Alcohol Extracts From Ganoderma lucidum Delay the Progress of Alzheimer’s Disease by Regulating DNA Methylation in Rodents

Age-related changes in methylation are involved in the occurrence and development of tumors, autoimmune disease, and nervous system disorders, including Alzheimer’s disease (AD), in elderly individuals; hence, modulation of these methylation changes may be an effective strategy to delay the progression of AD pathology. In this study, the AD model rats were used to screen the main active extracts from the mushroom, Ganoderma lucidum, for anti-aging properties, and their effects on DNA methylation were evaluated. The results of evaluation of rats treated with 100 mg/kg/day of D-galactose to induce accelerated aging showed that alcohol extracts of G. lucidum contained the main active anti-aging extract. The effects on DNA methylation of these G. lucidum extracts were then evaluated using SAMP8 and APP/PS1 AD model mice by whole genome bisulfite sequencing, and some methylation regulators including Histone H3, DNMT3A, and DNMT3B in brain tissues were up-regulated after treatment with alcohol extracts from G. lucidum. Molecular docking analysis was carried out to screen for molecules regulated by specific components, including ganoderic acid Mk, ganoderic acid C6, and lucidone A, which may be active ingredients of G. lucidum, including the methylation regulators of Histone H3, MYT, DNMT3A, and DNMT3B. Auxiliary tests also demonstrated that G. lucidum alcohol extracts could improve learning and memory function, ameliorate neuronal apoptosis and brain atrophy, and down-regulate the expression of the AD intracellular marker, Aβ1-42. We concluded that alcohol extracts from G. lucidum, including ganoderic acid and lucidone A, are the main extracts involved in delaying AD progression

Marx for his times. Book Review of: 'Karl Marx : greatness and illusion' by Gareth Stedman Jones

Potential downstream targets for CD274. RNA-sequencing was performed with WT and CD274-null LICs, and the candidate genes related to proliferation and cell cycle was analyzed. (PDF 116 kb

The role of Notch signalling in ovarian angiogenesis

Abstract In adults, the ovary is characterized with extensive angiogenesis and regular intervals of rapid growth. Ovarian function is dependent on the network of angiogenic vessels which enable the follicle and/or corpus luteum to receive oxygen, nutrients and hormonal support. Abnormal angiogenesis is involved in the induction and development of pathological ovary, such as polycystic ovary syndrome and ovarian cancer. Notch signalling pathway is one of the primary regulators of angiogenesis and a therapeutic target for ovarian diseases. Here, we will review literatures on the expression pattern of Notch pathway components in the ovary and on the role of Notch signalling pathway on ovarian angiogenesis

CEBPG suppresses ferroptosis through transcriptional control of SLC7A11 in ovarian cancer

Abstract Background Ovarian cancer (OC) has high mortality and poor prognosis for lacking of specific biomarkers and typical clinical symptoms in the early stage. CEBPG is an important regulator in tumor development, yet it is unclear exactly how it contributes to the progression of OC. Methods TCGA and tissue microarrays with immunohistochemical staining (IHC) were used to examine CEBPG expression in OC. A variety of in vitro assays were conducted, including colony formation, proliferation, migration, and invasion. The orthotopic OC mouse model was established for in vivo studies. Ferroptosis was detected by observing mitochondrial changes with electron microscopy, detecting ROS expression, and detecting cell sensitivity to drugs by CCK8 assay. The interaction between CEBPG and SLC7A11 was confirmed by CUT&Tag and dual luciferase reporter assays. Results A significantly higher expression level of CEBPG in OC when compared with benign tissues of ovary, and that high CEBPG expression level was also tightly associated with poor prognosis of patients diagnosed with OC, as determined by analysis of datasets and patient samples. Conversely, knockdown of CEBPG inhibited OC progression using experiments of OC cell lines and in vivo orthotopic OC-bearing mouse model. Importantly, CEBPG was identified as a new participator mediating ferroptosis evasion in OC cells using RNA-sequencing, which could contribute to OC progression. The CUT&Tag and dua luciferase reporter assays further revealed the inner mechanism that CEBPG regulated OC cell ferroptosis through transcriptional control of SLC7A11. Conclusions Our findings established CEBPG as a novel transcriptional regulator of OC ferroptosis, with potential value in predicting clinical outcomes and as a therapeutic candidate

Effects of Hypoxia Stress on Growth, Root Respiration, and Metabolism of Phyllostachys praecox

Hypoxia affects plant growth, hormone content, various enzyme activities, cell structure, peroxide production, and metabolic level, therefore reducing crop yield. This study assessed the physiological, biochemical, and metabolic characteristics of Phyllostachys praecox. Results revealed that hypoxia stress treatment significantly inhibited plant growth. Leaf chlorophyll contents was initially improved and then reduced with plant growth time. Under hypoxia stress, the root activity significantly was reduced, leading to the decrease in the nutrient absorption and transport. Yet, with low oxygen concentration, the contents of ethanol, acetaldehyde, and lactic acid were improved. With hypoxia stress, phospholipids and amino acids were the main metabolites of Phyllostachys praecox. Glycosphospholipid metabolism is the key pathway in responding to hypoxia stress significantly (p < 0.05), and lysophosphatidlycholine (lysoPC) and phosphatidylcholines (PC) in the metabolites of this metabolic pathway were significantly enhanced. Our study reveals the mechanism of Phyllostachys praecox cell membrane responding to hypoxia stress based on molecular level. This is conducive to finding targeted solutions to improve the productivity of Phyllostachys praecox to better optimize a mulching approach in the bamboo forest

