sAPPα Peptide Promotes Damaged Microglia to Clear Alzheimer's Amyloid-ß via Restoring Mitochondrial Function.

Alzheimer's disease (AD) is an age-related neurodegenerative disease with amyloid-ß (Aß) deposition as the main pathological feature. It's an important challenge to find new ways to clear Aß from Brain. The soluble amyloid precursor protein α (sAPPα) is a neuroprotective protein and can attenuate neuronal damage, including toxic Aß. However, the regulatory role of sAPPα in non-neuronal cells, such as microglia, is less reported and controversial. Here, we showed that sAPPα promoted the phagocytosis and degradation of Aß in both normal and damaged microglia. Moreover, the function of damaged microglia was improved by the sAPPα through normalizing mitochondrial function. Furthermore, the results of molecular docking simulation showed that sAPPα had a good affinity with Aß. We preliminarily reveal that sAPPα is similar to antibodies and can participate in the regulation of microglia phagocytosis and degradation of Aß after binding to Aß. sAPPα is expected to be a mild and safe peptide drug or drug carrier for AD.

ZNF26-Associated Genes as Prognostic Signatures in Colorectal Cancer with Broad Therapeutic Implications.

The identification of biomarkers correlated with colorectal cancer (CRC) prognosis holds substantial importance from both clinical and scientific perspectives. Zinc finger protein 26 (ZNF26) has not been previously investigated or documented in solid tumors; thus, further research is necessary to ascertain its prognostic value in CRC. Gene expression profiles and clinicopathological data were acquired from The Cancer Genome Atlas (TCGA) database. Subsequently, expression correlation was assessed utilizing the TCGA CRC cohort. The prognostic value of ZNF26 was evaluated through Kaplan-Meier (KM) and ROC curve analyses. Following this, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to perform enrichment analysis between high- and low-ZNF26 expression groups. The association between immune cells, immune checkpoint genes, and ZNF26 expression levels was examined. Lastly, the research findings were further validated using CRC tissue samples. The results revealed that, in comparison to healthy controls, CRC significantly reduced ZNF26 expression. Elevated ZNF26 expression was associated with poorer overall survival in CRC patients. Additionally, high ZNF26 expression exhibited an inverse relationship with the immunological score and immune checkpoint gene expression in CRC patients. The findings from the TCGA data analysis were corroborated by the PCR results obtained from CRC tissue samples. ZNF26 is markedly upregulated in colorectal cancer tissues, potentially serving as a biomarker for CRC.

Photorewriting, Time-Resolved Encryption, and Unclonable Anticounterfeiting with Artificial Intelligence Authentication via a Reversible Photoswitchable System.

In the fields of photolithographic patterning, optical anticounterfeiting, and information encryption, reversible photochromic materials with solid-state fluorescence are emerging as a potential class of systems. A design strategy for reversible photochromic materials has been proposed and synthesized through the introduction of photoactive thiophene groups into the molecular backbone of aryl vinyls, compounds with unique aggregation-induced emission properties, and solid-state reversible photocontrollable fluorescence and color-changing properties. This work develops novel photochromic inks, films, and cellulose hydrogels for enhancing the security of information encryption and anticounterfeiting technologies. They achieve rapid and reversible color change under ultraviolet light irradiation. Dependent upon the rate of color change, higher levels of time-resolved security can be achieved. This feature is important for enhancing the confidentiality of encrypted information and the reliability of security labels. Color-changing cellulose hydrogels, inks, and films consisting of three photochromic fluorescent molecules have quick photoactivity, great photoreversibility and photostability, and good processability, making them ideal for time-delayed anticounterfeiting and smart encryption. Furthermore, specialized algorithms are used to construct convolutional neural networks, and image analysis is performed on these systems, thus solving the current problem of the time-consuming information decryption process. This artificial intelligence method offers new opportunities for enhanced data encryption.

Platelets: A Potential Factor that Offers Strategies for Promoting Bone Regeneration.

