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Hypoxia triggers reactive microglial inflammation and lipid droplet (LD) accumulation under stroke conditions, although the mutual interactions between these two processes are insufficiently understood. Hence, the involvement of transforming growth factor (TGF)-β1 in inflammation and LD accumulation in cultured microglia exposed to hypoxia were analyzed herein. Primary microglia were exposed to oxygen-glucose deprivation (OGD) injury and lipopolysaccharide (LPS) stimulation. For analyzing the role of TGF-β1 patterns under such conditions, a TGF-β1 siRNA and an exogenous recombinant TGF-β1 protein were employed. Further studies applied Triacsin C, an inhibitor of LD formation, in order to directly assess the impact of LD formation on the modulation of inflammation. To assess mutual microglia-to-neuron interactions, a co-culture model of these cells was established. Upon OGD exposure, microglial TGF-β1 levels were significantly increased, whereas LPS stimulation yielded decreased levels. Elevating TGF-β1 expression proved highly effective in suppressing inflammation and reducing LD accumulation in microglia exposed to LPS. Conversely, inhibition of TGF-β1 led to the promotion of microglial cell inflammation and an increase in LD accumulation in microglia exposed to OGD. Employing the LD formation inhibitor Triacsin C, in turn, polarized microglia towards an anti-inflammatory phenotype. Such modulation of both microglial TGF-β1 and LD levels significantly affected the resistance of co-cultured neurons. This study provides novel insights by demonstrating that TGF-β1 plays a protective role against microglia-mediated neuroinflammation through the suppression of LD accumulation. These findings offer a fresh perspective on stroke treatment, suggesting the potential of targeting this pathway for therapeutic interventions. [ABSTRACT FROM AUTHOR]

This review summarizes the implications of the primary tumor suppressor protein phosphatase and tensin homolog (PTEN) in aggressive cancer development. PTEN interacts with other cellular proteins or factors suggesting the existence of an intricate molecular network that regulates their oncogenic function. Accumulating evidence has shown that PTEN exists and plays a role in the cytoplasmic organelles and in the nucleus. PTEN blocks phosphoinositide 3‐kinases (PI3K)–protein kinase B–mammalian target of rapamycin signaling pathway by dephosphorylating phosphatidylinositol (PI)‐3,4,5‐triphosphate to PI‐4,5‐bisphosphate thus counteracting PI3K function. Studies have shown that PTEN expression is tightly regulated at transcriptional, posttranscriptional, and posttranslational levels (including protein–protein interactions and posttranslational modifications). Despite recent advances in PTEN research, the regulation and function of the PTEN gene remain largely unknown. How mutation or loss of specific exons in the PTEN gene occurs and involves in cancer development is not clear. This review illustrates the regulatory mechanisms of PTEN expression and discusses how PTEN participates in tumor development and/or suppression. Future prospects for the clinical applications are also highlighted. [ABSTRACT FROM AUTHOR]

Background: The safety and the benefits of reducing the risk of bleeding complications via protamine administration during the percutaneous coronary intervention (PCI) remains unclear. This study aimed to systematically assessed the efficacy and safety of using protamine in PCI. Method: Potential academic studies were identified from PubMed, Cochrane Library, EMBASE, and Web of Science. The time range we retrieved from was that from the inception of electronic databases to March 31, 2022. Gray studies were identified from the references of included literature reports. Stata version 12.0 statistical software (StataCorp LP) was used to analyze the pooled data. Results: A total of seven studies were involved in our study. The overall participants of the protamine group were 4983, whereas it was 1953 in the nonprotamine group. This meta‐analysis indicated that protamine was preferable for PCI as its lower value of major bleeding (odds ratio [OR] = 0.489, 95% confidence interval [CI]: 0.362–0.661, p <.001) and minor bleeding (OR = 0.281, 95% CI: 0.123–0.643, p =.003). Additionally, the protamine did not tend to be related a higher incidence of mortality (p =.143), myocardial infarction (p =.990), and stent thrombosis (p =.698). Conclusions: Based on available evidence, use of protamine may reduce the risk of bleeding complications without increasing the risk of mortality, myocardial infarction, and stent thrombosis. Given the relevant possible biases in our study, adequately powered and better‐designed studies with long‐term follow‐up are required to reach a firmer conclusion. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis is a type of chronic, progressive, fibrotic lung disease of unclear cause with few treatment options. Cell therapy is emerging as a promising novel modality for facilitating lung repair. Mesenchymal stem cell (MSC)-based and macrophage-based cell therapies are regarded as promising strategies to promote lung repair, due to incredible regenerative potential and typical immunomodulatory function, respectively. Extracellular vesicles (EVs), including exosomes and microvesicles, are cell-derived lipid-bilayer membrane vesicles that are secreted from virtually every cell and are involved in intercellular communication by delivering expansive biological cargos to recipients. This review provides a deep insight into the recent research progress concerning the effects of MSC and macrophage-associated EVs on the pathogenesis of pulmonary fibrosis. In addition to discussing their respective vital roles, we summarize the importance of cross-talk, as macrophages are vital for MSCs to exert their protective effects through two major patterns, including attenuating macrophage activation and M1 phenotype macrophage polarization. Moreover, miRNAs are selectively enriched into EVs as essential components, and consideration is given to the particular effects of EV-associated miRNAs. [ABSTRACT FROM AUTHOR]

Objectives: Various stereotactic aspirations have been accepted; however, no standard stereotactic aspiration has been established for the treatment of spontaneous intracerebral hemorrhage (ICH). The authors explored an easy, fast, and effective procedure by using a new brain surgery head frame and location sticker for the removal of spontaneous hematoma. Patients and Methods: A retrospective database review was performed from January 2018 to March 2020 to identify patients with ICH who were treated with puncture and drainage for hematoma by using a new brain surgery head frame and location sticker for positioning and guidance. Results: A total of 45 patients with spontaneous ICH were enrolled in our study. The mean (± SD) surgical time was 29.3 ± 4.1 min. The average hematoma evacuation rate was 72.2%. The mean (± SD) preoperative Glasgow Coma Scale (GCS) score was 9.58 ± 2.92; the mean GCS score increased to 11.55 ± 2.59 (p = 0.006) and 12.86 ± 2.04 (p < 0.001) at 1 week after surgery and at the time of discharge, respectively. The mean (± SD) preoperative muscle force score was 1.25 ± 1.51; the mean muscle force score had improved to 2.20 ± 1.64 (p = 0.009) and 2.88 ± 1.64 (p < 0.001) at 1 week after the operation and the time of discharge, respectively. Out of these, one patient experienced postoperative rebleeding, however, no further hematoma expansion was found after the second aspiration and thrombolysis. Conclusion: Using this brain surgery, head frame and location sticker combined with urokinase infusion appears simple, safe, and effective for the removal of hematoma for patients with spontaneous ICH. However, randomized controlled trials are necessary to provide more concrete evidence-based results. [ABSTRACT FROM AUTHOR]

Neurons and neurogliocytes (oligodendrocytes, astrocytes, and microglia) are essential for maintaining homeostasis of the microenvironment in the central nervous system (CNS). These cells have been shown to support cell-cell communication via multiple mechanisms, most recently by the release of extracellular vesicles (EVs). Since EVs carry a variety of cargoes of nucleic acids, lipids, and proteins and mediate intercellular communication, they have been the hotspot of diagnosis and treatment. The mechanisms underlying CNS disorders include angiogenesis, autophagy, apoptosis, cell death, and inflammation, and cell-EVs have been revealed to be involved in these pathological processes. Ischemic stroke is one of the most common causes of death and disability worldwide. It results in serious neurological and physical dysfunction and even leads to heavy economic and social burdens. Although a large number of researchers have reported that EVs derived from these cells play a vital role in regulating multiple pathological mechanisms in ischemic stroke, the specific interactional relationships and mechanisms between specific cell-EVs and stroke treatment have not been clearly described. This review aims to summarize the therapeutic effects and mechanisms of action of specific cell-EVs on ischemia. Additionally, this study emphasizes that these EVs are involved in stroke treatment by inhibiting and activating various signaling pathways such as ncRNAs, TGF-β1, and NF-κB. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a whole joint disease characterized by synovitis, cartilage destruction, and subchondral bone sclerosis and cyst. Despite decades' study, effective treatment is rare for this chronic disease. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptosis bodies, are nano-sized vesicles with a cargo containing biologically active agents, such as nucleic acids, lipids, and proteins. As a group of short non-coding RNAs, microRNAs (miRNAs) can be delivered by parental cells secreted EVs. Negatively regulate the target mRNAs at the posttranscriptional level and regulate gene expression in recipient cells without modifying gene sequence. Recently, most studies focused on the function of EVs mediated miRNAs in the pathophysiological process of OA. However, all kinds of EVs specific and OA specific factors might influence the administration of EVs-miRNAs, especially the precise quantitative management. As a result, the flourishing of current research about EVs in the laboratory might not promote the relevant clinical transformation in OA treatment. In this review, we reviewed the present application of EVs-miRNAs in the therapeutic of OA and further analyzed the potential factors that might influence its application. Further progress in the quantitative management of EVs-miRNAs would accelerate the clinical transformation of miRNAs enriched EVs in the OA field. [ABSTRACT FROM AUTHOR]

Background: Protamine can decrease the risk of hemorrhage during carotid recanalization. However, it may cause severe side effects. There is no consensus on the safety and efficacy of protamine during surgery. Thus, we conduct a comprehensive review and meta-analysis to compare the differences between the protamine and the no-protamine group. Method: We systematically obtained literature from Medline, Google Scholar, Cochrane Library, and PubMed electronic databases. All four databases were scanned from 1937 when protamine was first adopted as a heparin antagonist until February 2021. The reference lists of identified studies were manually checked to determine other eligible studies that qualify. The articles were included in this meta-analysis as long as they met the criteria of PICOS; conference or commentary articles, letters, case report or series, and animal observation were excluded from this study. The Newcastle-Ottawa Quality Assessment Scale and Cochrane Collaboration's tool are used to assess the risk of bias of each included observational study and RCT, respectively. Stata version 12.0 statistical software (StataCorp LP, College Station, Texas) was adopted as statistical software. When I 2 < 50%, we consider that the data have no obvious heterogeneity, and we conduct a meta-analysis using the fixed-effect model. Otherwise, the random-effect model was performed. Result: A total of 11 studies, consisting of 94,618 participants, are included in this study. Our analysis found that the rate of wound hematoma had a significant difference among protamine and no-protamine patients (OR = 0.268, 95% CI = 0.093 to 0.774, p = 0.015). Furthermore, the incidence of hematoma requiring re-operation (0.7%) was significantly lower than that of patients without protamine (1.8%). However, there was no significant difference in the incidence of stroke, wound hematoma with hypertension, transient ischemic attacks (TIA), myocardial infarction (MI), and death. Conclusion: Among included participants undergoing recanalization, the use of protamine is effective in reducing hematoma without increasing the risk of having other complications. Besides, more evidence-based performance is needed to supplement this opinion due to inherent limitations. [ABSTRACT FROM AUTHOR]

Stroke is an acute cerebrovascular disease, including ischemic and hemorrhagic stroke. Stroke is the second leading cause of death after ischemic heart disease, which accounts for 9% of the global death toll. To explore the molecular mechanisms of the effects of the dysregulated factors, in the GEO database, we obtained transcriptome data from 24 h/72 h of mice with ischemic stroke and 24 h/72 h of normal mice. We then performed differential gene analysis, coexpression analysis, enrichment analysis, and regulator prediction bioinformatics analysis to identify the potential genes. We made a comparison between the ischemic stroke 72 h and the ischemic stroke for 24 h, and 5103 differential genes were obtained (p < 0.05). Four functional barrier modules were obtained by weighted gene coexpression network analysis. The critical genes of each module were ASTL, Zfp472, Fmr1 gene, and Nap1l1. The results of the enrichment analysis showed ncRNA metabolism, microRNAs in cancer, and biosynthesis of amino acids. These three functions and pathways have the most considerable count value. The regulators of the regulatory dysfunction module were predicted by pivotal analysis of TF and noncoding RNA, and