therapeutic

Neurotoxicity is increasingly recognized as a critical factor impacting long-term health, with growing evidence linking it to both neurodevelopmental and neurodegenerative diseases. Pesticides, widely used in agriculture and industry, have emerged as significant contributors to neurotoxic risk, given their capacity to disrupt key neurodevelopmental processes at low exposure levels. As conventional animal models present limitations in interspecies translation, human-derived neuron-based in vitro screening strategies are urgently needed to assess potential toxicants accurately. Human-induced pluripotent stem cells (hiPSCs) offer an innovative and scalable source for human-specific neuronal models that complement traditional animal-based approaches and support the development of predictive assays for neurotoxicity. Recent various stem cell models, including 2D cultures, 3D organoids, and microfluidic systems, are now available, advancing predictive neurotoxicology by simulating key aspects of human neural development and function. With the integration of High-Throughput (HT) and High-Content (HC) screening methodologies, these hiPSC-based systems enable efficient, large-scale evaluation of chemical effects on neural cells, enhancing our ability to detect early biomarkers of neurotoxic effects. Identifying early biomarkers of neurotoxic is essential to developing therapeutic interventions before irreversible damage occurs. This is particularly crucial in the context of developmental neurotoxicity, where early exposure to toxicants can have lifelong consequences. This review specifically presents an in-depth overview of the current progress in hiPSC-derived neural models and their applications in neurotoxicity testing, with a specific focus on their utility in assessing pesticide-induced neurotoxicity. Emphasizing future research priorities, we highlight the potential of these models to transform predictive toxicology, offering more human-relevant assessments and advancing the field toward a more precise evaluation of environmental neurotoxicants.

Congenital Dyserythropoietic Anaemia (CDA) is a rare genetic disorder that affects the maturation of red blood cells. The disorder is classified into different types, with a prevalence ranging from 1 in 100,000 to 1 in 1,000,000 individuals. Treatment strategies are designed with the primary focus on symptom management, the prevention and treatment of complications, and the underlying disease pathophysiology. The advent of bone marrow transplantation, gene therapy, and targeted therapies has considerably expanded the scope for therapeutic intervention in CDAs. Supportive care, including blood transfusions and iron chelation therapy, has demonstrated efficacy in managing iron overload and improving overall survival rates. The potential of gene therapy, targeted therapies, and hematopoietic growth factors in the treatment of CDA is currently being investigated. Further research and clinical trials are required to develop more effective and personalized therapeutic interventions.

Introduction: Busulfan (Bu)-based regimens are crucial for myeloablative conditioning in pediatric allogeneic stem cell transplantation. Despite its efficacy, Intravenous Bu has a narrow therapeutic index and variable pharmacodynamics especially in children, heightening the risk of adverse events. This study explores Bu dosing and related organ toxicities in pediatric patients at a tertiary center in Saudi Arabia.Methodology: This retrospective study at King Fahad Specialist Hospital in Dammam (KFSH-D), Saudi Arabia, included pediatric patients (≤16 years) treated with intravenous Bu before bone marrow transplantation from 2010 to 2022. Pharmacokinetic dose adjustments were based on AUC targets of 900-1350 µMol-min. Descriptive measures included mean, Standard Deviation (SD), median, minimum-maximum values, counts, and percentages. Statistical analyses used Kruskal-Wallis, Chi-square, and Fisher’s exact tests. Ethical approval was obtained from KFSH-D.Results: We identified 44 pediatric patients who underwent Bu prior to HSCT. Mean age was 4.95 ± 2.49 years, with a female majority (56.8%). Primary diseases included Beta Thalassemia (34.09%), Neuroblastoma (29.55%) among others. There was no significant difference in the cohort’s demographic and clinical features of the cohort. Nonetheless, higher infections were found in the Low-AUC group (66.7%) compared to the Target-AUC (40.0%) and Higher-AUC groups (0.0%) (p = 0.015).Conclusion: This study emphasizes the need for therapeutic drug monitoring and individualized Bu dosing in pediatric HSCT to minimize toxicity and improve outcomes. Larger multicenter studies are recommended to refine dosing strategies and enhance the safety and efficacy of Bu-based regimens.