Bone defects represent a prevalent category of clinical injuries, causing significant pain and escalating health care burdens. Effectively addressing bone defects is thus of paramount importance. Platelets, formed from megakaryocyte lysis, have emerged as pivotal players in bone tissue repair, inflammatory responses, and angiogenesis. Their intracellular storage of various growth factors, cytokines, and membrane protein receptors contributes to these crucial functions. This article provides a comprehensive overview of platelets' roles in hematoma structure, inflammatory responses, and angiogenesis throughout the process of fracture healing. Beyond their application in conjunction with artificial bone substitute materials for treating bone defects, we propose the potential future use of anticoagulants such as heparin in combination with these materials to regulate platelet number and function, thereby promoting bone healing. Ultimately, we contemplate whether manipulating platelet function to modulate bone healing could offer innovative ideas and directions for the clinical treatment of bone defects.

Antitumor Activity of Carboxymethyl Pachymaran with Different Molecular Weights Based on Immunomodulatory and Gut Microbiota.

Carboxymethyl pachymaran (CMP) was treated via high-temperature and cellulase hydrolysis to obtain HTCMP, HTEC-24, and HTEC-48. The chemical structure and in vivo antitumor activities of the four types of CMPs were investigated. Compared with CMP (787.9 kDa), the molecular weights of HTCMP, HTEC-24, and HTEC-48 were decreased to 429.8, 129.9, and 68.6 kDa, respectively. The viscosities and particle sizes of the CMPs could also decrease with the decline in the molecular weights. All the CMPs showed antitumor abilities, but HTEC-24 exhibited the best activity. In the animal study, when curing the spleen and thymus, CMPs displayed immunomodulatory effects by increasing the secretion of IFN-γ and IL2 in mice. The CMPs also exerted an antitumor ability by regulating the gut microbiota in tumor-bearing mice. Our results established a foundation to develop an antitumor drug with CMP.

A New Assistance Navigation Method for Substation Inspection Robots to Safely Cross Grass Areas.

With the development of intelligent substations, inspection robots are widely used to ensure the safe and stable operation of substations. Due to the prevalence of grass around the substation in the external environment, the inspection robot will be affected by grass when performing the inspection task, which can easily lead to the interruption of the inspection task. At present, inspection robots based on LiDAR sensors regard grass as hard obstacles such as stones, resulting in interruption of inspection tasks and decreased inspection efficiency. Moreover, there are inaccurate multiple object-detection boxes in grass recognition. To address these issues, this paper proposes a new assistance navigation method for substation inspection robots to cross grass areas safely. First, an assistant navigation algorithm is designed to enable the substation inspection robot to recognize grass and to cross the grass obstacles on the route of movement to continue the inspection work. Second, a three-layer convolutional structure of the Faster-RCNN network in the assistant navigation algorithm is improved instead of the original full connection structure for optimizing the object-detection boxes. Finally, compared with several Faster-RCNN networks with different convolutional kernel dimensions, the experimental results show that at the convolutional kernel dimension of 1024, the proposed method in this paper improves the mAP by 4.13% and the mAP is 91.25% at IoU threshold 0.5 in the range of IoU thresholds from 0.5 to 0.9 with respect to the basic network. In addition, the assistant navigation algorithm designed in this paper fuses the ultrasonic radar signals with the object recognition results and then performs the safety judgment to make the inspection robot safely cross the grass area, which improves the inspection efficiency.

Mapping of Rf20(t), a minor fertility restorer gene for rice wild abortive cytoplasmic male sterility in the maintainer line 'Zhenshan97B'.

Three-line hybrid rice has primarily been developed on wild abortive (WA)-type cytoplasmic male sterility (CMS) and has helped increase the yield of rice globally. The development of WA-type CMS lines and hybrids was expedited through the identification and mapping of the fertility restorer gene (Rf) in maintainers. This study observed fertile plants in WA-TianfengA/Zhenshan97B//TianfengB population, indicating that the maintainer line 'Zhenshan97B' should carry Rfs for WA-type CMS. Several advanced backcross populations were generated with the genetic background of the 'WA-TianfengA,' and the pollen fertility levels of the backcrossed individuals in BC3F1, BC4F1 and BC4F2 populations are governed by a new gene, Rf20(t), from 'Zhenshan97B.' Employing bulk segregant analysis of fertile and sterile pools from the BC4F1 population, Rf20(t) was genetically mapped to a candidate region on chromosome 10. Subsequently, Rf20(t) was located between RM24883 and RM24919 through recombination analysis of molecular markers using the BC4F2 population. Implementing a substitution mapping strategy, Rf20(t) was ultimately mapped to a 245-kb region between the molecular markers STS10-122 and STS10-126 and obtained the most likely candidate gene LOC_Os10g02650, which is predicted to encode pentatricopeptide repeat-containing (PPR) protein. These results enhance our understanding of the fertility restoration of WA-type CMS lines, facilitating the development of high-quality pairs of WA-type CMS and maintainer lines.

