Correlation of High-Grade Osteosarcoma Response to Chemotherapy with Enhanced Tissue Immunological Response: Analysis of CD95R, IFN-γ, Catalase, Hsp70, and VEGF.

High-grade osteosarcoma, a primary malignant bone tumour, is experiencing a global increase in reported incidence with varied prevalence. Despite advances in management, which include surgery and neoadjuvant chemotherapy often an unsatisfactory outcome is found due to poor or heterogeneous response to chemotherapy. Our study delved into chemotherapy responses in osteosarcoma patients and associated molecular expressions, focusing on CD95 receptor (CD95R), interferon (IFN)-γ, catalase, heat-shock protein (Hsp)70, and vascular endothelial growth factor (VEGF). Employing immunohistochemistry and Huvos grading of post-chemo specimens, we analysed formalin-fixed paraffin-embedded (FFPE) osteosarcoma tissue of resected post-chemotherapy specimens from Dr. Soetomo General Academic Hospital in Surabaya, Indonesia (DSGAH), spanning from 2016 to 2020. Results revealed varied responses (poor 40.38%, moderate 48.08%, good 11.54%) and distinct patterns in CD95R, IFN-γ, catalase, Hsp70, and VEGF expression. Significant differences among response groups were observed in CD95R and IFN-γ expression in tumour-infiltrating lymphocytes. The trend of diminishing CD95R expression from poor to good responses, accompanied by an increase in IFN-γ, implied a reduction in the count of viable osteosarcoma cells with the progression of Huvos grading. Catalase expression in osteosarcoma cells was consistently elevated in the poor response group, while Hsp70 expression was highest. VEGF expression in macrophages was significantly higher in the good response group. In conclusion, this study enhances our understanding of immune-chemotherapy interactions in osteosarcoma and identifies potential biomarkers for targeted interventions.

Relationship Between Disease Activity, Levels of IFN-a, IL-4, IL-6, and Anti-NMDA to Cognitive Dysfunction (MoCA-INA Score) in Systemic Lupus Erythematosus (SLE) Patients with Cognitive Dysfunction.

BACKGROUND: Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is a condition that impacts the patients' brain with SLE, and cognitive dysfunction (CD) is the most common manifestation. Subsequently, the CD hurts the life quality of SLE patients and creates impaired social function. Furthermore, the Montreal Cognitive Assessment (MoCA-INA) is a screening instrument to evaluate cognitive function. In the context of lupus, cytokines, and autoantibodies act as biomarkers in SLE disease control activities. PURPOSE: The aim of this study was to analyze the correlation between disease activity, IFN-a, IL-4, IL-6 and Anti-NMDA on CD (MoCA-INA Score) in SLE patients with CD. METHODS: This analytical observational study was performed with a cross-sectional design and included a sample of 56 SLE patients. The independent variables were the degree of the disease activity, and levels of IFN-a, IL-4, IL-6, and anti-NMDA. The dependent variable consisted of the degree of CD (MoCA-INA score), while the confounding variables were age, DM, gender, hypertension, obesity, and dyslipidemia. Subsequently, the CD was described as a MoCA-INA score <26, and disease activity was estimated based on the SLEDAI score. RESULTS: Increased IL-6 levels were correlated with decreased MoCA-INA scores (p=0.003; r= -0.387). Younger age was found to be associated with more severe CD (p=0.006) Conclusion:In conclusion, IL-6 levels can be used as a predictor severity of CD in SLE patients.

Pulsed Radiofrequency Decreases pERK and Affects Intracellular Ca2+ Influx, Cytosolic ATP Level, and Mitochondrial Membrane Potential in the Sensitized Dorsal Root Ganglion Neuron Induced by N-Methyl D-Aspartate.

