Silent information regulator 1 (SIRT1), a type of histone deacetylase, is a highly effective therapeutic target for protection against ischemia reperfusion (IR) injury (IRI). Previous studies showed ...that melatonin preserves SIRT1 expression in neuronal cells of newborn rats after hypoxia–ischemia. However, the definite role of SIRT1 in the protective effect of melatonin against cerebral IRI in adult has not been explored. In this study, the brain of adult mice was subjected to IRI. Prior to this procedure, the mice were given intraperitoneal with or without the SIRT1 inhibitor, EX527. Melatonin conferred a cerebral‐protective effect, as shown by reduced infarct volume, lowered brain edema, and increased neurological scores. The melatonin‐induced upregulation of SIRT1 was also associated with an increase in the anti‐apoptotic factor, Bcl2, and a reduction in the pro‐apoptotic factor Bax. Moreover, melatonin resulted in a well‐preserved mitochondrial membrane potential, mitochondrial Complex I activity, and mitochondrial cytochrome c level while it reduced cytosolic cytochrome c level. However, the melatonin‐elevated mitochondrial function was reversed by EX527 treatment. In summary, our results demonstrate that melatonin treatment attenuates cerebral IRI by reducing IR‐induced mitochondrial dysfunction through the activation of SIRT1 signaling.
Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Nucleotide‐binding oligomerization domain‐like receptor family ...pyrin domain‐containing 3 (NLRP3) inflammasome activation associated with the upregulation of apoptotic signaling pathway has been implicated in various inflammatory diseases including hemorrhagic insults. Melatonin is reported to possess substantial anti‐inflammatory properties, which is beneficial for early brain injury (EBI) after SAH. However, the molecular mechanisms have not been clearly identified. This study was designed to investigate the protective effects of melatonin against EBI induced by SAH and to elucidate the potential mechanisms. The adult mice were subjected to SAH. Melatonin or vehicle was injected intraperitoneally 2 hr after SAH. Melatonin was neuroprotective, as shown by increased survival rate, as well as elevated neurological score, greater survival of neurons, preserved brain glutathione levels, and reduced brain edema, malondialdehyde concentrations, apoptotic ratio, and blood–brain barrier (BBB) disruption. Melatonin also attenuated the expressions of NLRP3, apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC), cleaved caspase‐1, interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6); these changes were also associated with an increase in the anti‐apoptotic factor (Bcl2) and reduction in the pro‐apoptotic factor (Bim). In summary, our results demonstrate that melatonin treatment attenuates the EBI following SAH by inhibiting NLRP3 inflammasome‐associated apoptosis.
Background:
The mechanisms underlying the proliferation and apoptosis of glioma cells remain unelucidated. A recent study has revealed that microRNA-92b (miR-92b) inhibits apoptosis of glioma cells ...via downregulating DKK3. Notably, long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) is predicted to have a possible interaction with miR-92b.
Objective:
This study aimed to identify whether NEAT1 affects glioma cell proliferation and apoptosis via regulating miR-92b.
Methods:
The expression of NEAT1 was compared between glioma tissues and adjacent tissues as well as between glioma cells and normal astrocytes using quantitative real-time polymerase chain reaction. Glioma cell proliferation was determined by using the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and glioma cell apoptosis was determined by using the flow cytometry.
Results:
The expression of NEAT1 was low in glioma tissues and cells compared to the normal ones. Overexpression of NEAT1 inhibited proliferation and promoted apoptosis of glioma cell lines (U-87 MG and U251). The interaction between NEAT1 and miR-92b was confirmed using RNA immunoprecipitation, RNA pull-down assay, and luciferase reporter assay. Importantly, the tumor suppressor function of overexpressing NEAT1 was achieved by downregulating miR-92b and subsequently upregulating DKK3.
Conclusion:
Our findings indicated that NEAT1 acts as a tumor suppressor in glioma cells, which provides a novel target in overcoming glioma growth.
Sex differences in outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. Therefore, the aim of this study was to investigate the sex differences in the prognosis ...of patients with aSAH.
