Paeoniflorin suppresses ferroptosis after traumatic brain injury by antagonizing P53 acetylation.

BACKGROUND: Traumatic brain injury (TBI) could induce multiple forms of cell death, ferroptosis, a novel form of cell death distinct from apoptosis and autophagy, plays an important role in disease progression in TBI. Therapies targeting ferroptosis are beneficial for recovery from TBI. Paeoniflorin (Pae) is a water-soluble monoterpene glycoside and the active ingredient of Paeonia lactiflora pall. It has been shown to exert anti-inflammatory and antioxidant effects. However The effects and mechanisms of paeoniflorin on secondary injury after TBI are unknown. PURPOSE: To investigate the mechanism by which Pae regulates ferroptosis after TBI. METHODS: The TBI mouse model and cortical primary neurons were utilized to study the protective effect of paeoniflorin on the brain tissue after TBI. The neuronal cell ferroptosis model was established by treating cortical primary neurons with erastin. Liproxstatin-1(Lip-1) was used as a positive control drug. Immunofluorescence staining, Nissl staining, biochemical analyses, pharmacological analyses, and western blot were used to evaluate the effects of paeoniflorin on TBI. RESULTS: Pae significantly ameliorated neuronal damage after TBI, inhibited mitochondrial damage, increased glutathione peroxidase 4 (GPX4) activity, decreased malondialdehyde (MDA) production, restored neurological function and inhibited cerebral edema. Pae promotes the degradation of P53 in the form of proteasome, promotes its ubiquitination, and reduces the stability of P53 by inhibiting its acetylation, thus alleviating the P53-mediated inhibition of cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) by P53. CONCLUSION: Pae inhibits ferroptosis by promoting P53 ubiquitination out of the nucleus, inhibiting P53 acetylation, and modulating the SLC7A11-GPX4 pathway.

Gender potentially affects early postoperative hyponatremia in pituitary adenoma: XGBoost-based predictive modeling.

Purpose: The occurrence of hyponatremia is a prevalent complication following transnasal transsphenoidal surgery for pituitary adenoma surgery, which adversely affects patient prognosis, hospitalization duration, and rehospitalization risk. The primary objective of this study is to strengthen the correlation between clinical factors associated with pituitary adenoma and postoperative hyponatremia. Additionally, the study aims to develop a predictive model for postoperative hyponatremia in patients with pituitary adenoma, with the ultimate goal of establishing a basis for reducing the occurrence of postoperative hyponatremia following surgical interventions. Methods: The chi-square test or Fisher test was employed for nominal data, while the t-test or Mann-Whitney test was utilized for continuous data analysis. In cases where the data exhibited statistical differences, binary logistic analysis was conducted to examine the risk and protective factors associated with postoperative hyponatremia. XGBoost was employed to construct predictive models for hyponatremia in this study. The patients were partitioned into training and test sets, and the most suitable parameters were determined through five-fold cross-validation and subsequently utilized for training on the training set. The discriminatory capability was assessed on the internal validation set. Results and conclusions: Out of the total 280 patients included in this investigation, 82 patients experienced early postoperative hyponatremia. Among these individuals, male gender (P = 0.02, odds ratio = 1.98) was identified as a risk factor for early postoperative hyponatremia, while preoperative chloride levels (P = 0.021, odds ratio = 0.866) and surgery time (P = 0.039, odds ratio = 0.990) were identified as protective factors against postoperative hyponatremia. The XGBoost model exhibited a sensitivity of 94.2%, a specificity of 61.5%, a positive predictive value of 51.6%, a negative predictive value of 96%, and identified male gender, preoperative sodium, and preoperative cortisol as the most significant predictors. Our findings indicate that gender may have influence in the development of early postoperative hyponatremia in patients with pituitary adenomas.

Comparison of the preoperative diagnostic accuracy of BIPSS versus MRI for Cushing disease: a single-centre experience.