Background: The molecular mechanism of pulsed radiofrequency (PRF) in chronic pain management is not fully understood. Chronic pain involves the activation of specific N-Methyl D-Aspartate receptors (NMDAR) to induce central sensitization. This study aims to determine the effect of PRF on central sensitization biomarker phosphorylated extracellular signal-regulated kinase (pERK), Ca2+ influx, cytosolic ATP level, and mitochondrial membrane potential (Δψm) of the sensitized dorsal root ganglion (DRG) neuron following NMDAR activation. Methods: This study is a true experimental in-vitro study on a sensitized DRG neuron induced with 80 µM NMDA. There are six treatment groups including control, NMDA 80 µM, Ketamine 100 µM, PRF 2Hz, NMDA 80 µM + PRF 2 Hz, and NMDA 80 µM + PRF 2 Hz + ketamine 100 µM. We use PRF 2 Hz 20 ms for 360 seconds. Statistical analysis was performed using the One-Way ANOVA and the Pearson correlation test with α=5%. Results: In the sensitized DRG neuron, there is a significant elevation of pERK. There is a strong correlation between Ca2+, cytosolic ATP level, and Δψm with pERK intensity (p<0.05). PRF treatment decreases pERK intensity from 108.48 ± 16.95 AU to 38.57 ± 5.20 AU (p<0.05). PRF exposure to sensitized neurons also exhibits a Ca2+ influx, but still lower than in the unexposed neuron. PRF exposure in sensitized neurons has a higher cytosolic ATP level (0.0458 ± 0.0010 mM) than in the unexposed sensitized neuron (0.0198 ± 0.0004 mM) (p<0.05). PRF also decreases Δψm in the sensitized neuron from 109.24 ± 6.43 AU to 33.21 ± 1.769 AU (p<0.05). Conclusion: PRF mechanisms related to DRG neuron sensitization are by decreasing pERK, altering Ca2+ influx, increasing cytosolic ATP level, and decreasing Δψm which is associated with neuron sensitization following NMDAR activation.

The Effect of Salmonella AvrA Infection on Colon Cancer: An in-silico Study.

OBJECTIVE: Colorectal cancer (CRC) is one of the main causes of morbidity and mortality due to cancer. The purpose of this in-silico study was to examine the relationship of chronic infection mechanisms caused by Salmonella Anti virulence agent A (AvrA) to gene mutations in the carcinogenic process of CRC. METHODS: Gene expression data on the mouse colon was obtained from the GSE22215 dataset | Gene Expression Omnibus (GEO). Adjusted p-value was calculated using Benjamini & Hochberg False Discovery Rate (FDR<0.01). Gene expression in colon adenocarcicoma tumors was obtained from The Cancer Genome Atlas's (TCGA) Genomic Data Commons (GDC) dataset containing 458 colon tumor samples. RESULT: Expressions of MLH1, MSH2, EPCAM, APC, and PMS2 in cases of colon adenocarcinoma tumor showed a correlation with genes that underwent changes due to Salmonella AvrA infection. Among the gens of interest, EPCAM was the gene that had the highest correlation compared to other genes (MLH1, MSH2, APC, and PMS2) (n= 514, Gene r-p value < 0.01 =22355). There were 514 genes that had a correlation with cases of AvrA infection. Tumor Necrosis Factor (TNF), which is a gene that is upregulated in AvrA infection and correlates negatively with EPCAM, had the highest BC value compared to other gens (p= 0.0000768). Survival probability showed that EPCAM was highly expressed and it can increase survival time. In addition to TNF, our study indicated that IL1B (p= 0.000419), S100A8 (p= 2.02E-05), S100A9 (p=0.000419) correlated with the gene of interest. CONCLUSION: Late Salmonella AvrA infection affects the expression of genes involved in inflammation in colorectal cancer samples.

Akkermansia muciniphila and Faecalibacterium prausnitzii in Immune-Related Diseases.

Probiotics and synbiotics are used to treat chronic illnesses due to their roles in immune system modulation and anti-inflammatory response. They have been shown to reduce inflammation in a number of immune-related disorders, including systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and chronic inflammatory skin conditions such as psoriasis and atopic dermatitis (AD). Akkermansia muciniphila (A. muciniphila) and Faecalibacterium prausnitzii (F. prausnitzii) are two different types of bacteria that play a significant part in this function. It has been established that Akkermansia and Faecalibacterium are abundant in normal populations and have protective benefits on digestive health while also enhancing the immune system, metabolism, and gut barrier of the host. They have the potential to be a therapeutic target in diseases connected to the microbiota, such as immunological disorders and cancer immunotherapy. There has not been a review of the anti-inflammatory effects of Akkermansia and Faecalibacterium, particularly in immunological diseases. In this review, we highlight the most recent scientific findings regarding A. muciniphila and F. prausnitzii as two significant gut microbiota for microbiome alterations and seek to provide cutting-edge insight in terms of microbiome-targeted therapies as promising preventive and therapeutic tools in immune-related diseases and cancer immunotherapy.

