sCD163, sCD28, sCD80, and sCTLA-4 as soluble marker candidates for detecting immunosenescence.

BACKGROUND: Inflammaging, the characteristics of immunosenescence, characterized by continuous chronic inflammation that could not be resolved. It is not only affect older people but can also occur in young individuals, especially those suffering from chronic inflammatory conditions such as autoimmune disease, malignancy, or chronic infection. This condition led to altered immune function and as consequent immune function is reduced. Detection of immunosenescence has been done by examining the immune risk profile (IRP), which uses flow cytometry. These tests are not always available in health facilities, especially in developing countries and require fresh whole blood samples. Therefore, it is necessary to find biomarkers that can be tested using stored serum to make it easier to refer to the examination. Here we proposed an insight for soluble biomarkers which represented immune cells activities and exhaustion, namely sCD163, sCD28, sCD80, and sCTLA-4. Those markers were reported to be elevated in chronic diseases that caused early aging and easily detected from serum samples using ELISA method, unlike IRP. Therefore, we conclude these soluble markers are beneficial to predict pathological condition of immunosenescence. AIM: To identify soluble biomarkers that could replace IRP for detecting immunosenescence. CONCLUSION: Soluble costimulatory molecule suchsCD163, sCD28, sCD80, and sCTLA-4 are potential biomarkers for detecting immunosenescence.

The Long-Term Serological Profile of CoronaVac Vaccine Based on Comorbidities and History of SARS-CoV-2 Infection in Indonesia.

CoronaVac is one of the most widely administered COVID-19 vaccines in Indonesia. Previous studies have documented its effectiveness in protecting against COVID-19 in several countries. This study aimed to assess the long-term immunogenicity of CoronaVac in individuals with comorbidities or a history of SARS-CoV-2 infection. The total anti-N Ig and anti-S-RBD Ig levels at 7 and 26 weeks after the second dose of vaccine were documented in 194 health workers. The participants were divided into groups based on their comorbidities and history of SARS-CoV-2 infection. The antibody titers did not differ according to comorbidity status or history of SARS-CoV-2 infection. The total anti-nucleocapsid Ig and total anti-S-RBD Ig levels were significantly lower in individuals without a history of SARS-CoV-2 infection. These results indicate that CoronaVac induces a lower specific antibody response than natural infection and less long-term immunogenicity.

Vitamin D3 induces stem cell activation via Lgr5-Bmi1 expression and improving mouse colitis histology index.

Conventional therapy for inflammatory bowel disease using long-term anti-inflammatory drugs does not seem to provide optimal results. Adjuvant therapy using vitamin D3 is believed to have an essential role in repairing the colonic mucosa through the activation of colonic stem cells. The aim of this study was to demonstrate the effect of vitamin D3 in mucosal repair through stem cell activation, marked by leucin-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and B lymphoma Mo-MLV insertion region 1 (Bmi1) expression and decrease the mouse colitis histology index (MCHI) score. In this study, 50 Mus musculus strain BALB/c were divided into five groups: negative control group, colitis group, and colitis groups with vitamin D3 administration of 0.2 mcg, 0.4 mcg, and 0.6 mcg per 25 g body weight for seven days. Dextran sulfate sodium (DSS) 5% was used to induce colitis. Lgr5-Bmi1 expression was measured using immunodoublestain fluorescent labeling method. Our data suggested that administration of vitamin D3 significantly increased expression of Lgr5-Bmi1 in the colonic mucosa. The colitis group treated with the highest dose of vitamin D3 (0.6 mcg/25 gram) showed the lowest MCHI score (3.60±0.64) while the lowest dose of vitamin D3 had the highest MCHI score (12.60±1.47). In conclusion, by stimulating stem cells, vitamin D3 administration stimulates mucosal regeneration, as demonstrated by upregulated expression of Lgr5-Bmi-1.

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.

The Role of Vitamin D for Modulating the T Helper 1 Immune Response After the Coronavac Vaccination.

