Oligodendrocyte-derived exosomes-containing SIRT2 ameliorates depressive-like behaviors and restores hippocampal neurogenesis and synaptic plasticity via the AKT/GSK-3ß pathway in depressed mice.

AIMS: To investigate the antidepressant role of oligodendrocyte-derived exosomes (ODEXs)-containing sirtuin 2 (SIRT2) and the underlying mechanism both in vivo and in vitro. METHODS: Oligodendrocyte-derived exosomes isolated from mouse serum were administered to mice with chronic unpredictable mild stress (CUMS)-induced depression via the tail vein. The antidepressant effects of ODEXs were assessed through behavioral tests and quantification of alterations in hippocampal neuroplasticity. The role of SIRT2 was confirmed using the selective inhibitor AK-7. Neural stem/progenitor cells (NSPCs) were used to further validate the impact of overexpressed SIRT2 and ODEXs on neurogenesis and synapse formation in vitro. RESULTS: Oligodendrocyte-derived exosome treatment alleviated depressive-like behaviors and restored neurogenesis and synaptic plasticity in CUMS mice. SIRT2 was enriched in ODEXs, and blocking SIRT2 with AK-7 reversed the antidepressant effects of ODEXs. SIRT2 overexpression was sufficient to enhance neurogenesis and synaptic protein expression. Mechanistically, ODEXs mediated transcellular delivery of SIRT2, targeting AKT deacetylation and AKT/GSK-3ß signaling to regulate neuroplasticity. CONCLUSION: This study establishes how ODEXs improve depressive-like behaviors and hippocampal neuroplasticity and might provide a promising therapeutic approach for depression.

Melatonin suppresses tumor proliferation and metastasis by targeting GATA2 in endometrial cancer.

Endometrial cancer (EC) is a reproductive system disease that occurs in perimenopausal and postmenopausal women. However, its etiology is unclear. Melatonin (MT) has been identified as a therapeutic agent for EC; however, its exact mechanism remains unclear. In the present study, we determined that GATA-binding protein 2 (GATA2) is expressed at low levels in EC and regulated by MT. MT upregulates the expression of GATA2 through MT receptor 1A (MTNR1A), whereas GATA2 can promote the expression of MTNR1A by binding to its promoter region. In addition, in vivo and in vitro experiments showed that MT inhibited the proliferation and metastasis of EC cells by upregulating GATA2 expression. The protein kinase B (AKT) pathway was also affected. In conclusion, these findings suggest that MT and GATA2 play significant roles in EC development.

Dissection of action mechanisms of Zuogui Pill in the treatment of liver cancer based on machine learning and network pharmacology: A review.

This study aimed to investigate the underlying mechanism of Zuogui Pill in its efficacy against liver cancer, employing a combination of data mining approaches and network pharmacology methods. A novel clustering analysis algorithm was proposed to identify the core gene modules of Zuogui Pill. This algorithm successfully identified 5 core modules, with the first large module comprised of twelve proteins forming a 12-clique, representing the strongest connections among them. By utilizing GEO platform, ten key target proteins were detected, including FOS, PTGS2, and MYC. According to the GO annotation and KEGG analysis, desired target proteins were significantly enriched in various biological processes (BP). The analysis showed that ten key targets were strongly associated with signaling pathways mainly centered on MAPK and PI3K-Akt pathway. Additionally, molecular docking revealed strong binding affinities between core active ingredients of Zuogui Pill and these key targets, and the best affinity modes were observed for PTGS2-Sesamin, PRKCA-Sesamin, FOS-delta-Carotene. In order to establish the relationships between clinical symptoms and drug targets, a heterogeneous targets-related network was constructed. A total of 60 key target-symptom association pairs were detected, exemplified by the strongly association between fever and PTGS2 through the intermediary of Shu Di Huang. In summary, symptom-target associations are valuable in uncovering the underlying molecular mechanisms of Zuogui Pill. Our work reinforced the notion that Zuogui pill exhibits therapeutic potential on liver cancer through network targets, as well as synergistic effects of multi-component and multi-pathway. This study provided specific references for future experiments at the cost of less time.

The health-related quality of life for hemiarthroplasty and total hip arthroplasty in the elderly: A meta-analysis.

