Meta-analysis of Huangqi (Astragalus membranaceus) and Chinese Yam (Rhizoma Dioscoreae) for Diabetic Nephropathy.

Context: Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), has caused enormous economic pressure and serious health problems worldwide. TCM practitioners commonly use a combination of Astragalus membranaceus (A. membranaceus) and Rhizoma Dioscoreae (R. Dioscoreae) in the treatment of DN. Research is still lacking on the therapeutic effects of TCM for DN. Objective: The systematic review and meta-analysis intended to evaluate whether the combination of A. membranaceus and R. Dioscoreae together with Western medicine can provide better efficacy against DN than treatment with traditional Western medicine alone, to provide a clinical medical basis for the use of the TCM combination. Design: The research team performed a performed a systematic narrative review by searching the Web of Science, Science Direct, Pubmed, China National Knowledge Infrastructure (CNKI), VIP, Wanfang, Chinese Science and Technology Journal Database, and Biomedical Literature Chinese Database from databases' inceptions to May 2023. The team used the keywords astragalus and yam, diabetic nephropathy, antidiabetic, and 24-h urinary protein. Setting: The review and meta-analysis occurred at Jiangxi Hospital of Integrated Traditional China and Western Medicine in Nanchang, Jiangxi, China. Intervention: To perform a subgroup analysis, the research team divided the studies into two groups based on the TCM treatment course, with one subgroup receiving treatment for ≤4 weeks and the second receiving treatment for >4 weeks, to judge whether a time-dependence existed for the effects of the TCM combination on UP. Outcome Measure: All studies used 24-h urinary protein (UP) as the outcome measure. Results: In all studies, all heterogeneous (P < .01, I2 = 94%, the intervention groups had a significantly greater reduction in 24-h UP than the control groups did (P < .05). The heterogeneity for a treatment course of ≤4 weeks was P < .01, I2 = 97%, and for a course of >4 weeks was P < .01, I2 = 87%. For both ≤4 weeks and >4 weeks, the intervention groups had a significantly greater reduction in 24-h UP than the control groups did, with P < .01 and P < .01, respectively. The protein effect wasn't time dependent. Conclusions: A. membranaceus and R. Dioscoreae can significantly reduce UP production, and inhibition of UP wasn't time-dependent.

GID complex regulates the differentiation of neural stem cells by destabilizing TET2.

Brain development requires a delicate balance between self-renewal and differentiation in neural stem cells (NSC), which rely on the precise regulation of gene expression. Ten-eleven translocation 2 (TET2) modulates gene expression by the hydroxymethylation of 5-methylcytosine in DNA as an important epigenetic factor and participates in the neuronal differentiation. Yet, the regulation of TET2 in the process of neuronal differentiation remains unknown. Here, the protein level of TET2 was reduced by the ubiquitin-proteasome pathway during NSC differentiation, in contrast to mRNA level. We identified that TET2 physically interacts with the core subunits of the glucose-induced degradation-deficient (GID) ubiquitin ligase complex, an evolutionarily conserved ubiquitin ligase complex and is ubiquitinated by itself. The protein levels of GID complex subunits increased reciprocally with TET2 level upon NSC differentiation. The silencing of the core subunits of the GID complex, including WDR26 and ARMC8, attenuated the ubiquitination and degradation of TET2, increased the global 5-hydroxymethylcytosine levels, and promoted the differentiation of the NSC. TET2 level increased in the brain of the Wdr26+/- mice. Our results illustrated that the GID complex negatively regulates TET2 protein stability, further modulates NSC differentiation, and represents a novel regulatory mechanism involved in brain development.

Expression of PnSS Promotes Squalene and Oleanolic Acid (OA) Accumulation in Aralia elata via Methyl Jasmonate (MeJA) Induction.

Aralia elata is an important herb due to the abundance of pentacyclic triterpenoid saponins whose important precursors are squalene and OA. Here, we found that MeJA treatment promoted both precursors accumulation, especially the latter, in transgenic A. elata, overexpressing a squalene synthase gene from Panax notoginseng(PnSS). In this study, Rhizobium-mediated transformation was used to express the PnSS gene. Gene expression analysis and high-performance liquid chromatography (HPLC) were used to identify the effect of MeJA on squalene and OA accumulation. The PnSS gene was isolated and expressed in A. elata. Transgenic lines showed a very high expression of the PnSS gene and farnesyl diphosphate synthase gene (AeFPS) and a slightly higher squalene content than the wild-type, but endogenous squalene synthase (AeSS), squalene epoxidase (AeSE), and ß-amyrin synthase (Aeß-AS) gene were decreased as well as OA content. Following one day of MeJA treatment, the expression levels of PeSS, AeSS, and AeSE genes increased significantly. On day 3, the maximum content of both products reached 17.34 and 0.70 mg·g-1, which increased 1.39- and 4.90-fold than in the same lines without treatment. Transgenic lines expressing PnSS gene had a limited capability to promote squalene and OA accumulation. MeJA strongly activated their biosynthesis pathways, leading to enhance yield.