The purpose of this study was to observe the role of vitamin D levels with T helper 1 (Th1)-type cytokines, such as interferon γ (IFN-γ) and interleukin-12 (IL-12) efficacy, in those who had already received 2 injections of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccines (CoronaVac). We also observed if these cytokines played any significance in the CoronaVac effectiveness for preventing coronavirus disease 2019 (Covid-19) infection. One hundred ninety-four volunteers were monitored for 8 months upon receiving 2 inactivated SARS-CoV2 vaccination injections (CoronaVac, Sinovac Life Sciences). The rate of confirmed Covid-19 infections was the primary outcome. Six to 7 weeks after the second vaccine injection, and blood samples were obtained to measure the serum vitamin D, IFN-γ, and IL-12 levels. Low vitamin D level was defined if vitamin D level <30 ng/mL. Subjects with low vitamin D had lower IFN-γ and IL-12 levels (P = 0.04 and P = 0.04, respectively). The receiver operating characteristics curve analysis revealed that the area under curve for IFN-γ was 0.59, whereas IL-12 was 0.59 for predicting the low vitamin D levels. During follow-up, a higher incidence of Covid-19 infections was observed in subjects with low IFN-γ levels (P = 0.03). Kaplan-Meier survival analysis revealed that the cumulative hazard of confirmed Covid-19 cases was increased in subjects with low IFN-γ levels (log-rank test, P = 0.03). We concluded that lower vitamin D level was correlated with a lower Th1 immune response, whereas the adequate IFN-γ level was required to obtain better CoronaVac effectiveness.

Association Between the Effectiveness and Immunogenicity of Inactivated SARS-CoV2 Vaccine (CoronaVac) with the Presence of Hypertension among Health Care Workers.

OBJECTIVE: This study aimed to observe the association between the presence of hypertension with Covid-19 vaccine effectiveness among healthcare workers who received CoronaVac vaccination. METHODS: We conducted a prospective cohort study in Saiful Anwar General Hospital, Malang, Indonesia on 155 healthcare workers aged 18-59 years old who already received twice of the CoronaVac (Sinovac Life Science, Beijing, China) injection with 14-day intervals. Hypertension was diagnosed according to the 2020 International Society of Hypertension. Subjects were monitored for six months. The primary outcome was the rate of Covid-19 diagnosed by the pharyngeal swab for the real-time reverse transcription-polymerase chain reaction (RT-PCR) examination. The secondary endpoints were: (1) severity of Covid-19 among infected participants; (2) rate of hospitalizations; and (3) anti-SRBD antibody levels measured by ECLIA. RESULTS: Among 155 participants, 18.7% of them were diagnosed with hypertension, and 31.0% had the desirable BP target according to the current guidelines. Subjects with hypertension, especially those with uncontrolled blood pressure, had a higher incidence of Covid-19 infection than subjects without hypertension. Subjects with symptomatic Covid-19 and hospitalized because of Covid-19 were higher in participants with hypertension. The anti-SRBD antibody levels were lower in the second month after CoronaVac vaccination in hypertensive subjects. In contrast, comparable anti-SRBD levels were seen from both groups at sixth months after vaccination. CONCLUSION: Hypertension was associated with lower vaccine effectiveness in healthcare workers. Subjects with hypertension had a higher risk of being infected with Covid-19 despite getting a complete dose of vaccination and lower antibody production.

Low levels of vitamin D were associated with coagulopathy among hospitalized coronavirus disease-19 (COVID-19) patients: A single-centered study in Indonesia.

