PUBLIKASI

2022

Dwita Anastasia Deo, Elizabeth Henny Herningtyas, Umi Solekhah Intansari, Taufik Mulya Perdana, Elsa Herdiana Murhandarwati, and Marsetyawan HNE Soesatyo

ABSTRACT

Microscopic examination is the backbone of malaria diagnosis and treatment evaluation in Indonesia. This test has limited ability to detect malaria at low parasite density. Inversely, nested polymerase chain reaction (PCR) can detect parasites at a density below the microscopic examination’s detection limit. The objective of this study is to compare microscopic and PCR results when being used to identify malaria in suspected patients and patients who underwent dihydroartemisinin–piperaquine (DHP) therapy in the last 3–8 weeks with or without symptoms in Sumba Barat Daya, Nusa Tenggara Timur, Indonesia. Recruitment was conducted between April 2019 and February 2020. Blood samples were then taken for microscopic and PCR examinations. Participants (n = 409) were divided into three groups: suspected malaria (42.5%), post-DHP therapy with fever (4.9%), and post-DHP therapy without fever (52.6%). Microscopic examination found five cases of P. falciparum + P. vivax infection, while PCR found 346 cases. All microscopic examinations turned negative in the post-DHP-therapy group. Conversely, PCR result from the same group yielded 29 negative results. Overall, our study showed that microscopic examination and PCR generated different results in detecting Plasmodium species, especially in patients with mixed infection and in patients who recently underwent DHP therapy.

Keywords: subclinical malaria; asymptomatic malaria; high endemicity; nested PCR; microscopic examination

DOI: https://doi.org/10.3390/tropicalmed7080153

Neti Nurani, Tunjung Wibowo, Rina Susilowati, Janatin Hastuti, Madarina Julia, Mirjam M. Van Weissenbruch

ABSTRACT

Background: Compared to their appropriate-for-gestational-age (AGA) peers, small-for-gestational-age (SGA) infants are prone to growth deficits. As the first 6 months of exclusive breastfeeding is generally recommended, it is essential to understand how this intervention might impact SGA infants’ growth. This study aims to assess growth of exclusively breastfed SGA term infants in the first 6 months of life. Methods: A prospective cohort study was conducted on term infants born in Dr. Sardjito General Hospital and two private hospitals in Yogyakarta, Indonesia. SGA was defined as birth weight less than the 10th percentile according to Fenton criteria. Weight, length, and head circumference (HC) were measured at birth and monthly until 6 months old. Results: A total of 39 AGA and 17 SGA term infants who were exclusively breastfed in their first 6 months were included and followed. In SGA compared to AGA, birth weight, length, and HC (mean ± SD) were significantly lower (p < 0.001). During the first 6 months, the SGAs grew in weight and length in parallel with the AGAs. At sixth months of age, the weight and length (mean ± SD) of the SGAs were significantly lower compared to the AGAs (p < 0.001). However, HC (mean ± SD) of SGAs grew significantly faster than the AGAs (p < 0.005). At sixth months of age, there were no significant differences in HC between the two groups (p = 0.824). Conclusions: In the first 6 months, exclusively breastfed SGA term infants, in contrast to weight and length, only show catch up growth in HC, leading to HC comparable to their AGA peers at the age of 6 months. Keywords: Growth, Exclusively breastfed, Small for gestational age, Infant DOI: https://doi.org/10.1186/s12887-021-03080-6

Rizwan Ahmad, Muhammad Riaz, Mohammed Aldholmi, Muhammad Asif Qureshi, Shahab Uddin, Ajaz Ahmad Bhat, Pratheeshkumar Poyil, Mukhtiar Baig, Jalal Pourahmad, Trivadi Ganesan, Abdul Quaiyoom Khan, Zainab Siddiqui, Maha El-Demellawy, Maryam Gholamalizadeh, Dewajani Purnomosari, Elsayed I Salim, Seyedeh Zahra Mousavi Jarrahi, Jian-ye Zhang, Samad Mohammadnejad, Alireza Mosavi Jarrahi