The Tet2-Upf1 complex modulates mRNA stability under stress conditions.

Introduction: Environmental stress promotes epigenetic alterations that impact gene expression and subsequently participate in the pathological processes of the disorder. Among epigenetic regulations, ten-eleven Translocation (Tet) enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA and RNA and function as critical players in the pathogenesis of diseases. Our previous results showed that chronic stress increases the expression of cytoplasmic Tet2 in the hippocampus of mice exposed to chronic mild stress (CMS). Whether the cytoplasmic Tet2 alters RNA 5hmC modification in chronic stress-related processes remains largely unknown. Methods: To explore the role of cytoplasmic Tet2 under CMS conditions, we established CMS mice model and detected the expression of RNA 5hmC by dot blot. We verified the interaction of Tet2 and its interacting protein by co-immunoprecipitation combined with mass spectrometry and screened downstream target genes by cluster analysis of Tet2 and upstream frameshift 1 (Upf1) interacting RNA. The expression of protein was detected by Western blot and the expression of the screened target genes was detected by qRT-PCR. Results: In this study, we found that increased cytoplasmic Tet2 expression under CMS conditions leads to increase in total RNA 5hmC modification. Tet2 interacted with the key non-sense-mediated mRNA decay (NMD) factor Upf1, regulated the stability of stress-related genes such as Unc5b mRNA, and might thereby affect neurodevelopment. Discussion: In summary, this study revealed that Tet2-mediated RNA 5hmC modification is involved in stress-related mRNA stability regulation and may serve as a potential therapeutic target for chronic stress-related diseases such as depression.

Readiness for Hospital Discharge After a Cesarean Section and Associated Factors Among Chinese Mothers: A Single Centre Cross-Sectional Study.

Purpose: Knowledge of the readiness for hospital discharge can help health care professionals accurately determine the patients' discharge time. However, few studies were on the readiness for discharge and its related factors among mothers with cesarean sections. Thus, this study aims to examine the readiness for hospital discharge and its associated factors among Chinese mothers with cesarean sections. Patients and Methods: A single-centre cross-sectional study was conducted from September 2020 to March 2021 in Guangzhou, China. Three hundred thirty-nine mothers with cesarean sections completed the questionnaires on demographic and obstetric characteristics, readiness for hospital discharge, quality for discharge teaching, parenting sense of competence, family function, and social support. Multiple linear regression analysis was used to identify independent factors influencing readiness for hospital discharge among mothers with cesarean sections. Results: The total score of readiness for hospital discharge was 136.47 ± 25.29. The quality of discharge teaching, parenting sense of competence, number of cesareans, family function, and attending antenatal classes were independent factors influencing the readiness for hospital discharge (P < 0.05) among mothers with cesarean sections. Conclusion: The readiness for hospital discharge of mothers with cesarean sections need to be improved. Improving the quality of discharge teaching, parenting sense of competence, and family function may help improve the readiness for hospital discharge of mothers with cesarean sections.

Tet Enzyme-Mediated Response in Environmental Stress and Stress-Related Psychiatric Diseases.

Mental disorders caused by stress have become a worldwide public health problem. These mental disorders are often the results of a combination of genes and environment, in which epigenetic modifications play a crucial role. At present, the genetic and epigenetic mechanisms of mental disorders such as posttraumatic stress disorder or depression caused by environmental stress are not entirely clear. Although many epigenetic modifications affect gene regulation, the most well-known modification in eukaryotic cells is the DNA methylation of CpG islands. Stress causes changes in DNA methylation in the brain to participate in the neuronal function or mood-modulating behaviors, and these epigenetic modifications can be passed on to offspring. Ten-eleven translocation (Tet) enzymes are the 5-methylcytosine (5mC) hydroxylases of DNA, which recognize 5mC on the DNA sequence and oxidize it to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Tet regulates gene expression at the transcriptional level through the demethylation of DNA. This review will elaborate on the molecular mechanism and the functions of Tet enzymes in environmental stress-related disorders and discuss future research directions.

Microwave catalytic co-pyrolysis of waste cooking oil and low-density polyethylene to produce monocyclic aromatic hydrocarbons: Effect of different catalysts and pyrolysis parameters.

