BACKGROUND: The study aimed to investigate the potential pharmacological and toxicological differences between Vigabatrin (VGB) and its enantiomers S-VGB and R-VGB. The researchers focused on the toxic effects and antiepileptic activity of these compounds in a rat model.
METHODS: The epileptic rat model was established by intraperitoneal injection of kainic acid, and the antiepileptic activity of VGB, S-VGB, and VGB was observed, focusing on the improvements in seizure latency, seizure frequency and sensory, motor, learning and memory deficits in epileptic rats, as well as the hippocampal expression of key molecular associated with synaptic plasticity and the Wnt/β-catenin/GSK 3β signaling pathway. The acute toxic test was carried out and the LD50 was calculated, and tretinal damages in epileptic rats were also evaluated.
RESULTS: The results showed that S-VGB exhibited stronger antiepileptic and neuroprotective effects with lower toxicity compared to VGB raceme. These findings suggest that S-VGB and VGB may modulate neuronal damage, glial cell activation, and synaptic plasticity related to epilepsy through the Wnt/β-catenin/GSK 3β signaling pathway. The study provides valuable insights into the potential differential effects of VGB enantiomers, highlighting the potential of S-VGB as an antiepileptic drug with reduced side effects.
CONCLUSIONS: S-VGB has the highest antiepileptic effect and lowest toxicity compared to VGB and R-VGB.

BACKGROUND: Pulmonary embolism (PE) is the major complication of thromboembolic disease. While a few qualitative studies have explored patient experience after PE, to our knowledge no literature review is available to date. The aim of this work was to explore patient experience after a PE episode through a systematic review of the literature comprising: patient experience, clinicians\' perception of the patients\' attitude and knowledge, and the patients\' perception of VTE prevention strategies.
METHODS: A search of PubMed, Web of science, Cochrane and EMBASE databases. The search was conducted without filters. Search results were combined and duplicates were removed. The selection was blinded by two independent researchers using the Rayyan application.
RESULTS: Fifty studies were assessed for quality and 23 were included. Individual semi-structured interviews and focus groups were widely used to explore patient experience after a PE episode. Patients described deterioration in their quality of life, their psychological state and an initial feeling of carer abandonment. The trends observed appear to be more pronounced in patients with an episode characterized as unprovoked.
CONCLUSIONS: These preliminary results call for further longitudinal studies, the objective being to better understand the evolution of these factors in the short and long terms.

Cyclooxygenases-2 (COX-2) and Prostaglandin E2 (PGE2), which are important in chronic inflammatory diseases, can increase tumor incidence and promote tumor growth and metastasis. PGE2 binds to various prostaglandin E receptors to activate specific downstream signaling pathways such as PKA pathway, β-catenin pathway, NF-κB pathway and PI3K/AKT pathway, all of which play important roles in biological and pathological behavior. Nonsteroidal anti-inflammatory drugs (NSAIDs), which play as COX-2 inhibitors, and EP antagonists are important in anti-tumor immune evasion. The COX-2-PGE2 pathway promotes tumor immune evasion by regulating myeloid-derived suppressor cells, lymphocytes (CD8+ T cells, CD4+ T cells and natural killer cells), and antigen presenting cells (macrophages and dendritic cells). Based on conventional treatment, the addition of COX-2 inhibitors or EP antagonists may enhance immunotherapy response in anti-tumor immune escape. However, there are still a lot of challenges in cancer immunotherapy. In this review, we focus on how the COX-2-PGE2 pathway affects tumor-associated immune cells.

Prostaglandin E2 (PGE2) is one of the most abundant prostaglandins and has been implicated in various diseases. Here, we aimed to explore the role of the PGE2 pathway in mediating ferroptosis during acute kidney injury. When renal tubular epithelial cells stimulated by H2 O2 , the contents of glutathione (GSH) and glutathione peroxidase 4 (GPX4) decreased, whereas the level of lipid peroxide increased. Ferrostatin-1 can effectively attenuate these changes. In this process, the expression levels of cyclooxygenase (COX)-1 and COX-2 were up-regulated. Meanwhile, the expression of microsomal prostaglandin E synthase-2 was elevated, whereas the expression of microsomal prostaglandin E synthase-1 and cytosolic prostaglandin E synthase were down-regulated. Furthermore, the expression of 15-hydroxyprostaglandin dehydrogenase decreased. An excessive accumulation of PGE2 promoted ferroptosis, whereas the PGE2 inhibitor pranoprofen minimized the changes for COX-2, GSH, GPX4 and lipid peroxides. A decrease in the levels of the PGE2 receptor E-series of prostaglandin 1/3 partially restored the decline of GSH and GPX4 levels and inhibited the aggravation of lipid peroxide. Consistent with the in vitro results, increased PGE2 levels led to increased levels of 3,4-methylenedioxyamphetamine, Fe2+ accumulation and decreased GSH and GPX4 levels during renal ischaemia/reperfusion injury injury in mice. Our results indicate that the PGE2 pathway mediated oxidative stress-induced ferroptosis in renal tubular epithelial cells.

