patients with hypothyroidism have increased hs-CRP levels compared to a healthy control group and, thereby, a moderately increased cardiovascular risk. Achievement of euthyroidism by levothyroxine treatment decreased the levels of hs-CRP in patients with hypothyroidism.

Investigation of Early Growth Response Protein (EGR) Levels in Patients with Fibromyalgia Syndrome: A Cross-Sectional Study.

Fibromyalgia is a soft tissue rheumatism characterized by chronic and widespread musculoskeletal pain at specific points in the body. In this study, we aimed to investigate the relationship between Early Growth Response (EGR1, EGR2, and EGR3) protein levels in patients with Fibromyalgia Syndrome (FMS) and healthy controls. In our studies, 76 FMS patient group and 78 healthy control group who were newly diagnosed with primary FMS according to the 2010 American College of Rheumatology criteria for fibromyalgia in Sivas Cumhuriyet University Hospital, Physical Therapy, and Rehabilitation were used. Venous blood samples were taken from both groups for the measurement of EGR1, EGR2, and EGR3 protein plasma levels, and protein levels were determined using ELISA methods. Statistical parametric test assumptions were compared using the Independent Student's t-test. In addition, specificity, sensitivity, and AUC values were calculated with the ROC curve. The relationship between plasma EGR1 protein levels of FMS patients and control groups was statistically significant (p=0.001). EGR1 protein levels were found to be lower in the patient group diagnosed with FMS compared to the control group. It has been suggested that EGR1 protein levels can be important in the diagnosis of FMS disease.

Preliminary study on the role of the CSMD2 gene in bladder cancer

BackgroundCSMD2 has been reported as a potential prognostic factor in several cancers. However, whether CSMD2 affects bladder cancer (BC) remains unclear. MethodsPublic data were obtained from the TCGA (https://cancergenome.nih.gov) databases. CSMD2expression and its prognostic value were analyzed using bioinformatics methods. CSMD2 mRNA level in patients with BC and BC cell lines was evaluated via quantitative reverse transcriptase polymerase chain reaction. CSMD2 protein level in patients with BC was evaluated via immunohistochemistry. BC cell lines T24 and UMUC-3 were selected for loss-of-function assays targeting CSMD2. Cell viability was determined by CCK8 and clone formation experiments. Cell migration and invasion were evaluated using Transwell assays. Furthermore, the transcriptome of UMUC-3 with CSMD2 knockdown was sequenced to analyze potential signaling network pathways. Finally, the TIMER2.0 database was employed to identify the correlation between CSMD2 and immune cells in the tumor microenvironment. ResultsCSMD2 expression was up-regulated in BC tissues compared to adjacent tissues. High CSMD2 expression was associated with poor survival and could serve as an independent predictor for survival in patients with BC. Furthermore, down-regulation of CSMD2 notably restrained the viability, migration, and invasion abilities of T24 and UMUC-3 cells. Moreover, transcriptomic sequencing after CSMD2 knockdown in UMUC-3 cells revealed its involvement in the regulation of the malignant phenotype in BC. Finally, public databases suggest a connection between CSMD2 and immune cell infiltration in BC. ConclusionsThese findings suggest that CSMD2 may promote proliferation and tumorigenicity, and could represent a potential target for improving the prognosis of BC.

Cerebrospinal Fluid Protein Levels in Patients with Neurodegenerative Diseases Correlates with Cognitive and Motor Function

AbstractBackgroundBlood brain barrier (BBB) dysfunction is suggested to have a causal role in neurodegenerative disorders. Cerebrospinal fluid (CSF) total protein (TP) is a proxy for CSF albumin quotient, which is an indicator of BBB breakdown. Normative values for CSF TP are based on young and healthy individuals, and there is a lack of understanding of how this biomarker changes with aging and neurodegeneration. The aim of this study is to examine the CSF profile in a cohort of patients with ALS‐FTD spectrum disorders and to determine relationship between the CSF profile and cognitive and motor measures in these patients.MethodCSF from participants with ALS‐FTD spectrum disorders enrolled in the NIH protocol “Investigating Complex Neurodegenerative Disorders related to Amyotrophic Lateral Sclerosis and Frontotemporal Dementia” were included (n = 63). We described the distribution of the CSF profile in these participants and compared the findings with existing literature. We then examined the relationship between CSF measures and functional rating scales and cognitive and motor measures.ResultThe average total protein was 47.77 mg/dL (SD = 38.29). The average CSF glucose was 66.00 mg/dL (SD = 12.80). There was a negative correlation (p = 0.0102) between CSF TP and the ALS Functional Rating Score. We will further investigate the relationship between the CSF profile and measures of cognitive and motor performance.ConclusionOur findings show that CSF TP is elevated in patients with ALS‐FTD spectrum disorders and higher CSF TP level correlated with greater disease severity in ALS. We will further investigate the relationship between CSF TP and other measures of cognitive and motor function.