Purpose: What constitutes the optimal surgical plan for femoral neck fractures (FNFs) in elderly patients is controversial. The European quality of life 5-Dimension Questionnaire (EU-5Q) is an international scale used to measure the health-related quality of life (HRQoL) after surgery. We aim to verify the hip arthroplasty effect in elderly patients by analyzing HRQoL scores in the EU-5Q scale. Methods: We searched the EBSCO, Embase, PubMed, Ovid, Cochrane Library, and Web of Science databases using strict searching from established to 30 November 2022; used the Cochrane Library's Risk of Bias Assessment Tool and the Newcastle-Ottawa Scale to evaluate the literature; and used RevMan5.4.1 software to perform a meta-analysis. All the included studies used the EU-5Q scale to validate the overall outcomes for elderly hip arthroplasty. Results: The final included literature is composed of four RCTs, two cohort studies, three case-control trials, and three cross-sectional surveys. This study compared HRQoL scores measured by the EU-5Q scale, including 328 elderly patients with total hip arthroplasty (THA) and 323 elderly patients with hemiarthroplasty, which is statistically significant (OR = 0.05; 95% CI, 0.02~0.08; P = 0.002). The subgroups were as follows: unipolar vs. bipolar and cemented vs. uncemented hemiarthroplasty (OR = 0.06; 95% CI, 0.03~0.08; P < 0.001), follow-up time and age arthroplasty (OR = 0.16; 95% CI, 0.11~0.22; P < 0.001), molecular exercise and enhanced recovery after surgery (ERAS) (OR = 0.02; 95% CI,-0.03~0.07; P = 0.38), and analysis of hemiarthroplasty with cognitive dysfunction vs. the normal group (OR = 0.17; 95% CI, 0.08~0.26; P < 0.001). The outcome analysis was consistent with the included studies, and HRQoL of the EU-5Q scale is sensitive to surgical outcomes between THA and hemiarthroplasty. Conclusion: Surgeons still need to further evaluate and verify whether the hip arthroplasty surgical program or effect in elderly patients is optimal. Hemiarthroplasty operations in elderly patients have pointed toward a new direction for clinical treatment, and HRQoL scores measured by the EU-5Q can sensitively reflect the rehabilitation status after hip arthroplasty surgery. Moreover, the extensive correlation between surgical outcomes and perioperative neurocognitive function should be further investigated.

The changes of umami substances and influencing factors in preserved egg yolk: pH, endogenous protease, and proteinaceous substance.

The study investigated the changes of nucleotides, succinic acid, and free amino acids amounts in yolk and the causes leading to the changes after pickling to uncover the fundamental umami component of preserved egg yolk. The findings demonstrated that while the contents of 5'-adenosine monophosphate (AMP), 5'-cytidine monophosphate (CMP), 5'-guanosine monophosphate (GMP), 5'-uridine monophosphate (UMP), and succinic acid increased after slightly decreasing aspartic acid (Asp) content in preserved egg yolk increased gradually. The contents of 5'-inosine monophosphate (IMP) and other free amino acids were gradually decreased. Comparing the taste activity value (TAV), it was found that the single umami substance, succinic acid, played a key role in inducing the umami taste. In combination with the Spearman correlation analysis, it was shown that the proteinaceous substance, which is the most significant umami component in preserved egg yolk, tended to condense first and subsequently disintegrate in an alkaline environment. The orthogonal partial least squares analysis (OPLS) found that pH was also affected by the changes in proteinaceous substance. These findings offer suggestions for enhancing the pickling procedure and investigating the optimal pickling period for preserved eggs.

Early Rehabilitation Exercise after Stroke Improves Neurological Recovery through Enhancing Angiogenesis in Patients and Cerebral Ischemia Rat Model.

Among cerebrovascular diseases, ischemic stroke is a leading cause of mortality and disability. Thrombolytic therapy with tissue plasminogen activator is the first choice for clinical treatment, but its use is limited due to the high requirements of patient characteristics. Therefore, the choice of neurological rehabilitation strategies after stroke is an important prevention and treatment strategy to promote the recovery of neurological function in patients. This study shows that rehabilitation exercise 24 h after stroke can significantly improve the neurological function (6.47 ± 1.589 vs. 3.21 ± 1.069 and 0.76 ± 0.852), exercise ability (15.68 ± 5.95 vs. 162.32 ± 9.286 and 91.18 ± 7.377), daily living ability (23.37 ± 5.196 vs. 66.95 ± 4.707 and 6.55 ± 2.873), and quality of life (114.39 ± 7.772 vs. 168.61 ± 6.323 and 215.95 ± 10.977) of patients after 1 month and 3 months, and its ability to promote rehabilitation is better than that of rehabilitation exercise administered to patients 72 h after stroke (p < 0.001). Animal experiments show that treadmill exercise 24 h after middle cerebral artery occlusion and reperfusion can inhibit neuronal apoptosis, reduce the volume of cerebral infarction on the third (15.04 ± 1.07% vs. 30.67 ± 3.06%) and fifth (8.33 ± 1.53% vs. 30.67 ± 3.06%) days, and promote the recovery of neurological function on the third (7.22 ± 1.478 vs. 8.28 ± 1.018) and fifth (4.44 ± 0.784 vs. 6.00 ± 0.767) days. Mechanistic studies have shown that treadmill exercise increases the density of microvessels, regulates angiogenesis, and promotes the recovery of nerve function by upregulating the expression of vascular endothelial growth factor and laminin. This study shows that rehabilitation exercise 24 h after stroke is conducive to promoting the recovery of patients' neurological function, and provides a scientific reference for the clinical rehabilitation of stroke patients.

Isolation and screening of umami peptides from preserved egg yolk by nano-HPLC-MS/MS and molecular docking.