Sleep disorders represent a significant public health concern due to their widespread prevalence, impact on overall health, and the economic burden they impose. These disorders encompass a broad spectrum of conditions, ranging from insomnia and obstructive sleep apnea (OSA) to narcolepsy, restless legs syndrome (RLS), and parasomnias. They are often associated with comorbidities such as cardiovascular diseases, metabolic dysfunctions, and mental health disorders, making their identification and management critical.The publication of this work is of high interest as it contributes to the expanding body of literature focused on understanding the complex interplay between sleep disorders and health outcomes. By presenting detailed case reports, this study provides valuable insights into the diagnostic challenges, treatment modalities, and potential avenues for personalized interventions in sleep medicine. Case reports are particularly important in this field as they shed light on unique presentations and rare conditions that might otherwise go unnoticed in large-scale epidemiological studies. From an epidemiological perspective, sleep disorders are highly prevalent globally. According to the World Health Organization (WHO), approximately 30% - 45% of the global population experiences sleep disturbances. Obstructive sleep apnea, for instance, affects nearly 1 billion individuals worldwide, with varying prevalence across age, gender, and geographic regions. Insomnia affects roughly 10% - 30% of adults, with rates as high as 50% - 60% in older populations.Meanwhile, narcolepsy, though rare, is estimated to affect 1 in 2,000 people in the general population. These statistics underscore the pressing need for enhanced diagnostic methods, improved treatment strategies, and comprehensive patient management. By detailing real-world cases, this publication aims to bridge the gap between clinical observations and broader scientific understanding. The insights gained from these case studies have the potential to inform future research directions, improve clinical practices, and ultimately enhance patient outcomes in sleep medicine.Sleep disorders affect millions of individuals globally, disrupting physical, mental, and emotional well-being. Conditions such as insomnia, obstructive sleep apnea (OSA), narcolepsy, and restless legs syndrome (RLS) are among the most studied. This paper examines the etiology, diagnosis, and management of sleep disorders, presenting detailed case reports and integrating relevant sleep study findings. Figures such as polysomnography (PSG) outputs and statistical trends provide visual insights into diagnostic and therapeutic interventions. Sleep disorders encompass a wide range of conditions that significantly disrupt sleep quality and overall well-being. Common disorders such as insomnia, obstructive sleep apnea (OSA), narcolepsy, and restless legs syndrome (RLS) affect millions globally, posing risks to physical health, mental stability, and cognitive performance. This study explores the clinical presentation, diagnostic approaches, and management of sleep disorders through the lens of detailed case reports and sleep study data.Polysomnography (PSG), the gold standard for sleep disorder diagnosis, plays a pivotal role in identifying abnormal sleep patterns, respiratory irregularities, and neural disruptions. Multiple sleep latency tests (MSLT) and actigraphy complement PSG, offering insights into disorders like narcolepsy and circadian rhythm abnormalities. This paper presents three representative case reports: chronic insomnia, severe OSA, and narcolepsy with cataplexy. Each case is analyzed in-depth, highlighting patient history, PSG findings, treatment interventions, and outcomes. For chronic insomnia, cognitive-behavioral therapy for insomnia (CBT-I) and pharmacological intervention resulted in marked improvements in sleep latency and efficiency. In the OSA case, continuous positive airway pressure (CPAP) therapy significantly reduced the apnea-hypopnea index (AHI) and alleviated daytime symptoms. The narcolepsy case demonstrates the efficacy of modafinil and sodium oxybate in managing excessive daytime sleepiness and cataplexy.Despite advancements, challenges persist in the field, including patient adherence to therapy, accessibility to specialized sleep studies, and the ethical implications of AI-driven diagnostic tools. Future research should focus on scalable, patient-centric approaches and the role of emerging technologies in enhancing diagnostic accuracy and treatment efficacy. This paper aims to contribute to the evolving understanding of sleep disorders, bridging clinical case insights with the broader implications for sleep health and research.

