Fathul Huda

Purpose: Mesenchymal stem cells (MSCs) hold therapeutic promise for ischemic stroke through paracrine release of bioactive factors that promote angiogenesis and neurogenesis. This study evaluated the neurogenic potential of Macaca fascicularis UC-MSC secretome under hypoxic and normoxic conditions in an in vitro ischemic stroke model, and assessed its promise as a regenerative, cell-free therapy. Methods: mUC-MSCs were cultured under normoxic (21% O₂) and hypoxic (3% O₂) conditions for 48 hours. Secretomes were collected and analyzed for Brain-Derived Neurotrophic Factor (BDNF) and Stromal Cell-Derived Factor-1 (SDF-1) levels via enzyme-linked immunosorbent assay (ELISA), while exosome morphology was characterized using scanning electron microscopy (SEM). An in vitro ischemic stroke model was created using SH-SY5Y cells exposed to 6 hours of oxygen-glucose deprivation (OGD) followed by 24 hours of reperfusion. During reperfusion, cells were treated with normoxic or hypoxic secretome. Neurogenesis-related gene expression was assessed by RT-PCR and statistically analyzed. Results: The secretome from 3% O2 hypoxic preconditioning showed elevated levels of BDNF and SDF-1 compared to normoxic conditions. RT-qPCR analysis revealed significant upregulation of neurogenesis-related genes BDNF, TrkB, ERK1/2, Nestin, and β-tubulin following treatment with the hypoxic secretome, indicating enhanced neurogenic activity and neuronal survival in the in vitro ischemic stroke model. Conclusion: Hypoxia preconditioned UC-MSC secretome enhances neurogenesis by upregulating key neurogenic markers, promoting neuronal differentiation and regeneration in ischemic conditions. These results highlight the promise of this approach as a regenerative, cell-free therapy for promoting recovery following ischemic stroke.

Gabapentin is widely used for epilepsy and neuropathic pain. Beyond neurological indications, preclinical evidence suggests that gabapentin may exert anti-inflammatory effects that have not been systematically reviewed. A systematic review (2015–2025) was performed, resulting in thirteen in vitro and in vivo studies evaluating gabapentin’s impact on inflammatory signaling pathways, cytokine production, immune cell activity, and tissue inflammation. Outcomes included molecular pathways, inflammatory mediators, histopathological changes, and functional inflammatory measures. Risk of bias and study quality were assessed using the SYRCLE RoB tool for in vivo studies and the SciRAP approach for in vitro studies. Gabapentin demonstrated potential modulation of inflammatory responses in neuropathic pain, neuroinflammation, uveitis, and sepsis models through inhibition of MAPK and NF-κB signaling, reduction in pro-inflammatory cytokines, modulation of PPAR signaling pathways, and activation of Nrf2/HO-1 pathway. Gabapentin’s pharmacological actions extend beyond neuronal excitability to include modulation of inflammatory pathways, supporting a broader biological role for gabapentin. Although preclinical data support gabapentin’s potential anti-inflammatory properties, further targeted experimental and clinical studies are warranted to confirm these findings.

Introduction: Stroke is the second leading cause of death worldwide and ranks third as a cause of disability. The American Heart Association/American Stroke Association (AHA/ASA) recommends that treatment begin within three hours of onset with intravenous thrombolysis therapy. This scoping review aimed to identify the factors that influence the delay in intravenous thrombolysis (IVT) management in patients with ischemic stroke. Methods: We searched relevant studies in PubMed, ScienceDirect, and EBSCO and this review includes studies on ischemic stroke patients that analyze the factors contributing to delays in intravenous thrombolysis therapy, and it demonstrates that such delays are present in the management of IVT. Results: A total of 48 studies were included in this study. Among pre-hospital factors, the most frequently reported contributors to delays in IVT for acute ischemic stroke (AIS) patients were the use of Emergency Medical Services (EMS) (12 studies), mode of hospital presentation (12 studies), comorbidities (6 studies), symptom recognition (5 studies), and timing of event (5 studies), with several studies reporting statistically significant associations (p<0.05). Emergency department use shortened hospital admission time by an average of 30 minutes, p<0.05Regarding in-hospital delay factors, the main contributors to delays included long scan times (5 studies), low NIHSS scores (5 studies), and limited implementation of stroke programs (5 studies). Other in-hospital delay variables included delayed activation of stroke codes (3 studies), inefficiency of human resources (3 studies), suboptimal triage processes (2 studies), diagnostic process (1 study), and logistics (1 study). Conclusion: Delayed thrombolysis in ischemic stroke patients is caused by various factors, both pre-hospital and in-hospital. Community education and telemedicine can reduce delays by 30%. Collaboration between the community, stroke units, medical personnel, and the government through comprehensive programs is key in accelerating stroke treatment and improving patient clinical outcomes.

