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Melanin concentrating hormone (MCH) controls many brain functions, such as sleep/wake cycle and memory, and modulates the inflammation response. Previous studies have shown that influenza A virus (IAV) infection-induced neuroinflammation leads to central nervous damage. This study investigated the potential effects of MCH against neuroinflammation induced by IAV infection and its mechanism. MCH (1 and 2 mg/ml) was administrated for 5 consecutive days before IAV infection. Pentobarbital-induced sleep tests, an open-field test, and a Morris water maze were performed to measure sleep quality, spatial learning and memory ability. Neuronal loss and microglial activation were observed with Nissl staining and immunofluorescence assay. The levels of inflammatory cytokines and the expression of the JNK/ERK signaling pathway were examined by ELISA and western blot. IAV infection led to poor sleep quality, impaired the ability of spatial learning and memory, caused neuronal loss and microglial activation in mice’s hippocampus and cortex. Meanwhile the level of inflammatory cytokines increased, and the JNK/ERK signaling pathway was activated after IAV infection. MCH administration significantly alleviated IAV-induced neuroinflammation, cognitive impairment, and sleep disorder, decreased the levels of inflammatory cytokines, and inhibited neuronal loss and microglial activation in the hippocampus and cortex by regulating the JNK/ERK signaling pathway. Therefore, MCH alleviated the neuroinflammation, spatial learning and memory impairment, and sleep disorder in IAV-infected mice by regulating the JNK/ERK signaling pathway. Highlights IAV infection could cause the sleep disorder, impairment of the spatial learning and memory. IAV infection could cause the neuronal loss and activation of microglia, increase the inflammatory cytokines to result in neuroinflammation. MCH alleviated the cognitive impairment and sleep disorder in IAV-infected mice. MCH inhibited the neuron damage, microglia activation, and inflammatory cytokines expression, to alleviate the neuroinflammation in IAV-infected mice. MCH alleviated the neruoinflammation in IAV-infected mice by regulating the JNK/ERK signaling pathway.

Automated cell classification is an important yet a challenging computer vision task with significant benefits to biomedicine. In recent years, there have been several studies attempted to build an artificial intelligence-based cell classifier using label-free cellular images obtained from an optical microscope. Although these studies showed promising results, such classifiers were not able to reflect the biological diversity of different types of cell. While in terms of malignant cell, it is well-known that intracellular actin filaments are altered substantially. This is thought to be closely related to the abnormal growth features of tumor cells, their ability to invade surrounding tissues and also to metastasize. Therefore, being able to classify different types of cell based on their biological behaviors using automated technique is more advantageous. This article reveals the difference in the actin cytoskeleton structures between breast normal and cancer cells, which may provide new information regarding malignant changes and be used as additional diagnostic marker. Since the features cannot be well detected by human eyes, we proposed the application of convolutional neural network (CNN) in cell classification based on actin-labeled fluorescence microscopy images. The CNN was evaluated on a large number of actin-labeled fluorescence microscopy images of one human normal breast epithelial cell line and two types of human breast cancer cell line with different levels of aggressiveness. The study revealed that the CNN performed better in the cell classification task compared to a human expert.

Alzheimer's disease (AD) and diabetes mellitus (DM) often coexist in patients because having one of these conditions increases risk for the other. These two diseases share several pathophysiological mechanisms, such as specific inflammatory signaling pathways, oxidative stress, and cell apoptosis. It is still unclear exactly which mechanisms associated with DM are responsible for increased AD risk. Studies have found that even transient elevation of brain Aβ levels can allow T2DM to slightly disrupt the neural milieu in a way that encourages pathologies associated with the onset of memory deficits and AD. A recent study argues that a potential common pathogenetic mechanism underlying both DM and AD is evidenced by the cooccurrence of amyloid brain legions and deposits containing both tau and Aβ in pancreatic β cells. Given these links, an investigation detailing disease mechanisms as well as treatment options for patients with cooccurring DM and AD is urgently needed. The biological effects of resveratrol relevant to DM and AD treatment include its abilities to modulate oxidative stress and reduce inflammation. A rat model of DM and concomitant AD was created for this study using intraperitoneal injection of streptozotocin and hippocampal injection of Aβ1-40 to characterize resveratrol's potential protective action. Resveratrol significantly increased the Sirt1 expression, inhibited the memory impairment, the increased acetylcholinesterase, malondialdehyde, interleukin-1β and interleukin 6 levels, and the decreased levels of choline acetyltransferase (ChAT), superoxide dismutase (SOD), and glutathione in this rat model of diabetes and concomitant AD. The Sirt 1 inhibitor EX527 partially reversed the effects of resveratrol. This study suggests that resveratrol may have a neuroprotective action through activation of Sirt1 signaling in diabetes and AD with concurrent onset.