critical regulators including NFKB1 (NF-κB1), NFKBIA, CTNNB1, and SP1 were obtained. Finally, the pivotal target gene found that CTNNB1, NFKB1, NFKBia, and Sp1 are involved in 18, 32, 2, and 60 target genes, respectively. Therefore, we believe that NFKB1 and Sp1 have a potential role in the progression of ischemic stroke. The NFKB signaling pathway promotes inflammatory cytokines and regulates the progression of ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Although microscopic (MTSS) and endoscopic transsphenoidal surgery (ETSS) are both effective approaches for treating non-functioning pituitary adenomas (NFPA) and functioning pituitary adenomas (FPA), the consensus remains unidentified on whether there are differences in the risk of postoperative complications between the two surgical approaches. Method: A meta-analysis of the study of MTSS vs. ETSS for NFPA and FPA was conducted by searching the electronic databases of PubMed, Cochrane Library, and EMBASE, from the date of establishment of electronic databases to September 2020 based on the PRISMA guidelines. Results: In this study, a total of 16 studies were selected, hailing from Belgium, the USA, India, Finland, France, Korea, Spain, China, and Canada. We enrolled 1003 patients in the ETSS and 992 patients in the MTSS group. In patients with NFPA, the ETSS group was related to a higher incidence of post-operative gross-total resection (GTR). (OR = 1.655, 95% CI 1.131–2.421, P = 0.010). In participants with FPA, the results illustrated that the ETSS group had higher rates of visual improvement (OR = 2.461, 95% CI 1.109–5.459) and gross-total resection (OR = 2.033, 95% CI 1.335–3.096), as well as lower meningitis rates (OR = 0.195, 95% CI 0.041–1.923). In participants with acromegaly, no significant difference was shown in the postoperative complications. Conclusion: Based on current evidence, participants with NFPA treated by endoscopy were related to higher rates of GTR; patients with FPA treated by ETSS were related to higher rates of visual improvement and GTR, as well as a lower rates of meningitis. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether methylene blue (MB) treatment can reverse neuronal mitochondrial dysfunction caused by oxygen glucose deprivation/reoxygenation (OGD) injury and then investigate whether MB treatment can reduce neuronal apoptosis and improve blood-brain barrier (BBB) integrity in traumatic brain injury (TBI) animals. Methods: Reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and adenosine triphosphate (ATP) were used to evaluate mitochondrial function. The terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) assay was used to assess neuronal apoptosis in vitro. TUNEL and immunofluorescence staining for neuronal nuclei (NeuN) were combined to assess neuronal apoptosis in vivo. An Evans blue (EB) permeability assay and brain water content (BWC) were used to measure BBB permeability in vivo. The Morris water maze (MWM), rotarod test, and modified Neurological Severity Score (mNSS) test were employed to assess the prognosis of TBI mice. Results: MB treatment significantly reversed neuronal mitochondrial dysfunction caused by OGD injury. Both in vitro and in vivo , MB treatment reduced neuronal apoptosis and improved BBB integrity. In TBI animals, treatment with MB not only improved cognitive and motor function caused by TBI but also significantly improved overall neurological function. Conclusions: Our findings suggest that MB is a potential candidate for the treatment of TBI. Future research should focus on other therapeutic effects and mechanisms of MB in secondary brain injury. [ABSTRACT FROM AUTHOR]

Malignant melanoma (MM) is a highly aggressive cancer with a poor prognosis. Currently, although a variety of therapies are available for treating melanoma, MM is still a serious threat to the patient's life due to numerous factors, such as the recurrence of tumors, the emergence of drug resistance, and the lack of effective therapeutic agents. Exosomes are biologically active lipid-bilayer extracellular vesicles secreted by diverse cell types that mediate intercellular signal communication. Studies found that exosomes are involved in cancer by carrying multiple bioactive molecules, including non-- coding RNAs (ncRNAs). The ncRNAs have been reported to play an important role in regulating proliferation, angiogenesis, immune regulation, invasion, metastasis, and treatment resistance of tumors. However, the functional role of exosomal ncRNAs in MM remains unknown. Therefore, this review summarizes the current state of melanoma diagnosis, treatment, and the application of exosomal ncRNAs in MM patients, which may provide new insights into the mechanisms involved in melanoma progression and serve as biomarkers