It is promising to convert waste oil and plastics to renewable fuels and chemicals by microwave catalytic co-pyrolysis, enabling pollution reduction and resource recovery. The purpose of this study was to evaluate the effect of catalysts on the product selectivity of microwave-assisted co-pyrolysis of waste cooking oil and low-density polyethylene and optimize the pyrolysis process, including pyrolysis temperature, catalytic temperature, waste cooking oil to low-density polyethylene ratio, and catalyst to feedstocks ratio. The results indicated that catalysts had a great influence on the product distribution, and the yield of BTX (benzene, toluene, and xylenes), which increased in the following order: SAPO-34 < Hß < HY < HZSM-5. HZSM-5 was more active for the formation of light aromatic hydrocarbons as compared to others, where the concentrations of toluene, benzene and xylenes reached 252.59 mg/mL, 114.7 mg/mL and 132.91 mg/mL, respectively. The optimum pyrolysis temperature, catalytic temperature, waste cooking oil to low-density polyethylene ratio and catalyst to feedstocks ratio could be 550 °C, 450 °C, 1:1 and 1:2, respectively, to maximize the formation of BTX and inhibit the formation of polycyclic aromatic hydrocarbons.

Conversion of cotton textile wastes into porous carbons by chemical activation with ZnCl2, H3PO4, and FeCl3.

In this study, ZnCl2, H3PO4, and FeCl3 were used as activating agents to prepare porous carbons (PC-ZnCl2, PC-H3PO4, and PC-FeCl3) from cotton textile wastes at a relativity low temperature. The morphology and structure of carbons were characterized by SEM and XRD demonstrating that carbons with porous property were successfully obtained. Textural properties showed that the PC-ZnCl2 possessed the largest specific surface area of 1854.70 m2 g-1 with mesopores domination. Both of micropores and mesopores existed in PC-H3PO4. Micropores were well developed in PC-FeCl3, and the proportion of which was the highest. The FTIR and pHpzc analysis indicated that all the carbons had acidic characteristics, and more acid functional groups were appeared on the PC-FeCl3 than others. The different pyrolysis activation paths were proposed by the thermogravimetric analysis, which proved that the addition of activating agents promoted the formation of pores, lowered the pyrolysis temperature of cotton textile wastes, and inhibited the production of volatiles. The results of adsorption kinetics and isotherm revealed that PC-ZnCl2 exhibited the best adsorption capacity of Cr(VI), and chemical adsorption played a significant role. Meanwhile, surface functional groups of porous carbons also participated in the Cr(VI) adsorption via electrostatic interaction and reduction reaction. Graphical abstract.

Astragaloside IV inhibits astrocyte senescence: implication in Parkinson's disease.

BACKGROUND: Senescent astrocytes have been implicated in the aging brain and neurodegenerative disorders, including Parkinson's disease (PD). Astragaloside IV (AS-IV) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge and exerts anti-inflammatory and longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined. METHODS: Long culture-induced replicative senescence model and lipopolysaccharide/1-methyl-4-phenylpyridinium (LPS/MPP+)-induced premature senescence model and a mouse model of PD were used to investigate the effect of AS-IV on astrocyte senescence in vivo and in vitro. Immunocytochemistry, qPCR, subcellular fractionation, flow cytometric analyses, and immunohistochemistry were subsequently conducted to determine the effects of AS-IV on senescence markers. RESULTS: We found that AS-IV inhibited the astrocyte replicative senescence and LPS/MPP+-induced premature senescence, evidenced by decreased senescence-associated ß-galactosidase activity and expression of senescence marker p16, and increased nuclear level of lamin B1, and reduced pro-inflammatory senescence-associated secretory phenotype. More importantly, we showed that AS-IV protected against the loss of dopamine neurons and behavioral deficits in the mouse model of PD, which companied by reduced accumulation of senescent astrocytes in substantia nigra compacta. Mechanistically, AS-IV promoted mitophagy, which reduced damaged mitochondria accumulation and mitochondrial reactive oxygen species generation and then contributed to the suppression of astrocyte senescence. The inhibition of autophagy abolished the suppressive effects of AS-IV on astrocyte senescence. CONCLUSIONS: Our findings reveal that AS-IV prevents dopaminergic neurodegeneration in PD via inhibition of astrocyte senescence through promoting mitophagy and suggest that AS-IV is a promising therapeutic strategy for the treatment of age-associated neurodegenerative diseases such as PD.

Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiquitination and autophagy: implications for Parkinson disease.

