MSCs-released TGFß1 generate CD4+CD25+Foxp3+ in T-reg cells of human SLE PBMC.

BACKGROUND/PURPOSE: Regulatory T-cell (Treg) defects may cause autoreactivity of both T and B cells, leading to autoimmune disease including systemic lupus erythematosus (SLE). The immune response defects in SLE are characterized by the decreased expression of CD4, CD25, and Foxp3, known as inducible Treg (iTreg). Therefore, restoring iTreg expression can reverse autoimmunity states into immune tolerances leading to normal immune responses. Mesenchymal stem cells (MSCs) have immunomodulatory properties to control inflammatory milieu, including in SLE inflammation by releasing TGFß1, IL10, and PGE2, thus MSCs can potentially generate iTreg cells. However, the mechanisms of MSC-released TGFß1 to promote iTreg generation in human SLE remains unclear. This study aims to analyze the role of MSC-released TGFß1 in generating CD4+, CD25+, and Foxp3+ expression in iTreg cells from human SLE peripheral blood mononuclear cells (PBMCs). METHODS: This study used a post-test control group design. MSCs were obtained from human umbilical cord blood and characterized according to their surface antigen expression and multilineage differentiation capacities. PBMCs isolated from SLE patients were divided into five groups, including sham, control, and three treatment groups. The treatment groups were treated by co-culturing MSCs to PBMCs with ratio of 1:1 (T1), 1:25 (T2), and 1:50 (T3) for 72 h incubation. The expression of CD4, CD25, and Foxp3 in Treg was analyzed by flow cytometry assay while TGFß1 level was determined by Cytometric Bead Array (CBA). RESULTS: This study showed that the percentage of CD4+CD25+Foxp3+ iTreg cells was significantly increased in T1 and T2. This finding was aligned with the significant increase of TGFß1 level. CONCLUSION: MSCs promote iTreg cells generation from human SLE PBMCs by releasing TGFß1 to control SLE disease.

Mesenchymal Stem Cells Suppress Dendritic Cells and Modulate Proinflammatory Milieu Through Interleukin-10 Expression in Peripheral Blood Mononuclear Cells of Human Systemic Lupus Erythematosus.

Background: Immune-mediated inflammatory injury among systemic lupus erythematosus (SLE) individuals may be involved by dendritic cells (DCs) abnormality though the underlying mechanism remains incompletely understood. Objective: This study aimed to elaborate MSCs' potential in suppressing abnormal DCs cell function on peripheral blood mononuclear cells (PBMCs) among SLE patients. Methods: MSCs were isolated from human umbilical cord blood. On the other side, human PBMCs were isolated from 20 active SLE patients and 5 healthy controls. The PBMCs of SLE patients were divided into 5 groups: sham (Sh) and control (C) groups were treated with standard medium, and the treatment groups (T1, T2 and T3) was co-cultured with hUC-MSC at doses of 1:1, 1:25, and 1:50 (MSCs:PBMCs). The expression of CD11c in DCs was analyzed using flow cytometry, while the level of TNF-α, IFN-γ, IL-6 and IL-10 was analyzed using cytometric bead array (CBA). Results: The MSCs significantly downregulates CD11c of dendritic cells in all treatment groups. MSCs also significantly suppress the level of TNF-α, IFN-γ, IL-6 and the significantly enhance IL-10 level in all treatment groups. Conclusion: Therefore, MSCs could suppress DCs through regulating the proinflammatory milieu in PBMCs of SLE patients.

Taeniasis/cysticercosis in Bali, Indonesia.

Taenia solium and Taenia saginata are found in humans in Bali, Indonesia. During a field survey of 660 people in Bali from 2002-2009 of taeniasis/cysticercosis cases using mitochondrial DNA confirmation of the species, we detected 80 cases of T. saginata taeniasis, 2 dual T. saginata/T. solium infections with T. solium metacestodes in the brain and 12 neurocysticercosis (NCC) cases at Sanglah Hospital, Denpasar. Although the prevalence of NCC in Bali is low, sporadic cases are still present. There is no Taenia asiatica in Bali. We summarize here the field survey findings of taeniasis, including 1 dual infection with taeniasis and cysticercosis in 2007, and the reason why there are no T. asiatica cases and we describe 3 NCC cases admitted to Sanglah Hospital, Denpasar, Bali in 2004. Diagnosis was based on anamnesis, clinical examination, including CT Scan, histopathological, serological and mitochondrial DNA examinations. In order to prevent unexpected symptomatic NCC after treatment with praziquantel, we recommend introducing a rapid test to confirm taeniasis carriers and cysticercosis cases as a tool for real time diagnosis.

