Recent publications
Monitoring individuals’ laboratory data is essential for assessing their health status, evaluating the effectiveness of treatments, predicting disease prognosis and detecting subclinical conditions. Currently, monitoring is performed intermittently, measuring serum, plasma, whole blood, urine and occasionally other body fluids at predefined time intervals. The ideal monitoring approach entails continuous measurement of concentration and activity of biomolecules in all body fluids, including solid tissues. This can be achieved through the use of biosensors strategically placed at various locations on the human body where measurements are required for monitoring. High-tech wearable biosensors provide an ideal, noninvasive, and esthetically pleasing solution for monitoring individuals’ laboratory data. However, despite significant advances in wearable biosensor technology, the measurement capacities and the number of different analytes that are continuously monitored in patients are not yet at the desired level. In this review, we conducted a literature search and examined: (i) an overview of the background of monitoring for personalized laboratory medicine, (ii) the body fluids and analytes used for monitoring individuals, (iii) the different types of biosensors and methods used for measuring the concentration and activity of biomolecules, and (iv) the statistical algorithms used for personalized data analysis and interpretation in monitoring and evaluation.
Autosomal recessive proximal renal tubular acidosis (AR-pRTA) with ocular abnormalities is a rare syndrome caused by variants in the SLC4A4 gene, which encodes Na/HCO3 cotransporter (NBCe1). The syndrome primarily affects the kidneys, but also causes extra-renal manifestations. Pancreatic type NBCe1 is located at the basolateral membrane of the pancreatic ductal cells and together with CFTR chloride channel, it is involved in bicarbonate secretion. In vitro models have demonstrated that mutations in the pancreatic type NBCe1 lead to a reduction in pancreatic bicarbonate secretion. Although elevated amylase levels have been observed in some cases, there is no evidence of symptomatic pancreas involvement in children with AR-pRTA. This report presents the case of a seven-year-old girl with AR-pRTA and exocrine pancreatic insufficiency. This novel presentation with a novel mutation in SLC4A4 expands the extra-renal involvement in this rare disease. We recommend that these children be screened for exocrine pancreatic insufficiency.
Diabetes, a chronic metabolic disease, causes complications such as chronic wounds, which are difficult to cure. New treatments have been investigated to accelerate wound healing. In this study, a novel wound dressing from fibroblast-laden atelocollagen-based hydrogel with Cotinus coggygria extract was developed for diabetic wound healing. The antimicrobial activity of C. coggygria hexane (H), dichloromethane (DCM), dichloromethane:methanol (DCM-M), methanol (M), distilled water (DW) and traditional (T) extracts against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis and Candida albicans, as well as their cytotoxic effects on fibroblasts were determined. While fibroblast growth was significantly (p< 0.05) promoted with DCM (121.41 ± 1.04%), M (109.40 ± 5.89%) and DW (121.83 ± 6.37%) extracts at their lowest concentrations, 2000 μg ml⁻¹ DCM and 7.8 μg ml⁻¹ T extracts had both non-cytotoxic and antifungal effects. An atelocollagen-based hydrogel was produced by thermal crosslinking, and its pore size (38.75 ± 7.67 μm), water content (96.63 ± 0.24%) and swelling ratio (27.21 ± 4.08%) were found to be suitable for wound dressings. A significant increase in the deoxyribonucleic acid amount (28.27 ± 1.41%) was observed in the plain hydrogel loaded with fibroblasts after 9 d of incubation, and the hydrogel had an extensively interconnected cellular network. The hydrogels containing DW and T extracts were applied to wounds generated in an in vitro 3D type-2-diabetic human skin model. Although the incubation period was not sufficient for closure of the wounds in either of the treatments, the hydrogel with T extract stimulated more fibroblast migration. In the fibroblast-laden version of the hydrogel with T extract, no wound closure was observed but more keratinocytes migrated to the wound region. These positive outcomes underline the potential of the developed wound dressing as a powerful alternative to improve diabetic wound healing in clinical practice.