This study retrospectively analyzed the clinical data of aSAH patients admitted to the Department of Neurosurgery of General Hospital of Northern Theater Command, from April 2020 to January 2022. The modified Rankin Scale (mRS) was used to evaluate outcomes at 3-month post-discharge. Baseline characteristics, in-hospital complications and outcomes were compared after 1:1 propensity score matching (PSM).
A total of 665 patients were included and the majority (63.8%) were female. Female patients were significantly older than male patients (59.3 ± 10.9 years vs. 55.1 ± 10.9 years, P < 0.001). After PSM, 141 male and 141 female patients were compared. Comparing postoperative complications and mRS scores, the incidence of delayed cerebral ischemia (DCI) and hydrocephalus and mRS ≥ 2 at 3-month were significantly higher in female patients than in male patients. After adjustment, the analysis of risk factors for unfavorable prognosis at 3-month showed that age, sex, smoking, high Hunt Hess grade, high mFisher score, DCI, and hydrocephalus were independent risk factors.
Female patients with aSAH have a worse prognosis than male patients, and this difference may be because females are more vulnerable to DCI and hydrocephalus.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Prostate cancer (PCa) is a prevalent male malignancy that originates in the epithelial cells of the prostate. In terms of incidence and mortality of malignant tumors in men, PCa ranks second and ...fifth globally and first and third among men in Europe and the United States, respectively. These figures have gradually increased in recent years. The primary modalities used to diagnose PCa include prostate-specific antigen (PSA), multiparametric magnetic resonance imaging (mpMRI), and prostate puncture biopsy. Among these techniques, prostate puncture biopsy is considered the gold standard for the diagnosis of PCa; however, this method carries the potential for missed diagnoses. The preoperative evaluation of the patient in this study suggested advanced PCa. However, the initial prostate puncture biopsy was inconsistent with the preoperative diagnosis, and instead of waiting for a repeat puncture of the prostate primary, we performed a biopsy of the rib metastasis, which was later diagnosed as advanced PCa.
Introduction
As a rare type of cerebral venous thrombosis, isolated cortical vein thrombosis (ICVT) is easily misdiagnosed as brain tumor, especially in the cases with prominent signs of parenchymal ...brain lesions. Despite controversy concerning the efficacy and safety, anticoagulant treatment dominates in current therapeutic strategies for ICVT. As yet, surgical thrombectomy in the treatment of ICVT has not been reported. We present hereafter a female with ICVT previously misdiagnosed as brain tumor who had successful surgical thrombectomy.
Case description
A 54-year-old female with progressive left-sided limb weakness suddenly developed focal tonic-clonic epileptic seizure. Physical examination indicated strength of 0/5 in the left limbs. Magnetic resonance imaging (MRI) showed an irregular juxtacortical lesion surrounded with massive edema in the frontoparietal cortex, which was initially diagnosed as glioma. However, it turned out to be ICVT of the central sulcus vein during craniotomy. Then, venotomy and thrombectomy were performed, with instant recanalization of the vein noticed during surgery. In retrospect, we identified the suspected ICVT of the central sulcus vein in preoperative magnetic resonance venotography (MRV) and contrast MRI images. Laboratory tests also revealed homocysteinemia and hypercoagulable states in the patient. Follow-up MRV obtained 3 months after discharge showed cortical vein recanalization. At the one-year follow-up, she exhibited subtle sequelae of weakness in the left lower limb with a modified Rankin scale score of 1.
Discussion
Physicians should be aware of ICVT in the differential diagnoses in patients with risk factors, classical symptoms, and parenchymal brain lesions in or near cortex. Surgical thrombectomy excels at realizing definite recanalization and avoiding systematic complications of anticoagulation. It might be a therapeutic alternative for ICVT, especially when craniotomy is performed for treating intracranial hypertension or a definite diagnosis is made during craniotomy.