Clinical significance of IL-37 serum level and polymorphism in patients with endometrial cancer.

Endometrial cancer (EC) is recognized as the second most common type of cancer among women. Interleukin-37 (IL-37) is a recently discovered member of the IL-1 cytokine family characterized by its anti-inflammatory properties, which are believed to have both anti-tumour and tumorigenic effects. However, the precise role of IL-37 in the development of EC remains largely unknown. In the current study, we aimed to explore genotype and allele frequencies of the IL-37 gene (rs4241122) and measure IL-37 protein levels in patients with EC, with a view to determining the clinical significance in these patients. A total of 105 patients with confirmed EC and 105 healthy controls, aged 31-73, participated in the study. IL-37 serum levels were investigated using an ELISA method, while the frequency of genotypes and alleles of the IL-37 gene was determined using the ARMS-PCR method. The findings demonstrate a significant increase in IL-37 serum levels in EC patients compared to controls (p<0.0001). Moreover, higher levels of IL-37 were strongly associated with unfavourable indices, such as EC grade III, poorly differentiated tumours, and regional spread of tumour cells (p<0.05). However, genotyping of the IL-37 gene revealed no significant difference between the two groups, and there was no association between IL-37 genotype and IL-37 protein level or clinicopathological characteristics (p>0.05). The results of this study suggest that elevated serum levels of may contribute to tumour progression, probably through its immune suppressive activity. Clinically, IL-37 may serve as a promising factor and/or therapeutic target for EC management, although, further studies are warranted.

Investigation of the AgNOR (Argyrophilic Nucleolar Organizing Region) Protein Levels in Patients with Coronary Artery Diseases

Investigation of the AgNOR (Argyrophilic Nucleolar Organizing Region) Protein Levels in Patients with Coronary Artery Diseases

Prognostic model using postoperative normalization of C-reactive protein levels in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.

To improve the prediction of outcomes in patients who will undergo radical nephroureterectomy (RN U) for upper tract urothelial carcinoma (UTUC), we investigated the preoperative prognostic factors and developed a risk classification model. A total of 144 patients who underwent RNU with history of neither neoadjuvant nor adjuvant chemotherapy between 2008 and 2022 were retrospectively reviewed. Associations between perioperative/clinicopathologic factors and outcomes, including cancer-specific survival (CSS), were assessed. We specifically focused on preoperative serum C-reactive protein (CRP) and its postoperative normalization. Non-normalization of postoperative serum CRP level and pathologic T3 stage were identified as independent predictive factors of shorter CSS in univariate and multivariate analysis (p=0.0150 and 0.0037, hazard ratio: 3.628 and 4.470, respectively). We classified the patients into three groups using these factors and found that five-year CSS was 88%, 42.5%, and 0% in the low-risk group (zero factors), intermediate-risk group (one factor), and high-risk group (two factors), respectively (p<0.0001). Non-normalization of postoperative serum CRP level and pathologic T stage were identified as independent postoperative prognostic factors in patients with UTUC who underwent RNU. These factors can stratify three prognostic groups and may help urologists in clinical decision-making for adjuvant therapy.

Correlation of Aqueous, Vitreous, and Serum Protein Levels in Patients With Retinal Diseases.