ABSTRACT

The journal of APJCP (Asian Pacific Journal of Cancer Prevention) focuses to gather relevant and up-to-date novel information’s related to cancer sciences. The research methodologies and approaches adopted by the researcher are prone to variation which may be desirable in the context of novel scientific findings however, the  reproducibility for these studies needs to be unified and assured. The reproducibility issues are highly concerned when preclinical studies are reported in cancer, for natural products in particular. The natural products and medicinal plants are prone to a wide variation in terms of phytochemistry and phyto-pharmacology, ultimately affecting the end results for cancer studies. Hence the need for specific guidelines to adopt a best-practice in cancer research are utmost essential. The current AIMRDA guidelines aims to develop a consensus-based tool in order to enhance the quality and assure the reproducibility of studies reporting natural products in cancer prevention. A core working committee of the experts developed an initial draft for the guidelines where more focus was kept for the inclusion of specific items not covered
in previous published tools. The initial draft was peer-reviewed, experts-views provided, and improved by a scientific
committee comprising of field research experts, editorial experts of different journals, and academics working in different organization worldwide. The feedback from continuous online meetings, mail communications, and webinars resulted a final draft in the shape of a checklist tool, covering the best practices related to the field of natural products research in cancer prevention and treatment. It is mandatory for the authors to read and follow the AIMRDA tool, and be aware of the good-practices to be followed in cancer research prior to any submission to APJCP. Though the tool is developed based on experts in the field, it needs to be further updated and validated in practice via implementation in the field.
Keywords:
AIMRDA- submission guidelines- cancer- natural products- APJCP

DOI: 10.31557/APJCP.2021.22.12.3735

Suci Widhiati, Dewajani Purnomosari, Tri Wibawa, Hardyanto Soebono

ABSTRACT

The close relationship between the intestine and the skin has been widely stated, seen from gastrointestinal (GI) disorders often accompanied by skin manifestations. Exactly how the gut microbiome is related to skin inflammation and influences the pathophysiology mechanism of skin disorders are still unclear. Many studies have shown a two-way relationship between gut and skin associated with GI health and skin homeostasis and allostasis. This systematic review aimed to explore the associations between the gut microbiome with inflammatory skin disorders, such as acne, psoriasis, atopic dermatitis, and urticaria, and to discover the advanced concept of this relationship. The literature search was limited to any articles published up to December 2020 using PubMed and EBSCOHost. The review followed the PRISMA guidelines for conducting a systematic review. Of the 319 articles screened based on title and abstract, 111 articles underwent full-text screening. Of these, 23 articles met our inclusion criteria, comprising 13 atopic dermatitis (AD), three psoriasis, four acne vulgaris, and four chronic urticaria articles. Acne vulgaris, atopic dermatitis, psoriasis, and chronic urticaria are inflammation skin disorders that were studied recently to ascertain the relationship of these disorders with dysbiosis of the GI microbiome. All acne vulgaris, psoriasis, and chronic urticaria studies stated the association of gut microbiome with skin manifestations. However, the results in atopic dermatitis are still conflicting. Most of the articles agree that Bifidobacterium plays an essential role as anti-inflammation bacteria, and Proteobacteria and Enterobacteria impact inflammation in inflammatory skin disorders.

DOI: https://doi.org/10.4081/dr.2022.9188

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Nastiti Wijayanti, Faris Muhammad Gazali, Endah Supriyati, Mohamad Saifudin Hakim, Eggi Arguni, Marselinus Edwin Widyanto Daniwijaya, Titik Nuryastuti, Matin Nuhamunada, Rahma Nabilla, Sofia Mubarika Haryana, Tri Wibawa

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus responsible for the COVID-19 pandemic. The emergence of the new SARS-CoV-2 has been attributed to the possibility of evolutionary dynamics in the furin cleavage site (FCS) region. This study aimed to analyze the sequence of the FCS region in the spike protein of SARS-CoV-2 isolates that circulated in the Special Region of Yogyakarta and Central Java provinces in Indonesia. The RNA solution extracted from nasopharyngeal swab samples of confirmed COVID-19 patients were used and subjected to cDNA synthesis, PCR amplification, sequencing, and analysis of the FCS region. The sequence data from GISAID were also retrieved for further genome analysis. This study included 52 FCS region sequences. Several mutations were identified in the FCS region, i.e., D614G, Q675H, Q677H, S680P, and silent mutation in 235.57 C > T. The most important mutation in the FCS region is D614G. This finding indicated the G614 variant was circulating from May 2020 in those two provinces. Eventually, the G614 variant totally replaced the D614 variant from September 2020. All Indonesian SARS-CoV-2 isolates during this study and those deposited in GISAID showed the formation of five clade clusters from the FCS region, in which the D614 variant is in one specific cluster, and the G614 variant is dispersed into four clusters. The data indicated there is evolutionary advantage of the D614G mutation in the FCS region of the spike protein of SARS-CoV-2 circulating in the Special Region of Yogyakarta and Central Java provinces in Indonesia.