BACKGROUND: This study was aimed to explore the association of vitamin D in the risk of coagulopathy in coronavirus disease-19 (COVID-19). METHODS: Clinical and laboratory findings were obtained from 50 confirmed COVID-19 patients hospitalized in Saiful Anwar General Hospital, Malang, Indonesia, from September to November 2020. Thrombotic events during hospitalization were recorded, and the ISTH disseminated intravascular coagulation (DIC) score was used to classify overt DIC. Hypovitaminosis D was defined by serum vitamin D level <49.92 nmol/L. RESULTS: Among 50 patients, 42 (84%) had hypovitaminosis D, and 6 (12%) developed thrombotic events. Vitamin D levels were lower in patients with thrombotic events (p=0.015), D-dimer >2 mg/L (p=0.006), ISTH DIC score 5 (p=0.020), admitted on ICU (p=0.002), and non-survivor groups (p=0.007). Multivariate analysis for the risk in increased D-dimer levels showed low vitamin D as the only significant risk factor with OR 1.8 (1.2-4.4), p=0.034. Low vitamin D also increased the risk for developing overt DIC with OR. 5.4 (1.0-30.2), p=0.039. Vitamin D level had negative correlations with ferritin (R=-0.316, p=0.044) and CRP (R=-0.530, p=0.000). CONCLUSIONS: In conclusion, a low level of vitamin D was found in most hospitalized COVID-19 patients and might be associated with the development of coagulopathy.

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.

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.

Role of vitamin D in Wnt pathway activation for colonic epithelial cell differentiation.

OBJECTIVES: Inflammatory bowel disease (IBD) is a medical condition that represents a pathological form of inflammation, causing damage to the colonic mucosa. Adjunctive vitamin D therapy may activate the Wnt/ß-catenin pathway that results in cell differentiation and proliferation via stem cell signalling. This study aims to evaluate the effect of vitamin D on ß-catenin and cytokeratin 20 (KRT20) as markers of Wnt pathway activation for colonic cell repair. METHODS: For the experiment, we used 30 musculus mice strains of BALB/c, which were categorised into five groups; the control group (K-) and four other groups, where colitis was induced by dextran sulphate sodium (DSS) for seven days. On the seventh day, the remaining three groups were administered vitamin D with an initial dose of 0.2 µg/25.0 g, 0.4 µg/25.0 g and 0.6 µg/25.0 g until day 14. An objective index of disease activity and a histological score were required as markers of inflammation to evaluate the results of the clinical trials. RESULTS: ß-catenin and KRT20 showed a significant increase in the proliferation index of vitamin D at a dose of 0.6 µg/25.0 g (91.50 ± 4.09 and 48.75 ± 2.28, respectively; p < 0.05) compared to the colitis group. CONCLUSIONS: This study demonstrates that vitamin D could be used as an induction agent of Wnt activation for healing colonic mucosa via multipotent stem cells.

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.

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.

What is the Best Degree of Hyaluronic Acid Crosslinking in Increasing Growth Factors Level of Platelet-Rich Fibrin Lysate?

Introduction: Various therapeutic materials such as hyaluronic acid (HA) and platelet-rich fibrin lysate (PRF-L) have been represented to improve chronic fibroblast ulcers and premature aging. HA crosslinking is the most popular dermal filler presently in the therapy of aging skin. With the PRF-L properties that are rich in growth factors (GF), the combination of these materials is expected to produce synergistic and potentiation effects. Objective: This study aimed to determine the effect of various degrees of HA crosslinking on GF levels in PRF-L. Materials and Methods: PRF-L was obtained from PRF of healthy adult venous blood with 72 hours of incubation. HA was taken from preparations with 3 crosslinking degrees of 3%, 4%, and 10%. Measurement of GF levels was performed using sandwich ELISA method. Results: The GF levels released in PRF-L increased with the addition of HA crosslinking. The lower HA crosslinking degree (3%) triggered greater release of GF by PRF-L compared to higher HA crosslinking degree (4% & 10%). Conclusion: Low degree HA crosslinking elevated all measured GF levels in PRF-L. The lower HA crosslinking degree provoked higher release of GF.

Decreased expression of MUC2 due to a decrease in the expression of lectins and apoptotic defects in colitis patients.

INTRODUCTION: The involvement of mucin, lectin, and apoptosis in colitis is still unclear. This study aimed to investigate changes in MUC2 expression, inflammation, and changes in lectin expression in colitis patients. METHODS: A total of 17 patients were divided into two groups including 11 hemorrhoid patients as a control group and 6 colitis patients. MUC2 mutation analysis was carried out using immunofluorescent and FISH techniques. Assessment of caspase-3, Ki-67, NF-kB, and lectin expressions was also carried out by immunofluorescent technique then analyzed by confocal laser scanning microscope. RESULTS: The MUC2, caspase-3, and lectin expressions were significantly lower in the colitis group than in the control group (p < 0.05). CONCLUSIONS: It was concluded that in colitis there was a change in MUC2 expression due to changes in lectins accompanied by apoptotic defects.conclusion.