To assess preretinal abnormal tissue (PAT) using en face OCT in eyes with idiopathic macular holes (MHs).
Retrospective, observational study.
Patients with MH who received 6 × 6-mm spectral-domain-OCT scans.
Preretinal abnormal tissue was detected by en face OCT images with a custom slab, defined with an anterior boundary of 6 μm anterior to the internal limiting membrane (ILM) and a posterior boundary at 3 μm posterior to the ILM. The PAT was defined as any abnormal tissues observed in en face OCT.
Characteristics of preoperative and postoperative PAT.
Sixty eyes with MH from 60 patients were included. Fifty-one eyes underwent preoperative analysis, and 46 eyes underwent postoperative examination. Before surgery, 48 (94%) eyes had a mean (standard deviation [SD]) PAT of 6.6 (9.8) mm2. The corresponding cross-sectional OCT showed PAT consisting of epiretinal proliferation, epivascular glia, and a preretinal hyperreflective band. Preretinal abnormal tissue was contiguous to the hole (peri-MH PAT) in 12 eyes (24%), whereas others (36 eyes, 76%) had a scattered distribution (extrafoveal PAT). The area of PAT was greater in eyes with a peri-MH PAT than in eyes with an extrafoveal PAT (P < 0.0001). Compared to the eyes with the extrafoveal PAT, the eyes with the peri-MH PAT were associated with men (P = 0.0059) and worse baseline visual acuity (VA) (P = 0.0002). In eyes with ILM peeling (42 eyes), postoperative PAT proliferation was observed from the edge of the ILM peeling toward the periphery over a 1-year follow-up. The mean (SD) area of PAT at 2 weeks after surgery was 3.4 (3.6) mm2 and increased to 12.1 (6.4) mm2 at 12 months (P < 0.0001). However, no PAT increase was observed in 4 eyes that underwent vitrectomy without ILM peeling. The postoperative PAT size was not associated with the postoperative VA.
En face OCT revealed PAT in most eyes with MHs. Peri-MH PAT was associated with worse VA and was seen more frequently in male patients. Postoperative PAT proliferation may be triggered by ILM peeling, but it is not associated with worse VA.

Copper-zinc superoxide dismutase (Cu-Zn SOD) is downregulated in epilepsy, however, the role of Cu-Zn SOD in epilepsy remains unclear.
Based on the pilocarpine hydrochloride-induced rat model of epilepsy, cortical-striatum brain slices of rats were examined based on field excitatory post-synaptic potentials. Pathological changes were observed by transmission electron microscope. Also using SH-SY5Y cells, flow cytometry and TUNEL staining were applied to investigate cell apoptosis, and ELISA was applied to detect SOD activity. In addition, qRT-PCR and western blot were performed to detect SCN2A/Nrf2/HO-1 gene and protein expression levels, respectively.
Cu-Zn SOD over-expression suppressed epilepsy in vivo. In addition, Cu-Zn SOD knockdown notably decreased SOD activity and induced apoptosis in SH-SY5Y cells. Moreover, Cu-Zn SOD silencing decreased the levels of SCN2A, Nrf2 and HO-1. Lastly, Cu-Zn SOD was shown to modulate the NaV1.2/Nrf2/HO-1 axis in rats.
In this model, Cu-Zn SOD attenuated epilepsy and was shown to alter the expression level of proteins of the NaV1.2 /Nrf2/HO-1 signalling pathway, indicating that Cu-Zn SOD might be a target for the treatment of epilepsy.

Objectives  Ecchordosis physaliphora (EP) is a benign notochord lesion of the clivus arising from the same cell line as chordoma, its malignant counterpart. Although usually asymptomatic, it can cause spontaneous cerebrospinal fluid (CSF) rhinorrhea. Benign notochordal cell tumor (BNCT) is considered another indolent, benign variant of chordoma. Although aggressive forms of chordoma require maximal safe resection followed by proton beam radiotherapy, BNCT and EP can be managed with close imaging surveillance without resection or radiotherapy. However, while BNCT and EP can be distinguished from more aggressive forms of chordoma, differentiating the two is challenging as they are radiologically and histopathologically identical. This case series aims to characterize the clinicopathological features of EP and to propose classifying EP and BNCT together for the purposes of clinical management. Design  Case series. Setting  Tertiary referral center, United Kingdom. Participants  Patients with suspected EP from 2015 to 2019. Main Outcome Measures  Diagnosis of EP. Results  Seven patients with radiological suspicion of EP were identified. Five presented with CSF rhinorrhea and two were asymptomatic. Magnetic resonance imaging features consistently showed T1-hypointense, T2-hyperintense nonenhancing lesions. Diagnosis was made on biopsy for patients requiring repair and radiologically where no surgery was indicated. The histological features of EP included physaliphorous cells of notochordal origin (positive epithelial membrane antigen, S100, CD10, and/or MNF116) without mitotic activity. Conclusion  EP is indistinguishable from BNCT. Both demonstrate markers of notochord cell lines without malignant features. Their management is also identical. We therefore propose grouping EP with BNCT. Close imaging surveillance is required for both as progression to chordoma remains an unquantified risk.