2‐Thiohydantoin derivatives, including different substitutions at N‐1 and C‐5 (5‐methyl‐, 5‐isopropyl‐, 1‐acetyl‐5‐methyl‐, and 1‐acetyl‐5‐isopropyl‐) ( 1–4 , respectively), were synthesized by the known literature methods. In these synthetic pathways, it was reported that enantiomerically pure 2‐thiohydantions were obtained in the absence of any solvent via the reaction of L ‐amino acids with thiourea ( 1&2 ) and via the reaction of L ‐amino acids with NH 4 SCN and acetic anhydride ( 3&4 ). However, in this study, in contrary to the previous literature studies, racemic mixtures of 2‐thiohydantoins were obtained although the same synthetic methods were used. The racemic nature of 2‐thiohydantoin derivatives ( 1–4 ) was proved by using ¹ H NMR analysis in the presence of (1 R ,2 S )‐(−)‐ephedrine as a chiral auxiliary. In addition, the enantiomers of 3&4 were also resolved on chiral stationary phases by HPLC analyses. Furthermore, newly synthesized unsymmetrical chiral thioureas ( S ‐1& S ‐2 ) and previously synthesized symmetrical ones ( SS ‐3& SS ‐4 ) were used as chiral solvating agent (CSA) for the enantiodiscrimination of the thiohydantoins ( 5&6 ), previously reported. Optimal CSA/substrate ratios were determined for the best enantiodiscrimination.
Background
Placental syndrome, mainly composed of preeclampsia and fetal growth restriction, has an impact on the health of mother and baby dyads. While impaired placentation is central to their pathophysiology, the underlying molecular mechanisms remain incompletely understood. This study investigates the association between placental syndrome and metabolic alterations in 1-deoxysphingolipids (1-deoxySLs) and polyamines, along with their regulatory enzymes.
Methods
This prospective case-control study involved 26 healthy pregnant women and 17 with placental syndrome. Blood samples were collected from maternal, uterine venous, and umbilical cord veins. Levels of 1-deoxySL, spermine, and spermidine, as well as related enzymes of polyamine metabolism such as ornithine decarboxylase (ODC), spermidine/spermine N1-acetyltransferase (SSAT), polyamine oxidase (PAO), and spermine oxidase (SMO), were measured using the techniques of LC-MS and ELISA, respectively.
Results
Women with placental syndrome had significantly higher levels of 1-deoxySL, spermine, and spermidine in all blood samples compared to the healthy pregnancy group. Additionally, ODC and SSAT levels were reduced significantly in the placental syndrome group, while PAO and SMO levels showed no significant differences. Strong positive correlations were found between the studied enzymes and biomolecules in healthy pregnancies, which were notably weaker in the placental syndrome group.
Conclusion
This study demonstrates significantly altered levels of 1-deoxySL and polyamines, with corresponding enzyme activity changes, in placental syndrome compared to healthy pregnancies. The disrupted correlations between these biomolecules suggest alterations in their metabolic pathways and potential utility as biomarkers. Further mechanistic studies are warranted to elucidate their role in placental syndrome pathophysiology.
Background The factors affecting the prolonged air leak (PAL) and expansion failure in the lung in patients undergoing resection for lung malignancy were analyzed. In this context, the value of the percentage of low attenuation area (LAA%) measured on preoperative quantitative chest computed tomography (Q-CT) in predicting the development of postoperative PAL and the expansion time of the remaining lung (ET) in patients undergoing resection for lung malignancy was investigated.
Methods The data of 202 cases who underwent lung resection between July 2020 and December 2022 were analyzed. The factors affecting the development of PAL and ET were investigated using univariate and multivariate analyses. The cut-off value for LAA% was determined and its relationship with postoperative results was examined.