The phenotype of CD3-CD56bright and CD3-CD56dim natural killer cells in systemic lupus erythematosus patients and its relation to disease activity.

Introduction: Systemic lupus erythematosus (SLE) patients have decreased natural killer (NK) cell counts. The decrease in the number of NK cells has implications for a decrease in the function of NK cells which can affect the progression of SLE disease. The study aim was to determine profiles of CD3-CD56bright and CD3-CD56dim NK cells in SLE patients and their relation to disease activity. Material and methods: This study included 36 patients of SLE who fulfilled the ACR 1997/SLICC 2012 criteria, women aged 18-49 years. Disease activity was assessed by the Mex-SLEDAI. Peripheral blood samples from SLE patients were analyzed by flow cytometry to evaluate NK cell subsets, according to differential expression of the main subset of NK cells, which is CD3-CD56bright and CD3-CD56dim. Results: The mean percentage of regulatory NK cell count (CD3-CD56bright) in active SLE patients was significantly lower (p = 0.000) than in inactive SLE patients. The mean percentage of cytotoxic NK cell count (CD3-CD56dim) in active SLE patients was significantly (p = 0.000) higher than in inactive SLE patients. A correlation was observed between two subsets of NK cells with disease activity (p = 0.00). The percentage of CD3-CD56bright NK cells was negatively correlated with disease activity (r = -0.766), whereas the percentage of CD3-CD56dim NK cells positively correlated with disease activity (r = 0.761). Conclusions: There is a difference in the mean percentage of the number of NK cells (CD3-CD56+) in both a subset of regulatory NK cells (CD3-CD56bright) and cytotoxic NK cells (CD3-CD56dim) in active and inactive SLE patients and it is closely related to SLE disease activity.

Serine racemase interaction with N-methyl-D-aspartate receptors antagonist reveals potential alternative target of chronic pain treatment: Molecular docking study.

Serine racemase (SR) catalyzes L-serine racemization to activate the N-methyl-D-aspartate receptor (NMDAR). NMDAR activation is associated with the progression of acute-to-chronic neuropathic pain. This study aimed to investigate NMDAR antagonist interactions with SR to obtain potential chronic pain target therapy. Several NMDAR antagonist drugs were obtained from the drug bank, and malonate was used as a control inhibitor. Ligands were prepared using the open babel feature on PyRx. The SR structure was obtained from Protein data bank (PDB) (3l6B) and then docked with ligands using the AutoDock Vina. Haloperidol had a lower binding affinity than malonate and other ligands. Ethanol had the highest binding affinity than other drugs but could bind to the Adenosine triphosphate (ATP)-binding domain. Haloperidol is bound to reface that function for reprotonation in racemization reaction to produce D-serine. Halothane bond with Arg135 residues aligned negatively charged substrates to be reprotonated properly by reface. Tramadol is bound to amino acid residues in the triple serine loop, which determines the direction of the SR reaction. Several NMDAR antagonists such as haloperidol, halothane, ethanol, and tramadol bind to SR in the specific binding site. It reveals that SR potentially becomes an alternative target for chronic pain treatment.

Possible autoimmune hemolytic anemia induced by secukinumab: a case report.

Secukinumab, an anti-IL-17 monoclonal antibody, has been used to treat psoriasis and psoriatic arthritis since 2015. Several adverse events were reported, such as diarrhea, upper respiratory tract infection, middle ear infection, and neutropenia. Here we report a probable case of autoimmune hemolytic anemia in a 39 years old male with psoriasis and psoriatic arthritis treated with secukinumab. Hemolytic anemia detected after first maintenance dose after completion of induction dose of secukinumab. The patient also had other comorbids, soft tissue infection that also predisposed to autoimmune hemolytic anemia, but secukinumab is still a possible etiology for drug-induced autoimmune hemolytic anemia based on Naranjo´s score. The patient decided to continue secukinumab treatment, interestingly hemoglobin levels improved.