DOI: https://doi.org/10.1007/s10123-022-00239-8

Ika Fidianingsih, Teguh Aryandono, Sitarina Widyarini, Sri Herwiyanti, Sunarti Sunarti

ABSTRACT

Background: Breast cancer prevention still needs to be improved. Calorie restriction is thought to prevent breast cancer through the induction of autophagy. Maranta arundinacea L. (MA) has the potential for calorie restriction because it contains high fiber. This research aimed to observe the effect of dietary MA against dimethylbenz(a)anthracene (DMBA)-induced mammary cancer in Sprague Dawley rats related to autophagy. Methods: Twenty-five Sprague Dawley rats were randomly divided into five groups: 1) control group without DMBA-induced with a standard diet, 2) 20 mg/kg BW of DMBA two times a week for five weeks with a standard diet, 3) DMBA and diet modification with 30% of MA, 4) DMBA and diet modification with 45% of MA, and 5) DMBA and diet modification with 60% of MA. Examination of the nodule was conducted once every week for 22 weeks. Breast tissue/tumor examination underwent histology examination with hematoxylin-eosin. Examinations of immunohistochemical staining against Beclin1, LC3B, and SQSTM1 were conducted to reveal autophagy. The difference of autophagy protein expression was analyzed using One way ANOVA with 95% confidence level and significance set as p<0.05. Results: Cancer was detected in four rats of DMBA standard diet, two rats of 30% MA, one rat of 45% MA. No cancer was detected in the rats of control and rats with 60% of MA group. The Beclin1 expressions showed that the 60% of MA group had the
highest score (2.5±0.52) followed by the 45% of MA group (1.87±0.49), control group (1.77±0.11), 30% of MA group
(1.28±0.75), and DMBA with standard diet had the lowest score (1.28±0.91). The difference of Beclin1 expressions was statistically significant (p-value=0.03). However, the difference of the LC3B expressions (p-value=0.11) and SQSTM1 expressions (p-value=0.225) were not statistically significant. Conclusion: Dietary modifications with MA potentially prevent breast cancer and induce initiation of autophagy.
Keywords:
Maranta arundinacea– breast cancer- DMBA- Arrowroot- autophagy

DOI: 10.31557/APJCP.2022.23.3.985

Denise U Putri, Po-Hao Feng, Chiou-Feng Lin, Sofia M Haryana, Marsetyawan HNE Soesatyo, Kang-Yun Lee, Chia-Li Han

ABSTRACT

Local administration of attenuated mycobacterium has been used as a cancer treatment adjuvant to re-boost patient immune responses with variable clinical outcomes. We aimed to clarify the impact of attenuated heat-killed tuberculosis (HKTB) on tumor-associated macrophages which play critical roles in shaping immunological regulation in the tumor microenvironment. Upon HKTB stimulation, both primary macrophages derived from the peripheral blood of healthy subjects and from lung cancer patients as well as THP1-derived classically activated macrophages (Ms) and tumor-educated macrophages (TEMs) were polarized into the proinflammatory phenotype, as characterized by increased expression cluster of differentiation 86. A quantitative proteomic analysis revealed that stimulated TEMs were unable to activate the toll-like receptor 2, signal transducer and activator of transcription 1, or nuclear factor-κB signaling. Instead, they showed distinct intercellular adhesion molecule 1 signaling, impaired cell adhesion, and mitochondrial dysfunction. These molecular mechanisms might contribute to lower cytotoxicity of HKTB-stimulated TEMs against A549 cells via the release of distinct inflammatory cytokines compared to HKTB-stimulated Ms. Our study provides an unbiased and systematic interpretation of cellular and molecular alterations of HKTB-reeducated macrophages which should help illuminate potential strategies of HKTB-stimulated macrophage-based combination therapy for cancer treatment.

DOI: https://doi.org/10.1038/s41598-022-10463-x

Eggi Arguni, Endah Supriyati, Mohamad Saifudin Hakim, Edwin Widyanto Daniwijaya, Firdian Makrufardi, Ayu Rahayu, Anwar Rovik, Utari Saraswati, Farida Nur Oktoviani, Nenes Prastiwi, Titik Nuryastuti, Tri Wibawa, Sofia Mubarika Haryana

ABSTRACT

Background

Growing evidence shows that viral co-infection is found repeatedly in patients with Coronavirus Disease–2019 (COVID-19). This is the first report of SARS-CoV-2 co-infection with viral respiratory pathogens in Indonesia.

Methods

Over a one month period of April to May 2020, SARS-CoV-2 positive nasopharyngeal swabs in our COVID-19 referral laboratory in Yogyakarta, Indonesia, were tested for viral respiratory pathogens by real-time, reverse transcription polymerase chain reaction (RT-PCR). Proportion of co-infection reported in percentage.

Results

Fifty-nine samples were positive for other viral respiratory pathogens among a total of 125 samples. Influenza A virus was detected in 32 samples, Influenza B in 16 samples, Human metapneumovirus in 1 sample, and adenovirus in 10 samples. We did not detect any co-infection with respiratory syncytial virus. Nine (7.2%) patients had co-infection with more than two viruses.