Single-cell transcriptome analysis revealed heterogeneity in glycolysis and identified IGF2 as a therapeutic target for ovarian cancer subtypes

Abstract Background As the most malignant tumor of the female reproductive system, ovarian cancer (OC) has garnered increasing attention. The Warburg effect, driven by glycolysis, accounts for tumor cell proliferation under aerobic conditions. However, the metabolic heterogeneity linked to glycolysis in OC remains elusive. Methods We integrated single-cell data with OC to score glycolysis level in tumor cell subclusters. This led to the identification of a subcluster predominantly characterized by glycolysis, with a strong correlation to patient prognosis. Core transcription factors were pinpointed using hdWGCNA and metaVIPER. A specific transcription factor regulatory network was then constructed. A glycolysis-related prognostic model was developed and tested for estimating OC prognosis with a total of 85 machine-learning combinations, focusing on specific upregulated genes of two subtypes. We identified IGF2 as a key within the prognostic model and investigated its impact on OC progression and drug resistance through in vitro experiments, including the transwell assay, lactate production detection, and the CCK-8 assay. Results Analysis showed that the Malignant 7 subcluster was primarily related to glycolysis. Two OC molecular subtypes, CS1 and CS2, were identified with distinct clinical, biological, and microenvironmental traits. A prognostic model was built, and IGF2 emerged as a key gene linked to prognosis. Experiments have proven that IGF2 can promote the glycolysis pathway and the malignant biological progression of OC cells. Conclusions We developed two novel OC subtypes based on glycolysis score, established a stable prognostic model, and identified IGF2 as the marker gene. These insights provided a new avenue for exploring OC’s molecular mechanisms and personalized treatment approaches

Effect of Hypoxic Stress and Levels of Mn on the Physiology and Biochemistry of <i>Phyllostachys praecox</i>

Hypoxic environments have an adverse effect on the growth and development of P. praecox, and this is accompanied by the production of reducing substances such as Fe and Mn. In this study, the effect of hypoxic stress and Mn concentrations on leaf chlorophyll contents, root morphology, root activity, element absorption, antioxidant enzymes, and respiratory enzyme system of P. praecox were evaluated in a hydroponics environment. The results revealed that application of Mn2+ during hypoxic stress enhanced leaf chlorophyll contents and boosted up the indexes of the root system. The root activity of P. praecox was reduced with stresses of hypoxia. The treatment of Mn2+ initially improved and then decreased the root activity of P. praecox, and attained its maximum with application of 300 μmol/L Mn2+ compared with control. The indexes of antioxidant enzymes of P. praecox were higher than that of 8 mg/L oxygen concentrations except for variable superoxide dismutase (SOD) in the treatment of 300 μmol/L Mn2+ with hypoxia stress. The application of Mn had inhibited the absorption of mineral elements in P. praecox. The activities of pyruvate decarboxylase (PDC), alcohol dehydrogenase (ADH), and lactic dehydrogenase (LDH) were initially improved and then diminished with hypoxia stress. It is concluded that hypoxia is a key factor affecting the growth and degradation of P. praecox, while combining it with the increase of Mn concentration enhances the damage to Phyllostachys pubescens. Our research is helpful for the sustainable management and scientific fertilization management of Phyllostachys praecox

Prebiotic Effect of Fructooligosaccharides from Morinda officinalis on Alzheimer’s Disease in Rodent Models by Targeting the Microbiota-Gut-Brain Axis

Gut microbiota influences the central nervous system disorders such as Alzheimer’s disease (AD). The prebiotics and probiotics can improve the host cognition. A previous study demonstrated that fructooligosaccharides from Morinda officinalis (OMO) exert effective memory improvements in AD-like animals, thereby considered as potential prebiotics; however, the underlying mechanism still remains enigma. Thus, the present study investigated whether OMO is effective in alleviating AD by targeting the microbiota-gut-brain axis. OMO was administered in rats with AD-like symptoms (D-galactose- and Aβ1-42-induced deficient rats). Significant and systematic deterioration in AD-like animals were identified, including learning and memory abilities, histological changes, production of cytokines, and microbial community shifts. Behavioral experiments demonstrated that OMO administration can ameliorate the learning and memory abilities in both AD-like animals significantly. AD parameters showed that OMO administration cannot only improve oxidative stress and inflammation disorder, but also regulate the synthesis and secretion of neurotransmitter. Histological changes indicated that OMO administration ameliorates the swelling of brain tissues, neuronal apoptosis, and down-regulation of the expression of AD intracellular markers (Tau and Aβ1-42). 16S rRNA sequencing of gut microbiota indicated that OMO administration maintains the diversity and stability of the microbial community. In addition, OMO regulated the composition and metabolism of gut microbiota in inflammatory bowel disease (IBD) mice model treated by overdosed antibiotics and thus showed the prebiotic potential. Moreover, gut microbiota plays a major role in neurodevelopment, leading to alterations in gene expression in critical brain and intestinal regions, thereby resulting in perturbation to the programming of normal cognitive behaviors. Taken together, our findings suggest that the therapeutic effect of the traditional medicine, M. officinalis, on various neurological diseases such as AD, is at least partially contributed by its naturally occurring chemical constituent, OMO, via modulating the interaction between gut ecology and brain physiology