To further establish aqueous humor (AH) as a clinically suitable source of protein biomarkers in retinal diseases by evaluating the correlation of a large panel of proteins between AH, vitreous humor (VH), and serum (SE). We enrolled 60 subjects (eyes) with various non-infectious retinal diseases. AH, VH, and SE proteins were analyzed using the Olink Target 96 platform (1196 protein assays in total). We compared these three matrices in terms of quantification overlap, principal component analysis, and correlation. In the AH, VH, and SE samples, 841, 917, and 1133 proteins, respectively, were consistently quantified above the limit of detection in more than 30% of patients. AH and VH shared 812 of these proteins. AH and VH samples overlapped along principal component 1, but SE samples were distinct. We identified 490 proteins with significant (false discovery rate [FDR]-adjusted P < 0.05) and relevant correlations (correlation coefficient > 0.5) between AH and VH, compared to only 33 and 40 proteins for VH and SE and for AH and SE, respectively. Due to a close correlation between protein concentrations in the AH and VH and a clear difference from the SE, AH has the potential to serve as a substitute for VH and may hold significance in identifying protein biomarkers and novel targets related to retinal diseases. This study further supports AH as a clinically suitable source of protein biomarkers in retinal diseases. In addition, the identified AH and VH correlations can inform the selection of protein biomarker candidates in future translational research.

Relationship among Dietary Intake of Vitamin E, Lipid Peroxidation Markers, and C-Reactive Protein in Flu-Like Patients Diagnosed with COVID-19.

This research aimed to assess the intake of vitamin E and its relationship with lipid peroxidation markers and C-reactive protein levels in patients with flu symptoms and COVID-19 diagnosis. A cross-sectional study with 121 patients of both sexes assisted at two basic health units in the city of Teresina, Piauí, with COVID-19 diagnosis confirmed through real-time reverse transcription polymerase chain reaction, was performed between the 3rd and 7th days of flu symptoms. The global nutritional status and the measurement of waist circumference were assessed according to the World Health Organization recommendations. The dietary energy intake, macronutrients, and vitamin E consumption were assessed through the 24 hr food recall method. The malondialdehyde plasmatic concentration (MDA) was measured through the method of thiobarbituric acid-reactive substances. Myeloperoxidase (MPO) was assessed through the oxidation speed of the o-dianisidine substrate in the presence of hydrogen peroxide. C-reactive protein (CRP) levels were measured by a high-sensitivity immunoturbidimetry method. The most common symptoms reported by the participants were sore throat, fever, and cough. Regarding the global nutritional status evaluation, the majority of the sample had overweight. The dietary intake of vitamin E was 100% inadequate and presented a mild correlation (r = 0.197) with MDA, a redox status marker. No correlation was observed among MPO, CRP, and the dietary intake of vitamin E. The dietary intake of vitamin E was related to MDA as the marker of redox status.

Investigation of Conjunctival Goblet Cell and Tear MUC5AC Protein in Patients With Graves' Ophthalmopathy.

The aim of this study was to investigate conjunctival goblet cell density (GCD) and tear mucin-5AC (MUC5AC) protein levels in patients with Graves' ophthalmopathy (GO) and their association with dry eye indicators. A total of 99 patients with GO (54 active, 45 inactive) and 40 healthy controls were recruited. Comprehensive ophthalmic examinations, including the external eye, ocular surface, GCD, and tear MUC5AC ELISA, were performed. The GCD examination was performed in temporal bulbar conjunctiva, including IVCM GCD by in vivo confocal microscopy (IVCM) and filled GCD of cytokeratin-7 and MUC5AC-positive co-immunomarkers by impression cytology. Tear MUC5AC protein was detected using samples extracted from Schirmer strips. The GO group showed a significant decrease in IVCM GCD, filled GCD, and normalized tear MUC5AC protein compared to controls, with the active GO group showing the greatest decrease (all P<0.05). Tear MUC5AC protein levels in GO correlated with those of IVCM GCD (r = 0.40, P<0.001) and filled GCD (r = 0.54, P<0.001, respectively). Higher ocular surface disease index (r = -0.22, P<0.05; r = -0.20, P<0.05; r = -0.21, P<0.05) and lisamine green staining (r = -0.23, P<0.05; r = -0.38, P<0.001; r = -0.42, P<0.001) were associated with lower tear MUC5AC protein levels, IVCM GCD, and filled GCD, respectively, which decreased with increasing clinical activity score (r = -0.24, P<0.05; r = -0.28, P<0.01; r = -0.27, P<0.01) and conjunctival congestion score (r = -0.27, P<0.01; r = -0.33, P<0.001; r = -0.42, P<0.001). The goblet cell count and tear MUC5AC protein in GO eyes were decreased, possibly due to ocular surface inflammation. This study observed the change of tear film mucin in GO patients.