Conclusion

Viral co-infection with SARS-CoV-2 is common. These results will provide a helpful reference for diagnosis and clinical treatment of patients with COVID-19.

Key Words: COVID-19, SARS-CoV-2, Co-infection, Viral respiratory pathogens, Coronavirus

DOI: https://doi.org/10.1016/j.amsu.2022.103676

Indah K. Murni, Dian C. Sulistyoningrum, Rina Susilowati, Madarina Julia, and Kacie M. Dickinson

ABSTRACT

Background and objective: Poor diets, characterized by excess fat, sugar and sodium intakes, are considered to be one of the most important modifiable risk factors for cardiovascular disease. Diet patterns and intakes during adoles-cence may persist into adulthood and impact on risk for chronic disease later in life. We aimed to evaluate the dietary intake of obese adolescents and its relationship to cardiometabolic health including lipid status and glycemic control. Methods and study design: This was a cross-sectional study of obese children aged 15 to < 18 years in Yogyakarta, Indonesia. All children had a medical history performed including a physical examination and fasting blood sample. Dietary intake was assessed using a semi-quantitative recall food frequency questionnaire. Multivariable linear regression model was performed to determine the relationship between dietary intakes and cardiovascular disease risks and to adjust for potential confounders. Results: Of 179 adolescents, 101 (57.4%) were male and median age was 16.4 (15.0–17.9) years. The majority of ado-lescents (98%) had inadequate intake of fibre and exceeded intakes of total fat (65%) and total sugar (36%). There was statistically significant correlation found in the multivariable linear regression analysis between fibre intake and HDL cholesterol after adjusting for potential confounders (β = 0.165; p = 0.033). Conclusions: This study demonstrates that there is a high proportion of obese Indonesian adolescents with poor dietary intakes. There was relationship observed between intake of nutrients of concern (fibre) and cardiometabolic risk factor among this sample of obese adolescents. Future research should examine overall dietary patterns in more detail among this population to elucidate the role of poor diet intakes in development of cardiovascular disease risk factors in young people transitioning into adulthood.
Keywords: Dietary intake, Cardiovascular disease, Obese, Adolescents, Indonesia

DOI: https://doi.org/10.1186/s12887-022-03341-y

Sukma Diani Putri, Siti Rahma Yunianda Nanza, Irianiwati Widodo, Dewajani Purnomosari

ABSTRACT

Objective: This study aimed to investigate the association between intra-tumoral and stromal VDR expressions with molecular subtypes and clinicopathological factors.

Methods: A total of 75 formalin-fixed paraffin embedded tissue samples were stained using immunohistochemical methods. The VDR expressions were measured by counting brown-stained nuclei in intra-tumoral and stromal areas. The association of VDR expression with molecular subtypes and clinopathological factors was examined. Statistical analysis was performed by chi square tests.

Results:
High intra-tumoral VDR expression was found in carcinomas with luminal molecular subtypes (p=0.039) and low
histological degrees (p=0.035). High VDR expression in the stroma was found in breast carcinomas with large tumor sizes. Conclusions: High intra-tumoral VDR expression is found in breast carcinomas with luminal subtypes and low histological grade (I/II). Both factors are known to have a good prognosis. These findings further strengthen the function of VDR as anti-tumorigenesis.


Keywords:
Breast carcinoma- tumor microenvironment- vitamin D receptor- clinicopathological factors

DOI: 10.31557/APJCP.2022.23.4.1169

Chia-Wen Lin, Dian E Septyaningtrias, Hsu-Wen Chao, Mikiko Konda, Koji Atarashi, Kozue Takeshita, Kota Tamada, Jun Nomura, Yohei Sasagawa, Kaori Tanaka, Itoshi Nikaido, Kenya Honda, Thomas J McHugh, Toru Takumi

ABSTRACT

Objective: This study aimed to investigate the association between intra-tumoral and stromal VDR expressions with molecular subtypes and clinicopathological factors. Methods: A total of 75 formalin-fixed paraffin embedded tissue samples were stained using immunohistochemical methods. The VDR expressions were measured by counting brown-stained nuclei in intra-tumoral and stromal areas. The association of VDR expression with molecular subtypes and clinopathological factors was examined. Statistical analysis was performed by chi square tests.

Results:
High intra-tumoral VDR expression was found in carcinomas with luminal molecular subtypes (p=0.039) and low
histological degrees (p=0.035). High VDR expression in the stroma was found in breast carcinomas with large tumor sizes. Conclusions: High intra-tumoral VDR expression is found in breast carcinomas with luminal subtypes and low histological grade (I/II). Both factors are known to have a good prognosis. These findings further strengthen the function of VDR as anti-tumorigenesis.