Overview of Immunological Responses and Immunomodulation Properties of Trichuris sp.: Prospects for Better Understanding Human Trichuriasis.

Trichuris sp. infection has appeared as a pathological burden in the population, but the immunomodulation features could result in an opportunity to discover novel treatments for diseases with prominent inflammatory responses. Regarding the immunological aspects, the innate immune responses against Trichuris sp. are also responsible for determining subsequent immune responses, including the activation of innate lymphoid cell type 2 (ILC2s), and encouraging the immune cell polarization of the resistant host phenotype. Nevertheless, this parasite can establish a supportive niche for worm survival and finally avoid host immune interference. Trichuris sp. could skew antigen recognition and immune cell activation and proliferation through the generation of specific substances, called excretory/secretory (ESPs) and soluble products (SPs), which mainly mediate its immunomodulation properties. Through this review, we elaborate and discuss innate-adaptive immune responses and immunomodulation aspects, as well as the clinical implications for managing inflammatory-based diseases, such as inflammatory bowel diseases, allergic, sepsis, and other autoimmune diseases.

Mesenchymal stem cells under hypoxia condition inhibit peritoneal adhesion by suppressing the prolonged release of interleukin-6.

Aim To investigate the role of hypoxia-preconditioned mesenchymal stem cells (H-MSCs) in preventing peritoneal adhesion by regulating IL-6 at days 6 and 12. Methods Twenty-four PAs rat model weighing 250 g to 300 g were randomly allocated into 4 groups: sham (Sh), control (C), H-MSCs treatment group at dose 1.5 x 106(T1) and 3 x 106(T2). To induce H-MSCs, all MSCs population were incubated under hypoxia state (5% O2 ), 5% CO2, and 37oC for 24 hours. Expression level of IL-6 was performed using ELISA. Morphological appearance of adhesion was observed by visualizing the existence of adhesion formation in intestinal. Results In this study we found that there was a trend of decrease of IL-6 level on day 6 following MSCs treatments. Interestingly, there was a significant decrease of IL-6 level on day 12 in all treatment groups. Also, no adhesion occurred in T2 group. Conclusions H-MSCs prevent PA development by suppressing the prolonged release of IL-6 at proliferation phase.

Soil-transmitted helminth infections and taeniasis on Samosir Island, Indonesia.

Soil-transmitted helminth (STH) infections are important causes of morbidity in poorer areas of developing countries, with high endemicity in Southeast Asia. Humans are most often exposed to the infective forms of STHs in areas with sub-standard sanitation. The number of STH infections globally was estimated at 1.5 billion in 2018. In Indonesia, the prevalence of STH infections ranges from 2.5% to 62.0%. STH and taeniasis infections were evaluated on Samosir Island, North Sumatra, Indonesia. Field surveys were conducted in January 2003, February 2005, and February 2006 in Simanindo Subdistrict, with a subsequent survey conducted in the subdistricts of Simanindo and Ronggurnihuta in September 2015. A total of 371 individuals were screened between 2003 and 2006 and 368 were screened in 2015 (314 from Simanindo and 54 from Ronggurnihuta). Fecal samples were collected and examined microscopically by the Kato-Katz technique. The prevalence of STH infections in Simanindo for the years 2003, 2005, 2006, and 2015 was 41.4%, 52.2%, 55.7%, and 46.8%, respectively. The 2015 prevalence of STH infections in Ronggurnihuta was 66.7%. Taenia asiatica taeniasis prevalence was 3.4% and 2.2% for the years 2003 and 2005, respectively, with no cases detected in 2006 or 2015. The prevalence of STH infections in Simanindo and Ronggurnihuta was similar to other STH prevalence values reported for Indonesia. Country-level values have not changed substantially from those reported in the 1980s and 1990s, where prevalence ranged from 40% to 70%. Improvement of personal hygiene and environmental sanitation for control of STH infections on Samosir Island will require collaboration among multiple sectors.

Massive orbital myiasis arising from nasal myiasis in an Indonesian patient with diabetes.

