Medical Journal of Indonesia

Effects of digoxin in inhibiting ACE2 and SARS-CoV-2 binding for attenuating COVID-19 in human adipocytes

Meity Ardiana — 2024-12-03

BACKGROUND Angiotensin-converting enzyme 2 (ACE2) has a role in SARS-CoV-2 incidence, and digoxin is a competitive inhibitor of SARS-CoV-2-ACE2 binding. This study aimed to investigate the effects of digoxin on SARS-CoV-2-ACE2 binding, proinflammatory cytokines, and prothrombotic factors in adipocytes of patients with COVID-19.

METHODS This in vitro study used adipocyte cultures, which were divided into negative control, positive control (SARS-CoV-2 S1 spike protein only), SARS-CoV-2 S1 spike protein with digoxin, and SARS-CoV-2 S1 spike protein with human recombinant soluble ACE2 (hrsACE2). Data were analyzed using one-way ANOVA and Pearson correlation.

RESULTS SARS-CoV-2 significantly elevated ACE2 and increased interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), tissue factor (TF), and plasminogen activator inhibitor-1 (PAI-1) compared to the negative control group (p<0.001). No SARS-CoV-2-ACE2 binding was detected in SARS-CoV-2 with digoxin and hrsACE2 groups, compared to the positive control group (0 ng/ml versus 0 ng/ml versus 36.33 [1.58] ng/ml, p<0.001). Digoxin significantly decreased IL-6 (48.94 [1.80] ng/ml versus 90.93 [4.29] ng/ml; p<0.001), TNF-α (87.65 [6.88] ng/ml versus 307.95 [57.34] ng/ml; p<0.001), TF (5.33 [0.32] ng/ml versus 6.85 [0.22] ng/ml; p<0.001), and PAI-1 levels (2.92 [0.168] ng/ml versus 4.86 [0.11] ng/ml; p<0.001), compared to positive control group. ACE2 positively correlated with IL-6 (p = 0.004, r = 0.763) and TF (p = 0.004, r = 0.768) but was not correlated with IL-1β, TNF-α, and PAI-1 levels.

CONCLUSIONS This study promoted digoxin therapy to prevent cytokine storm and thromboembolism by decreasing IL-6, TNF-α, TF, and PAI-1 in adipocyte cultured models at an early stage of COVID-19.

Effect of adipose-derived stem cells-conditioned medium extracellular vesicles on senescent fibroblast and E2F1 expression

Vidya Hana Dwi Ayuningtyas — 2024-12-03

BACKGROUND Adipose-derived stem cells (ADSCs) are well-known for their regenerative properties, especially towards senescent cells. Extracellular vesicles derived from ADSCs are believed to influence the expression level of the E2 promoter binding factor (E2F1) protein, one of the key proteins regulating the cell cycle. This study aimed to investigate the impact of extracellular vesicles from ADSC-conditioned medium (ADSC-CM) on E2F1 levels and their potential to improve aging cells.

METHODS Extracellular vesicles from ADSC-CM were introduced into senescent fibroblasts through transfection. Then, the E2F1 protein levels were measured and compared between transfected and untransfected cells. A total of 18 samples were calculated based on Federer’s formulas. E2F1 protein levels were counted using a cell-based enzyme-linked immunosorbent assay. Senescence-associated beta-galactosidase staining was used to quantify the number of senescent cells in each group, and the microculture tetrazolium technique assay was used to assess cellular metabolic activity.

RESULTS The number of senescent cells was lower in the transfected group compared to the untransfected group. ADSC-CM extracellular vesicles-transfected fibroblasts exhibited higher levels of E2F1 protein (0.19 [0.17] ng/ml) compared to untransfected fibroblast (0.06 [0.049] ng/ml; p = 0.048). Higher E2F1 protein levels were associated with reduced senescent fibroblasts and increased metabolic viable fibroblasts in the transfected group.

CONCLUSIONS ADSC-CM extracellular vesicles positively affected senescent cells by enhancing the level of E2F1.

Touch DNA viability on various substrates from different shedder levels

Vira Saamia — 2024-12-03

BACKGROUND Touch DNA samples are frequently discovered at crime scenes, including those found at the scene, on the victim, with the suspect, or on objects related to the incident. This study aimed to investigate 3 key factors affecting touch DNA samples: the characteristics person that shed the DNA, surfaces variants where the DNA was deposited, and different sampling methods effectiveness that influence DNA quantity, quality, and detection.

METHODS 9 participants grouped into high, intermediate, and low shedder levels simultaneously tied 2 types of ropes, non-porous and porous. The first person will hold a rope for 5 min then pass it to the second person to hold on the same spot for another 5 min. DNA was collected from each rope using the double swab and tape-lift method, extracted, and quantified using real-time polymerase chain reaction (PCR). Touch DNA profile at 20 short tandem repeat loci was amplified in PCR system and detected on capillary electrophoresis.

RESULTS Type of substrate (p = 0.97) or sampling method (p = 0.053) used for touch DNA collection did not significantly impact the DNA yield or profiling outcomes. A notable difference (p<0.001) was found in DNA quantity between high, intermediate, and low shedders, regardless of the substrate or method used.