Keywords: Breast carcinoma- tumor microenvironment- vitamin D receptor- clinicopathological factors

DOI: 10.31557/APJCP.2022.23.4.1169

2021

Open Access Macedonian Journal of Medical Sciences. 2021 Nov 08; 9(F):523-533.
https://doi.org/10.3889/oamjms.2021.6984

BACKGROUND: Alzheimer’s Dementia (AD) cases are increasing with the global elderly population. To study the part of the brain affected by AD, animal models for hippocampal degeneration are still necessary to better understand AD pathogenesis and develop treatment and prevention measures. AIM: This study was a systematic review of toxic substance-induced animal models of AD using the Morris Water Maze method in determining hippocampal-related memory impairment. Our aim was reviewing the methods of AD induction using toxic substances in laboratory rodents and evaluating the report of the AD biomarkers reported in the models. METHODS: Data were obtained from articles in the PubMed database, then compiled, categorized, and analyzed. Eighty studies published in the past 5 years were included for analysis. RESULTS AND DISCUSSION: The most widely used method was intracerebroventricular injection of amyloid-β substances. However, some less technically challenging techniques using oral or intraperitoneal administration of other toxic substances also produce successful models. Instead of hippocampal neurodegeneration, many studies detected biomarkers of the AD pathological process while some reported inflammation, oxidative stress, neurotrophic factors, and changes of cholinergic activity. Female animals were underrepresented despite a high incidence of AD in women. CONCLUSION: Toxic substances may be used to develop AD animal models characterized with appropriate AD pathological markers. Characterization of methods with the most easy-handling techniques and more studies in female animal models should be encouraged.

European Journal of Plastic Surgery
https://doi.org/10.1007/s00238-021-01904-3

Background: Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. In various combinations, a high frequency of facial bone fractures has been reported. However, the results are still conflicting. Methods: We retrospectively reviewed medical records of patients with maxillofacial trauma who were admitted to Dr. Sardjito Hospital, Yogyakarta, Indonesia, between January 2016 and December 2017. Results: A total of 70 patients with maxillofacial trauma were involved (57 males and 13 females, 18–65 years). Moreover, most of them were 18–25-year-old males (34.3%). The average patient age was 35.5 ± 14 years. No significant association was found between the sex and age group of the patient (p = 0.774). Motorcycle accident was the most frequent cause of maxillofacial fractures (84%) with midfacial and multiple maxillofacial fractures being the most frequent types found in patients (40% and 40%, respectively). The most common facial fracture was in the zygomatic bone (28%) and most cases showed mild facial injury (81%). A significant association was found between the Glasgow Coma Scale (GCS) and types of traumatic brain injury (TBI) (p = 0.031). However, when GCS was compared with facial injury, no statistically significant level was reached and its correlation was low (p = 0.267, r = 0.134). Conclusions: There was a significant association between types of traumatic brain injury with head injury severity. However, we found no correlation between head injury severity and facial injury severity. To explain and validate our results, further multicenter studies with a larger sample size are required. Level of evidence: Level IV, Risk/Prognostic.

PLoS One. 2021 Oct 15;16(10):e0258617.
doi: 10.1371/journal.pone.0258617. PMID: 34653200; PMCID: PMC8519449.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519449/

Background: It has been shown that vitamin D is associated with obesity and the development of atherosclerosis. Less is known about this association among adolescents with obesity. Objectives To determine the association of vitamin D level and metabolic risk factors with carotid intima-media thickness (CIMT) among obese adolescents. Methods: We conducted a cross-sectional study among obese children aged 15 to 17 years in Yogyakarta, Indonesia. The association of vitamin D and other metabolic risk factors (triglyceride, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR)) with CIMT was explored by multivariable linear regression models. Results: Out of 156 obese adolescents, 55.8% were boys. Compared to girls, boys had higher BMI z-score, waist circumference, and HDL-cholesterol. After adjustment for age, sex and second-hand smoke exposure, high HOMA-IR, total cholesterol, LDL-cholesterol and triglyceride levels were associated with higher odds of elevated CIMT. In analyses stratified by sex, a similar trend was observed in boys, while none of the risk factors were associated with CIMT in girls. We observed no association between vitamin D and CIMT. Conclusions: Hyperinsulinemia, higher total cholesterol and LDL cholesterol were associated with greater odds of elevated CIMT among obese adolescent boys.