Bioinformatics Analysis Build Autophagy Prognosis Model of Cremastra Intervention Breast Cancer and Explore the Prognostic Markers.

Objective: Autophagy is the catabolic process where the components of eukaryotes experience damage, and the affected or superfluous components undergo self-degradation. However autophagy can promote cancer cell apoptosis or facilitate cell growth. This work aimed to investigat the significance of autophagy-related genes (ARGs) in predicting the prognosis of breast cancer (BC) intervened with Cremastra. Methods: Active ingredients and action targets were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction. Then, the BC transcriptome and clinical data were downloaded in The Cancer Genome Atlas (TCGA), whereas ARGs were collected in the Human Autophagy Database (HADb). Meanwhile, Perl and R software were used for data processing and analysis. Firstly, the transcriptome data of BC were mapped to ARGs to screen the BC-ARGs. Secondly, the above genes were mapped to the action targets of Cremastra, ARGs of Cremastra-intervened BC were then screened out. Moreover, an enrichment analysis of biological function was carried out. Univariate Cox regression was carried out on ARGs of BC for preliminarily selecting the independent prognostic genes and constructing the autophagy prognosis model. These genes were mapped to ARGs involved in Cremastra-intervened BC. Finally, those mapped genes were optimized by multi-factor Cox regression, and the key ARGs and potential compounds were obtained. Finally, all cases were classified as low- or high-risk group based on the median risk score. Receiver operating characteristic (ROC) curve, Kaplan-Meier (K-M) survival, independent prognosis and clinical correlation analyses were conducted for model evaluation and identification of factors to independently predict prognosis. Results: Altogether, 66 active components and 38 targets of the Cremastra-intervened autophagy of BC were screened and the autophagy prognosis model demonstrate good predictive performance. As suggested by the survival curve, low-risk patients had a markedly increased survival rate compared with high-risk patients (P < .01). Besides, the gene expression levels of the high-risk group increased with the increases in patients' risk scores. Upon univariate regression, 34 differentially expressed ARGs related to BC treatment were screened. Multivariate regression identified 4 key ARGs, which were mainly derived from glycosides, lignans, flavonoids, and dibenzyl compounds. Thereafter, key genes were subjected to correlation analysis between clinicopathological features and prognosis, among which BCL2 and TP63, showed independent prognostic value. Conclusions: In this study, an autophagy prognosis model was established, and BCL2 and TP63 were predicted for the Cremastra intervention of BC by Bioinformatics, which will be applied to further work.

FAM210A is essential for cold-induced mitochondrial remodeling in brown adipocytes.

Cold stimulation dynamically remodels mitochondria in brown adipose tissue (BAT) to facilitate non-shivering thermogenesis in mammals, but what regulates mitochondrial plasticity is poorly understood. Comparing mitochondrial proteomes in response to cold revealed FAM210A as a cold-inducible mitochondrial inner membrane protein. An adipocyte-specific constitutive knockout of Fam210a (Fam210aAKO) disrupts mitochondrial cristae structure and diminishes the thermogenic activity of BAT, rendering the Fam210aAKO mice vulnerable to lethal hypothermia under acute cold exposure. Induced knockout of Fam210a in adult adipocytes (Fam210aiAKO) does not affect steady-state mitochondrial structure under thermoneutrality, but impairs cold-induced mitochondrial remodeling, leading to progressive loss of cristae and reduction of mitochondrial density. Proteomics reveals an association between FAM210A and OPA1, whose cleavage governs cristae dynamics and mitochondrial remodeling. Mechanistically, FAM210A interacts with mitochondrial protease YME1L and modulates its activity toward OMA1 and OPA1 cleavage. These data establish FAM210A as a key regulator of mitochondrial cristae remodeling in BAT and shed light on the mechanism underlying mitochondrial plasticity in response to cold.