Association of the premature immunosenescence with the presence and severity of anemia among patients with systemic lupus erythematosus.

INTRODUCTION: One of the possible mechanisms that contribute to the development of anemia in systemic lupus erythematosus (SLE) is the presence of premature immunosenescence in SLE. This study aimed to observe the correlation between immunosenescence with anemia in SLE. METHODS: This research was a cross-sectional study with the subject was 60 women with SLE aged 16-45 years old. Subjects were recorded for the demographic and clinical data, complete blood counts, iron status (iron serum, total iron-binding capacity, and transferrin saturation), ferritin, inflammatory markers (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), and anti-dsDNA levels. Immunosenescence was observed by measuring the senescent T cells from peripheral blood mononuclear cells (PBMC) by flow cytometry, counted as CD4+CD57+ and CD8+CD57+ T cells. Serum IL-2 and IFNγ as the cytokines associated with immunosenescence were also measured from all subjects. Subjects were divided into anemic and non-anemic groups according to the classification of anemia from WHO (Hb < 12 gr/dl). RESULTS: Anemic SLE patients had higher CD4+CD57+, CD8+CD57+, and IFNγ, while IL-2 was lower in SLE patients with anemia. Multivariate linear regression revealed that the decreasing levels of Hb were associated with the increase of CD8+CD57+ percentages and IFNγ levels. Anti-dsDNA, ESR, CRP, ferritin, iron serum, and transferrin saturation were correlated with CD8+CD57+. IFNγ level also correlated with the anti-dsDNA, iron serum, and ferritin levels. No correlation was found between the iron status and inflammatory markers with CD4+CD57+ percentages and IL-2 levels. Multivariate regression analysis showed that IFNγ was positively associated with anti-dsDNA and negatively associated with iron serum and transferrin saturation, while CD8+CD57+ percentages were positively associated with the ferritin levels. CONCLUSION: Immunosenescence is associated with anemia by modulating the inflammatory response and causing iron dysregulation in SLE.

Modulation of T-cell Regulators Associated with Advanced Stage of Prostate Cancer.

BACKGROUND: Benign prostatic hyperplasia (BPH) and prostate cancer are the most common prostate diseases. The possible role of the immune system in the pathogenesis of BPH and prostate cancer in recent years has begun to be widely studied. Although many studies have focused on T lymphocytes on the development of BPH and prostate cancer, the role of regulatory T-cells in the pathogenesis of BPH and prostate cancer is still not well known. OBJECTIVE: To determine the amount of regulatory T-cells in prostate cancer and BPH so that it can contribute to the concept of understanding the pathogenesis of prostate cancer and BPH. METHODS: This study used cross-sectional design study. Total samples were 24 patients, with 13 subjects prostate cancer group, and 11 subjects BPH group. Furthermore, peripheral blood samples are taken and then the amount of regulatory T-cells is calculated. After obtaining data on the amount of CD4+ CD25+ Foxp3+ regulatory T-cells in the blood, data analysis was performed between groups of patients diagnosed with prostate cancer and benign prostatic hyperplasia. RESULTS: The average amount of regulatory T-cells in the CRPC group was 53.44±29.43, prostate cancer group was 57.02±22.49 and the BPH group 89.71±9.31. One Way ANOVA test results showed that the average amount of regulatory T-cells between treatment groups gave a significant difference in regulatory T-cells with a p-value (0,003) <0.05. It can be concluded that there are differences in the average amount of regulatory T-cells, so we continued the testing with Tukey test. We continue to Pearson correlation study and resulted in significantly correlated with p value = 0.011 (P<0.05) and r = 0.414. CONCLUSIONS: It can be concluded there was significant difference between the average number of regulator T-cells in the BPH group compared with prostate cancer and CRPC patient. Further research is needed regarding the number of regulator T-cells CD4 + CD25 + FOXP3 + in prostate cancer patients (grouped according to Gleason score) and benign prostatic hyperplasia before and after therapy with bigger samples.