Activation of BZW1 by CEBPB in macrophages promotes eIF2α phosphorylation-mediated metabolic reprogramming and endoplasmic reticulum stress in MRL/lpr lupus-prone mice

BackgroundLupus nephritis (LN) is associated with significant mortality and morbidity, while effective therapeutics and biomarkers are limited since the pathogenesis is complex. This study investigated the roles of the CEBPB/BZW1/eIF2α axis in metabolic reprogramming and endoplasmic reticulum stress in LN.MethodThe differentially expressed genes in LN were screened using bioinformatics tools. The expression of CEBPB in the renal tissue of patients with LN and its correlation with the levels of creatinine and urinary protein were analyzed. We used adenoviral vectors to construct LN mice with knockdown CEBPB using MRL/lpr lupus-prone mice and analyzed the physiological and autoimmune indices in mice. Chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP–qPCR) and dual-luciferase reporter assays were conducted to explore the regulation of BZW1 by CEBPB, followed by glycolytic flux analysis, glucose uptake, and enzyme-linked immunosorbent assay (ELISA). Finally, the role of eIF2α phosphorylation by BZW1 in bone marrow-derived macrophages (BMDM) was explored using eIF2α phosphorylation and endoplasmic reticulum stress inhibitors.ResultsCEBPB was significantly increased in renal tissues of patients with LN and positively correlated with creatinine and urine protein levels in patients. Downregulation of CEBPB alleviated the autoimmune response and the development of nephritis in LN mice. Transcriptional activation of BZW1 by CEBPB-mediated glucose metabolic reprogramming in macrophages, and upregulation of BZW1 reversed the mitigating effect of CEBPB knockdown on LN. Regulation of eIF2α phosphorylation levels by BZW1 promoted endoplasmic reticulum stress-amplified inflammatory responses in BMDM.ConclusionTranscriptional activation of BZW1 by CEBPB promoted phosphorylation of eIF2α to promote macrophage glycolysis and endoplasmic reticulum stress in the development of LN.

Changes of Serum C-Reactive Protein Level in Patients With Depressive Disorders After Treatment With Agomelatine Combined With Aerobic Exercise and Its Significance.

Depressive disorders constitute a series of debilitating diseases. This study investigated the therapeutic effect of agomelatine (AG) combined with aerobic exercise (AE) on patients with moderate-severe depression (MSD) and the changes of the serum C-reactive protein (CRP) level in patients after treatment as well as its significance. A total of 178 MSD patients were randomly assigned to the AG group (N = 90) and AG + AE group (N = 88). The severity of depressive disorders and anhedonia was assessed using the Hamilton Rating Scale for Depression (HAM-D), Beck Depression Inventory, and Snaith-Hamilton Pleasure Scale scores. The serum CRP level in MSD patients was detected by turbidity assay. Patients were defined as remitters, responders, and nonresponders according to the HAM-D17 score, and the treatment efficacy was analyzed, followed by evaluation of the serum CRP level in patients with different treatment responses. Finally, the adverse reactions of patients during treatment were statistically analyzed. After treatment, the HAM-D, Beck Depression Inventory, and Snaith-Hamilton Pleasure Scale scores and the serum CRP level of the 2 groups were reduced, and changes in the AG + AE group was more significant than that in the AG group. The clinical efficacy of the AG + AE group was better than that of the AG group. After treatment, the serum levels of CRP in remitters and responders were reduced, but not significantly in nonresponders. The incidence of adverse events in the AG + AE group was lower than that in the AG group. AG + AE reduced the serum level of CRP in MSD patients and had good therapeutic effects on MSD patients.

CASP3 gene expression and the role of caspase 3 in the pathogenesis of depressive disorders

BackgroundThe aim of our study was to evaluate the expression of the CASP3 gene at both mRNA and protein levels in patients with depressive disorders and to determine the impact of caspase 3 in the pathogenesis of depression;MethodsA total of 290 subjects, including 190 depressed patients and 100 healthy controls, participated in the study. Socio-demographic and clinical data were collected, and the severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale. Venous blood was collected and gene expression was evaluated using RT-PCR and ELISA at the mRNA and protein levels, respectively;ResultsThe expression of the CASP3 gene was significantly lower in depressed patients compared to healthy controls at both the mRNA and protein levels. Additionally, a positive correlation was observed between CASP3 gene expression and disease duration as well as the number of depressive episodes;ConclusionsFurther studies are needed to investigate the role of caspase 3 in depressive disorders.