The amniotic membrane, used for over a century, is a widely recognized therapeutic tool in regenerative medicine and reconstructive surgery. Its primary indication is in the treatment of deep partial-thickness burns, where it facilitates epithelialization by providing an optimal environment for tissue regeneration. However, its versatility allows its use in various clinical scenarios, particularly in wounds or trauma where immediate closure is not possible, either due to the patient’s condition or the characteristics of the wound itself. Its most notable benefits include the prevention of necrosis due to desiccation, minimizing the loss of essential proteins, fluids, and electrolytes, reducing the risk of infection by acting as a physical barrier and alleviating pain by covering and stabilizing the wound.Additionally, its ability to act as a temporary biological cover offers a valuable solution in complex cases, improving both the prognosis and the patient’s management.A case series is presented demonstrating various applications of the amniotic membrane.

Bilateral trigeminal neuralgia refractory to medical therapy is a rare occurrence and it is mandatory to choose therapeutic procedures minimizing possible bilateral sensitive deficit due to the employment of bilateral mininvasive ablative techniques.  A patient affected by bilateral trigeminal neuralgia refractory to medical therapy secondary to multiple sclerosis is presented. Multiple therapeutic tools were employed in this challenging pathology. The second and third left trigeminal divisions were involved by the neuralgia, while the third division was involved in the right facial side. Controlled radiofrequency thermocoagulation was employed for the isolated right third division, then radiosurgery was conducted for the left hemifacial side.  After one month, because of the persistence of pain attacks of the left second trigeminal division, peripheral authorizations were performed. Control of pain, with the withdrawal of medical therapy (BNI scale class I), was achieved in this patient with a multi-therapeutic approach. Radiofrequency thermorizotomy was performed for the right third division because neuralgia was very acute, and immediate pain relief was achieved. Pain in the left third trigeminal division regressed after radiosurgery, while pain in the left second division continued after radiosurgery, then peripheral alcoholization was performed with pain control.Bilateral trigeminal neuralgia refractory to medical therapy should be treated by the dedicated neurosurgeon, avoiding bilateral ablative techniques for the same division and using neurosurgical techniques according to the trigeminal division interested by the neuralgia and according to the intensity of pain.

Double-Positive Patients (DPPs), characterized by the simultaneous presence of Anti-Neutrophil Cytoplasmic Antibody (ANCA) and anti-Glomerular Basement Membrane (anti-GBM) antibodies, represent a rare subset in systemic vasculitis. We present two cases of DPPs with renal involvement and review the existing literature to elucidate the clinical characteristics, histopathological findings, management strategies, and prognostic outcomes associated with this condition. Both cases exhibited renal involvement with rapidly progressive glomerulonephritis, requiring renal replacement therapy. Renal biopsies confirmed crescentic glomerulonephritis with features of both anti-GBM disease and ANCA-associated vasculitis. Management included high-dose glucocorticoids, cyclophosphamide, and consideration of plasma exchanges. Double-positive ANCA and anti-GBM vasculitis pose challenges in management and prognosis. Further research is essential to improve therapeutic strategies for this rare and heterogeneous condition.

Kalanchoe pinnata is a widely recognized medicinal plant known for its antioxidant and anti-inflammatory properties. This study explores its in vitro antioxidant and anti-inflammatory activities, highlighting its potential for pharmaceutical and biomedical applications. The research innovatively assesses its bioactive components using DPPH radical scavenging, nitric oxide inhibition assays, and phenolic content analysis. Results demonstrated significant antioxidant activity with IC50 values comparable to ascorbic acid, along with notable anti-inflammatory effects via nitric oxide inhibition. These findings emphasize Kalanchoe pinnata’s potential as a source for developing antioxidant and anti-inflammatory therapeutics. Further investigation into bioactive compound isolation and mechanistic pathways is recommended to clarify its pharmacological efficacy.