Association between senescence of T cells and disease activity in patients with systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) patients are predisposed to chronic immune activation, leading to accelerated immunosenescence. The aging of the immune system causes the T cells to express several senescence markers such as CD57 and KLRG1, which produce pro-inflammatory cytokine interferon γ (IFN-γ). Immunosenescence was associated with high morbidity and mortality in other diseases. This research was conducted to prove the association between senescent T cells and SLE disease activity. MATERIAL AND METHODS: This research was an observational cross-sectional study on 53 women aged 16-45 years diagnosed with SLE based on SLICC 2012 criteria. All subjects were recorded for demographic and clinical data, and their SLE disease activity index (SLEDAI) score was measured to evaluate disease activity. Active disease was defined as SLEDAI score ≥ 3. The CD57 antigen and KLRG1 expression on CD4+ and CD8+ T cells were calculated from peripheral blood mononuclear cells (PBMC) by flow cytometry. Interferon γ was measured from serum using ELISA. The comparison was done using the Mann-Whitney U test, and correlation was tested using the Spearman test. Associations between variables were calculated using linear regression models. RESULTS: Systemic lupus erythematosus patients with active disease had markedly higher CD4+KLRG1+ (3.1 [1.3-5.5]% vs. 0.3 [0.1-0.5]%), CD8+CD57+ (11.6 ±7.1% vs. 2.4 ±2.0%, p = 0.000), and CD8+KLRG1+ T cell percentages (13.7 ±7.5% vs. 0.3 ±0.1%, p = 0.000), and IFN- γ levels (208.9 [148.3-233.8] vs. 146.7 [130.2-210.8] pg/ml, p = 0.048), compared to the inactive patients. Positive correlation and association was found between the CD8+CD57+ and CD8+KLRG1+ percentages with the SLEDAI score (p = 0.007 and p = 0.007, for the linear regression analysis, respectively). CONCLUSIONS: Systemic lupus erythematosus patients showed significantly higher senescence T cell markers compared to controls, and the increase of T cell senescence, especially in the CD8 compartment, has some association with increased disease activity in patients with SLE.

miRNA-21 as Reliable Serum Diagnostic Biomarker Candidate for Metastatic Progressive Prostate Cancer: Meta-analysis Approach.

BACKGROUND: Prostate cancer is the second leading cause of cancer death in men, moreover when it develops metastasis. However, PSA detection in serum as current gold standard to measure disease progressivity had wide variability leading to confounding outcomes. MicroRNA-21 has diagnostic values for cancer over period of time researched, yet results are still inconclusive. OBJECTIVE: The aim of the study was to conduct recent meta-analysis to assess reliability of miRNA-21 as diagnostic biomarker especially in progressivity of prostate cancer. METHODS: Published papers from PubMed, Science Direct, and Embase" as of 1 July 2021 assessing circulating miRNA-21 in progressivity of prostate cancer patients were analyzed using Comprehensive Meta-Analysis tool. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR) and SROC assessed with 95 % confidence intervals were estimated using fixed-effects or random-effects models. RESULTS: In total, we included 6 papers total of 651 samples reporting miRNA-21 capability of detecting progressive prostate cancer. The pooled sensitivity and specificity showed 0.91 (95% CI 0.88-0.94, I2=0%) and 0.89 (95% CI 0.85-0.92, I2=44.8%), respectively. Positive and negative likelihood ratio showed 7.18 (95% CI 4.31-11.96, I2=56%) and 0.11 (95% CI 0.07-0.16, I2=11.8%). SROC were assessed and got Area Under Curve around 97.4%. CONCLUSION: miRNA-21 could serve as biomarkers of prostate cancer progressivity since remarkable diagnostic value of circulating miRNA-21 in prostate cancer metastasis process.

miRNA-21 Serum Evaluation in BPH, Hormone Sensitive Prostate Cancer, and Castrate Resistant Prostate Cancer: Attempt for Diagnostic Biomarker Evaluation.