Background Cardio‐cerebrovascular events continue to pose major life‐threatening risks worldwide. Though approved for treatment of angina pectoris and ischemic stroke, the effects of tongxinluo, as a traditional Chinese medicine, on stroke and major adverse cardiovascular events (MACE) after atherosclerotic cardiovascular disease (ASCVD) remain controversial. Objective This study aims to assess the efficacy of tongxinluo in the secondary prevention of ASCVD. Methods The present systematic review was conducted following PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. In this study‐level meta‐analysis, we conducted a comprehensive search of medical libraries and clinical trial registries, spanning from their inception until November 20, 2024, and randomized controlled trials (RCTs) comparing tongxinluo versus no tongxinluo in a secondary prevention. The ASCVD population was included. The primary outcome was stroke and MACE. The secondary outcome was MACE and myocardial infarction. Results and conclusion Four RCTs, including 7087 patients with known coronary artery disease, ischemic stroke, or carotid artery plaque, were included in the analysis. Compared to placebo, tongxinluo numerically decreased the risk of stroke with a RR of 0.84 (95% CI: 0.61–1.17, p = 0.31). For the outcome of MACE, tongxinluo reduced the risk by 28% (RR: 0.72, 95% CI: 0.59–0.88, p = 0.001). Patients randomized to tongxinluo had a RR of 0.70 (95% CI: 0.54–0.92, p = 0.01) for cardiovascular mortality and 0.74 (95% CI: 0.56–0.92, p = 0.01) for all‐cause mortality. In summary, in patients with ASCVD, tongxinluo tended to decrease the incidence of stroke, and reduced the composite of stroke, myocardial infarction, and cardiovascular mortality by 28%. This systematic review and meta‐analysis aims to evaluate the efficacy of tongxinluo in the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). In summary, among patients with ASCVD, tongxinluo was associated with a trend toward a reduced incidence of stroke and a 28% lower risk of major adverse cardiovascular events (MACE), which supports its potential role in the clinical management of patients with atherosclerotic disease.

Background Chronic cerebral hypoperfusion (CCH) is the leading cause of cerebral small vessel disease (CSVD). CCH is strongly associated with blood–brain barrier (BBB) dysfunction and white matter lesions (WMLs) in CSVD. However, the effects of CCH on BBB integrity and components and the cellular and molecular mechanisms underlying the effects of BBB dysfunction remain elusive. Whether maintaining BBB integrity can reverse CCH-induced brain damage has also not been explored. Methods In this study, we established a rat model of CSVD via permanent bilateral common carotid artery occlusion (2VO) to mimic the chronic hypoperfusive state of CSVD. The progression of BBB dysfunction and components of the BBB were assessed using immunostaining, Western blotting, transmission electron microscopy (TEM) and RNA sequencing. We also observed the protective role of imatinib, a tyrosine kinase inhibitor, on BBB integrity and neuroprotective function following CCH. The data were analyzed using one-way or two-way ANOVA. Results We noted transient yet severe breakdown of the BBB in the corpus callosum (CC) following CCH. The BBB was severely impaired as early as 1 day postoperation and most severely impaired 3 days postoperation. BBB breakdown preceded neuroinflammatory responses and the formation of WMLs. Moreover, pericyte loss was associated with BBB impairment, and the accumulation of serum protein was mediated by increased endothelial transcytosis in the CC. RNA sequencing also revealed increased transcytosis genes expression. BBB dysfunction led to brain damage through regulation of TGF-β/Smad2 signaling. Furthermore, imatinib treatment ameliorated serum protein leakage, oligodendrocyte progenitor cell (OPC) activation, endothelial transcytosis, microglial activation, and aberrant TGF-β/Smad2 signaling activation. Conclusions Our results indicate that reduced pericyte coverage leads to increased BBB permeability via endothelial transcytosis. Imatinib executes a protective role on the BBB integrity via inhibition of endothelial transcytosis. Maintenance of BBB integrity ameliorates brain damage through regulation of TGF-β/Smad2 signaling following CCH; therefore, reversal of BBB dysfunction may be a promising strategy for CSVD treatment.