Reviews in Cardiovascular Medicine 2021, Vol. 22 Issue (3): 919-924
DOI: 10.31083/j.rcm2203099
https://rcm.imrpress.com/EN/10.31083/j.rcm2203099

Central obesity is associated with increased level and activity of endothelin-1. The waist and hip circumferences are simple indicators of central obesity. Waist circumference correlates with visceral adiposity, whereas hip circumference associates with gluteofemoral peripheral adiposity. Both measurements have independent and opposite correlation with coronary artery disease (CAD) risk factors. The relation between serum endothelin-1 in stable CAD and both parameters of central obesityneeds to be investigated. This study aims to examine the correlation between serum endothelin-1 level and waist and hip circumferences as parameters of central obesity in patients with stable CAD. This was a cross-sectional study. Consecutive subjects were enrolled among those who underwent elective coronary angiography with significant CAD. Serum endothelin-1 was measured from peripheral blood samples taken before coronary angiography procedure. The measurement of waist circumference, hip circumference, and ratio derived from them, was performed. Central obesity was determined by waist circumference cut-off for Indonesian population. The correlation analysis was performed with Pearson test. The multivariate analysis was performed with multiple linear regression test. The comparison of serum endothelin-1 level between groups was performed with Student T test. We enrolled 50 subjects. The majority of subjects was male (80.0%), hypertensive (86.0%), dyslipidemic (68%) and smoker (52%). Most subjects had history of acute coronary syndrome (64%). Mean waist circumference was 87.6 +/- SD cm, hip circumference was 95.3 cm +/- SD, mean waist-to-hip ratio was 0.92 +/- SD and mean waist-to-height ratio was 0.54 +/- SD. Central obesity occurred in 32% of subjects. Mean serum endothelin-1 level was 2.2 ± 0.7 pg/mL. Serum endothelin-1 level tended to be higher in subjects with central obesity as compared to those without. Serum endothelin-1 level was significantly correlated with age, hemoglobin level, waist circumference (coefficient of 0.311, p value = 0.023) and hip circumference (coefficient of 0.359, p value = 0.010). Multivariable analysis indicated that age (coefficient of -0.353, p value = 0.007) and hip circumference (coefficient of 0.335, p value = 0.011) were independently correlated with serum endothelin-1. For conclusion, in patients with stable CAD, serum endothelin-1 was positively correlated with both waist circumference and hip circumference. Hip circumference independently and positively correlated with serum endothelin-1 level.

Sci Rep. 2021 Aug 9;11(1):16077.
DOI: 10.1038/s41598-021-95381-0. PMID: 34373489; PMCID: PMC8352923

While there has been significant progress in the molecular characterization of the childhood brain cancer medulloblastoma, the tumor proteome remains less explored. However, it is important to obtain a complete understanding of medulloblastoma protein biology, since interactions between proteins represent potential new drug targets. Using previously generated phosphoprotein signaling-profiles of a large cohort of primary medulloblastoma, we discovered that phosphorylation of transcription factor CREB strongly correlates with medulloblastoma survival and associates with a differentiation phenotype. We further found that during normal cerebellar development, phosphorylated CREB was selectively expressed in differentiating cerebellar granule neuron progenitor (CGNP) cells. In line, we observed increased differentiation in CGNPs treated with Forskolin, Bmp6 and Bmp12 (Gdf7), which induce CREB phosphorylation. Lastly, we demonstrated that inducing CREB activation via PKA-mediated CREB signaling, but not Bmp/MEK/ERK mediated signalling, enhances medulloblastoma cell sensitivity to chemotherapy.

Sci Rep. 2021 Aug 9;11(1):16077.
doi: 10.1038/s41598-021-95381-0

While there has been significant progress in the molecular characterization of the childhood brain cancer medulloblastoma, the tumor proteome remains less explored. However, it is important to obtain a complete understanding of medulloblastoma protein biology, since interactions between proteins represent potential new drug targets. Using previously generated phosphoprotein signaling‑profiles of a large cohort of primary medulloblastoma, we discovered that phosphorylation of transcription factor CREB strongly correlates with medulloblastoma survival and associates with a differentiation phenotype. We further found that during normal cerebellar development, phosphorylated CREB was selectively expressed in differentiating cerebellar granule neuron progenitor (CGNP) cells. In line, we observed increased differentiation in CGNPs treated with Forskolin, Bmp6 and Bmp12 (Gdf7), which induce CREB phosphorylation. Lastly, we demonstrated that inducing CREB activation via PKA‑mediated CREB signaling, but not Bmp/MEK/ERK mediated signalling, enhances medulloblastoma cell sensitivity to chemotherapy.