BACKGROUND: Some of prostate cancer cases could progress to be Castrate Resistant Prostate Cancer (CRPC). However it is still a challenge to early diagnose it since no reliable examination could be done except PSA, which has high variability. It is now known that miRNAs are involved in nearly all inflammatory responses. Several malignancies in humans that specifically express miRNA have been detected and identified. The expression values of miRNA-21 also correlates with the occurrence of resistant castration of prostate cancer and metastases, therefore miRNA-21 is expected to be a biomarker to estimate the progression of cancer. OBJECTIVE: The purpose of this study was to analyze the expression values and cut-off markers of miRNA-21 as markers of CRPC progression. METHODS: This study used a retrospective cohort design with observational analysis. The forty-eight total sample was obtained from serum, then the RT-PCR was performed to obtain expression values of miRNA-21. Data were analyzed using One Way ANOVA to see the difference in the expression values of miRNA-21. Furthermore, to determine the cut-off analysis was carried out using the ROC curve. RESULTS: In the BPH group, an average expression value of miRNA-21 was 33,785±1.80 ng/dL, in the Prostate cancer group the average miRNA-21 was 34.51±1.32 ng/dL, while in the CRPC group, an average miRNA-21 was obtained, reaching to 34.51±1.32 ng/dL. The cut-off value of miRNA-21 from the BPH category was <33,595, PPV = 50%, NPV = 80% with a value of p = 0.081, the prostate Ca category was 33.595-35.21, PPV = 87.5%, NPV = 66.7% with p value = 0.003, while the value of miRNA-21 in the CRPC category was> 35.21, PPV = 80%, NPV = 58.3 with a value of p = 0.04. CONCLUSION: There is a significant difference in the expression values of miRNA-21 between BPH with CRPC and Prostate cancer and CRPC, therefore, miRNA-21 cut-off point is potential to differentiate the diagnosis.

Periodontal Comparison on Systemic Lupus Erythematosus Patients and Healthy Subjects: A Cross-Sectional Study

ABSTRACT Objective: To analyze periodontal comparison between Systemic Lupus Erythematosus (SLE) subject and healthy control. Material and Methods: This descriptive cross-sectional study included 122 subjects, 61 SLE patients and 61 healthy subjects who visited the Rheumatology Department, Dr. Saiful Anwar General Hospital, Malang, during 2017-2018. Clinical examination of SLE was using Mexican SLE Disease Activity Index and oral cavity conditions were assessed using the periodontal index, gingival index, calculus index, bleeding on probing, clinical attachment loss and mobility teeth. Results: The age of SLE patients ranged from 18-55 years old with the mean age of 29.50 ± 9.57 years old. Periodontitis was higher in SLE patients (88.5%) than healthy subjects (22.95%). In addition, periodontitis occurrence in SLE (2.66 ± 1.02) was significantly different (p<0.001) compared to healthy subjects (0.51 ± 0.81). Conclusion: This study found higher rates of periodontitis, gingivitis, bleeding on probing, clinical attachment loss, and mobility tooth among SLE patients compared to healthy subjects. Periodontitis was also found to be higher along with more severe SLE group.

Role of Lymphocytes CD4/CD8 Ratio and Immunoglobulin G Cytomegalovirus as Potential Markers for Systemic Lupus Erythematosus Patients with Periodontal Disease.

OBJECTIVES: The aim of the study was to analyze the correlation between periodontitis severity in systemic lupus erythematosus (SLE) with CD4/CD8 lymphocytes ratio and cytomegalovirus gamma immunoglobulin (IgG CMV) level. MATERIALS AND METHODS: This is a descriptive study using a cross-sectional approach that included 93 subjects who were diagnosed with SLE in Rheumatology Department, Saiful Anwar Hospital, during 2017 to 2019. Periodontitis severity was assessed by periodontal Index (PI). CD4/CD8 lymphocyte ratio was determined using flow cytometry and IgG CMV levels using enzyme-linked immunosorbent assay. STATISTICAL ANALYSIS: The differences among the three groups were analyzed using analysis of variance. Correlation among the groups was calculated using Spearman/Pearson correlation coefficient test, while regression analysis was done using Statistical Package for the Social Sciences. RESULTS: The mean of periodontitis severity and standard deviation in SLE was 2.66 ± 1.02. There were negative correlation between CD4/CD8 lymphocyte ratio with periodontal index (r = -0.971) and positive correlation between IgG CMV level with periodontal index (r = 0.977). CONCLUSIONS: Inverted CD4/CD8 ratio and IgG CMV were found associated with periodontitis severity in SLE patient. Further research was recomended that CD4/CD8 lymphocytes ratio and IgG CMV can be used as a potensial marker of periodontitis severity in SLE patients.