Bcl2-associated athanogene 3 ( BAG3 ) gene mutations cause dilated cardiomyopathy and myofibrillar myopathy. Recently, a novel c.625C>T (p.Pro209Ser) mutation in BAG3 was reported to cause axonal Charcot–Marie–Tooth (CMT) disease in three families. Here, we describe two patients with adult-onset and moderate CMT in a Chinese family. Nerve conduction velocity studies revealed an axonal sensorimotor neuropathy, which was supported by sural nerve biopsy. Lower limb magnetic resonance imaging (MRI) revealed fatty infiltration more severe in the soleus and deep posterior compartment muscles than in the medial gastrocnemius and anterior compartment muscles. Whole exome sequencing identified the same c.625C>T (p.Pro209Ser) mutation in BAG3 , which co-segregated with the CMT disease in this family. This study further enforces the association between BAG3 gene and CMT disease, indicating that BAG3 should be considered in the genetic testing for CMT. The p.Pro209Ser mutation with different ethnic origins might be another hotspot mutation of BAG3 . MRI is helpful to detect accurate extent of muscle involvement.

Guillain–Barré syndrome (GBS) is an acute immune-mediated peripheral neuropathy typically characterized by a monophasic course; however, atypical or relapsing presentations suggest that sustained immune dysregulation contribute to disease heterogeneity. We report a 33-year-old man with progressive limb weakness diagnosed as motor-predominant acute inflammatory demyelinating polyradiculoneuropathy (AIDP), supported by albuminocytologic dissociation and demyelinating features on nerve conduction studies with preserved sensory conduction. Immunological evaluation revealed B lymphocyte expansion, elevated interleukin-6 and interleukin-8 levels, and strong thyroid autoantibody positivity consistent with Graves’ disease, while anti-ganglioside and paraneoplastic antibodies were negative. The clinical course was marked by immune-triggered relapses and the patient responded well to intravenous immunoglobulin (IVIg) and FcRn inhibition with efgartigimod. Further investigation identified papillary thyroid carcinoma harboring a BRAF V600E mutation, after which neurological symptoms stabilized following thyroidectomy. This case illustrates a rare concurrence of relapsing AIDP, Graves’ disease, and papillary thyroid carcinoma, and supports the hypothesis that persistent systemic immune activation underlies relapsing GBS, rather than a chronic demyelinating process. Clinically, it highlights the importance of considering underlying autoimmune and neoplastic conditions in atypical or relapsing GBS to guide individualized management.

Circular RNAs (circRNAs) are covalently closed, single-stranded RNAs generated via backsplicing. They are highly stable and evolutionarily conserved, making them promising candidates for cancer therapy and diagnosis. CircRNAs regulate cancer progression by modulating genome instability, angiogenesis, metastasis, stemness, and chemoresistance. They do so through mechanisms including microRNA (miRNA) sponging, protein interaction, translational templating, and transcription/translation regulation. CircRNAs play a critical role in cancer immunotherapy. They modulate immune checkpoint blockade (ICB) responses and cytokine secretion to reshape the tumor immune microenvironment (TME). CircRNAs also serve as stable platforms for neoantigen-based cancer vaccines and improve in vivo chimeric antigen receptor T cell (CAR-T) therapy by replacing unstable linear mRNA. Additionally, circRNAs are potential noninvasive biomarkers due to their abundance in body fluids and differential tumor-normal expression. Despite challenges such as unclear regulatory networks, off-target effects, and inefficient delivery, this review systematically summarizes the biogenesis of circRNAs, their functional mechanisms, their roles in cancer progression, and their applications in cancer immunotherapy. The review also highlights their utility as biomarkers and future translational directions, providing a focused overview of their potential to advance cancer immunotherapy.