Introduction: Mesenchymal stem cells (MSCs) have a paracrine impact and may regenerate a variety of tissues. This represents a new prospect in cell-based stroke treatment. Several in vitro and in vivo investigations have demonstrated the neuroprotective and neurogenesis properties of MSCs and their secretome. Purpose: This review provides a comprehensive analysis of the therapeutic effects of MSCs and their secretome on stroke models in vitro and in vivo. Methods: A coverage evaluation is undertaken in accordance with PRISMA-ScR principles. The selection procedure includes the identification of items. Scopus site, PubMed and ScienceDirect, are used for in vitro and in vitro research, including electronic searches. The search terms include “ischemic stroke” or “MCAO”, “MSC”, “secretome”, and “neurogenesis” or “angiogenesis”. The searches are limited to English-language articles with full text availability. Results: After selecting 390 papers from two search engines, 94 publications satisfied the review criteria for using MSCs and secretomes for ischemic stroke treatment. We comprehensively review both in vitro and in vivo studies, analyzing aspects such as the source and treatment of MSCs and secretomes, as well as administration, dosage, and mechanisms of therapeutic effects in stroke models. Conclusion: MSC and secretome therapy for stroke have shown promising results in both in vitro and in vivo models. Exploration of alternative MSC sources, refining of isolation techniques, transfection of various proteins, and combination with herbal medicine are all efforts to improve the preclinical model. This work can be used as a reference for preclinical researchers to help with research design and translational research in clinical trials.

Background and Aim: Angiogenesis and anti-apoptosis play crucial roles in ischemic stroke recovery. The mesenchymal stem cell (MSC) secretome, rich in bioactive molecules, presents a promising therapeutic avenue. However, optimizing the culture conditions to enhance the expression of angiogenic markers remains a challenge. This study examines the effect of hypoxic preconditioning on the expression of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), and microRNA (miRNA-128) in the secretome of umbilical cord-derived MSCs (UC-MSCs) from Macaca fascicularis. Materials and Methods: UC-MSCs were cultured under normoxic (21% O2) and hypoxic conditions (1%, 3%, and 5% O2) for 48 h. The secretome was isolated, and reverse transcription-quantitative polymerase chain reaction was used to quantify the expression of VEGF, MCP-1, MMP-2, and miRNA-128. Expression levels were normalized to housekeeping genes and analyzed using statistical methods to determine significant differences among groups. Results: Hypoxic preconditioning significantly upregulated VEGF (1% O2), MCP-1 (5% O2), and miRNA-128 (5% O2) expression compared to normoxic conditions. Conversely, MMP-2 expression was highest in normoxic conditions and downregulated under hypoxia. In addition, miRNA-128 was found to be predominantly secreted into the extracellular space under hypoxic conditions rather than retained within cells. Conclusion: Keywords: angiogenesis, hypoxic preconditioning, ischemic stroke, mesenchymal stem cells, microRNA-128, secretome.

Objective: This study is targeted at assessing the chemotherapy factor of the ethanol extract of Vernonia amygdalina Delile (VAD). Methods: U87 glioblastoma cells were treated with extract and a fraction of Vernonia amygdalina Delile (VAD) was harvested from the herbarium. Cytotoxicity was evaluated to determine the IC50 through microscopic observation followed by an MTT assay. Subsequently, flow cytometry with a FACS type was employed to conduct cell cycle and apoptosis analyses. Annexin V/PI and PI markers were used to assess apoptosis and cell cycle progression. Result: The ethanol extract and ethyl acetate fraction of VAD showed promising effects as cancer chemotherapy in glioblastoma cells. The IC50 values for the extract and fraction were notably low, at 37.65 µg/ml and 10.12 µg/ml, respectively, for U87 cells. Analysis of apoptosis using FACS revealed a more pronounced apoptotic effect of the 15 µg/ml fraction of VAD on both early and late apoptosis compared to the 75 µg/ml extract of VAD. Although some differences in cell cycle properties were observed, there were no significant differences in cell cycle analysis between the extract and fraction. Conclusion: These findings underscore the efficacy of VAD’s ethanol extract and ethyl acetate fraction as chemotherapeutic agents against U87 cancer cells. The low IC50 values and significant induction of early apoptosis highlight the cytotoxic effects of these treatments on U87 cells.