BACKGROUND: Cushing disease (CD) arises due to a pituitary corticotroph adenoma, which is the most common cause of Cushing syndrome (CS). Bilateral inferior petrosal sinus sampling (BIPSS) is a safe method for differentiating CD from ectopic adrenocorticotropic hormone (ACTH)-dependent CS. Enhanced high-resolution magnetic resonance imaging (MRI) can localize tiny pituitary lesions. The aim of this study was to compare the preoperative diagnostic accuracy of BIPSS versus MRI for CD in CS patients. We performed a retrospective study of patients who underwent BIPSS and MRI between 2017 and 2021. Low- and high-dose dexamethasone suppression tests were performed. Blood samples were collected simultaneously from the right and left catheter and femoral vein before and after desmopressin stimulation. MRI images were obtained, and endoscopic endonasal transsphenoidal surgery (EETS) was performed in confirmed CD patients. Dominant sides of ACTH secretion during BIPSS and MRI were compared with surgical findings. RESULTS: Twenty-nine patients underwent BIPSS and MRI. CD was diagnosed in 28 patients, 27 of whom received EETS. Localizations of microadenomas by MRI and BIPSS agreed with the EETS findings in 96% and 93% of the cases, respectively. BIPSS and EETS were successfully performed on all patients. CONCLUSION: BIPSS was the most accurate method (gold standard) for establishing a preoperative diagnosis of pituitary-dependent CD and was more sensitive than MRI in diagnosing microadenoma. High-resolution MRI with enhancement had an advantage over BIPSS in microadenoma lateralization diagnostics. The combined use of MRI and BIPSS could improve the preoperative diagnosis accuracy in ACTH-dependent CS patients.

PDK4 Decrease Neuronal Apoptosis via Inhibiting ROS-ASK1/P38 Pathway in Early Brain Injury After Subarachnoid Hemorrhage.

Aims: Metabolic disorders may play key roles in oxidative stress and neuronal apoptosis in response to early brain injury (EBI) after subarachnoid hemorrhage (SAH). Pyruvate dehydrogenase (PDH) is related to oxidative stress in EBI, and its activity obviously decreases after SAH. We discovered that only pyruvate dehydrogenase kinase 4 (PDK4) expression was obviously increased among the four PDK isozymes after SAH in preliminary experiments. Therefore, we attempted to investigate the effects and corresponding mechanisms of PDK4 on oxidative stress after SAH. Results: First, we confirmed that PDK4 overexpression promoted PDH phosphorylation, inhibited PDH activity, and changed cell metabolism after SAH. A small interfering RNA (siRNA) targeting PDK4, a lentiviral PDK4 overexpression vector, and dichloroacetic acid (DCA) were used to regulate the expression and activity of PDK4. The siRNA decreased PDH phosphorylation, promoted reactive oxygen species (ROS) production, activated the apoptosis signal-regulating kinase 1 (ASK1)/P38 pathway, and induced neuronal apoptosis. The lentivirus further attenuated PDH activity, oxidative stress, and neuronal apoptosis. DCA inhibited the activity of PDK4, but increased the expression of PDK4 due to a feedback mechanism. Inactivated PDK4 did not effectively suppress PDH activity, which increased ROS production, activated the ASK1/P38 pathway, and led to neuronal apoptosis. Innovation: This study provides new insights into the potential antioxidant and antiapoptotic effects of the PDK4-PDH axis on EBI after SAH. Conclusions: The early overexpression of PDK4 after SAH may attenuate neuronal apoptosis by reducing oxidative stress via the ROS/ASK1/P38 pathway. PDK4 may be a new potential therapeutic target to ameliorate EBI after SAH. Antioxid. Redox Signal. 36, 505-524.

Microbial communities inhabiting the fairy ring of Floccularia luteovirens and isolation of potential mycorrhiza helper bacteria.

Floccularia luteovirens, an important edible mushroom widely distributed in the Qinghai-Tibet plateau, is ecologically important as an ectomycorrhizal fungus and can form the fairy ring. To explore the influence of F. luteovirens fairy ring on soil microbial communities, we compared the soil microbial communities in three different fairy ring zones (inside the fairy ring (IN); beneath the fairy ring (ON); and outside the fairy ring (OUT)). A total of 1.77 million bacterial reads and 1.59 million fungal reads were obtained. Moreover, sequence clustering yielded 519,613 (57,735 per sample) bacterial OTUs, and 513,204 (57,023 per sample) fungal OTUs representing. Microbial diversity was lower in samples from the ON zone compared with the other two zones. Mycorrhiza helper bacteria (MHB) such as Bradyrhizobium and Paenibacillus were more common in the ON zone, and we isolated four potential MHB from rhizosphere soil. Canonical correspondence analysis showed that the soil nutritional condition and physical changes caused by F. luteovirens shaped the microbial communities in the ON zone. This is the first report on the study of soil microbial diversity influenced by fairy ring F. luteovirens, and further studies need to be conducted to study the ecological function influenced by this species.

Genetic variation and phylogenetic relationships of the ectomycorrhizal Floccularia luteovirens on the Qinghai-Tibet Plateau.