Results In univariate analyses, for PAL, age (p = 0.022), presence of chronic obstructive pulmonary disease (COPD; p < 0.001), body mass index (BMI; p = 0.006), FEV1 (p = 0.020), FEV1/FVC (p < 0.001), LAA% (p = 0.008), diagnosis (p = 0.007), and surgical procedure (p < 0.001); for ET, diagnosis (p < 0.001) and surgical procedure (p = 0.001) were significant factors. A negative correlation between ET and BMI and FEV1/FVC (p < 0.01) and a positive correlation (p < 0.05) was detected with LAA%. The cut-off value for LAA% was calculated as 1.065. Multivariate analyses showed that the probability of developing PAL, increased 3.17-, 7.68-, and 3.08-fold in patients with COPD, lobectomy, and those above the cut-off value for LAA%, respectively (p = 0.045, p < 0.001, and p = 0.011). In addition, FEV1/FVC (p = 0.027), BMI (p = 0.016), and surgical procedure (p = 0.001) were shown to be independent factors affecting ET.
Conclusion Our study revealed the factors affecting PAL and expansion failure in the lung. Within this scope, it was concluded that preoperative Q-CT may have an important role in predicting the development of PAL and ET in the postoperative period and that LAA% measurement is an effective, objective, and practical method for taking precautions against possible complications.
In this study, the in vitro photodynamic therapy (PDT) activity of two zinc phthalocyanines (ZnPc1 and ZnPc2) was systematically examined in human umbilical vein endothelial cells, focusing on PDT-induced cytotoxicity, reactive oxygen species (ROS) generation, and inhibition of angiogenic processes. Both the ZnPcs demonstrated minimal cytotoxicity in the absence of light, confirming their safety as photosensitizers. ZnPc-PDT led to significant cell death via apoptosis. ZnPc1 exhibited enhanced ROS generation, particularly at elevated concentrations. Furthermore, ZnPc1-mediated PDT showed more pronounced inhibition of endothelial cell migration, invasion, and capillary-like tube formation than ZnPc2. Wound-healing assays revealed a substantial delay in human umbilical vein endothelial cell (HUVEC) migration following ZnPc1-PDT, which also displayed a more significant inhibition of VEGF-induced directional migration and invasion. Endothelial tube formation was more effectively disrupted by ZnPc1-PDT, even at lower concentrations, compared to ZnPc2. Collectively, these findings highlight the superior cytotoxic and anti-angiogenic properties of ZnPc1 compared with ZnPc2, highlighting its potential as a highly effective photosensitizer for photodynamic therapy. The ability of ZnPc1 to simultaneously target tumor cells and disrupt angiogenesis establishes it as a potent candidate for integrated cancer therapies that combine both antitumor and antiangiogenic strategies, offering a more effective approach to combat cancer progression.
Introduction
Gaining clinical judgment competence among student nurses is a significant outcome of nursing education. In this education process, an assessment tool based on observable behaviors is needed for evaluating students’ clinical judgment skills.
Objective
This study aimed to evaluate the validity and reliability of the Turkish version of the Lasater Clinical Judgment Rubric, which assesses student nurses’ stages of clinical judgment competency in simulation-based education.
Method
This study was conducted using a cross-sectional methodological design between April and August 2024. For the cultural adaptation and psychometric evaluation of the rubric, simulation videos of 3rd and 4th-year nursing students from a foundation university were used. The language validity of the rubric was performed according to the 10-step translation and cultural adaptation guide of the International Society for Pharmacoeconomics and Outcomes Research; expert opinions were obtained for content validity. The final version of the rubric comprises four stages of the Tanner Model of Clinical Judgment (noticing, interpreting, responding, and reflecting) and 11 dimensions. Four levels of achievement describe the development of each of the 11 dimensions. Sixty-four scenario records of the simulation-based education of 4th -year students in the nursing undergraduate program of a foundation university were examined, and the students were evaluated by two independent observers using the Turkish version of the rubric. The construct validity of the scale was examined using confirmatory factor analysis, and reliability was measured using Cronbach’s alpha coefficient. Interobserver agreement was analyzed using the kappa and intraclass correlation coefficients. Moreover, the discrimination of the rubric was evaluated using an independent samples t-test between the lower and upper 27% groups.