CONCLUSIONS Individual shedder level has a greater influence on the results of touch DNA analysis regarding the DNA quantity and profiling quality than substrate type and sample procedure.

NF-κB, neutrophil extracellular traps, and microglial in mice with Streptococcus suis serotype 2 meningitis infection

Ni Made Susilawathi — 2024-12-03

BACKGROUND Streptococcus suis is the most frequent etiology of zoonotic bacterial meningitis, potentially initiating an outbreak. Acute bacterial meningitis caused by S. suis has various manifestations, often accompanied by sepsis with multiple organ involvement. This study aimed to evaluate the pattern of S. suis outgrowth in the brain, which is associated with nuclear factor-κappaB (NF-κB) activation, neutrophil extracellular traps (NETs) release (NETosis), and microglial activation as three crucial pathological mechanisms of bacterial meningitis.

METHODS This study used 64 female BALB/c mice aged 6 weeks and weighed 18−20 g, grouped into infected and non-infected as the control group. Both groups were administered 1 ml of S. suis serotype 2 suspension (1 × 10⁷ colony forming-unit/ml) and normal saline intraperitoneally. The bacterial colony count of S. suis was evaluated, along with NF-κB and NET levels in blood and brain, as well as meningeal inflammation and microglial activation in the brain at Days 1, 3, 5, and 7 post-infection.

RESULTS The invasion of S. suis into the brain slightly induced NF-κB activation, leading to a burst of inflammatory responses, neutrophil infiltration with NET releases, and microglia activation that co-occurred, showing their peaks on Days 3 and 5 after onset.

CONCLUSIONS The S. suis invasion into the mice’s brain increased NF-κB activation, NETosis, and microglia activation during S. suis meningitis infection.

Systemic amyloidosis following inflammatory bowel disease, follicular lymphoma, and diffuse large B-cell lymphoma: a case report

Lugyanti Sukrisman — 2024-12-03

Systemic amyloidosis is a rare disorder characterized by the widespread deposition of misfolded amyloid proteins in several organs, leading to organ failure and potentially death if not promptly recognized. The occurrence of inflammatory bowel disease (IBD), follicular lymphoma, and diffuse large B-cell lymphoma (DLBCL) developing into systemic amyloidosis is uncommon. Here is a case of a 55-year-old Asian woman with a history of IBD, follicular lymphoma, and abdominal DLBCL who developed systemic amyloidosis affecting her gastrointestinal, cardiac, and renal organs. Gastrointestinal symptoms (abdominal pain and melena) initially manifested in this patient with systemic amyloidosis. She underwent treatment with three cycles of rituximab and bendamustine. However, she passed away after 2 months of hospitalization due to multiple organ failure. Hence, physicians must be vigilant in recognizing amyloidosis as a potential complication of lymphoma or other inflammatory diseases, as early recognition can contribute to improved clinical outcomes.

Rare nephrostomy complication mimicking rupture of abdominal aortic aneurysm: a case report

Kiwah Andanni Bangsawan — 2024-12-03

Percutaneous nephrostomy (PCN) is a routine procedure in urology with up to 99% success rate and less than 6% of total complications dominated by minor cases. This was a case report of a 59-year-old male patient with an unusual major bleeding complication after PCN that mimicked a ruptured abdominal aortic aneurysm. The laparotomy exploration identified the bleeding source from the right lobar artery, thus renorrhaphy was performed. Proper visualization of anatomic layout, color Doppler imaging, and selecting a guiding method and technique could reduce bleeding complications following PCN.

Cotton swabs for the measurement of NF-ĸB, IFN-γ, and FOXP3+Treg from lesions of anogenital wart patients

Hernayati Hutabarat — 2024-12-03

BACKGROUND Local tissue immunity plays a significant role in anogenital warts’ (AGW) pathomechanism and persistence. Assessing biomarkers from lesions instead of serum is recommended to evaluate therapeutic response. Since biopsy is invasive, it is necessary to find less invasive and more comfortable methods. This study aimed to assess the reliability of cotton swabs and tape stripping for evaluating AGW’s lesions biomarkers.

METHODS We compared cotton swab versus tape stripping method to quantify nuclear factor-κappaB (NF-ĸB), interferon-gamma (IFN-γ), and FOXP3+regulatory T cell (FOXP3+Treg) from 3 patients with AGW in the preliminary study. The method was selected based on contamination possibility, side effects, and a simpler approach. The main study examined 48 patients with AGW for reliability and reproducibility using the best sampling method from preliminary result and Spearman’s Rho analysis, while considering the HIV status and CD4+ counts.

RESULTS Both cotton swabs and tape stripping obtained adequate protein content for biomarkers examination. However, the tape stripping method was causing serum contamination and painful for patients due to the stripping. The total lesion volume in cotton swab method was positively correlated with all patients’ NF-ĸB (p = 0.001). IFN-γ had a negative correlation in all reactive HIV patients (p = 0.012). FOXP3+Treg and CD4+ counts were negatively correlated with total volume in reactive HIV patients (p = 0.046 and 0.017, respectively).