Objective: Glioblastoma Multiforme (GBM) poses a significant challenge due to its high aggressiveness and unfavorable prognosis, with existing treatments demonstrating limited efficacy in prolonging survival rates. This study aimed to assess the anticancer properties of Aaptos suberitoides extracts and fraction on the U87 cell line, serving as a representative model for GBM. Methods: U87 cells were treated with ethanol extracts derived from Aaptos suberitoides, specifically two extracts (OAA-1 and OAA-2) and one ethyl acetate fraction (EA) isolated from specimens collected on Pramuka Island and Tinjil Island. The evaluation encompased microscopic observation and MTT assay to determine the IC50. Subsequently, antiproliferative effects were investigated through apoptosis and cell cycle assays. Results: The extract demonstrated cytotoxic activity against U87 cells, with OAA-1 and OAA-2 exhibiting IC50 values of 35.78 μg/mL and 25.38 μg/mL, respectively. OAA-1 notably induced apoptosis at 50 μg/mL and induced cell cycle arrest. On other hand, OAA-2, while also inducing apoptosis significantly, had a lesser impact on cell cycle arrest. In contrast, EA induced significant apoptosis at a concentration of 100 μg/mL. Conclusion: The ethanol extracts and the ethyl acetate fraction of Aaptos suberitoides emerged as a promising candidate for Glioblastoma Multiforme cancer therapy, showing potential in inhibiting cell proliferation and inducing apoptosis.

Background: The occurrence of spinal fracture due to tetanus nowadays is extremely rare, as compared to the 1950s, since the widely available anti-tetanus and antispasmodic therapy. The spinal fracture in tetanus patients is usually reported in higher thoracic vertebrae, previously with a rate as high as 57.5%. Spondylitis is the most common form of skeletal tuberculosis (TB) and can cause a spinal fracture. In Indonesia, tetanus is still reported, while tuberculosis is still endemic; however, co-infection of both diseases is rarely reported. Case Presentation: A 36-year-old male was brought to our hospital with jaw stiffness, accompanied by fever. A history of dental cavities was present, and 5 days prior, he experienced a fishing hook wound on his right index finger. There was no history of TB. Physical examination showed meningismus, 2 cm trismus, abdominal spasm, opisthotonus, and spontaneous muscle spasms, without dysautonomia. In the third week of hospitalization, while his tetanus condition improved, he complained of weakness in both legs. A thorough history taking revealed a history of backache for 3 years. A wedge-shaped fracture on his 11th and 12th thoracic vertebrae was observed on radiographic examination. A spinal TB diagnosis was made, and treatment was started. He refused to get spinal surgery, then went home with 4 out of 5 motor strength scale. After three months, he returned to his routine activity as a food hawker with no motor deficits. Conclusion: Tetanus spinal fracture is extremely rare nowadays; a thorough history of spinal problems/medication is compulsory for anticipation. This patient’s spinal fracture was deemed due to a preexisting TB spinal infection that was precipitated by prolonged continuous tetanic spasm due to general tetanus.

Introduction: Spinocerebellar ataxia type-3 (SCA3) is an adult-onset autosomal dominant neurodegenerative disease. It is caused by expanding of CAG repeat in ATXN3 gene that later on would affect brain structures. This brain changes could be evaluated using brain MRI volumetric. However, findings across published brain volumetric studies have been inconsistent. Here, we report MRI brain volumetric analysis in a family of SCA 3 patients, which included pre-symptomatic and symptomatic patients.Methodology: The study included affected and unaffected members from a large six-generation family of SCA 3, genetically confirmed using PolyQ/CAG repeat expansion analysis, Sanger sequencing, and PCR. Clinical evaluation was performed using Scale for the Assessment and Rating of Ataxia (SARA). Subjects' brains were scanned using 3.0-T MRI with a 3D T1 BRAVO sequence. Evaluations were performed by 2 independent neuroradiologists. An automated volumetric analysis was performed using FreeSurfer and CERES (for the cerebellum).Result: We evaluated 7 subjects from this SCA3 family, including 3 subjects with SCA3 and 4 unaffected subjects. The volumetric evaluation revealed smaller brain volumes (p < 0.05) in the corpus callosum, cerebellar volume of lobules I-II, lobule IV, lobule VIIB and lobule IX; and in cerebellar gray matter volume of lobule IV, and VIIIA; in the pathologic/expanded CAG repeat group (SCA3).Conclusion: Brain MRI volumetry of SCA3 subjects showed smaller brain volumes in multiple brain regions including the corpus callosum and gray matter volumes of several cerebellar lobules.