Results
Confirmatory factor analysis revealed that the scale formed a four-factor structure of noticing, interpreting, responding, and reflecting in accordance with the original rubric. Furthermore, confirmatory factor analysis showed that the four-factor structure model had an acceptable and generally good fit and was statistically significant and valid. The fit indices for the model were calculated as χ2/df = 1.70, root mean square error of approximation = 0.06, comparative fit index = 0.94, and root mean square residual = 0.03. Kappa values ranged between 0.72 and 0.92, indicating a significant fit for all the items. The intraclass correlation coefficient values ranged between 0.70 and 0.90 and were statistically significant for all the items. The Cronbach’s alpha value of the rubric was 0.91 and ranged between 0.80 and 0.84 in its subdimensions.
Conclusion
Therefore, the Turkish version of the rubric is a valid and reliable tool for evaluating student nurses’ clinical judgment competency in simulation-based training.
Purpose: Human amniotic fluid stem cells (hAFSCs) have shown significant regenerative potential in treating hair loss, wound healing, and tissue repair. This study aims to evaluate the effects of human amniotic fluid (hAF) on hair follicle (HF) regeneration and immune system modulation.
Materials and Methods: The hAF used was pooled, acellular, and gamma-irradiated to standardize its contents and enhance its stability. Both irradiated (FAFI) and non-irradiated (FAF) hAF were assessed for their efficacy and safety in promoting hair growth and modulating immune responses in a rat model of hair loss. The study examined HF regeneration, transition to the anagen phase, and macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype.
Results: Both FAF and FAFI treatments significantly increased HF density, with FAFI exhibiting enhanced effects. Histological analysis demonstrated improved HF regeneration, increased M2 macrophages, and reduced collagen fiber deposition in treated areas. Gamma irradiation likely improved the efficacy of FAFI by stabilizing active components and inhibiting protease activity.
Conclusions: Irradiated hAF is a safe and effective therapeutic candidate for alopecia and HF growth disorders. These findings support further evaluation of hAF in clinical trials to validate its potential for hair regeneration therapies.
The treatment of patients with osteonecrosis (ON) of the femoral head has changed over the last 30 years from the concept of saving the femoral head at all costs to the more recent concept of treating symptomatic femoral head collapse, in the setting of ON, with total hip arthroplasty (THA). The reported prevalence of ON of the femoral head has increased over the past 10 years, which may be due in part to diagnostic advancement [1–5]. Approximately 20,000 patients are diagnosed in the United States with ON of the femoral head every year [6] with the average age at presentation being 38 years. Although femoral head core decompression, with or without adjunctive measures for the early stages of ON is still performed with reasonable success, it plays no role in the patient with collapse [7]. Adjunctive measures, in the setting of core decompression, have been directed towards enhancing results and include bone graft, synthetic bone substitutes, bone morphogenetic proteins, tantalum rods, or adjunctive cells [8]. The results of cell enhanced core decompression have provided early positive results and come with the advantage of less invasive procedures as compared to bone grafting, particularly vascularized bone grafting [9]. Proximal femoral redirectional osteotomies are described in the treatment of ON where collapse may be present with the aim of shifting the affected areas of the femoral head away from weight-bearing regions [10]. These osteotomies have been described as a treatment option in cases of younger patients with modest-sized lesions [11]. However, they are technically demanding surgeries with significant associated complications and can make any subsequent THA more difficult [12].