PURPOSE: Orbital myiasis is a rare condition. We report a case of massive orbital myiasis (ophthalmomyiasis profunda) arising from nasal myiasis and caused by Chrysomya bezziana in a patient with diabetes. OBSERVATIONS: A 55-year-old woman presented with massive orbital myiasis from larvae invading the entire orbit, with only a small part of sclera and bulbar conjunctiva left of the ocular structures left unaffected. The patient complained of breathing difficulty and drooping of the left eyelid with no other significant complaints. Computed tomography of paranasal sinuses was performed to determine the extent of intraocular invasion of larvae and the surrounding area that might be involved. The larvae filled the nasal and orbital cavity with bony destruction. The patient had a history of diabetes mellitus with uncontrolled blood sugar. CONCLUSIONS AND IMPORTANCE: Orbital myiasis is an infestation of any anatomical structure of the orbit with larvae from the order Diptera. To our knowledge, this is the first reported case of massive orbital myiasis arising from nasal myiasis caused by C. bezziana in a patient with diabetes. Eliminating the causative larvae and topical treatment with antibiotics eye ointment therapy improved the patient's symptoms. Epidemiological data are required to improve documentation of the incidence rate of myiasis.

Cryptosporidium Sp. Findings and Its Symptomatology among Immunocompromised Patients.

BACKGROUND: Cryptosporidium sp. is an apicomplexan protozoa, and it is related to an immunocompromised state. As it develops diverse clinical manifestations, mild to life-threatening conditions, administration of anti-parasitic medication and its management remain problematic. AIM: The study aimed to provide Cryptosporidiosis symptomatology and its prevalence among HIV-infected patients in a tertiary referral hospital, Haji Adam Malik General Hospital, Medan, Indonesia. MATERIAL AND METHODS: Symptomatology was noted using short-questionnaire, and laboratory findings were obtained from the hospital medical record registry on the same day of admission. We enrolled 24 patients were suffered from HIV infection for a certain period and more than one-week diarrhoea including 18 males and 6 females. Routine faeces examination using wet mount, Kinyoun-gabet, and trichrome staining was performed for all samples in Parasitology Department, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia. Numerical data were evaluated using the Mann-Whitney test while Fisher Exact test was used to determine any association between categorical variables. RESULTS: Our study found that 8 of 24 patients were positive with Cryptosporidium sp. while its symptomatology including abdominal cramp (66.7%), nausea and vomiting (70.8%), and fever (62.5%) is prevalent from our study. We obtained significant association between CD4 cell count (p = 0.006), diarrhea duration (p = 0.007), abdominal pain (p = 0.005), and nausea and vomiting (p = 0.021) with cryptosporidiosis. CONCLUSION: High consideration of several symptoms related to cryptosporidiosis leads a clinician to initiate prompt management particularly in a high-risk population.

Cigarette Smoking and Hyperglycaemia in Diabetic Patients.

BACKGROUND: The incidence rate of diabetes mellitus has increased throughout the year. Various studies indicate that smoking may affect glucose metabolism and cause hyperglycemia in diabetes mellitus. This study aimed to compare the blood glucose and HbA1c level in diabetic smoking patients and non-smoking diabetic patients. METHODS: This study used the cross-sectional approach. The study population consisted of 30 diabetic smoking patients and 30 non-smoking diabetic patients. The diabetes history and the smoking status of the study population obtained by questionnaire-based interview, the blood glucose and HbA1c level were measured by hexokinase and immunoturbidimetry method using cobas 6000 analyser module c501 (Roche Diagnostics, Switzerland). RESULTS: The result in this study showed the fasting blood glucose, postprandial blood glucose, and HbA1c were higher by 23.64 mg/dl (p = 0.325), 58.00 mg/dl (p = 0.016), 0.39% (p = 0.412) in smoking diabetic patients compared to non-smoking diabetic patients. After statistical analysis, there was a significant difference (p < 0.05) of postprandial glucose level between smokers group and non-smokers group, but the non-significant difference of fasting blood glucose and HbA1c. CONCLUSIONS: This study concluded that there was a significant difference in postprandial glucose level between smokers group and non-smokers group but the non-significant difference of fasting blood glucose and HbA1c.

Correlation between Soil-Transmitted Helminths Infection and Serum Iron Level among Primary School Children in Medan.