Background The Cardiometabolic Index (CMI) represents a novel anthropometric measurement, which combines characteristics of adiposity and lipids. Since obesity, lipid metabolism, and inflammation may collectively facilitate the occurrence of stroke, we hypothesize that a combination of elevated levels of the CMI and high-sensitivity C-reactive protein (hs-CRP) increases the risk of future stroke among middle-aged and older Chinese adults. Methods This study included 8,973 participants aged 45 years or older from the China Longitudinal Study on Health and Retirement (CHARLS), who were stroke-free and underwent baseline evaluations between 2011 and 2012, with followed-up at 2013, 2015 and 2018. The exposures were CMI and hs-CRP, with CMI calculated using the formula [waist circumference (cm)/height (cm)] × [triglycerides (mmol/L)/HDL-C (mmol/L)]. The primary outcome was the occurrence of new-onset stroke events. Cox proportional hazards models and restricted cubic spline (RCS) analyses were conducted to examine the associations between CMI, hs-CRP, and their combined effects on stroke risk. Sensitivity analysis was further implemented to verify the robustness of the results. Results A total of 629 participants (7.01%) suffered new-onset stroke during follow-up. The risk for stroke increased with each elevating quartile of baseline CMI levels, with adjusted HRs and 95% CIs being 1.27 (0.98–1.66), 1.41 (1.08–1.83), and 1.46 (1.09–1.96) for Q2, Q3, and Q4, respectively. Moreover, participants with levels of hs-CRP ≥ 2 mg/L also had significantly higher stroke incidence compared to those with CRP levels < 2 mg/L (adjusted HR 1.24, 95% CI 1.05–1.47, p  = 0.012). Specifically, those concurrently with the highest CMI quartile and levels of hs-CRP ≥ 2 mg/L had the highest risk of stroke (adjusted HR 1.90, 95% CI 1.32–2.74). The subsequent sensitivity analyses yielded consistent results, further corroborating the initial findings. Conclusions The combination of CMI and hs-CRP exhibited a significant association with stroke risk among middle-aged and older Chinese adults, highlighting the importance of joint assessments of these biomarkers for refining risk stratification and enhancing primary prevention strategies for stroke.

The aims of the study were to characterize the clinical manifestations and outcomes of patients with antibody-negative severe autoimmune encephalitis (AE). This retrospective, monocentric study recruited patients from the Neurology Department of Henan Provincial People's Hospital between April 2017 and December 2023. All patients underwent neural antibody testing in both blood and cerebrospinal fluid (CSF) and met the diagnostic criteria for autoantibody-negative but probable severe AE, with available 1-year follow-up data. In total, 124 patients with autoantibody-negative severe AE were analyzed. Among them, 27.4% achieved good functional outcomes at discharge. Older age (OR 1.034, 95% confidence interval [CI] 1.010-1.058, = 0.004) and the presence of dyskinesia/dystonia (OR 8.463, 95% CI 3.282-21.820, < 0.001) were predictive of poor short-term outcomes. At the 1-year follow-up, 54.8% experienced favorable long-term outcomes. Independent predictors of unfavorable long-term outcomes included older age (OR 1.076, 95% CI 1.018-1.136, = 0.009), longer hospital stays (OR 1.264, 95% CI 1.105-1.446, = 0.001), the presence of refractory status epilepticus (OR 14.765, 95% CI 1.759-123.935, = 0.013) and higher CASE scores at discharge (OR 2.079, 95% CI 1.450-2.980, < 0.001). Additionally, 30.6% of patients had relapsed, with refractory status epilepticus being an independent risk factor for relapse. Although patients with antibody-negative severe AE experience significant disability in the early stages of their disease, the majority eventually regain independent functioning. Older age at disease onset, longer hospital stays, the presence of refractory status epilepticus and higher CASE scores at discharge may predict a poor long-term prognosis.