Accelerated immune aging was correlated with lupus-associated brain fog in reproductive-age systemic lupus erythematosus patients.

AIMS: Cognitive impairment is common in systemic lupus erythematosus (SLE) patients with substantial adverse effects on function and quality of life. One hypothesis to understand the mechanisms of cognitive impairment in SLE is accelerated immunosenescence. The aim of this study is to observe the correlation between immunosenescence with cognitive impairment in patients with SLE. METHODS: Sixty-one female SLE patient were measured for CD4 and CD8 T cell-associated senescence markers, including percentage of end-stage differentiated T cells (CD4 and CD8 T cells expressing CD57+ or loss of CD28 expression), of naïve T cells (CD4+ CD45RA+ and CD8+ CD45RA+ ), memory T cells (CD4+ CD45RO+ and CD8+ CD45RO+ ), and antigen-experienced T cells (CD4+ KLRG1+ and CD8+ KLRG1+ ) which were measured using flow cytometry. One hallmark of immunosenescence called immune risk profile (IRP) was defined by an inverted ratio of CD4 and CD8. Cognitive functions were measured by Mini-Mental State Examination (MMSE) and Montréal Cognitive Assessment (MOCA) questionnaire. RESULTS: Thirty-six (59.1%) SLE patients who had IRP develop significantly lower attention and recall from both MMSE (P = .005 and P = .000) and MOCA (P = .017 and P = .000) examinations. Decreased visuospatial ability was also found in patients with IRP measured by MOCA (P = .046). There was a negative correlation between memory CD4+ CD45RO+ T cells with recall and visuospatial domain (R = -0.204, P = .039 and R = -0.250, P = .033; respectively), and negative correlation between CD8+ CD28- T cells with recall and attention domain (R = -0.249, P = .027 and R = -0.145, P = .048, respectively). CONCLUSION: Systemic lupus erythematosus patients develop an accelerated immunosenescence which contributes to cognitive dysfunction, especially in attention, recall, and visuospatial domains.

Periodontal Tissue Condition on Systemic Lupus Erythematosus Patients: A Clinical Study

Abstract Objective: To evaluate periodontal tissue condition on systemic lupus erythematosus (SLE) patients and its characteristics. Material and Methods: This descriptive and cross-sectional study involved 61 SLE patients. Clinical examination of the oral cavity was performed using periodontal index (PI), gingival index (GI), clinical attachment loss (CAL) and number of loose teeth. Also, we evaluated SLE duration, treatment duration, ethnics, marital status, educational background, family income, and occupation. Results: In the evaluation of periodontal tissue, 93.4% had bleeding on probing, 80.3% clinical attachment loss, and 16.3% loose teeth. A total of 54 patients (88.5%) with SLE had periodontitis. Seven subjects had no periodontitis, 11 mild periodontitis, 29 moderate periodontitis and 14 severe periodontitis. Mean Periodontal Index score, Gingival Index, Clinical Attachment Loss (mm), and the number of mobility teeth, Plaque Index and Calculus Index respectively were 2.66 ± 1.20, 1.95 ± 1.02, 0.75 ± 0.59 mm, 1,49 ± 1.77. There was a significant difference in periodontal index score, shown periodontitis between employment and unemployment subjects (p=0.004) and a moderate correlation between periodontitis and occupation. Conclusion: Periodontitis found as manifestations SLE patients, followed by bleeding on probing and loose teeth. Its characteristics is playing a role in periodontitis in SLE patients.