Asian Pac J Cancer Prev. 2021 Aug 1;22(8):2363-2370.
doi: 10.31557/APJCP.2021.22.8.2363
http://journal.waocp.org/?sid=Entrez:PubMed&id=pmid:34452547&key=2021.22.8.2363

Objective: To investigate the correlation between TLR3 and pro-inflammatory cytokines (TNFα, IL6) expression with the distribution of macrophage M2 and Treg on Epstein Barr virus-encoded RNAs (EBER+) nasopharyngeal carcinoma (NPC) tissues. Methods: A total of 23 FFPE NPC tissue samples were obtained from patients in Dr. Sardjito General Hospital, Yogyakarta, Indonesia in 2008–2010, which expressed EBER was collected. The expressions of TLR3, TNFα, and IL6 were examined using an immunofluorescence assay. The distribution of macrophage M2 and Treg were examined by immunohistochemistry with anti-CD163 and -FOXP3 antibodies, respectively. The quantification of fluorescence intensity was analyzed by the RGB space method using ImageJ software. The M2 interpretation was done by the eyeballing method and the M2 scores were divided into 0 (negative), 1 (scant), 2 (focal), 3 (abundant). The average number of Treg FOXP3+ cells in five high power fields was counted. The relationship between variables was tested by the Spearman correlation test, and the coefficient correlation was used to see the correlation between variables. Results: All EBER+ NPC specimens showed TLR3 expression intracellularly. The expression of TNFα could be observed in the cell membranes and secreted extracellularly, while IL6 was secreted to the extracellular area. The expression of TNFα was two times higher than IL6. Most specimens showed low M2 score (56.52%) and high Treg (52.17%). A positive correlation was found between TLR3 and IL6 (12.9%). TNFα was positively correlated with the M2 distribution of 13.7% and Treg distribution of 12.9%, while the rest were explained by other factors. Conclusion: TNFα has a positive correlation with M2 and Treg distribution, but mostly through a different mechanism other than EBER-TLR3 interaction. Possibly, other pro-inflammatory and anti-inflammatory cytokines are involved in the formation of the NPC microenvironment, especially related to the presence of M2 and Treg, which provide immunosuppressive effects in NPC tumors

The Indonesian Biomedical Journal, Vol.13, No.2, June 2021, p.106-220
DOI: 10.18585/inabj.v13i2.1463

BACKGROUND: Single nucleotide variations (SNV) have been mapped to be associated with several human conditions and diseases. To validate the association between SNV to certain human traits or diseases, a large number of subjects must be included. Thus, in need of a fast, relatively economic, and reliable genotyping method. This can be achieved through the use of tetra-primer amplification refractory mutation system polymerase chain reaction (Tetra-primer ARMS PCR). This study reports strategy to develop Tetra-primer ARMS PCR-based genotyping of CHRNA3 rs8040868. METHODS: The optimization of Tetra-primer ARMS PCR was done through these steps: identification of gene sequence and position of single mutation; designing outer and inner PCR primers; amplification of target gene fragments through PCR by using outer primer; confirming genotype of the PCR product by using sequencing; determining an optimum ratio of outer and inner primer; and determining optimum annealing temperature and cycles for the PCR program. The PCR products were run in 2% gel agarose electrophoresis and visualized under UV illumination. RESULTS: Outer and inner primer ratio of 1:3 with annealing temperature of 64.4oC and 40x cycles was found to be the most optimum condition. Tetra-primer ARMS PCR was able to confirm the results of the DNA sequence of 2 samples, confirming wild-type variants (TT allele) and the heterozygous mutant (CT allele). CONCLUSION: Tetra-primer ARMS PCR was able to genotype rs8040868 of the CHRNA3 gene.

Intractable & Rare Diseases Research. 2021; 10(2):88-94.
DOI: 10.5582/irdr.2020.03150

Epidermolysis bullosa (EB) is a group of inherited blistering skin diseases known to have heterogenicity of phenotypes and genotypes. There are four main types of EB: Simplex, junctional, dystrophic, and Kindler syndrome, which are further classified into 34 distinct subtypes. Twenty different gene mutations are responsible for the loss of function and integrity of the basal membrane zone. In limited-resource settings such as Indonesia, diagnoses of hereditary skin disease often rely on clinical features. This limitation was managed by using the Clinical Diagnostic Matrix EB for clinical diagnosis support and whole-exome sequencing for genetic analysis. This study is the first whole-exome sequencing analysis of Javanese Indonesian patients with EB. The genetic analysis from four patients with EB identified all novel mutations unreported in the dbSNP database. There is Kindler syndrome with FERMT1 frameshift mutation in exon 4, at c.388A (p.I130fs), which causes truncated protein; junctional EB generalized intermediate (JEB-GI) subtype with missense mutation at LAMB3 gene position c.A962C (p.H321P); and recessive dystrophic EB (RDEB) a missense mutation at COL7A1 gene position c.G5000T (p.G1667V). The whole-exome sequencing was further verified by Sanger sequencing. The new mutations’ finding is possibly due to the limited genetic database in the Malayo-Polynesian ethnic group. Indonesia has hundreds of ethnic groups, and the Javanese is the largest ethnic group that populates Indonesia. Genetic data of these ethnic groups is important to be established in the international genetic database. This combination of clinical diagnostic and genetic analysis tools with whole-exome sequencing confirmed the challenging diagnosis of epidermolysis bullosa.

