Comprehension of Calcitriol Levels in Pregnant Women With Latent Tuberculosis and Immune Function in their Newborns.

Background: Pregnant women with latent tuberculosis infection (LTBI) may develop active tuberculosis infection and could infect their neonates, which could impair the child's immune system due to infection-mediated immunological responses. In order to develop a preventative TB program in this study, we desired to understand the impact of calcitriol in LTBI pregnant women and immunological responses in neonates. Patients and Methods: In three hospitals in Medan, North Sumatra, we implemented a case-control design with 84 pregnant women in their third trimester and their newborns. We determined the levels of calcitriol, cathelicidin, and interferon gamma (IFN-γ) in women between December 2021 and July 2022. These measurements were then compared to the newborns' levels of calcitriol, cathelicidin, IFN-γ, and Toll-Like Receptor (TLR) 2. Analyses were performed using the Chi-squared and Fisher's tests, while Spearman correlations were employed to assess for correlations. Results: 42 pregnant women with LTBI (interferon gamma release assay (IGRA) positive) and 42 pregnant women without LTBI (IGRA negative) participated in the study. The findings demonstrated that pregnant women with LTBI were at increased risk for calcitriol deficiency (Odds Ratio (OR) = 3.667, p = 0.006), which had an impact on the calcitriol levels of their unborn children (p = 0.038). TLR2 levels and calcitriol levels were substantially associated with LTBI pregnant women and their healthy neonates (p = 0.048; p = 0.005). Cathelicidin levels in the newborns of non-LTBI pregnant women were influenced by their higher calcitriol levels (p = 0.043). Pregnant women with LTBI had higher levels of cathelicidin and IFN-γ than those without it (p = 0.03; p = 0.001). Conclusion: Pregnant LTBI women's calcitriol levels had an impact on the calcitriol levels of their newborns. Mother's immunological responses and babies' calcitriol levels affected the levels of cathelicidin, IFN-γ, and TLR2 in newborns.

Effect of Phaleria Macrocarpa (Scheff.) Boerl Leaf Ethanol Extract on Serum IL-6 and TNF-α Levels in Diabetic Rats.

Background: Hyperglycemia conditions in diabetes mellitus (DM) can turn on pro-inflammatory cytokines like IL-6 and TNF-α. These cytokines play a role in insulin resistance and the development of DM complications. People in Indonesia have used Phaleria macrocarpa to treat diabetes, but the leaf of this plant has not been studied to see if it can reduce inflammation. Objective: This study aims to analyze the effect of ethanolic extract of Phaleria macrocarpa leaves (EEPML) in serum IL-6 and TNF-α levels of diabetic rats. Methods: This study was an experiment with a post-test-only control group design. Thirty 8-week-old male Wistar rats were used in the study. They were split into six groups: K1 was the normal control group; K2 was the DM control group; K3, K4, and K5 were given EEPML at doses of 125, 250, and 500 mg/KgBW; and K6 was given metformin 45 mg/KgBW orally once a day for 14 days. A high-fat diet and a 30 mg/KgBWi.p injection of streptozotocin were used to make the diabetic rat model. ELISA method for measuring serum IL-6 and TNF-α levels. The Kruskal-Wallis and the Mann-Whitney test were used to examine the differences between the groups. Results: There were significant differences between treatment groups in the mean levels of serum IL-6 (p=0.017), but there were no significant differences in the mean levels of serum TNF-α (p>0.05). Conclusion: Administration of Phaleria macrocarpa leaf ethanol extract 125 mg/KgBW reduced serum IL-6 levels but could not significantly reduce serum TNF-α levels in diabetic rats.

Study of the Molecular Dynamics Stability in the Inhibitory Interaction of Tenofovir Disoproxil Fumarate against CTLA-4 in Chronic Hepatitis B Patients.