Factors associated with health care seeking behavior for musculoskeletal pain in Indonesia: A cross-sectional study.

AIM: To assess the factors defining healthcare-seeking behavior of people with musculoskeletal pain in the urban community of Malang City, East Java, Indonesia. METHODS: A cross-sectional survey was performed in Malang City, East Java, Indonesia. In total, 2067 participants aged 16-93 years were interviewed. The sociodemographic and socioeconomic factors of healthcare seeking behavior, musculoskeletal pain, disability, and adverse drug reactions were assessed using the validated Indonesian version of Community Oriented Program for the Control of Rheumatic Disease (COPCORD) protocol by International League of Associations for Rheumatology and the World Health Organization core questionnaire. Chi-square test was applied to assess the determinants of health-seeking behavior for musculoskeletal pain. RESULTS: Slightly more than one-third of the respondents (36%) with musculoskeletal pain, described as osteoarthritis, low back pain, gouty arthritis, soft tissue rheumatism, and autoimmune arthritis, were assessed for their health-seeking behavior. About 73% of all those participants sought treatment for their musculoskeletal symptoms. Treatment modality used was modern healthcare, traditional healthcare, self-treatment using traditional medication, self-treatment using modern medication with the proportions of 20.94%, 25.23%, 33.95%, 25.77%, respectively. Disability significantly affected health-seeking behavior as the major determinant (prevalence ratio [PR] 1.087, 95% CI 1.031-1.146, P = 0.002), followed by age (PR 1.043, 95% CI 1.000-1.087, P = 0.049). Healthcare-seeking behavior was associated with the presence of adverse drug reactions (P < 0.001). CONCLUSION: Factors associated with musculoskeletal pain health-seeking behavior were disability and age. Self and traditional healthcare treatment were further associated with an adverse drug reaction.

Periodontitis is associated with disease severity and anti-double stranded DNA antibody and interferon-gamma levels in patients with systemic lupus erythematosus.

OBJECTIVES: To analyse the correlation between periodontitis severity and disease activity, anti-double stranded DNA (anti-dsDNA) antibody, and interferon-gamma (IFN-γ) levels in patients with systemic lupus erythematous (SLE). METHODS: We selected 61 patients with SLE (age 18-55 years) selected from a hospital in Malang, Indonesia. Clinical examination and laboratory tests were performed to assess disease activity. The severity of SLE was measured using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), while periodontitis severity was measured according to the Periodontal Index (PI) criteria. Levels of anti-dsDNA and IFN-γ were determined using an enzyme-linked immunosorbent assay. Optical density at 450 nm was measured using an automated plate reader. RESULTS: The mean age of the subjects with SLE was 29 years, and mean disease duration was 2.8 years. Fifty-four of 61 (88.53%) subjects with SLE had periodontitis according to the PI. SLE subjects exhibited other clinical manifestations such as lupus nephritis, vasculitis, arthritis, mucocutaneous manifestation, fatigue, fever, and/or leukopenia. SLE severity was assessed according to the average SLEDAI score (17.70 ± 12.70), and average anti-dsDNA (122.6 ± 81.01 U/mL), and IFN-γ (14.64 ± 11.17 pg/mL) levels. There was a significantly positive correlation between periodontitis score and SLEDAI score (r = 0.927; p ≤ 0.0001), anti-dsDNA antibody (r = 0.948; p ≤ 0.0001), and IFN-γ (r = 0.951; p ≤ 0.0001) levels. CONCLUSION: Results of the present study demonstrated that periodontitis was associated with SLE disease activity, and was a biomarker of immune aging. Furthermore, this biomarker could be a reliable predictor of periodontal condition and prognosis of periodontitis and can also help in selecting the most appropriate treatment strategy for periodontitis in patients with SLE.