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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]

The efficacy and safety of traditional Chinese medicine (TCM) paired with western medicine in the treatment of patients with COVID-19 remains controversial. This meta-analysis was performed to identify the effects of TCM. Seven electronic databases were reviewed from the inception of these databases to 30 June 2022. A quality assessment of the included studies was performed with the Cochrane Collaboration's tool to provide a score of high, unclear, or low risk of bias. The standard software program (Stata, version 12.0, statistical software) was used for endpoint analyses. A total of 13 RCTs involving 1398 patients conducted in China were included. The cross-sectional data from various studies were plotted, and the results illustrated that the statistically higher rates of total effectiveness (RR, 1.357; 95% CI, 1.259 to 1.464; P < 0.001), improvement of chest CT (RR, 1.249; 95% CI, 1.143 to 1.356; P < 0.001), and cough improvement (RR, 1.228; 95% CI, 1.057 to 1.570; P = 0.012) and a lower incidence of conversion to severe cases (RR, 0.408; 95% CI, 0.275 to 0.605; P < 0.001) were demonstrated in the TCM group than that of the control group. Of note, the subgroup on specific TCM of Lianhua Qingwen (LQ) revealed that the experiment group was associated with a higher rate of total effectiveness (RR, 1.248; 95% CI, 1.136 to 1.371; P < 0.001) and improvement of chest CT (RR, 1.226; 95% CI, 1.110 to 1.356; P < 0.001) and a lower rate of conversion to severe cases (RR, 0.469; 95% CI, 0.311 to 0.707; P < 0.001). However, there was no significant difference in fever improvement (RD, 0.110; 95% CI, -0.063 to 0.283; P = 0.213). The findings of this meta-analysis suggest that TCM combined with western medicine is more effective in treating COVID-19 via relieving symptoms, promoting patients' recovery, and cutting the rate of patients developing into severe conditions. However, 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]

Eukaryotic cells release different types of extracellular vesicles (EVs), including exosomes, apoptotic bodies and microvesicles. EVs carry proteins, lipids and nucleic acids specific to cells and cell states. Autophagy is an intracellular degradation process, which, along with EVs, can significantly affect the development and progression of neurological diseases and, therefore, has been the hotspot. Generally, EVs and autophagy are closely associated. EVs and autophagy can interact with each other. On the one hand, the level of autophagy in target cells is closely related to the secretion and transport of EVs. In another, the application of EVs provides a great opportunity for adjuvant treatment of neurological disorders, for which autophagy is an excellent target. EVs can release their cargos into target cells, which, in turn, regulate the autophagic level of target cells through autophagy-related proteins directly and the non-coding RNA, signal transducer and activator of transcription 3 (STAT3), phosphodiesterase enzyme (PDE) 1-B, etc. signaling pathways indirectly, thus regulating the development of related neurological disorders. [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]

Nuclear paraspeckle assembly transcript 1 (Neat1) located at chromosome 11 is a long non-coding RNA that is widely expressed in mammalian cell types, and which is overexpressed in several inflammation-related disorders. Inflammation implies a plethora of mutual interactions between both soluble factors and cells due to various stimuli including tissue injury. Although there is no doubt that inflammation is critically involved in multiple biological and pathological processes alike, the precise mechanisms being involved are still open for debate. In this context, the role of Neat1 as a regulator of inflammation, microglial activation, and lipid accumulation under various inflammatory conditions remains elusive. Herein, we review the regulation of Neat1 and how it modulates the expression of its target genes. Thereafter, we will review the impact of Neat1 on inflammation by activating or inhibiting various signaling pathways, such as microRNAs, AKT, TLR4, TRAF6, and NF-κB. [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]

As a crucial kind of pervasive gene, long noncoding RNAs (lncRNAs) are abundant and key players in brain function as well as numerous neurological disorders, especially ischemic stroke. The mechanisms underlying ischemic stroke include angiogenesis, autophagy, apoptosis, cell death, and neuroinflammation. Inflammation plays a vital role in the pathological process of ischemic stroke, and systemic inflammation affects the patient's prognosis. Although a great deal of research has illustrated that various lncRNAs are closely relevant to regulate neuroinflammation and microglial activation in ischemic stroke, the specific interactional relationships and mechanisms between lncRNAs and neuroinflammation have not been described clearly. This review aimed to summarize the therapeutic effects and action mechanisms of lncRNAs on ischemia by regulating inflammation and microglial activation. In addition, we emphasize that lncRNAs have the potential to modulate inflammation by inhibiting and activating various signaling pathways, such as microRNAs, NF‐κB and ERK. [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]

Background and purpose: Previous studies have identified many risk factors related to the recurrence of chronic subdural hematomas (CSDHs). Among these factors, there may be deviations in measuring the midline shift, preoperative hematoma volume (PreHV), postoperative hematoma residual volume, and postoperative pneumocephalus in bilateral CSDHs. The aims of this study were to eliminate the impact of complicated situations on parameter measurement and to identify actual predictors for CSDH recurrence, and finally, to develop a grading system to predict unilateral CSDH (uCSDH) recurrence. Patients and methods: A total of 342 patients with uCSDH were identified. Predictors of uCSDH recurrence were obtained from univariable and multivariable logistic regression models. A prognostic grading system was developed based on the results of multivariable logistic regression and receiver operating characteristic (ROC) analyses. All patients were scored according to the grading system, and differences in the recurrence rate were reanalyzed according to the scores. Results: Age, antiplatelet or anticoagulant use, midline shift, severe brain atrophy, drainage volume, and the ratio of the postoperative pneumocephalus volume (PostPV) to the postoperative hematoma cavity volume (PostHCV) were identified as independent risk factors for predicting the recurrence of uCSDH. The cut-off values of age, drainage volume, midline shift, and the ratio of the PostPV to the PostHCV were 67 years, 101 mL, 11.2 mm, and 31.61%, respectively. The recurrence rates were 1.7%, 12.4%, 19.4%, 53.3%, and 58.3% for scores of 0–1, 2, 3, 4, and 5–6, respectively, which significantly increased as the score increased (P<0. 001). Conclusion: The prognostic grading system for uCSDH on the basis of multivariable logistic regression and ROC analyses is applicable and reliable. [ABSTRACT FROM AUTHOR]

Purpose: Genetic factors play a vital role in intracranial aneurysm (IA) onset and development. Studying the relationship between IA and the Sox17 polymorphisms in diverse populations is essential for establishing credibility. Patients and methods: We collected blood samples derived from a total of 596 sporadic IA patients and 600 individual controls in several medical institutes in China. We used the Sequenom MassArray system for single nucleotide polymorphisms (SNPs) genotyping after DNA extraction. The SNPs data was tested and analyzed in PLINK (version 1.9). Multiple-testing was performed in PLINK to make the statistics more rigorous and accurate. Results: We found that the allelic G of rs1072737 (OR=1.303, genomic-control corrected P-value =0.001032) is a risk allele, while the allelic G of rs9298506 (OR=0.7253, genomic-control corrected P-value =0.01559) is a protective allele in Chinese Han people. Conclusion: The allelic G of rs1072737 is a risk factor for IA, while the allelic G of rs9298506 serves as a protective factor for IA in Chinese Han people. [ABSTRACT FROM AUTHOR]