Background: Tenofovir disoproxil fumarate (TDF) is a first-line nucleotide analog (NA) drug for hepatitis B therapy. Long-term NA therapy increases peripheral T cell levels to enhance antiviral response, while CTLA-4 inhibits the activation. Objective: This study analyzed the interaction between TDF and CTLA-4 through molecular docking. Methods: Target protein and ligand data mining were performed, and proteins were prepared by removing water molecules in the Discovery Studio 2019 software. The energy minimization was performed on ligands using Pyrx v.0.9.8 software. Protein-ligand docking was performed using Autodock Vina integrated with Pyrx v.09.8. Meanwhile, the docking of proteins was accomplished using the Haddock server. The BioVia Discovery Studio 2019 software visualized the interaction between the compound and the docked protein. Molecular dynamics simulations were carried out using the YASARA Dynamic program developed by Biosciences GmbH. Results: TDF ligand has good and stable inhibitory activity against the CTLA-4/B7-1 and CTLA4/B7-2 complexes. TDF docking has been shown to initiate conformational changes, indicating the ligand's inhibitory activity. The significant conformational changes based on superimposition results were shown by the CTLA-4/TDF/B7-2 and CTLA-4/B7-1/TDF complexes. TDF in all ligands undergoes bonding and displacement of binding sites. Conclusion: Treatment with TDF was predicted to have inhibitory activity against CTLA-4, especially in its complex form with B7-1 and B7-2.

Phytochemical Analysis by FTIR of Zanthoxylum Acanthopodium, DC Fruit Ethanol Extract, N-hexan, Ethyl Acetate and Water Fraction.

Background: Andaliman fruit is used as spice in Batak cuisine, North Sumatera, Indonesia. The potency of andaliman fruit extract as herbal medicine is widely studied. Many studies elaborate the benefits of andaliman fruit extract as an antioxidant, antibacterial or anticancer. Objective: The aim of this study was to identify the phytochemical compounds of andaliman fruit extract and its fractions. Methods: The andaliman fruit was originated from Balige city, Tobasa Regency, North Sumatera. The extract was made by maceration within ethanol and followed by fractionation with n-hexan, ethyl acetate and water. The phytochemical screening by chemical reactions, thin layer chromatography, and Fourier Transform Infrared Spectrophotometer were performed. Results: This study found andaliman fruit ethanol extract consists of alkaloids, flavonoids, glycosides, tannins, triterpens, and steroids. The n-hexan fraction consists of triterpens and steroids, ethyl acetate fraction consists of flavonoids and glycosides, and water fraction consists of alkaloid, flavonoid, and glycosides. Andaliman fruit ethanol extract had eight color spots, n-hexan and ethyl acetate fraction had five color spots and water fraction had two color spots. Andaliman fruit ethanol extract had functional group of C-H alkanes, =C-H alkenes (aliphatic), O-H, C=C alkenes, C=C aromatics, C≡C alkynes, C-O, C=O, and NO2. The n-hexan fraction had C-H alkanes, =C-H alkenes (aliphatic), O-H, C=C alkenes, C-O, C=O, and NO2. The ethyl acetate fraction had C-H alkanes, =C-H alkenes (aliphatic), O-H, C=C alkenes, C=C aromatics, C-O, C=O, and NO2. The water fraction had C-H alkanes, =C-H alkenes (aliphatic), O-H, C=C aromatics, C≡C alkynes, and C-O. Conclusion: Phytochemical screening found that andaliman fruit ethanol extract, n-hexan, ethyl acetate and water fraction positive of phytochemical compounds. The FTIR of andaliman fruit ethanol extract, n-hexan fraction, ethyl acetate fraction, and water fraction showed the absorbance of C-H alkanes, O-H, C-O, and C=C alkenes indicating the presence of alkaloids, flavonoids, and triterpenoid saponin.

The Role of Mesenchymal Stem Cell Secretome in the Inflammatory Mediators and the Survival Rate of Rat Model of Sepsis.