Gene II Protein (Gp2/P2) is a nicking enzyme of the M13 bacteriophage that plays a role in the DNA replication of the viral genome. P2 recognizes a specific sequence at the f1 replication origin and nicks one of the strands and starts replication. This study was conducted to address the limitations of previous experiments, improve methodologies, and precisely determine the biochemical activity conditions of the P2 enzyme in vitro. For these purposes, the gene encoding P2 was cloned in Escherichia coli and expressed as a hybrid protein together with a green fluorescent protein (P2-GFP). P2-GFP was purified via metal affinity chromatography, and its nicking activity was determined by conversion of supercoiled DNA to open circular or linear forms. We discovered that, among the two loops of the f1 origin defined previously, P2 can recognize just the A1 loop. When a supercoiled plasmid containing the f1 origin was treated with P2-GFP, the plasmid was present in an open circular form, indicating that a nick was created on only one of the strands. However, when the A1 loop sequence was inserted into the 3 ′ ends of both strands by cloning a PCR product obtained by primers with the A1 loop sequence, the plasmid was linearized by treatment with P2-GFP, indicating that nicks were created on both strands. Certain infectious diseases are caused by single-stranded DNA viruses, and some of them have specific nicking enzymes that enable strand displacement and free 3 ′ end of a single strand that works as a primer for their replication mechanisms like M13 bacteriophages, such as parvovirus B19. Despite there being different host viruses such as bacteria and humans, their DNA replication mechanisms are very similar in this concept. Investigating the features of the P2-nicking enzyme may deepen the understanding of human pathogenic single-stranded viruses and facilitate the development of drugs that inhibit viral replication.
Cortical spreading depolarization (CSD), the neurophysiological event believed to underlie aura, may trigger migraine headaches through inflammatory signaling that originates in neurons and spreads to the meninges via astrocytes. Increasing evidence from studies on rodents and migraine patients supports this hypothesis. The transition from pro-inflammatory to anti-inflammatory mechanisms is crucial for resolving inflammation. However, the resolution of inflammation in the context of CSD and migraine headaches remains poorly understood. This study aims to elucidate the progression of post-CSD inflammatory signaling and its resolution in neurons, astrocytes, and microglia in mouse brains.
CSD was triggered optogenetically or by pinprick. HMGB1 release, caspase-1 activation, and cell-specific activation of NF-κB pairs, along with ensuing transcriptomic changes, were evaluated using immunofluorescence, Western blotting, co-immunoprecipitation, FRET analysis, and cell-specific transcriptomics.
Our findings indicate that after the initial burst, HMGB1 release from neurons ceased, and caspase-1 activation, which peaked 1-hour post-CSD, diminished within 3-5 hours. This suggests that pro-inflammatory stimuli driving inflammatory signaling decreased within hours after CSD. Pro-inflammatory NF-κB p65:p50 pairs, along with anti-inflammatory cRel:p65 pairs, were detected in astrocyte nuclei shortly after CSD. However, 24 hours post-CSD, the former had disappeared while the latter persisted, indicating a shift from pro-inflammatory to anti-inflammatory activity in astrocytes. Pathway analysis of cell-specific transcriptomic data confirmed NF-κB-related pro-inflammatory transcription in astrocytes 1-hour post-CSD, while no such activity was observed in neurons. Detailed transcriptomic analysis with Bayesian cell proportion reconstruction revealed that microglia exhibited transcriptional changes trending towards an anti-inflammatory profile, along with upregulation of several chemokines and cytokines (e.g., TNF). This suggests that microglia may play a role in supporting the inflammatory responses in astrocytes through the release of these mediators. The upregulation of genes involved in chemotaxis (e.g., Ccl3) and spine pruning (e.g., C1q) in microglia implies that microglia may contribute to synaptic repair, while inflammatory signaling in astrocytes could potentially modulate meningeal nociceptor activity through an extensive astrocyte endfeet syncytium abutting subarachnoid and perivascular spaces although direct evidence remains incomplete. This nuanced understanding of the inflammatory response in CNS cell types highlights the intricate cellular interactions and responses to CSD.
Following a single CSD, distinct transcriptomic responses occur in neurons, astrocytes, and microglia, driving inflammatory and anti-inflammatory responses, potentially contributing to headache initiation and resolution.