CONCLUSIONS The cotton swab method was reliable in examining NF-ĸB, IFN-γ, and FOXP3+Treg due to its convenience and lack of serum contamination from AGW lesions, potentially improving patient comfort and practical benefits.

Placental nutrient and transport system in fetus with small for gestational age and growth restriction compared to appropriate for gestational age

Aria Wibawa — 2024-12-03

BACKGROUND Fetal growth restriction (FGR) has multifactorial etiology, including nutrition. Fetal nutrient status depends not only on an adequate supply of key nutrients but also optimal delivery, served by the placenta as a major metabolic and transport organ. This study aimed to evaluate the status of placental oxygen and nutrient concentration and their transporters between appropriate for gestational age (AGA), small for gestational age (SGA), and FGR.

METHODS This cross-sectional study was conducted at Cipto Mangunkusumo Hospital, Jakarta, from July 2018 to December 2020. Patients were divided into 3 groups, namely AGA, SGA, and FGR. The placental samples were taken following delivery. Placental concentration of glucose, amino acids (AAs), and fatty acids (FAs) were measured by calorimetric assay, liquid chromatography-tandem mass spectrometry, and gas chromatography-mass spectrometry, respectively. Placental concentration of vascular endothelial growth factor (VEGF), glucose transporter 1 (GLUT1), system y+L, and fatty acid transport protein 1 (FATP1) were examined using enzyme-linked immunosorbent assay.

RESULTS A total of 57 subjects participated in the study. Compared with the AGA group, the SGA and FGR groups had lower placental AA concentration (p = 0.004), higher placental FA concentration (p = 0.048), higher placental expression of VEGF (p = 0.003), system y+L (p = 0.07), and FATP1 (p = 0.021). No difference in placental glucose and GLUT1 concentration was observed among all groups (p = 0.301).

CONCLUSIONS The similar profile of macronutrient concentration with increased expression of oxygen and several nutrient transporters in SGA and FGR groups might indicate similar pathogenesis between these groups.

Potential use of dance game simulator in eye-leg coordination improvement: study on healthy participants

Ezra Bernardus Wijaya — 2024-12-03

BACKGROUND Game-based therapy has the potential to enhance patients’ participation in neurorehabilitation by making it more engaging and inspiring. Thus, this research aimed to investigate the efficacy and validity of a dance game simulator to improve eye-leg coordination diagnosis and treatment.

METHODS 59 healthy participants aged 19–38 were assessed using a foot tapping test (FTT), lower extremity motor coordination test (LEMOCOT), modified agility ladder drill test, and total game score. The dance game system used 50, 100, and 150 beats per minute (bpm) songs to improve eye-leg coordination. The intervention group, consisting of 10 participants, received 15 sessions of 10-min play (3 songs each), while the control group, with 8 participants, had only 2 sessions: 1 at the start and 1 at the end. Rank correlation test compared game-based tests to validity, and t-tests analyzed pre- and post-game treatment results.

RESULTS The validity of the LEMOCOT and the dance game with 100–150 bpm tempo in 59 healthy participants is showing correlation coefficients of r = 0.302 (right leg) and r = 0.305 (left leg), with p<0.01 for each leg. The dance game simulator improved FTT, left LEMOCOT, modified agility ladder drill test, and the overall dance game score after 15 sessions in the intervention group. However, these improvements were not statistically significant compared to the control group.

CONCLUSIONS Game-based therapy offers an efficient alternative to traditional eye-leg coordination testing, providing a practical, clinically effective home rehabilitation method. Further research could enhance neurorehabilitation outcomes.

Stone recurrence among Indonesian kidney stone formers: a comprehensive analysis of genetic polymorphism, demographic, and clinical factors

Widi Atmoko — 2024-12-03

BACKGROUND The recurrence rate of kidney stone disease (KSD) can exceed 50% within 5 years. This study aimed to investigate factors associated with stone recurrence based on single nucleotide polymorphisms (SNPs) of the calcium-sensing receptor (CaSR) rs1801725 and rs1042636, demographic, and clinical profiles.

METHODS We collected data on the demographic and clinical characteristics of 80 adult kidney stone formers from April 2021 to September 2022, including peripheral blood samples, morning and 24-hour urine, and 7-day water intake records. Real-time polymerase chain reaction was used to evaluate SNP. Comparisons were made between patients with recurrent and first-time stones.

RESULTS 41% of 80 patients have experienced stone recurrence. Recurrent stone formers exhibited significantly higher 24-hour urine calcium excretion (p = 0.03) and lower serum calcium levels (p = 0.019) than first-time stone formers. Hypocitraturia (100%), low urine volume (78%), and hyperoxaluria (55%) were the main abnormalities of all patients. No significant differences were found in CaSR gene polymorphisms and other demographic, biochemical, or clinical parameters.

CONCLUSIONS Recurrent stone formers had higher 24-hour urine calcium excretion and lower serum calcium levels. Other risk factors and CaSR polymorphisms may insignificantly affect KSD recurrence.

Future of telerobotic surgery

Agus Rizal Ardy Hariandy Hamid — 2024-12-03

[No abstract available]

Front & Back Matter

Medical Journal of Indonesia — 2024-12-03