In sepsis, simultaneously elevated levels of pro-inflammatory cytokines and interleukin (IL)-10 indicate immune response dysregulation, increasing the mortality of the host. As mesenchymal stem cell (MSC) secretome is known to have immunomodulatory effects, we aim to assess the role of MSC secretome in the inflammatory mediators (NF-κB p65 and p50, TNF-α, IL-10) and the survival rate of a rat model of sepsis. In this study, forty-eight male Rattus norvegicus rats were divided into one sham group and three groups with sepsis induction: the control group and the sepsis-induced rat groups treated with 150 µL (T1) and 300 µL (T2) of secretome. The survival rate was observed per 6 h for 48 h and plotted using the Kaplan-Meier method. Compared to the control group, T2 showed a significant decrease in the relative expression of NF-κB and the serum TNF-α level, and a significant increase in the serum IL-10 level. Meanwhile, T1 showed a significant decrease in the serum TNF-α level compared to the control group. The Kaplan-Meier Log Rank test did not show significance in the distribution of survival between T1, T2, and the control group. However, from the 18th to the 36th hour, the survival rate of T2 was lower than the survival rate of the control group and T1, with a noticeable difference between T2 and the control group, as well as T1 at the 36th hour. At the 42nd hour, the survival rate of T2 was the same as the control group and remained lower than T1. In conclusion, MSC secretome regulated the inflammatory mediators in rat model of sepsis, with a dose of 150 µL being more effective.

Association Between Serum Cytotoxic T Lymphocyte Antigen (CTLA)-4 Level and Disease Progression in Patients With Chronic Hepatitis B.

Backgroud: Immune impairment, marked by increased expression of cytotoxic T lymphocyte antigen (CTLA)-4, promotes the disease progression of chronic hepatitis B. Objective: This study aimed to determine the association between serum CTLA-4 level and disease progression in patients with chronic hepatitis B. Methods: A cross-sectional study was conducted at Haji Adam Malik General Hospital Medan, Indonesia between October 2021 to September 2022. A total of 150 participants were enrolled. Patients aged 18 years or older with evidence of chronic hepatitis B, HBV-related liver cirrhosis, and HBV-related hepatocellular carcinoma (HCC) were enrolled. Exclusion criteria were history of chronic hepatotoxic drug consumption, underlying liver abnormalities other than HBV infection, and liver injury due to metastasized malignancy from other sites. Serum CTLA-4 level was determined from serum using human CTLA-4 enzyme linked immunosorbent assay kit. Results: Most participants were males and aged between 40 and 60 years. Serum CTLA-4 level was positively associated with chronic hepatitis B progression (P<0.001). Serum CTLA-4 level was negatively correlated with serum platelet (P<0.001) and albumin levels (P<0.001) but positively correlated with serum ALT (P=0.045) and total bilirubin levels (P<0.001). Conclusions: Serum CTLA-4 level is associated with disease progression in patients with chronic hepatitis B.

Degree of kidney injury due to artificial pelvic-ureteric junction obstruction with level of neutrophil gelatinase-associated lipocalin, interleukin 18, and histopathological descriptions in Wistar: experimental research.

Pelvic-ureteric junction obstruction (PUJO) is considered the most common pathology for hydronephrosis in neonates. Full recovery of kidney impairment due to PUJO is possible, especially when pyeloplasty is indicated as surgery is mostly conducted when deterioration is identified, early detection should be considered to prevent further complications. Commonly used kidney damage biomarkers are not sensitive enough to predict kidney damage. Neutrophil gelatinase-associated lipocalin (NGAL) and urinary interleukin 18 (IL-18) are markers of early kidney damage with different characteristics. This study aimed to evaluate the relationship between these two markers with the degree of histopathological kidney damage in Wistar rats induced by PUJO. Methods: A total of thirty male Wistar rats, 200-250 g, were divided into three groups: (1) control, (2) sham, (3) PUJO (4th, 7th, 14th, and 21st days). Urine NGAL, IL-18 levels, and renal histopathology were observed on day 0, 4, 7, 14, and 21. Statistical analysis was performed using the Kruskal-Wallis and Mann-Whitney test with P less than 0.05 considered significant. Results: There was no significant difference in urine NGAL levels between groups, while IL-18 levels were significantly different based on the Kruskal-Wallis test (P 0.031). The results of the Mann-Whitney test showed a significant difference in IL-18 levels between the control group and the PUJO group on day 4 (P=0.028); the Sham surgery group with the PUJO group on day 4 (P=0.014); the PUJO group on day 4 with the PUJO group on the 7th day (P=0.008); and the PUJO group on the 7th day with the PUJO group on the 14th day (P=0.033). Conclusion: Urinary IL-18 levels can be used as a predictor of kidney damage in acute-subacute PUJO cases.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) as a marker of coronary lesion severity in stable coronary artery disease (CAD) patients.