Introduction: Behçet’s disease is a rare, systemic, inflammatory condition that primarily affects young adults. It is characterized by a variety of clinical manifestations. However, neurological and cardiac presentations remain uncommon and often delayed in diagnosis. This disease can lead to severe complications, such as ischemic strokes and myocarditis, highlighting the systemic and complex nature of the condition.Case presentation: A 27-year-old patient was hospitalized after experiencing an ischemic stroke and myocarditis, which revealed Behçet’s disease. He had a history of oral and cutaneous ulcers, without a prior diagnosis of Behçet. Upon admission, brain imaging confirmed an ischemic stroke, and echocardiography and cardiac MRI showed acute myocarditis. Biological tests confirmed elevated systemic inflammation, which guided the treatment plan. The initial treatment included corticosteroids, immunosuppressors (azathioprine), and cardioprotective therapy. The patient showed significant clinical improvements, although mild deficits persist.Discussion: Myocarditis in Behçet’s disease is a rare but severe manifestation resulting from inflammation of the heart walls, often associated with other systemic vascular involvement. Although less common than oral or cutaneous ulcers, myocarditis can lead to acute heart dysfunction and even heart failure if not treated promptly. It is generally caused by an excessive inflammatory response, often associated with immune system activation, which affects the coronary circulation and damages the cardiac muscle. Treatment for myocarditis in this context relies on high-dose corticosteroids to control inflammation, followed by long-term immunosuppressive medications like azathioprine. While the initial treatment often leads to a rapid improvement in cardiac function, the risk of long-term complications, such as dilated cardiomyopathy or heart failure, remains high. Close follow-up is therefore essential to prevent these complications and optimize the long-term cardiac prognosis of patients with this rare disease.Conclusion: The progression of myocarditis in Behçet’s disease can be favorable if diagnosed and treated early, with significant improvement in cardiac function achieved through the use of corticosteroids and immunosuppressive therapy. However, the long-term prognosis remains uncertain due to the risk of chronic cardiac complications, such as dilated cardiomyopathy or heart failure.

Introduction: Membranoproliferative glomerulonephritis (MPGN) is a significant cause of glomerulopathy and chronic kidney disease (CKD) or end-stage renal disease (ESRD) in children. The deposition of circulating immune complexes in the glomerulus and abnormal activation of the alternative complement pathway is believed to trigger the disease. However, there is limited knowledge regarding the optimal treatment and prognosis for children with immune complex-associated MPGN (IC-MPGN) and C3 glomerulopathy (C3G).Case report: We report the case of a 14-year-old child admitted for rapidly progressive glomerulonephritis with anuria managed on haemodialysis. The kidney biopsy showed an appearance compatible with MPGN on light microscopy, with immunoglobulin and complement C3 deposits on direct immunofluorescence. The prognosis was poor, with rapid progression to ESRD despite treatment combining corticosteroid therapy and immunosuppressants.Discussion and conclusion: Evaluating the effectiveness of different therapeutic approaches for MPGN in children is challenging due to the small sample sizes and the short duration of the published controlled studies. As a result, it is crucial to conduct more comprehensive trials that focus on both prognosis and treatment options.

Severe fever with thrombocytopenia syndrome (SFTS) is caused by a virus that induces acute infections. Despite its expansion beyond China, where it first appeared in 2009, no specific drug exists to treat the disease. The discovery that antibodies targeting the SFTS virus surface glycoprotein (Glycoprotein N, GN) significantly enhance patient survival has driven the development of antibodies, particularly nanobodies. Nanobodies targeting the GN protein are a promising therapeutic approach. This paper presents a systematic study of the purification process for a recombinant nanobody-Fc fusion designed to treat the SFTS virus HB29. The study evaluated a sequential purification approach using affinity (AFF), ion exchange (IEC), and hydrophobic interaction chromatography (HIC) techniques to gradually remove impurities. The results demonstrate that this approach achieves an overall yield of more than 50% and a total purity of 95%. Efficient nanobody purification methods, as outlined here, can pave the way for novel treatments to manage this disease.