for diagnosis and therapeutic targets., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Stroke stimulates reactive astrogliosis, aquaporin 4 (AQP4) depolarization and neuroinflammation. Preconditioned extracellular vesicles (EVs) from microglia exposed to hypoxia, in turn, reduce poststroke brain injury. Nevertheless, the underlying mechanisms of such effects are elusive, especially with regards to inflammation, AQP4 polarization, and cerebrospinal fluid (CSF) flow. Methods: Primary microglia and astrocytes were exposed to oxygen-glucose deprivation (OGD) injury. For analyzing the role of AQP4 expression patterns under hypoxic conditions, a co-culture model of astrocytes and microglia was established. Further studies applied a stroke model, where some mice also received an intracisternal tracer infusion of rhodamine B. As such, these in vivo studies involved the analysis of AQP4 polarization, CSF flow, astrogliosis, and neuroinflammation as well as ischemia-induced brain injury. Results: Preconditioned EVs decreased periinfarct AQP4 depolarization, brain edema, astrogliosis, and inflammation in stroke mice. Likewise, EVs promoted postischemic CSF flow and cerebral blood perfusion, and neurological recovery. Under in vitro conditions, hypoxia stimulated M2 microglia polarization, whereas EVs augmented M2 microglia polarization and repressed M1 microglia polarization even further. In line with this, astrocytes displayed upregulated AQP4 clustering and proinflammatory cytokine levels when exposed to OGD, which was reversed by preconditioned EVs. Reduced AQP4 depolarization due to EVs, however, was not a consequence of unspecific inflammatory regulation, since LPS-induced inflammation in co-culture models of astrocytes and microglia did not result in altered AQP4 expression patterns in astrocytes. Conclusions: These findings show that hypoxic microglia may participate in protecting against stroke-induced brain damage by regulating poststroke inflammation, astrogliosis, AQP4 depolarization, and CSF flow due to EV release., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Stroke, a cerebrovascular accident, is prevalent and the second highest cause of death globally across patient populations; it is as a significant cause of morbidity and mortality. Mesenchymal stem cell (MSC) transplantation is emerging as a promising treatment for alleviating neurological deficits, as indicated by a great number of animal and clinical studies. The potential of regulating the immune system is currently being explored as a therapeutic target after ischemic stroke. This study will discuss recent evidence that MSCs can harness the immune system by interacting with immune cells to boost neurologic recovery effectively. Moreover, a notion will be given to MSCs participating in multiple pathological processes, such as increasing cell survival angiogenesis and suppressing cell apoptosis and autophagy in several phases of ischemic stroke, consequently promoting neurological function recovery. We will conclude the review by highlighting the clinical opportunities for MSCs by reviewing the safety, feasibility, and efficacy of MSCs therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tan, Xin, Huang and Mao.)

Ischemia-reperfusion injury occurs when blood supply to an organ is disrupted-ischemia-and then restored-reperfusion-and is commonly found under different pathological settings such as cerebral, myocardial, renal, and hepatic ischemia-reperfusion injuries. Despite apparent differences as to the cause of these diseases, emerging evidence suggests that common signaling pathways, such as exosomes and microRNAs (miRNAs), are involved in this context. Although miRNAs are also found in the extracellular milieu, plenty of miRNAs are found in exosomes and are thus protected from degradation. miRNAs selectively sorted into exosomes potentially regulate specific aspects of the onset and progression of ischemic stroke. Such mechanisms involve the regulation of cell survival, inflammation, angiogenesis, and neurogenesis. Likewise, miRNAs shuttled into exosomes are involved in the pathogenesis of myocardial, renal, and hepatic ischemia-reperfusion injuries. This review will discuss recent evidence on the exosome-facilitated progression of four ischemia-reperfusion conditions, particularly concerning miRNAs within these vesicles. The notion is given to miRNAs participating in more than one of the four conditions, indicating a considerable degree of overlap across ischemia-reperfusion conditions. We will conclude the review by highlighting clinical opportunities of such exosome-derived miRNAs both as biomarkers and as therapeutic targets., Competing Interests: The authors have declared that no competing interests exist., (© 2022 The Author(s).)