Adenosine A2A receptor antagonist istradefylline has been approved this year for manufacturing and marketing in Japan. We, therefore, did this meta-analysis to systematically assess the efficacy and ...safety of istradefylline as augmentation to levodopa in patients with Parkinson’s disease (PD). We systematically review the relative randomized controlled trials (RCTs) up to March 2014, which compared istradefylline to placebo for the short course of treatment for PD in adults. The primary outcome was daily OFF time and secondary outcome was UPDRS Part III score (on state). Data were obtained from seven RCTs, including 2205 patients. Compared to placebo on primary and secondary outcome, istradefylline group both showed significant reductions (WMD −0.60,
p
= 0.0001; WMD −1.07,
p
= 0.002). Subgroup analysis suggested that istradefylline 20, 40, and 60 mg/day in both group showed significant reductions on the two outcomes. Based on these results, Istradefylline could be an efficacy and safety augmentation drug added on to levodopa or other existing anti-Parkinsonian therapies. Limited by the number of studies, future large-scale studies are needed to verify these results, assess the long-term effect of istradefylline and the effect of istradefylline as monotherapy, and find the most effective dose of istradefylline.
Spontaneous renal rupture is a rare clinical condition characterized by spontaneous bleeding in the renal subcapsular and perinephric spaces in patients without a history of trauma. It occurs mainly ...in pathologic kidneys and after some renal surgeries. We report a 40-year-old male patient admitted with a diagnosis of gallstones with cholecystitis due to fever and abdominal pain after unilateral ureteral calculi. The patient developed delayed right renal rupture hemorrhage during treatment, controlled after selective arterial embolization (SAE). Still, the patient developed spontaneous left renal rupture due to a systemic inflammatory response. Finally, the patient’s life was saved after several selective embolizations of the renal artery. We retrospectively analyzed this case to improve our understanding of the disease.
Bladder cancer (BLCA) is a malignant urothelial carcinoma and has a high mortality rate. EPDR1 (ependymin related 1) is a type II transmembrane protein and related to calcium-dependent cell adhesion.
...We explored the potential oncogenic roles of EPDR1 in BLCA basing on the multiple public datasets.
We found that EPDR1 expression had a significant difference in BLCA and adjacent normal bladder tissues, and the level of EPDR1was up-regulated with advanced tumor stage and metastasis in BLCA. Meanwhile, the high expression group of EPDR1 had a shorter OS compared to the low or medium expression-group. Furthermore, EPDR1 expression was associated with tumor-infiltrating immune cells (TIICs), including NK cells, CD8 + T cells, CD4 + T cells, Macrophages cells, and so on. Moreover, EPDR1 also involved in several signaling pathways as well as PI3K/AKT pathway, Cytokine receptor interaction, and apoptosis.
EPDR1 can be used as a novel prognostic biomarker as well as an effective target for diagnosis and treatment in BLCA.
RNA methylation modifications, such as N1-methyladenosine/N6-methyladenosine /N5-methylcytosine (m
A/m
A/m
C), are the most common RNA modifications and are crucial for a number of biological ...processes. Nonetheless, the role of RNA methylation modifications of m
A/m
A/m
C in the pathogenesis of renal interstitial fibrosis (RIF) remains incompletely understood.
Firstly, we downloaded 2 expression datasets from the GEO database, namely GSE22459 and GSE76882. In a differential analysis of these datasets between patients with and without RIF, we selected 33 methylation-related genes (MRGs). We then applied a PPI network, LASSO analysis, SVM-RFE algorithm, and RF algorithm to identify key MRGs.
We eventually obtained five candidate MRGs (WTAP, ALKBH5, YTHDF2, RBMX, and ELAVL1) to forecast the risk of RIF. We created a nomogram model derived from five key MRGs, which revealed that the nomogram model may be advantageous to patients. Based on the selected five significant MRGs, patients with RIF were classified into two MRG patterns using consensus clustering, and the correlation between the five MRGs, the two MRG patterns, and the genetic pattern with immune cell infiltration was shown. Moreover, we conducted GO and KEGG analyses on 768 DEGs between MRG clusters A and B to look into their different involvement in RIF. To measure the MRG patterns, a PCA algorithm was developed to determine MRG scores for each sample. The MRG scores of the patients in cluster B were higher than those in cluster A.
Ultimately, we concluded that cluster A in the two MRG patterns identified on these five key m
A/m
A/m
C regulators may be associated with RIF.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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