Oral Hygiene and Dental Caries Status on Systemic Lupus Erythematosus Patients: A Cross-Sectional Study

Abstract Objective: To evaluate the oral hygiene and dental caries status on Systemic Lupus Erythematosus (SLE) patients, also it's with SLE disease activity. Material and Methods: This is a descriptive study with a cross-sectional approach. The study was conducted on 93 SLE patients from 2017 to 2019 on Saiful Anwar Hospital Indonesia. All SLE patients had clinical examination using DMF-T, Personal Hygiene Performance-Modified (PHP-M), Calculus Index (CI), Debris Index (DI), Plaque Index (PI) and Simplified Oral Hygiene Index (OHI-S). Clinical examination and laboratory tests are conducted to assess the activity of SLE measured using. The data were analyzed by One Way ANOVA test. Results: A total of 74% of subjects with SLE had dental caries. PHP-M with SLE severity was found significant (p<0.001) and a strong positive correlation (r=0.982). Plaque with SLE severity was found significant (p=0.001) and a strong positive correlation (r=0.938). OHI-S with SLE severity was found significant (p<0.001) and a strong positive correlation (r=0.953). DMF-T levels with SLE severity was found significant (p=0.001) and a strong positive correlation (r=0.974). It showed that the severity of disease activity was related to poor oral hygiene and a high incidence of dental caries. Conclusion: There is a correlation between oral hygiene, dental caries and SLE severity.

Molecular docking of genistein on estrogen receptors, promoter region of BCLX, caspase-3, Ki-67, cyclin D1, and telomere activity.

OBJECTIVES: This study aims to investigate the modulation of estrogen receptors by estrogen and the role of genistein in the transcriptional process that regulates genes involved in the proliferation, apoptosis, and telomere activity. METHODS: The research was conducted in silico, wherein docking, the most important method, was carried out using Hex 8.0 software and HADDOCK web server. Interaction analysis was subsequently done to observe the interactions between genistein and several related proteins and BCLX, Casp3, Ki-67, CyclinD1, hTERT, and POT1 genes using Discovery Studio, LigPlus, and NUCPLOT. RESULTS: The interaction between ERα with genistein was not found to form a single bond. Thus, the interaction that may occur will not be effective because it is not stable. Conversely, when interacting with ERß, two hydrogen bonds and four hydrophobic bonds, MPP dihydrochloride interacted with ERα via two hydrogen bonds and three hydrophobic bonds. The ERß/eNOS complex will be comparatively easier to induced by the transcriptional activation of BCLX, Casp3, Ki-67, CyclinD1, hTERT and POT1 genes. CONCLUSIONS: Administration of genistein can increase the genomic activities of the estrogen-eNOS receptor complexes related to apoptosis, proliferation, and telomere activity.

Effect of Hyperglycemia to The mRNA Level and Protein Expression of Perlecan at Rat Model of Osteoarthritis with Diabetes Mellitus Type 1.

INTRODUCTION: Previous research found that diabetes mellitus capable to aggravate osteoarthritis disease. In brief, the hyperglycemia condition in diabetes mellitus has an impact on protein glycation of all joint components, including molecule, such as perlecan. The protein expression of perlecan reflects the presence amount of perlecan in the matrix of articular cartilage. However, the impact of hyperglycemia on articular perlecan has not been explained. Moreover, the role of perlecan as a mechanotransducer for chondrocytes in type 1 Diabetes mellitus remains unclear. AIM: This research aims to analyze the effect of hyperglycemia in type 1 Diabetes mellitus to the mRNA level and protein expression of perlecan. METHODS: Thirty-five adult male rats were divided into seven groups, such as three groups of rat model with anterior cruciate ligament transection (ACLT) at right knee (ACLT1, ACLT2, ACLT3); three groups of rats with ACLT at right knee which followed by Streptozotocin injection for diabetic mice model (DM1, DM2, DM3); and control group (N). Rat sacrificed at the third week, fourth week, and sixth week after two months of maintenance. The mRNA level and protein expression were analyzed by using PCR and Western blot. All of data was analyzed by ANOVA. RESULTS: Protein expression of perlecan in ACLT mice with diabetes mellitus (DM1, DM2, DM3 group) was gradually decreased according to the increased hyperglycemia duration. Whilst, protein expression of perlecan within ACLT mice without diabetes mellitus (ACLT1, ACLT2, ACLT3 group) was increased. The similar result also demonstrated by the mRNA level of perlecan. Group of DM1, DM2, DM3 exhibited decreased mRNA level of perlecan over the hyperglycemia duration. While, ACLT1, ACLT2, and ACLT3 group had a gradually increased of perlecan mRNA level. CONCLUSION: Hyperglycemia on osteoarthritic condition decreased mRNA level and protein expression of perlecan which increased the severity of osteoarthritis disease.