Mitochondria are essential intracellular organelles that significantly influence various cellular processes, including metabolism, stress response, and cell fate. Their precise regulation is crucial for maintaining both organelle and cellular homeostasis. Wound healing is a complex, multifactorial process that relies on the coordinated actions of multiple cell types and numerous cellular mechanisms. Dysregulation in this process can lead to chronic wounds, which pose substantial challenges for healthcare systems and present limited treatment options due to their intricate pathogenesis. Recent research has increasingly focused on the role of mitochondria in wound healing, revealing their involvement in critical processes such as metabolism, apoptosis, and redox signaling. Mitochondrial dynamics play a vital role in wound healing by adapting to cellular demands and environmental cues. Moreover, mitophagy, the selective degradation of damaged mitochondria, is crucial for maintaining mitochondrial integrity and function during the healing process. Mitochondria are not only pivotal in energy production but also in calcium homeostasis and the generation of mitochondrial reactive oxygen species, which are essential for signaling during wound repair. As wound healing progresses through distinct yet overlapping stages mitochondria facilitate the energy demands of repair and contribute to cytoskeletal remodeling necessary for wound closure. Understanding the multifaceted roles of mitochondria in wound healing could lead to novel therapeutic approaches for chronic wounds. Future research should prioritize investigating mitochondrial dynamics and functions in human tissues to develop targeted strategies for enhancing wound healing outcomes.

Blood cell production through hematopoiesis within the bone marrow serves both to maintain blood equilibrium and to respond to tissue injury and infectious demands. Hematopoietic stem cell (HSC) therapy developments have revolutionized medical treatment approaches for anemia leukemia and bone marrow failure caused by chemotherapy or radiation exposure. The therapeutic compounds present in medicinal plants have traditionally supported blood health and researchers now understand these plants could help regenerate bone marrow tissue. The analysis investigates how phytochemicals affect HSC proliferation and differentiation while supporting HSC survival. The medicinal plants Panax ginseng, Astragalus membranaceus, and Curcuma longa receive special attention for their documented ability to enhance hematopoiesis in preclinical and clinical settings. This review examines the challenges that include standardization issues, toxicity concerns, and regulatory barriers alongside future perspectives about combining plant-based therapies with traditional treatments to improve bone marrow recovery and health results. 

Bartholinitis, or Bartholin's gland abscess, is a relatively common gynecological condition among women of reproductive age. Its annual incidence is estimated at approximately 0.5 per 1,000 women, which corresponds to a lifetime cumulative risk of about 2%. The condition primarily affects patients between 20 and 50 years old, with a peak frequency observed between 35 and 50 years.After menopause, due to the natural involution of the gland, Bartholin's cysts and abscesses become less frequent, although they can still occur. Moreover, in women over 50, the appearance of a new mass in the gland region should prompt caution, as it may, in rare cases, indicate a carcinoma of the Bartholin's gland or an adjacent vulvar cancer. Therefore, for patients over 40 presenting with a newly emerged cyst or abscess, clinical guidelines recommend performing a biopsy or excision to rule out malignancy. We present the case of a 50-year-old woman with no significant medical history, who was urgently referred to the gynecological emergency department due to confusion, unexplained fever of 40 °C, and resistant leucorrhoea following a week of corticosteroid antibiotic therapy. Clinical examination revealed a large, tender right vulvar mass, indicative of an acute Bartholin's abscess. The patient exhibited signs of septic shock and was admitted to the ICU. Following a diagnosis of sepsis, broad-spectrum antibiotic therapy was initiated, alongside fluid resuscitation and norepinephrine support. Surgical drainage of the abscess confirmed the presence of E. coli. The patient's condition improved rapidly, and she was discharged on postoperative day 8 with no complications. This case underscores that while Bartholin's abscess is typically benign, severe complications, including septic shock, can occur—especially in patients over 50. The appearance of a new Bartholin's region mass in older women should prompt consideration of malignancy, necessitating biopsy or excision. Recent studies compare various therapeutic approaches including simple incision and drainage, Word catheter placement, marsupialization, silver nitrate application, and complete gland excision. Each method has its advantages and drawbacks, with marsupialization offering lower recurrence rates and higher patient satisfaction in many instances. 