Background: Acrocyanosis is a functional peripheral vascular disorder, currently categorized under the canopy of acrosyndromes, i.e., a group of clinically similar and significantly overlapping vascular disorders involving the acral skin. The disorder might be primary or secondary, depending on the cause. Recently, there has been a remarkable surge in acrocyanosis prevalence along with the COVID-19 pandemic. Both COVID-19 infection and vaccines for COVID-19 have been affixed to the list of disorders instigating acrocyanosis.
Objectives: The goal of this narrative review was to evaluate the existing literature, project acrocyanosis from the viewpoint of dermatologists in the face of the COVID-19 pandemic, and assess the need for targeted research, education, and/or clinical practice.
Methods: An English literature search was conducted using PubMed and Google. All abstracts on acrocyanosis, irrespective of the article type and publication date, were retrieved and reviewed and those most relevant for the focus of this article were selected and summarized.
Discussion/Results: A narrative review was carried out. There is paucity of randomized, double-blind, placebo-controlled studies on acrocyanosis in the English literature, implicating the need for targeted research. Pertinent information still relies on anecdotal observations, case reports, case series, or scarce reviews, which are dated rather old and published in vascular-oriented journals. The scarcity of published literature on acrocyanosis in dermatology-oriented journals points to the necessity of professional education and improvement of clinical diagnostic skills for dermatologists.
Conclusions: Although acrocyanosis is the least known and the least studied acrosyndrome, it is increasingly more commonly confronted in the COVID-19 era. The diagnosis still largely relies on clinical findings. Accordingly, it has become a growing necessity for a dermatologist to remain updated on this peculiar disorder and be able to differentiate acrocyanosis from clinically similar cold-induced or cold-exacerbated acrosyndromes. Acrocyanosis is still misdiagnosed, underdiagnosed, underreported, and undertreated by the dermatology community.
This study aims to evaluate the clinical course of critical pertussis illness to the pediatric intensive care unit in Istanbul. The study was conducted as a multicenter, retrospective study between January 1, 2023, and December 31, 2023. Cases with positive polymerase chain reaction testing for Bordetella pertussis of nasopharyngeal swab samples within the first 24 h of pediatric intensive care unit admission were recorded. We divided the patients into exchange blood transfusion group and non-exchange blood transfusion group, comparing related factors and clinical characteristics among each group. A total of 50 children with severe pertussis were enrolled in the study, including 29 males (58%), with a median age of 9.14 weeks (range, 7.29–15.3 weeks). The mortality rate for severe pertussis was 8%. Exchange blood transfusion was performed in eight patients (16%). There were no significant differences between patients who received exchange blood transfusion and those who did not in terms of age, male gender, gestational age, birth weight, comorbidities, presenting symptoms, duration of cough, prior antibiotic use, vaccination status, coinfections, PICU length of stay, or mortality (p > 0.05). Children who underwent exchange blood transfusion had significantly higher white blood cell (WBC) counts, lymphocyte counts, neutrophil counts, and C-reactive protein (CRP) levels compared to those who did not receive the procedure (p < 0.05). Pulmonary hypertension was observed in 50% of the children who received exchange blood transfusion, while it was present in only 11.8% of those who did not undergo the procedure (p < 0.05). Additionally, patients who received exchange blood transfusion had higher incidences of respiratory failure, cardiac failure or arrest, inotrope requirement, and mechanical ventilation compared to those who did not receive the transfusion (p < 0.05). Conclusions: Pertussis can lead to severe complications and mortality in critically ill infants. Most severe pertussis occurred in young, unimmunized infants. Children admitted with pertussis with high CRP level, high WBC and lymphocyte, and cardiac and respiratory failure can need exchange blood transfusion. What is Known:
• Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis, which primarily affects infants. Despite vaccination efforts, pertussis remains a significant cause of morbidity and mortality in infants, particularly those too young to be fully vaccinated.