HPV16 infection promotes the malignant transformation of the esophagus and progression of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) may be correlated with HPV infection, and the mechanism underlying the ESCC formation induced by HPV16 infection remains elusive. Here, we overexpressed HPV16 E6 and E7 and coordinated the overexpression of these two genes in EPC2 and ESCC cells. We found that E7 and coordinated expression of E6 and E7 promoted the proliferation of EPC2 cells, and upregulation of shh was responsible for cell proliferation since the use of vismodegib led to the failure of organoid formation. Meanwhile, overexpression of E6 and E7 in ESCC cells promoted cell proliferation, migration, and invasion in vitro. Importantly, E6 and E7 coordinately increased the capability of tumor growth in nude mice, while vismodegib slowed the growth of tumors in NCG mice. Moreover, a series of genes and proteins changed in cell lines after overexpression of the E6 and E7 genes, the potential biological processes and pathways were systematically analyzed using a bioinformatics assay. Together, these findings suggest that the activation of the hedgehog pathway induced by HPV16 infection may initially transform basal cells in the esophagus and promote following malignant processes in ESCC cells. The application of hedgehog inhibitors may represent a therapeutic avenue for ESCC treatment.

Development of an immunogenic cell death prognostic signature for predicting clinical outcome and immune infiltration characterization in stomach adenocarcinoma.

Stomach adenocarcinoma (STAD) is a common gastric histological cancer type with a high mortality rate. Immunogenic cell death (ICD) plays a key factor during carcinogenesis progress, whereas the prognostic value and role of ICD-related genes (ICDRGs) in STAD remain unclear. The MSigDB database collecting ICDRGs were selected by univariate Cox regression analysis and LASSO algorithm to establish a novel risk model. The Kaplan-Meier survival analysis indicated a significant difference of OS rate of patients by risk score stratification. ESTIMATE, CIBERSORT, and single sample gene set enrichment analysis (ssGSEA) algorithms were conducted to estimate the immune infiltration landscape by risk stratification. Subgroup analysis and tumor mutation burden analysis were also analyzed to identify characteristics between groups. Differences in therapeutic responsiveness to chemotherapeutic drugs and targeted drugs were also analyzed between high-risk group and low-risk group. The impact of one ICDRG, GPX1, on the proliferation, migration and invasiveness of was confirmed by in vitro experiments in GC cells to test the reliability of bioinformatics results. This study gives evidence of the involvement of ICD process in STAD and provides a new perspective for further accurate assessment of prognosis and therapeutic efficacy in STAD patients. Stomach adenocarcinoma (STAD) is a common gastric histological cancer type with a high mortality rate. Immunogenic cell death (ICD) plays a key factor during carcinogenesis progress, whereas the prognostic value and role of ICD-related genes (ICDRGs) in STAD remains unclear. The MSigDB database collected ICDRGs were selected by univariate Cox regression analysis and LASSO algorithm to establish a novel risk model. The Kaplan-Meier survival analysis indicated a significant difference of OS rate of patients by risk score stratification. ESTIMATE, CIBERSORT, and single sample gene set enrichment analysis (ssGSEA) algorithms were conducted to estimate the immune infiltration landscape by risk stratification. Subgroup analysis and tumor mutation burden analysis were also analyzed to identify characteristics between groups. Differences in therapeutic responsiveness to chemotherapeutic drugs and targeted drugs were also analyzed between high-risk group and low-risk group. The impact of one ICDRG, GPX1, on the proliferation, migration and invasiveness of was confirmed by in vitro experiments in GC cells to test the reliability of bioinformatics results. This study gives evidence of the involvement of ICD process in STAD and provides a new perspective for further accurate assessment of prognosis and therapeutic efficacy in STAD patients.

Online education isn't the best choice: evidence-based medical education in the post-epidemic era-a cross-sectional study.