BACKGROUND: The latest estimates indicate that more than 2 billion people worldwide are infected by Soil-Transmitted Helminths (STH). The burden of STH infection is mainly attributed to the chronic effect on health and quality of life of those infected. It is also contributed to micronutrient deficiencies such as iron-deficiency anaemia. The prevalence of worm infection in Public Primary School students in Medan was quite high (40.3%), and 33.3% was anaemic in the latest study. AIM: To determine the correlation between STH infection with serum iron (SI) level on primary school children, as well as to determine the prevalence of SI level and worm infection, and the type of worm that infects the most of them. METHODS: This study was conducted in the cross-sectional method. Consecutive sampling technique was used and a total of 132 students age 8-12 years old were included. The study took places in Public Primary School 060925 Amplas, Medan and 101747 Hamparan Perak, Deli Serdang throughout May-October 2016. Fisher Exact test was used to analyse the correlation between STH infection and SI level. RESULTS: The prevalence of STH infection was 7.6%, and low SI was 11.4%. CONCLUSION: There was no significant correlation between STH infection and SI level (P = 0.317). The prevalence of low SI level was not significantly dependent on STH infection (RP = 1.877, 95% CI = 0.481-7.181).

Correlation between Soil Transmitted Helminth Infection and Eosinophil Levels among Primary School Children in Medan.

BACKGROUND: Soil Transmitted Helminth infection is one of most prevalent health problems worldwide, especially in environments with poor sanitation. Based on World Health Organisation (WHO) data, more than 2 billion people, or 24% of the world's population, are infected with intestinal parasite. The highest prevalence is located in areas of poor sanitation and unsafe water supplies. In Indonesia, the prevalence of parasite infections is 15% of the entire population. AIM: The purpose of this study was to determine the relationship between Soil Transmitted Helminth infection on levels of eosinophils among primary school children. In addition, this study also aimed to determine the prevalence of different types of worm infections and the levels of eosinophils in children infected with worms. MATERIAL AND METHODS: This study was analytic observational using a cross-sectional method. The sampling technique was consecutive and in total 132 samples was obtained. The study involved primary school children in Amplas Medan and Hamparan Perak, Deli Serdang through May to October 2016. Univariate analysis was performed to determine STH infection prevalence and bivariate analysis was used to find the correlation between STH infection and eosinophil levels through a Chi square (χ2) test. RESULTS: The results showed that the prevalence of Soil Transmitted Helminth was 7.6%. The most common types of STH infection were 3.8% with Trichuris trichiura and 3% with Ascaris lumbricoides. A significant correlation was found between Parasite infection and eosinophil levels (Contingency Coefficient (C) = 0.2, χ2 = 5.3, p = 0.021) and the risk of STH infection that caused eosinophilia or increased eosinophil levels in the children with a Prevalence Ratio (PR) of 1.56 (Confidence Interval (CI) 95%: 1.10-2.22). CONCLUSION: It is recommended that schools at similar risk improve and maintain hygiene and healthy behaviour in the school environment and that parents and teachers pay greater attention to the cleanliness of their children.

The relation between immunocompromised status and Strongyloides stercoralis infection: case-control study.

Strongyloides stercoralis infection is caused by intestinal nematodes in the human body, which in immunocompromised individual, may cause severe morbidity and fatality. This study aimed to reveal the current prevalence of S. stercoralis infection among the stool samples sent to Parasitology Laboratory FMUI and identify its association with the status of immunocompromised. A case-control study with consecutive sampling method was, conducted between March-June 2013. Subjects were the patients of hospitals/laboratory who sent their stool samples to the Parasitology laboratory of FMUI. All stools were examined through direct examination, followed by Harada-mori culture. The immune status of the patients was identified through their medical records. The total number of stools collected was 170 consisted of 108 males and 62 females. The age of the patients ranged from 2 to 80 years old (average 33.41±22.65 years); 18.2% (31/170) was immunocompromised and 81.8% (139/170) was immunocompetent. A total of 18/170 (10.6%) stools were positive of S. stercoralis larvae; 6 stools (19.4%, 6/31) were from the immunocompromised and 12 stools (8.6%, 12/139) originated from the immunocompetent. The result suggested that immunocompromised status has a positive relation towards S. stercoralis infection. Results from this study could serve as input for clinicians for better management of cases with diarrhoea, especially among the immunocompromised.