The material basis leading to the rich umami flavor of preserved egg yolk is poorly understood. This study used nano-high-performance liquid chromatography - tandem mass spectrometry (nano-HPLC-MS/MS) to isolate, identify, and screen umami peptides from preserved egg yolk. Five novel umami peptides-AGFMPLP, APYSGY, PPMF, SLSSLMK, and VAMNPVDHPH-were identified. Molecular docking showed that Phe527 on the taste receptor T1R1/T1R3 (T1R1, taste receptor type 1 member 1; T1R3, taste receptor type 1 member 3) was the key interaction site. Hydrogen bonding, electrostatic interactions, and hydrophobic interactions were the main binding forces between T1R1/T1R3 and umami peptides. These results contribute to understanding the umami peptides in preserved egg yolk and the interaction mechanism between umami peptides and umami receptors.

Improvement of gel properties and digestibility of the water-soluble polymer of tea polyphenol-egg white under thermal treatment.

In this study, the improvement of gel properties and digestibility of the water-soluble polymer of tea polyphenol (TP)-egg white protein (TEP) under heat induction (HTEP), was studied. Results indicated that the particle size and turbidity of TEP increased with TP concentration, and the absolute value of ζ-potential decreased. After heat induction, the surface hydrophobicity of HTEP decreased with TP concentration, and the degree of protein aggregation increased. Microstructure and T2 showed that the gel structure became compact and stable, and HTEP had a strong water-binding ability. The ionic and disulfide bonds were the main chemical bonds in HTEP. The hardness and disulfide bond increased, but the digestion of HTEP increased initially and then decreased (caused by the change of gel structure). Infrared spectroscopy indicated the mutual conversion of intermolecular and intramolecular ß-sheets. In short, TP could modify egg white gel through forming stable disulfide bonds and dense gel network structures.

Rapidly growing giant solitary fibrous tumor of the pleura: a case report and review of the literature.

Solitary fibrous tumors of the pleura (SFTPs) are rare slowly-growing tumors that originate from mesenchymal cells of the submesothelial tissue of the pleura. A 57-year-old female presented to our institute, and complained of mild chest discomfort for one year. The computed tomography (CT) showed a thoracic mass measuring 3.4×1.5 cm. She refused surgical removal, and turned to the medical treatment with oral herbs with unknown specific ingredients; however, she had persistence of her symptoms and gradually developed general fatigue and severe dyspnea six months before presentation. The CT scan revealed a giant mass measuring 33×20×15 cm in the right hemithorax, leading to total atelectasis of the lung. After preoperative embolization of the tumor-supplying arteries, the tumor was completely removed. The diagnosis of SFTP was confirmed by subsequent histopathologic and immunohistochemical examinations. The postoperative course was uneventful with a 15-day length of stay, and the patient was in good health at the 15-month follow-up.

Stress injuries and autophagy in mouse hippocampus after chronic cold exposure.

Cold exposure is an external stress factor that causes skin frostbite as well as a variety of diseases. Estrogen might participate in neuroprotection after cold exposure, but its precise mechanism remains unclear. In this study, mice were exposed to 10°C for 7 days and 0-4°C for 30 days to induce a model of chronic cold exposure. Results showed that oxidative stress-related c-fos and cyclooxygenase 2 expressions, MAP1LC3-labeled autophagic cells, Iba1-labeled activated microglia, and interleukin-1ß-positive pyramidal cells were increased in the hippocampal CA1 area. Chronic cold exposure markedly elevated the levels of estrogen in the blood and the estrogen receptor, G protein-coupled receptor 30. These results indicate that neuroimmunoreactivity is involved in chronic cold exposure-induced pathological alterations, including oxidative stress, neuronal autophagy, and neuroimmunoreactivity. Moreover, estrogen exerts a neuroprotective effect on cold exposure.

Angelica injection improves functional recovery and motoneuron maintenance with increased expression of brain derived neurotrophic factor and nerve growth factor.

This study assessed the neuroprotective effects of angelica injection in the rat sciatic nerve crush injury (SCI). Forty eight male Sprague Dawley rats were randomly divided into 4 groups: one was the sham group (S), which received sham surgery and given saline injection and the others were received SCI surgery and given saline injection, high and low dose angelica injection for 4 weeks, respectively. The sciatic functional index (SFI) in walking-track analysis, conductive velocity (CV), the number of fluorogold labeled motoneurons, and the expression patterns of brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the sciatic nerve and spine were examined. The results showed that SFI descended gradually on day 7, and dropped more quickly on day 28 in treatment groups (Low and High dose group). The CV in treatment groups was higher than control group (C). The numbers of motoneurons in treatment groups were larger than C group (P<0.05), but less than that in S group (P<0.01). The expressions of BDNF and NGF protein in the groups received SCI surgery were significantly lower than in S group, but the protein expressions in the groups received angelica injections were significantly higher than that in C group (P<0.01). These findings suggested that angelica injection can improve the sciatic nerve crush injury, and the mechanism might be through the increase of BDNF and NGF protein expression.