This study\'s purpose is to investigate the neuroprotective role of ethyl pyruvate (EP) in the pathogenesis of diabetic intracerebral hemorrhage.
The present study used a mouse model of collagenase-induced intracerebral hemorrhage (ICH) and streptozotocin-induced diabetes. The C57BL/6 mice were randomly divided into 3 groups: sham operation, diabetic cerebral hemorrhage, and diabetic cerebral hemorrhage with EP. The EP (80 mg/kg) and EP (50 mg/kg) were injected intraperitoneally one day and one hour before modeling. The protein expression levels of high mobility group box 1 (HMGB1) and NOD-like receptors 3 (NLRP3) were detected with western blot. The mRNA levels of HMGB1 and toll-like receptor 4 (TLR4) were measured by quantitative real-time polymerase chain reaction (PCR). Immunofluorescence and ELISA were performed to confirm some inflammatory factors.
Compared to the normal diabetic intracerebral hemorrhage group, the mRNA and protein expression levels of HMGB1 and TLR4 were downregulated in the EP-affected group with diabetic cerebral hemorrhage, together with the downregulation of the expression of inflammasomes, including NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase 1.
EP can reduce the inflammatory response after diabetic intracerebral hemorrhage and may inhibit the activation of inflammasomes by the HMGB1/TLR4 pathway.

Attention has recently been paid to the duodenum as the pathophysiologic center of functional dyspepsia. However, the precise mechanisms of symptom generation remain unknown. We here investigated the effect of acid on duodenal prostaglandin E2 and localization of prostaglandin E2 related receptors. Sprague-Dawley rats were used for this study. Hydrochloric acid was administered in the duodenum, then prostaglandin E2 levels in the duodenum were measured using the ELISA. The expression and localization of prostaglandin receptors (EP1-4) and the mRNAs of prostaglandin synthases were investigated using in situ hybridization histochemistry in duodenal tissue. After acid perfusion, prostaglandin E2 levels in the duodenum significantly increased. EP3 was expressed mainly at the myenteric plexus in the duodenal mucosa, and EP4 at both the epithelial surface and myenteric plexus. Contrary, EP2 was sparsely distributed in the villi and EP1 were not clearly seen on in situ hybridization histochemistry. Prostaglandin-synthetic enzymes were also distributed in the duodenal mucosa. The prostaglandin E2 levels in the duodenum increased after acidification. Prostaglandin E2 receptors and prostaglandin E2-producing enzymes were both observed in rat duodenum. These observations suggest that duodenal prostaglandin E2 possibly play a role in the symptom generation of functional dyspepsia.

Rhythmic transcranial magnetic stimulation (rTMS) has long been actively used in the treatment of depressive disorders in various mental illnesses. At the same time, the question of the predictability of the results of this method for an individual patient remains open. Based on the existing ideas about the relationship of rTMS mechanisms with changes in the state of neural networks, one of the most perspective line is the search for prognostically significant neurophysiological markers. The study analyzed a wide range of EEG characteristics and evoked potentials recorded before treatment in the groups of responders and nonresponders in patients with depressive symptoms in schizophrenia, who have completed a course of rhythmic transcranial magnetic stimulation. The study revealed associations between an unfavorable treatment outcome and greater coherence in the alpha range (mainly in the caudal regions bilaterally) and less coherence in the beta1 range (involving temporal leads and left-hemisphere asymmetry). At the same time, such indicators as the amplitude of the N100 wave and the negativity of the mismatch were uninformative in terms of predicting the effectiveness of therapy.
Ритмическая транскраниальная магнитная стимуляция (рТМС) давно и активно используется при лечении депрессивных расстройств в рамках различных психических заболеваний. Вместе с тем открытым остается вопрос прогнозируемости результатов применения данного метода для отдельного пациента. Исходя из существующих представлений о связях механизмов рТМС с изменением состояния нейронных сетей, одним из наиболее перспективных направлений представляется поиск прогностически значимых нейрофизиологических маркеров. В исследовании проводился анализ широкого спектра характеристик ЭЭГ и вызванных потенциалов, зафиксированных до начала лечения, в группах респондеров и нонреспондеров у пациентов с депрессивной симптоматикой при шизофрении, прошедших курс ритмической транскраниальной магнитной стимуляции. В результате исследования были выявлены ассоциации между неблагоприятным исходом лечения и большей когерентностью в альфа-диапазоне (преимущественно в каудальных отделах билатерально) и меньшей — в бета1-диапазоне (с вовлечением височных отведений и с левополушарной асимметрией). В то же время такие показатели, как амплитуда волны N100 и негативность рассогласования, оказались неинформативными в плане прогноза эффективности терапии.