What is New:
• In pertussis, exchange blood transfusion may be considered in cases of severe pulmonary hypertension or cardiogenic shock, as indicated by echocardiographic findings, in conjunction with leukocytosis observed on laboratory tests.
By lowering the significant adverse effects of traditional medications, this study intends to create cream formulations based on microemulsions that contain extract from Allium sativum L. for the treatment of acne vulgaris. Characterization experiments were carried out on the developed cream formulations based on microemulsions. Textural profile analysis and spreadability tests were conducted. Furthermore, cell culture studies and toxicity analysis were performed. As a result, the pH and viscosity values of the developed formulations were found between 6.43 ± 0.00 and 6.66 ± 0.01, and between 13.90 ± 0.080 and 137.20 ± 8.02 P, respectively. The highest‐performing empty and loaded cream formulations in terms of spreadability and textural profile analysis were those with the highest beeswax content. The highest‐performing empty and loaded cream formulations in terms of spreadability and textural profile analysis were those with the highest beeswax content. According to the visual physical evaluation of the formulations, it was observed that the developed formulations were neat, smooth, and homogeneous. The optimum formulation developed was non‐cytotoxic, which maintained cell viability by over 90%. Additionally, the skin irritation experiment was also non‐irritant with a relative cell viability of 92.6%. In conclusion, the developed A. sativum extract‐loaded microemulsion‐based cream formulations appear to be promising formulations for the acne vulgaris treatment, without malodors.
Epilepsy is a chronic neurological disorder marked by recurrent seizures, significantly impacting individuals worldwide. Current treatments are often ineffective for a third of patients and can cause severe side effects, necessitating new therapeutic approaches. Glial cells, particularly astrocytes, microglia, and oligodendrocytes, are emerging as crucial targets in epilepsy management. Astrocytes regulate neuronal homeostasis, excitability, and synaptic plasticity, playing key roles in maintaining the blood–brain barrier (BBB) and mediating neuroinflammatory responses. Dysregulated astrocyte functions, such as reactive astrogliosis, can lead to abnormal neuronal activity and seizure generation. They release gliotransmitters, cytokines, and chemokines that may exacerbate or mitigate seizures. Microglia, the innate immune cells of the CNS, contribute to neuroinflammation, glutamate excitotoxicity, and the balance between excitatory and inhibitory neurotransmission, underscoring their dual role in seizure promotion and protection. Meanwhile, oligodendrocytes, primarily involved in myelination, also modulate axonal excitability and contribute to the neuron–glia network underlying seizure pathogenesis. Understanding the dynamic interactions of glial cells with neurons provides promising avenues for novel epilepsy therapies. Targeting these cells may lead to improved seizure control and better clinical outcomes, offering hope for patients with refractory epilepsy.
Rare diseases may affect the quality of life of patients and be life-threatening. Therapeutic opportunities are often limited, in part because of the lack of understanding of the molecular mechanisms underlying these diseases. This can be ascribed to the low prevalence of rare diseases and therefore the lower sample sizes available for research. A way to overcome this is to integrate experimental rare disease data with prior knowledge using network-based methods. Taking this one step further, we hypothesized that combining and analyzing the results from multiple network-based methods could provide data-driven hypotheses of pathogenic mechanisms from multiple perspectives.
We analyzed a Huntington’s disease transcriptomics dataset using six network-based methods in a collaborative way. These methods either inherently reported enriched annotation terms or their results were fed into enrichment analyses. The resulting significantly enriched Reactome pathways were then summarized using the ontological hierarchy which allowed the integration and interpretation of outputs from multiple methods. Among the resulting enriched pathways, there are pathways that have been shown previously to be involved in Huntington’s disease and pathways whose direct contribution to disease pathogenesis remains unclear and requires further investigation.
In summary, our study shows that collaborative network analysis approaches are well-suited to study rare diseases, as they provide hypotheses for pathogenic mechanisms from multiple perspectives. Applying different methods to the same case study can uncover different disease mechanisms that would not be apparent with the application of a single method.
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