Floccularia luteovirens, as an ectomycorrhizal fungus, is widely distributed in the Qinghai-Tibet Plateau. As an edible fungus, it is famous for its unique flavor. Former studies mainly focus on the chemical composition and genetic structure of this species. However, the phylogenetic relationship between genotypes remains unknown. In this study, the genetic variation and phylogenetic relationship between the genotypes of F. luteovirens in Qinghai-Tibet Plateau was estimated through the analysis on two protein-coding genes (rpb1 and ef-1α) from 398 individuals collected from 24 wild populations. The sample covered the entire range of this species during all the growth seasons from 2011 to 2015. 13 genotypes were detected and moderate genetic diversity was revealed. Based on the results of network analysis, the maximum likelihood (ML), maximum parsimony (MP), and Bayesian inference (BI) analyses, the genotypes H-1, H-4, H-6, H-8, H-10, and H-11 were grouped into one clade. Additionally, a relatively higher genotype diversity (average h value is 0.722) and unique genotypes in the northeast edge of Qinghai- Tibet plateau have been found, combined with the results of mismatch analysis and neutrality tests indicated that Southeast Qinghai-Tibet plateau was a refuge for F. luteovirens during the historical geological or climatic events (uplifting of the Qinghai-Tibet Plateau or Last Glacial Maximum). Furthermore, the present distribution of the species on the Qinghai-Tibet plateau has resulted from the recent population expansion. Our findings provide a foundation for the future study of the evolutionary history and the speciation of this species.

Inhibition of myeloid differentiation factor 88(MyD88) by ST2825 provides neuroprotection after experimental traumatic brain injury in mice.

Myeloid differentiation factor 88(MyD88) is an endogenous adaptor protein that plays an important role in coordinating intracellular inflammatory responses induced by agonists of the Toll-like receptor and interleukin-1 receptor families. MyD88 has been reported to be essential for neuronal death in animal models and may represent a therapeutic target for pharmacologic inhibition following traumatic brain injury (TBI). The purpose of the current study was to investigate the neuroprotective effect of MyD88 specific inhibitor ST2825 in an experimental mouse model of TBI. Intracerebroventricular (ICV) injection of high concentration (20µg/µL) ST2825 (15min post TBI) attenuated the development of TBI in mice, markedly improved neurological function and reduced brain edema. Decreased neural apoptosis and increased neuronal survival were also observed. Biochemically, the high concentration of ST2825 significantly reduced the levels of MyD88, further decreased TAK1, p-TAK1, nuclear p65 and increased IκB-α. Additionally, ST2825 significantly reduced the levels of Iba-1 and inflammatory factors TNF-α and IL-1ß. These data provide an experimental rationale for evaluation of MyD88 as a drug target and highlight the potential therapeutic implications of ST2825 in TBI.

Expression and Cell Distribution of SENP3 in Brain Tissue After Traumatic Brain Injury in Mice: A Pilot Study.

SUMO-specific proteases 3 (SENP3) is a member of the small ubiquitin-like modifier-specific protease family and deconjugates SUMO2/3 from protein substrates. To date, the expression and function of SENP3 in traumatic brain injury (TBI) are unclear. The present study examined dynamic changes in SENP3 expression in the cerebral cortex and in its cellular localization, using an acute TBI model in adult mice. SENP3 expression was examined at 3, 6, 12, 24 h, 3, and 5 days after TBI using Western Blot analysis and quantitative real-time PCR. Immunohistochemistry and immunofluorescence were examined to detect SENP3 localization. Western Blot indicated that SENP3 protein levels gradually increased from 3 h after TBI and peaked at 24 h. Quantitative real-time PCR demonstrated a gradual increase in SENP3 expression, which peaked 12 h after TBI and declined subsequently. Immunohistochemical staining demonstrated that SENP3-positive cells were observed in both the sham and 24 h post-TBI groups. However, robust expression of SENP3 was seldom observed in the sham group, while it was notably enhanced after TBI. Furthermore, immunofluorescence results revealed that the expression of SENP3 increased more significantly in neurons at day 1 after TBI compared with sham group and less significantly in astrocytes and microglia. Moreover, the SENP3-positive cells that were co-expressed with NeuN also expressed caspase-3, indicating a potential correlation between SENP3 and apoptosis after TBI. Collectively, our results showed obvious up-regulation of SENP3 expression in the brain after TBI, especially in the neurons. However, the full role of SENP3 and its therapeutic potential in TBI needs further investigation.

[Difference of immunological and inflammatory indices between mild type and severe type of adult pandemic (H1N1) patients].