Background: Studies explored the therapeutic role of agents inhibiting RAS in epilepsy. Fewer studies addressed the electrophysiological changes associated with angiotensin converting enzyme inhibitors (ACEIs) in terms of sustained seizures (status epilepticus). Sodium valproate (SVPA), a broad-spectrum anticonvulsant, has been associated with adverse cardiac events upon long-term use, in contrast to the beneficial role of ACEIs in cardiovascular disorders.  This work explored the potential effects of ramipril, an ACEI, compared to SVPA, on the behavior, and electrophysiology of the brain and heart in a rat model of status epilepticus. The dose dependent pattern of the presumed ramipril activities was investigated. Methods: Adult male rats were assigned into seven groups, controls, IP pyridostigmine (36 mg/kg)-induced status epilepticus (PISE), oral SVPA (5 mg/kg), and three groups receiving oral ramipril at respective doses of 5 (R5), 10 (R10), and 20 mg/kg (R20). Rat behavior was assessed using Racine’s motor convulsion scoring for 10 minutes.  Blood pressure was recorded, and electroencephalography (EEG) and electrocardiography (ECG) were performed on the sedated rats 24 hours after recovery. Results: Despite the partial behavioral improvement of motor convulsions with R5 and R10 exhibited epileptogenic activity, as indicated by the increased relative power of fast and slow gamma waves and total EEG power. R10 triggered arrhythmia and cardiac ischemia as indicated by absence of P wave, along with ST elevation and tall T wave, slowed heart rate and prolonged QRS, QTc, and RR intervals. Conclusion: PISE was resistant to sodium valproate and ramipril. Ramipril at low and moderate doses induced epileptogenic activity and, especially at moderate dose, precipitated cardiac ischemia and arrhythmia. SummaryThe debatable role of ramipril in epilepsy was studied in a rat model of pyridostigmine-induced status epilepticus, compared to sodium valproate. Increasing ramipril doses did not resolve status epilepticus in rats. Instead, low and moderate doses exhibited epileptogenic activity, opposite to high dose ramipril and sodium valproate. Blood pressure was dose-dependently reduced with ramipril. Electrocardiography showed evidence of cardiac arrythmia and ischemia, especially with the moderate ramipril dose. The behavioral and EEG indices correlated with systolic blood pressure and ECG changes.

Citrus sinensis is a rich source of bioactive compounds  and has attracted attention due to its medicinal benefits. Historically regarded as agricultural waste, orange peel is rich in flavonoids, polyphenols, tannins, and essential oils with antibacterial, anti-inflammatory, and antioxidant qualities. The phytochemicals in Citrus sinensis peel were used as natural reducing and stabilizing agents in the green synthesis method used in this work to create silver nanoparticles (AgNPs). This method is an environmentally friendly alternative to conventional nanoparticle production, eliminating the need for hazardous chemicals. Based on the study’s results, green-synthesized silver nanoparticles derived from Citrus sinensis peel extract offer a sustainable and biocompatible substitute for biomedical applications. The pharmaceutical and healthcare industries may find therapeutic uses for them due to their exceptional antibacterial, antioxidant, and anticancer properties.