Hypoxia is a central pathophysiological component in cancer, myocardial infarction and ischemic stroke, which represent the most common medical conditions resulting in long-term disability and death. Recent evidence suggests common signaling pathways in these diverse settings mediated by non-coding RNAs (ncRNAs), which are packaged in extracellular vesicles (EVs) protecting ncRNAs from degradation. EVs are a heterogeneous group of lipid bilayer-covered vesicles released from virtually all cells, which have important roles in intercellular communication. Recent studies pointed out that ncRNAs including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are selectively sorted into EVs, modulating specific aspects of cancer development, namely cell proliferation, migration, invasion, angiogenesis, immune tolerance or drug resistance, under conditions of hypoxia in recipient cells. In myocardial infarction and stroke, ncRNAs shuttled via EVs have been shown to control tissue survival and remodeling post-hypoxia by regulating cell injury, inflammatory responses, angiogenesis, neurogenesis or neuronal plasticity. This review discusses recent evidence on EV-associated ncRNAs in hypoxic cancer, myocardial infarction and stroke, discussing their cellular origin, biological function and disease significance. The emerging concept of lncRNA-circular RNA/ miRNA/ mRNA networks is outlined, upon which ncRNAs synergistically respond to hypoxia in order to modify disease responses. Particular notion is given to ncRNAs participating in at least two of the three conditions, which revealed a large degree of overlaps across pathophysiological conditions. Possible roles of EV-ncRNAs as therapeutic products or theranostic markers are defined., Competing Interests: Competing Interests: D.M.H., B.G. and T.R.D. hold a patent on extracellular vesicles for the treatment of inflammatory conditions (US9877989B2)., (© The author(s).)

Atherosclerosis is a leading cause of cardiovascular disease, and atherosclerotic cardiovascular disease accounts for one-third of global deaths. However, the mechanism of atherosclerosis is not fully understood. It is well-known that the Rho GTPase family, especially Rho A, plays a vital role in the development and progression of arteriosclerosis. Rho guanine nucleotide exchange factors (Rho GEFs), which act upstream of Rho GTPases, are also involved in the atheromatous pathological process. Despite some research on the role of Rho GEFS in the regulation of atherosclerosis, the number of studies is small relative to studies on the essential function of Rho GEFs. Some studies have preliminarily revealed Rho GEF regulation of atherosclerosis by experiments in vivo and in vitro . Herein, we review the advances in research on the relationship and interaction between Rho GEFs and atheroma to provide a potential reference for further study of atherosclerosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Jiao, Xin, Niu, Liu, Song, Wang, Yang and Liang.)

Background: The incidence of stroke or death in carotid endarterectomy (CEA) versus carotid artery stenting (CAS) cannot be estimated accurately. We aimed to compare periprocedural stroke or death in patients with symptomatic or asymptomatic carotid artery stenosis (CS) treated with CEA versus CAS., Methods: Ten randomized trials (with ≥100 randomized patients per trial) compared the relative effectiveness of CAS and CEA for the prevention of stroke or death., Results: In the symptomatic group during the periprocedural period, the results showed that the risk of death or any stroke [risk ratio (RR): 0.627; 95% CI: 0.497-0.792; P<0.001] and the risk of any stroke (RR: 0.654; 95% CI: 0.522-0.820; P<0.001) were significantly greater with CAS than with CEA. The difference in the risk of periprocedural stroke was mostly attributed to nondisabling stroke (RR: 0.407; 95% CI: 0.264-0.627; P<0.001), which was driven especially by ipsilateral ischemic stroke (RR: 0.649; 95% CI: 0.494-0.851; P=0.002) and bradycardia or hypotension (RR: 0.105; 95% CI: 0.051-0.217; P<0.001). However, we found that the CEA group had a higher rate of myocardial infarction than the CAS group (RR: 2.496; P=0.025). Meanwhile, ipsilateral stenosis >70% increased the incidence of periprocedural death or stroke for post-CEA patients (RR: 2.166, 95% CI: 1.112 to 4.220, P=0.023), but no risk factors were identified for post-CAS. Regarding the asymptomatic group, the results demonstrated that patients randomized to CEA had a significantly reduced risk of periprocedural stroke (RR: 0.518; 95% CI: 0.281-0.954; P=0.035), which seems to be driven by periprocedural minor stroke (RR: 0.482; 95% CI: 0.231-0.982; P=0.046)., Conclusions: Among patients with symptomatic CS, CEA was associated with reduced rates of periprocedural stroke and periprocedural nondisabling stroke. Among patients with asymptomatic CS, the rates of minor stroke and stroke in general were higher with stenting than with CEA. Based on the current data, CEA is more beneficial than CAS for 30-day stroke prevention., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-4620). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Purpose: The development of intracranial aneurysm (IA) has been linked to genetic factors. The current study examines the potential role of genes encoding disintegrin and metalloproteinase using thrombospondin motifs (ADAMTS) in IA development., Material and Methods: High-throughput whole-genome and whole-exome sequencing were used when screening for deleterious single-nucleotide variants (SNVs) in ADAMTS genes using samples from 20 Han Chinese patients: 19 with familial IA and one patient with sporadic IA. The variant frequencies in these subjects were compared to those in control individuals found in the Genome Aggregation Database. Transcriptome sequencing and methylation sequencing data were retrieved from the Gene Expression Omnibus (GEO) database to identify differentially expressed ADAMTS genes and their methylation sites. We predicted the network of interactions among proteins encoded by the overlapping set of ADAMTS genes showing deleterious variants and both differential expression and abnormal methylation in IA. Possible candidate proteins linked to IA were validated using Western blot analysis. The associations between IA and SNVs rs11750568 in ADAMTS2 , as well as rs2301612 and rs2285489 in ADAMTS13 , were verified using the Sequenom MassArray system on a separate sample set of 595 Han Chinese patients with sporadic IA and 600 control individuals., Results: A total of 16 deleterious variants in 13 ADAMTS genes were identified in our patients, and seven of these genes overlapped with the genes found to be differentially expressed and differentially methylated in the GEO database. Protein-protein interaction analysis predicted that ADAMTSL1 was at the center of the seven genes. ADAMTSL1 protein was lower expressed in IA tissue than in the control cerebral artery. Frequencies of the IA-related SNVs rs11750568 in ADAMTS2 and rs2301612 and rs2285489 in ADAMTS13 were not significantly different between sporadic IA patients and controls., Conclusion: IA is associated with genetic variants, differential expression, and abnormal methylation in ADAMTS genes, ADAMTSL1 in particular., Competing Interests: The authors declare there are no competing interests., (©2020 Chen et al.)

BACKGROUND In an atherosclerotic artery wall, monocyte-derived macrophages are the principal mediators that respond to pathogens and inflammation. The present study aimed to investigate potential genetic changes in gene expression between normal tissue-resident macrophages and atherosclerotic macrophages in the human body. MATERIAL AND METHODS The expression profile data of GSE7074 acquired from the Gene Expression Omnibus (GEO) database, which includes the transcriptome of 4 types of macrophages, was downloaded. Differentially expressed genes (DEGs) were identified using R software, then we performed functional enrichment, protein‑protein interaction (PPI) network construction, key node and module analysis, and prediction of microRNAs (miRNAs)/transcription factors (TFs) targeting genes. RESULTS After data processing, 236 DEGs were identified, including 21 upregulated genes and 215 downregulated genes. The DEG set was enriched in 22 significant Gene Ontology (GO) terms and 25 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the PPI network constructed with these DEGs comprised 6 key nodes with degrees ≥8. Key nodes in the PPI network and simultaneously involved in the prime modules, including rhodopsin (RHO), coagulation factor V (F5), and  bestrophin-1 (BEST1), are promising for the prediction of atherosclerotic plaque formation. Furthermore, in the miRNA/TF-target network, hsa-miR-3177-5p might be involved in the pathogenesis of -atherosclerosis via regulating BEST1, and the transcription factor early growth response-1 (EGR1) was found to be a potential promoter in atherogenesis. CONCLUSIONS The identified key hub genes, predicted miRNAs/TFs, and underlying molecular mechanisms may be involved in atherogenesis, thus potentially contributing to the treatment and diagnosis of patients with atherosclerotic disease.