BACKGROUND: The COVID-19 pandemic led many educational institutions to shift to online courses, making blended education a significant trend in teaching. We examined the effectiveness of blended learning in an evidence-based medicine course. METHODS: We compared the examination scores of a blended learning group, an online only group, and a traditional offline group and conducted a questionnaire survey on students' preferences for different learning modes and the reasons for their preferences. A total of 2100 undergraduate students in clinical medicine were included in this cross-sectional study. Examination results were collected, and questionnaires were administered to the study participants. We compared the mean scores and exam pass rates of the three teaching groups using ANOVA and c2test for multiple comparisons. RESULTS: The blended group's exam scores and pass rate were significantly higher than those of the offline and online groups. Furthermore, 71.6% preferred the blended teaching mode. In the survey on " learning effectiveness", the majority of the students believed that blended education could better enhance the initiative of learning, the interest of the course, the pertinence of the learning content, the comprehension of evidence-based medical thinking, and the basic skills of evidence-based practice. Subsequently, in a questionnaire administered to a blended group of students, their foremost reason for liking online instruction was 'flexible in time and space' (99%), followed by 'can be viewed repeatedly, facilitating a better understanding of knowledge points' (98%). Their foremost reason for liking offline teaching was 'helps to create a good learning atmosphere' (97%), followed by 'teachers can control students' learning status in real time' (89%). CONCLUSIONS: This study explored the effectiveness of learning in evidence-based medicine courses by comparing the learning outcomes and personal perceptions of three different teaching modes. This is the first cross-sectional study in which three different teaching models are compared and discussed in an evidence-based medicine course. We also elaborate on the specific instructional protocols for each model. This study shows that using a blended education approach in evidence-based medicine courses can improve students' learning motivation, autonomy, and satisfaction. It also enhances instructional efficiency, thereby improving students' understanding of the course content.

Construction of a multi-scale effectiveness evaluation system for ecological restoration and protection of territorial space.

The ecological restoration and protection of territorial space is a systematic project for the protection and restoration of ecosystems damaged or degraded by human disturbance. Effectiveness evaluation is of great significance to the optimization, adjustment, and sustainability of ecological restoration and protection. Current research and practices tend to focus on a single element and the site scale. Based on the study on the connotation of ecological restoration and protection of territorial space and the multi-scale characteristics of ecosystems, we constructed a multi-scale effectiveness evaluation system for ecological restoration and protection of territorial space and a full-cycle monitoring system for effectiveness evaluation. The multi-scale effectiveness evaluation system consisted of the regional/watershed scale, the protection and restoration unit scale, and the sub-project scale. The full-cycle monitoring system contained the basic information investigation system before construction, the construction monitoring system during construction, and the multi-scale effectiveness evaluation system after construction. At the regional/watershed scale, structure, quality, and services of ecosystem were concerned and remote sensing was used as the main method to capture data. At the protection and restoration unit scale, ecological stress factors, ecosystem quality and services were concerned, and the main methods were remote sensing combined with field survey. At the sub-project scale, engineering technology measures were concerned and the field survey was used as the main method. In the implementation of the multi-scale effectiveness evaluation, it would be necessary to focus on and solve the key issues including the spillover effect, transmission mechanism, and potential impact of ecological restoration.

Comparative efficacy of various exercise interventions on depression in older adults with mild cognitive impairment: A systematic review and network meta-analysis.

BACKGROUND: Exercise is a promising nonpharmacological treatment for improving depression in older adults with MCI, but it is unclear which exercises are most effective. The objectives of this study were to compare and rank the effectiveness of various exercise interventions for depression in mild cognitive impairment (MCI) and to investigate the effects of exercise on depression. METHODS: The PRISMA-NMA guidelines were applied to the development and reporting of review criteria. The Cochrane Library, Web of Science, PsycINFO, PubMed, EMBASE, CINAHL, and Scopus databases were systematically searched by combining search terms for randomized controlled trial studies (RCTs) published in English from individual databases with the earliest available date set to March 10, 2023. Two evaluators independently selected and evaluated eligible studies of changes in depression in older adults with MCI after an exercise intervention. A protocol for this systematic review was registered in PROSPERO (Registration number: CRD42022377052). RESULTS: A network meta-analysis was conducted on 15 eligible RCTs consisting of 4271 subjects, including aerobic (n = 6), mind-body (n = 6) and multicomponent (n = 3) exercise trials. Compared to controls, mind-body exercise showed the strongest improvement in depressive symptoms (SMD = -0.63, 95% CI: -1.13, -0.14), followed by aerobic (SMD = -0.57, 95% CI: -0.88, -0.26) and multicomponent exercise (SMD = -0.53, 95% CI: -1.02, -0.03). Notably, there were no statistically significant differences between exercise types: aerobic vs. mind-body (SMD = 0.06, 95% PrI: -0.71, 0.84), multicomponent vs. mind-body (SMD = 0.11, 95% PrI: -0.75, 0.97), or multicomponent vs. aerobic (SMD = 0.04, 95% PrI: -0.771, 0.86). CONCLUSIONS: In this review, we found that mind-body exercise was most effective when compared to conventional controls and that multiple exercise modalities (aerobic, mind-body, and multicomponent exercise) had beneficial and comparable effects in reducing depressive states in older adults with MCI. These findings may guide clinical geriatric stakeholders and allied health professionals in providing more scientifically optimal exercise prescriptions for older adults with MCI. In the future, more high-quality, long-term clinical trials are needed to support the exploration of longer-term dynamic effects.