Front Pediatr. 2021 May 25;9:680869.
doi: 10.3389/fped.2021.680869. PMID: 34113592; PMCID: PMC8185158.

Background: Interactions between the genome and intrauterine environment can affect bone mineralization in newborns and even in adult life. Several studies show that intrauterine fetal bone mineralization or early postnatal bone condition influences the risk of osteoporosis in later life. Objectives: To determine whole body bone mineral content (WB BMC) and factors that influence neonatal WB BMC in Indonesian term newborns. Subjects/Methods: A cross-sectional study was conducted in Dr. Sardjito General Hospital, Yogyakarta, Indonesia. A total of 45 term, appropriate for gestational age (AGA) newborns were included in this study. BMC was assessed by dual-energy x-ray absorptiometry (DXA) in the first week of life. Weight (g), length (cm) and head circumference (cm) were measured at birth. Data on maternal characteristics were obtained from the maternal health records or reported by the mothers. Results: WB BMC measured in the present study (mean ± SD: 33.2 ± 9.3 g) was lower than WB BMC of similar populations in developed countries. Multiple linear regression showed that birth weight, birth length, and gestational age had a positive association with WB BMC (p = 0.048, 0.017, and <0.001, respectively), while maternal cigarette exposure had a negative association with WB BMC (p = 0.012). Male infants had significantly higher of WB BMC than female (p = 0.025). These determinants contribute to 55% variability of WB BMC. Conclusions: WB BMC in Indonesian term newborns is lower than populations in developed countries. Birth weight, length, gestational age, sex, and maternal cigarette exposure during pregnancy are significantly associated with WB BMC observed in Indonesian newborns.

Asian Pacific Journal of Cancer Prevention. Volume 22, Issue 11, Pages 3447 – 3453
DOI: 10.31557/APJCP.2021.22.11.3447

Objective: This study aimed to identify the distribution of M2 macrophage and Treg in Nasopharyngeal Carcinoma (NPC) tumor tissue samples. The presence of these two groups of cells was further correlated to clinical stage, tumor size, the lymphatic node involvement, and metastasis. Methods: The total of 50 formalin-fixed paraffin-embedded (FFPE) NPC tissue samples was collected retrospectively (27 samples) and prospectively (23 samples). Samples were FFPE tissue slices. Immunohistochemistry was done on the FFPE tissue slides using anti-CD-163 and anti-FoxP-3 antibodies for M2 macrophage and Treg detection, respectively. The M2 macrophage interpretation was performed by eye-balling method and the score was divided into 0 (negative), 1 (scant), 2 (focal), and 3 (abundant). The average number of Treg FOXP3+ cells in 5 high power fields (HPF) was calculated. The relationship of M2 macrophage and Treg was tested with Spearman’s correlation. The relationship between M2 macrophage and Treg with clinical stage, tumor size, node involvement and metastasis was tested by chi square, with p<0.1. Results: M2 macrophage and Treg were positive correlated (r=0.469, p<0.001). The presence of M2 macrophage and regulatory T cell (Treg) was significantly correlated to tumor size (p= 0.091 for M2 macrophage and p=0.022 for Treg) and clinical stage (p= 0.030 for M2 macrophage and p= 0.002 for Treg), but did not correlate with lymphatic node involvement and metastasis. Conclusions: In Epstein-Barr virus related NPC tumor microenvironment, the presence of M2 macrophage was correlated with Treg, and both types of the cells were correlated with tumor size and clinical stages.

Septyaningtrias DE, Susilowati R. Neurological Involvement of COVID-19: from Neuroinvasion and Neuroimmune Crosstalk to Long-term Consequences. Rev Neurosci. 2021 Feb 1;32(4):427-442.  doi: 10.1515/revneuro-2020-0092.

As the coronavirus disease 2019 (COVID-19) pandemic continues to be a multidimensional threat to humanity, more evidence of neurological involvement associated with it has emerged. Neuroimmune interaction may prove to be important not only in the pathogenesis of neurological manifestations but also to prevent systemic hyperinflammation. In this review, we summarize reports of COVID-19 cases with neurological involvement, followed by discussion of possible routes of entry, immune responses against coronavirus infection in the central nervous system and mechanisms of nerve degeneration due to viral infection and immune responses. Possible mechanisms for neuroprotection and virus-associated neurological consequences are also discussed.