Coronary artery disease (CAD) remains a significant global health concern with considerable high morbidity and mortality and its development is influenced by various genetic and environmental factors. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a vital regulator of low-density lipoprotein receptor (LDLR) metabolism, directly impacting serum cholesterol levels. However, its role in development of CAD is not fully understood. The aim of this study was to assess the association between the level of PCSK9 and coronary lesion severity in patients with CAD. A case-control study using consecutive sampling was conducted among CAD patients at H. Adam Malik General Hospital and Murni Teguh Memorial Hospital, Medan, Indonesia. A total of 200 CAD patients were divided into two groups based on the SYNTAX score: control (score ≤22, n=100) and case (score >22, n=100). Plasma PCSK9 levels were measured from venous blood using quantitative sandwich enzyme immunoassay. The Chi-squared test was used to analyze the data. Our data suggested that PCSK9 level was associated with coronary lesion severity (p<0.001) of which high PCSK9 level was associated with severe coronary lesion. We also found that hypertension (p<0.001), smoking (p=0.072), diabetes (p<0.001), dyslipidemia (p<0.001), obesity (p=0.023), and family history (p=0.001) were associated with lesion severity. Using the receiver operating characteristic (ROC) curve analysis, the cut-off 70.35 ng/mL of PCSK9 had sensitivity 75% and specificity 78% to predict severe coronary lesion. This study highlights that PCSK9 level has moderate sensitivity and specificity to predict the coronary lesion severity among CAD patients.

Comparison of Gambier Extract (Uncaria Gambier Robx) and Angiotensin Receptor Blocker on Proteinuria Reduction and Antioxidants - Enhancement in Nephrotic Rat Models.

Background: Proteinuria is a significant clinical manifestation that causes edema in several diseases, including Nephrotic Syndrome (NS). Untreated proteinuria is strongly linked to the progression of kidney failure. One of the adjuvant therapies could be used to reduce proteinuria such as Angiotensin Receptor Blocker (ARB) including Losartan®. Gambier is a traditional medicinal plant widely known for its antioxidant effects. Catechin, a compound contained in Gambier Extract (GE), has been used to reduce microalbuminuria in diabetics. However, its application in NS has not been widely studied. Objective: This study compared the effects of GE and ARB in reducing proteinuria and increasing antioxidant activity levels, as well as reported histopathological findings in the nephrotic Wistar rat model. Methods: An experimental design study with a control group and a posttest was conducted. The experimental animals were divided into four groups: the control group (K1), the group with puromycin aminonucleoside (PAN) injection (K2), the group with PAN injection + GE (K3), and the group with PAN injection + Losartan® (K4). The standard GE used was Sarie Uncariae® by Toyo Brothers, PT while the ARB (Losartan®) was obtained from Novell, PT. Protein urine, the activity level of total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were assessed using the colorimetric method. Renal histopathology was assessed based on Rollerman's criteria. Results: Gambier extract significantly reduced proteinuria, as depicted by a decrease in protein/volume urine (p = 0.009), increased antioxidant activity, as illustrated by an elevation in T-SOD activity levels (p = 0.007), and tended to decrease MDA levels compared to Losartan®. Based on histopathological findings, GE tended to reduce the percentage of kidney damage in rats induced by puromycin. Conclusion: Gambier extract has been shown a higher antioxidant effect by increasing T-SOD activity levels, reducing proteinuria and also exhibiting a tendency to diminish kidney damage.

Factors affecting HBV DNA suppression in chronic hepatitis B patients treated with tenofovir disoproxil fumarate.