OBJECTIVE: To study the difference of immunological and inflammatory indices between mild type and severe type of adult pandemic (H1N1) patients. METHODS: White blood cell, lymphocyte, monocyte, CD4(+) and CD8(+) T lymphocyte counts, level of C3 and C4, CH50, immunoglobulin A/G/M and CRP from 166 pandemic (H1N1) patients during acute and recovery phases were recorded and analyzed. RESULTS: A lowered lymphocyte count and an elevated monocyte count were observed in both groups during acute phase. And both were corrected during recovery phase. The absolute values of CD4(+) and CD8(+) T lymphocytes were much lower in severe group than those in mild group. During acute phase, the level of c-reactive protein (CRP) was elevated in both groups while it was higher in the severe group than that in the mild group. During recovery phase, the CRP level fell after a rise in both groups while it was quicker in the severe group than that in the mild group. During acute phase, the majority of CH50 became mildly elevated. And it was higher in severe patients than mild ones. CONCLUSION: Lymphocyte count, CD4(+) & CD8(+) T lymphocyte counts and CRP & CH50 values provide useful information for the diagnosis of pandemic (H1N1) and the evaluation of its severity.

[Research on infrared safety protection system for machine tool].

In order to ensure personal safety and prevent injury accident in machine tool operation, an infrared machine tool safety system was designed with infrared transmitting-receiving module, memory self-locked relay and voice recording-playing module. When the operator does not enter the danger area, the system has no response. Once the operator's whole or part of body enters the danger area and shades the infrared beam, the system will alarm and output an control signal to the machine tool executive element, and at the same time, the system makes the machine tool emergency stop to prevent equipment damaged and person injured. The system has a module framework, and has many advantages including safety, reliability, common use, circuit simplicity, maintenance convenience, low power consumption, low costs, working stability, easy debugging, vibration resistance and interference resistance. It is suitable for being installed and used in different machine tools such as punch machine, pour plastic machine, digital control machine, armor plate cutting machine, pipe bending machine, oil pressure machine etc.

[Analysis of severe acute respiratory syndrome in Beijing].

OBJECTIVE: To study the clinical, laboratory, and radiologic features of 34 cases of severe acute respiratory syndrome (SARS) in Beijing. METHODS: All patients were admitted to the isolation wards. Their demographic, clinical, laboratory, and radiologic characteristics were analyzed. Univariate and multivariate analyses were performed. RESULTS: Eight patients came from a family, and 15 patients were medical staff. The mean age of patients was (33.4 +/- 13.4) years. The latent period varied from 2 to 14 days (median 4 days). The most common symptoms were fever (100%), palpitation (91.7%), myalgia (79.2%), headache (70.8%), diarrhea (73.9%) and cough (58.3%). The mean leucocyte count was (4.6 +/- 1.4) x 10(9)/L, and the mean lymphocyte ratio was 0.27 +/- 0.11. 68.4% of the patients had lymphopenia (absolute lymphocyte count < 1.3 x 10(9)/L). Other common findings included elevated levels of serum alanine aminotransferase, lactate dehydrogenase and erythrocyte sedimentation (76.2%, 28.6% and 47.8%, respectively), and decreased levels of serum iron and albumin (63.2% and 47.8%, respectively). Thirty-two cases had abnormal chest radiographs. In 2 cases in whom typical lung opacities could not be found on the initial plain chest radiographs, thoracic CT proved to be useful. Postmortem examination of 1 patient revealed marked edema with foci of hemorrhage and hyaline membrane formation in the lungs, hemorrhage necrosis and a obvious decline of cells in lymph glands. In a multivariate analysis (Stata 7.0), the independent predictor of an adverse outcome was advanced age (odds ratio per decade of life, 1.6; 95% CI, 1.08 to 2.63; P = 0.007). CONCLUSIONS: Fever, lymphopenia, low serum iron and chest radiograph are helpful to diagnose SARS early; age is the independent predictor of an outcome.

[Changes of blood cells in patients with severe acute respiratory syndrome].

OBJECTIVE: To investigate the changes of blood corpuscles of patients with severe acute respiratory syndrome (SARS) in Beijing. METHODS: Totally 43 patients (21 male and 22 female, 19-74 years old age range) diagnosed as of probable SARS were included in this study. Their corpuscles in the peripheral blood were tested every two days, and the results were analyzed. RESULTS: Patients with SARS were more likely to develop leukocytopenia, lymphopenia and thrombocytopenia in the early period of disease than those in control group. The situation, especially lymphopenia and thrombocytopenia, could not be reversed in patients who died. Persistent low counts of lymphocytes and platelets at presentation might be associated with adverse outcomes. CONCLUSION: Low counts of leukocytes, lymphocytes and platelets were common among patients in the early stage of SARS. Persistent Lymphopenia and thrombocytopenia may be associated with the prognosis.