Advances in understanding the pathogenesis of post-traumatic epilepsy: a literature review.

Severe head trauma can lead to seizures. Persistent epileptic seizures and their progression are associated with the severity of trauma. Although case reports have revealed that early use of anti-seizure drugs after trauma can prevent epilepsy, clinical case-control studies have failed to confirm this phenomenon. To date, many brain trauma models have been used to study the correlation between post-traumatic seizures and related changes in neural circuit function. According to these studies, neuronal and glial responses are activated immediately after brain trauma, usually leading to significant cell loss in injured brain regions. Over time, long-term changes in neural circuit tissues, especially in the neocortex and hippocampus, lead to an imbalance between excitatory and inhibitory neurotransmission and an increased risk of spontaneous seizures. These changes include alterations in inhibitory interneurons and the formation of new, over-recurrent excitatory synaptic connections. In this study, we review the progress of research related to post-traumatic epilepsy to better understand the mechanisms underlying the initiation and development of post-traumatic seizures and to provide theoretical references for the clinical treatment of post-traumatic seizures.

Research progress on correlations between trace element levels and epilepsy.

Research investigating the correlation between human trace element levels and disease alterations is growing. Epilepsy, a common nervous system disease, has also been found to be closely related to abnormal levels of trace elements. Studies continue to explore mechanisms of various trace elements involved in epileptic seizures through experimental animal models of epilepsy. Thus, we reviewed the research progress on the correlation between trace element levels and epilepsy in recent years and found that the trace elements most closely related to epilepsy are mainly metal ions such as selenium, iron, copper, zinc, and manganese. These results indicate that the changes in some trace elements are closely related to the increase in epilepsy susceptibility. In addition, after treatment with drugs and a ketogenic diet, the concentration of trace elements in the serum of patients with epilepsy changes. In other words, the abnormality of trace element concentrations is of great significance in the occurrence and development of epilepsy. This article is a literature update on the potential role of trace element imbalance in the development of epilepsy, providing new references for the subsequent prevention and treatment of epilepsy.

Effects of degradation on the physicochemical and antioxidant properties of carboxymethyl pachymaran.

Poria cocos (Schw.) Wolf is a well-known edible and medicinal fungus. The polysaccharide in the sclerotium of P. cocos was extracted and prepared into carboxymethyl pachymaran (CMP). Three different degradation treatments including high temperature (HT), high pressure (HP) and gamma irradiation (GI) were used to process CMP. The changes in physicochemical properties and antioxidant activities of CMP were then comparatively investigated. We found that the molecular weights of HT-CMP, HP-CMP, and GI-CMP decreased from 787.9 kDa to 429.8, 569.5 and 6.0 kDa, respectively. Degradation treatments had no effect on the main chains of →3-ß-D-Glcp-(1 â†’ while changed the branched sugar residues. The polysaccharide chains of CMP were depolymerized after high pressure and gamma irradiation treatments. The three degradation methods improved the stability of CMP solution while decreased the thermal stability of CMP. In addition, we found that the GI-CMP with lowest molecular weight had the best antioxidant activity. Our results suggest that gamma irradiation treatment could degrade CMP as functional foods with strong antioxidant activity.

Astragaloside II enhanced sensitivity of ovarian cancer cells to cisplatin via triggering apoptosis and autophagy.