Aging-related, nonresolving inflammation in both the central nervous system (CNS) and periphery predisposes individuals to the development of neurodegenerative disorders (NDDs). Inflammasomes are thought to be especially relevant to immune homeostasis, and their dysregulation contributes to inflammation and NDDs. However, few agents have been clinically shown to reduce NDD incidence by targeting inflammasomes. Our study indicated that NLRP3 (NLR family, pyrin domain containing 3) inflammasome is involved in Parkinson disease (PD) progression in patients and various murine models. In addition, the small molecule kaempferol (Ka) protected mice against LPS- and SNCA-induced neurodegeneration by inhibiting NLRP3 inflammasome activation as evidenced by the fact that Ka reduced cleaved CASP1 expression and disrupted NLRP3-PYCARD-CASP1 complex assembly with concomitant decreased IL1B secretion. Mechanically, Ka promoted macroautophagy/autophagy in microglia, leading to reduced NLRP3 protein expression, which in turn deactivated the NLRP3 inflammasome. Intriguingly, ubiquitination was involved in Ka-induced autophagic NLRP3 degradation. These findings were further confirmed in vivo as knockdown of Atg5 expression or autophagy inhibitor treatment significantly inhibited the Ka-mediated NLRP3 inflammasome inhibition and neurodegeneration amelioration. Thus, we demonstrated that Ka promotes neuroinflammatory inhibition via the cooperation of ubiquitination and autophagy, suggesting that Ka is a promising therapeutic strategy for the treatment of NDDs. Abbreviations: 3-MA: 3-methyladenine; AAV: adeno-associated virus; ACTB: actin, beta; AIF1/IBA1: allograft inflammatory factor 1; ATG5: autophagy related 5; ATG7: autophagy related 7; BafA1: bafilomycin A1; BECN1: beclin 1, autophagy related; CASP1: caspase 1; CNS: central nervous system; CQ: chloroquine; DA neurons: dopaminergic neurons; DAMPS: damage-associated molecular patterns; DAPI: 4',6-diamidino-2-phenylindole; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; GFAP: glial fibrillary acidic protein; IP: immunoprecipitation; i.p.: intraperitoneally; Ka: kaempferol; KD: knockdown; KO: knockout; LPS: lipopolysaccharide; IL1B: interleukin 1 beta; IL6: interleukin 6; Ly: lysate; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NC: negative control; NDD: neurodegenerative diseases; NLRP3: NLR family, pyrin domain containing 3; OE: overexpression; PD: Parkinson disease; poly-Ub: poly-ubiquitin; PTM: post-translational modification; PYCARD/ASC: PYD and CARD domain containing; Rapa: rapamycin; RFP: red fluorescent protein; SN: supernatant; SNCA: synuclein alpha; SNpc: substantia nigra pars compacta; SQSTM1: sequestosome 1; TH: tyrosine hydroxylase; TNF/TNF-alpha: tumor necrosis factor; Ub: ubiquitin; WT: wild type.

α-Synuclein disrupts the anti-inflammatory role of Drd2 via interfering ß-arrestin2-TAB1 interaction in astrocytes.

BACKGROUND: α-Synuclein (α-Syn)-induced neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD). Dopamine D2 receptor (Drd2) has been regarded as a potential anti-inflammatory target in the therapy of neurodegenerative diseases. However, the effect of astrocytic Drd2 in α-Syn-induced neuroinflammation remains unclear. METHODS: The effect of Drd2 on neuroinflammation was examined in mouse primary astrocyte in vitro and A53T transgenic mice in vivo. The inflammatory responses of astrocyte were detected using immunofluorescence, ELISA, and qRT-PCR. The details of molecular mechanism were assessed using Western blotting and protein-protein interaction assays. RESULTS: We showed that the selective Drd2 agonist quinpirole suppressed inflammation in the midbrain of wild-type mice, but not in α-Syn-overexpressed mice. We also found that Drd2 agonists significantly alleviated LPS-induced inflammatory response in astrocytes, but failed to suppress α-Syn-induced inflammatory response. The anti-inflammation effect of Drd2 was dependent on ß-arrestin2-mediated signaling, but not classical G protein pathway. α-Syn reduced the expression of ß-arrestin2 in astrocytes. Increased the ß-arrestin2 expression restored in the anti-inflammation of Drd2 in α-Syn-induced inflammation. Furthermore, we demonstrated that α-Syn disrupted the anti-inflammation of Drd2 via inhibiting the association of ß-arrestin2 with transforming growth factor-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and promoting TAK1-TAB1 interaction in astrocytes. CONCLUSIONS: Our study illustrates that astrocytic Drd2 inhibits neuroinflammation through a ß-arrestin2-dependent mechanism and provides a new strategy for treatment of PD. Our findings also reveal that α-Syn disrupts the function of ß-arrestin2 and inflammatory pathways in the pathogenesis of PD.