Background: This study aims to determine the factors affecting HBV DNA suppression in chronic hepatitis B patients with tenofovir disoproxil fumarate (TDF). Methods: A case-control was carried out from October 2021 to August 2022 on 182 chronic hepatitis B patients who had TDF therapy regularly for 24 weeks at H. Adam Malik and USU Hospitals in Medan, Indonesia. The history of the samples was obtained, followed by physical examination, and blood collection. CTLA-4 polymorphism examination was carried out using real-time PCR, while the serum CTLA-4 levels were assessed with ELISA. Results: The CTLA-4 -1661G>A polymorphism, genotype GG+AG, increased 1.52 times risk of not achieving HBV DNA suppression to TDF compared to genotype AA (p=0.041). High CTLA-4 levels increased 2.28 times risk, high HBV DNA levels increased 2.09 times risk, low ALT levels increased 1.95 times risk of not achieving HBV DNA suppression (p= 0.009, 0.026, 0.036, respectively). There was no relationship between gender, age, ethnicity, obesity, baseline AST, HBeAg, genotype, liver fibrosis and HBV DNA suppression after 24 weeks of treatment (p>0.05). Conclusions: The levels of CTLA-4, HBV DNA, ALT, and CTLA-4 -1661G>A polymorphism have a potential relationship with the suppression of HBV DNA in chronic hepatitis B patients with TDF.

A therapeutic effect of Nigella sativa extract on female Wistar rats vulvovaginal candidiasis model.

Aim Vulvovaginal candidiasis (VVC) is a disease mostly caused by Candida albicans and affects the quality of life of women especially in the form of chronic recurrent vulvovaginal candidiasis(RVVC). Nigella sativa is known to have several effects such as antimicrobial, anti-inflammatory, immune stimulation and anticancer properties. The aim of this study was to evaluate the effect of Nigella sativa on vulvovaginal candidiasis. Methods This study is a true experimental design, we used 28 Wistar strain rats divided into 4 groups, all groups were conditioned in a pseudoestrus state. Candida albicans was inoculated into the rats' vagina for 3 consecutive days. All groups were observed every 24 hours, 48 hours and 72 hours to evaluate the number of Candida albicans colonies, IgG and IgM anti Candida. Results After administration of intervention, there was a significant difference in the amount of fungal colonization after the treatment in each group (p<0.001). There was no significant difference in the effectiveness of Nigella sativa and fluconazole in supressing Candida albicans colonies after 72 hours (p=0.101). The administration of Nigella sativa showed a significant difference in the increase in IgM levels compared to the others group (p<0.001), while the IgG level did not show a significant difference (p=0.423). Conclusion Nigella sativa provides a therapeutic effect by decreasing the number of fungal colonies and increasing IgM levels.

Herlyn Werner Wunderlich Syndrome with Hematocolpos Symptom.

BACKGROUND: Uterodidelphys with obstructed hemivagina and ipsilateral renal agenesis is referred to as the Herlyn Werner Wunderlich (HWW) syndrome. Herlyn-Werner-Wunderlich (HWW) syndrome is a very rare congenital anomaly of the urogenital tract involving Müllerian ducts and Wolffian structures, and it is Werner by the triad of uterus didelphys, obstructed hemivagina and ipsilateral renal agenesis. CASE REPORT: Here, we describe a 17-year-old female patient presented with severe and increasing cyclical abdominal pain. She attained menarche 3 years back. The patient had irregular and scanty menstruation associated with dysmenorrhoea. On physical examination, secondary sexual characters were well developed, and on palpation, lower abdomen tenderness was not present. Diagnosed with HWW syndrome, who was taken up for diagnostic sonography and MRI, followed by vaginal septal resection. CONCLUSION: In addition to a definitive diagnosis, this approach helped in symptomatic relief to the patient.

The Influence of Health Promotion on Female Students' Behaviour in SMA An - Nizam Medan about Endometriosis.

Endometriosis is a gynaecological disorder that is often characterised by dysmenorrhea, dyspareunia and or infertility. These symptoms are very common and often found as a symptom of other diseases so that endometriosis is more difficult to diagnose or often diagnosed late. Therefore, diseases like this would be better if we prevent them before they suffer. Although endometriosis is caused by multifactor, we can still do simple prevention and be positive. However, several other factors cause this prevention not to be applied in daily life such as lack of knowledge, inadequate facilities or an environment that does not support. Therefore, health promotion as a medium of information and the establishment of community self-reliance is expected to shift bad habits or form new good habits to be more vigilant and prevent endometriosis. The study was conducted using a quasi-experimental design with the pretest-posttest method and was processed using the Wilcoxon signed-rank test. Based on the results of data analysis, there is a significant increase in the behaviour of female students before and after health promotion.