Cisplatin (DDP) based chemotherapy occurs a reduced therapeutic effect on the later treatment of ovarian cancer (OC) due to DDP resistance. Astragaloside II (ASII), a natural product extracted from Radix Astragali, has shown promising anticancer effects. However, the effects of ASII on OC have not been clarified. In this study, we found that ASII inhibited cell growth and promoted cell apoptosis of DDP-resistant OC cells in vitro and in vivo. Further study showed that ASII downregulated multidrug resistance-related protein MDR1 and cell cycle-related protein Cyclin D1 and PCNA, and also upregulated apoptosis-related protein leaved PRAP and cleaved caspase-3. In addition, ASII induced autophagy, characterized by upregulation of LC3II expression, downregulation of p62 expression, and elevation of LC3 punctuation, may be associated with inhibition of the AKT/mTOR signaling pathway. Moreover, the messenger RNA-sequencing was used to identify potential molecules regulated by ASII. In conclusion, these findings indicated that ASII increased sensitivity of DDP in the treatment of OC.

Untargeted metabonomic analysis of non-alcoholic fatty liver disease with iron overload in rats via UPLC/MS.

BACKGROUND/AIMS: In recent years, many metabolites specific to nonalcoholic fatty liver disease (NAFLD) have been identified thanks to the application of metabolomics techniques. This study aimed to investigate the candidate targets and potential molecular pathways involved in NAFLD in the presence of iron overload. METHODS: Male Sprague Dawley rats were fed with control or high-fat diet with or without excess iron. After 8, 16, 20 weeks of treatment, urine samples of rats were collected for metabolomics analysis using ultra-performance liquid chromatography/mass spectrometry (UPLC-MS). Blood and liver samples were also collected. RESULTS: High-fat, high-iron diet resulted in increased triglyceride accumulation and increased oxidative damage. A total of 13 metabolites and four potential pathways were identified. Compared to the control group, the intensities of adenine, cAMP, hippuric acid, kynurenic acid, xanthurenic acid, uric acid, and citric acid were significantly lower (p < 0.05) and the concentration of other metabolites was significantly higher in the high-fat diet group. In the high-fat, high-iron group, the differences in the intensities of the above metabolites were amplified. CONCLUSION: Our findings suggest that NAFLD rats have impaired antioxidant system and liver function, lipid disorders, abnormal energy, and glucose metabolism, and that iron overload may further exacerbate these disorders.

Phosphoglycerate kinase (PGK) 1 succinylation modulates epileptic seizures and the blood-brain barrier.

Epilepsy is the most common chronic disorder in the nervous system, mainly characterized by recurrent, periodic, unpredictable seizures. Post-translational modifications (PTMs) are important protein functional regulators that regulate various physiological and pathological processes. It is significant for cell activity, stability, protein folding, and localization. Phosphoglycerate kinase (PGK) 1 has traditionally been studied as an important adenosine triphosphate (ATP)-generating enzyme of the glycolytic pathway. PGK1 catalyzes the reversible transfer of a phosphoryl group from 1, 3-bisphosphoglycerate (1, 3-BPG) to ADP, producing 3-phosphoglycerate (3-PG) and ATP. In addition to cell metabolism regulation, PGK1 is involved in multiple biological activities, including angiogenesis, autophagy, and DNA repair. However, the exact role of PGK1 succinylation in epilepsy has not been thoroughly investigated. The expression of PGK1 succinylation was analyzed by Immunoprecipitation. Western blots were used to assess the expression of PGK1, angiostatin, and vascular endothelial growth factor (VEGF) in a rat model of lithium-pilocarpine-induced acute epilepsy. Behavioral experiments were performed in a rat model of lithium-pilocarpine-induced acute epilepsy. ELISA method was used to measure the level of S100ß in serum brain biomarkers' integrity of the blood-brain barrier. The expression of the succinylation of PGK1 was decreased in a rat model of lithium-pilocarpine-induced acute epilepsy compared with the normal rats in the hippocampus. Interestingly, the lysine 15 (K15), and the arginine (R) variants of lentivirus increased the susceptibility in a rat model of lithium-pilocarpine-induced acute epilepsy, and the K15 the glutamate (E) variants, had the opposite effect. In addition, the succinylation of PGK1 at K15 affected the expression of PGK1 succinylation but not the expression of PGK1total protein. Furthermore, the study found that the succinylation of PGK1 at K15 may affect the level of angiostatin and VEGF in the hippocampus, which also affects the level of S100ß in serum. In conclusion, the mutation of the K15 site of PGK1 may alter the expression of the succinylation of PGK1 and then affect the integrity of the blood-brain barrier through the angiostatin / VEGF pathway altering the activity of epilepsy, which may be one of the new mechanisms of treatment strategies.