Paeonol represses A549 cell glycolytic reprogramming and proliferation by decreasing m6A modification of Acyl-CoA dehydrogenase.

Aberrant glycolytic reprogramming is involved in lung cancer progression by promoting the proliferation of non-small cell lung cancer cells. Paeonol, as a traditional Chinese medicine, plays a critical role in multiple cancer cell proliferation and inflammation. Acyl-CoA dehydrogenase (ACADM) is involved in the development of metabolic diseases. N6-methyladenosine (m6A) modification is important for the regulation of messenger RNA stability, splicing, and translation. Here, we investigated whether paeonol regulates the proliferation and glycolytic reprogramming via ACADM with m6A modification in A549 cells (human non-small cell lung cancer cells). Cell counting kit 8, 5-Bromo-2-deoxyuridine, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, flow cytometry analysis, western blotting and seahorse XFe24 extracellular flux analyzer assays showed that paeonol had a significant inhibitory effect against A549 cell proliferation and glycolysis. Mechanistically, ACADM was a functional target of paeonol. We also showed that the m6A reader YTH domain containing 1 plays an important role in m6A-modified ACADM expression, which is negatively regulated by paeonol, and is involved in A549 cell proliferation and glycolytic reprogramming. These results indicated the central function of paeonol in regulating A549 cell glycolytic reprogramming and proliferation via m6A modification of ACADM.

Intestinal segment and vitamin D3 concentration affect gene expression levels of calcium and phosphorus transporters in broiler chickens.

Two experiments were conducted in this research. Experiment 1 investigated the spatial expression characteristics of calcium (Ca) and phosphorus (P) transporters in the duodenum, jejunum, and ileum of 21-day-old broilers provided with adequate nutrient feed. Experiment 2 evaluated the effects of dietary vitamin D3 (VD3) concentration (0, 125, 250, 500, 1,000, and 2,000 IU/kg) on growth performance, bone development, and gene expression levels of intestinal Ca and P transporters in 1-21-day-old broilers provided with the negative control diet without supplemental VD3. Results in experiment 1 showed that the mRNA levels of calcium-binding protein 28-kDa (CaBP-D28k), sodium-calcium exchanger 1 (NCX1), plasma membrane calcium ATPase 1b (PMCA1b), and IIb sodium-phosphate cotransporter (NaPi-IIb) were the highest in the broiler duodenum. By contrast, the mRNA levels of inorganic phosphate transporter 1 (PiT-1) and 2 (PiT-2) were the highest in the ileum. Results in experiment 2 showed that adding 125 IU/kg VD3 increased body weight gain (BWG), feed intake (FI), bone weight, and percentage and weight of Ca and P in the tibia and femur of 1-21-day-old broilers compared with the negative control diet (p < 0.05). The rise in dietary VD3 levels from 125 to 1,000 IU/kg further increased the BWG, FI, and weights of the bone, ash, Ca, and P (p < 0.05). No difference in growth rate and leg bone quality was noted in the broilers provided with 1,000 and 2,000 IU/kg VD3 (p > 0.05). Supplementation with 125-2,000 IU/kg VD3 increased the mRNA abundances of intestinal Ca and P transporters to varying degrees. The mRNA level of CaBP-D28k increased by 536, 1,161, and 28 folds in the duodenum, jejunum, and ileum, respectively, after adding 1,000 IU/kg VD3. The mRNA levels of other Ca and P transporters (PMCA1b, NCX1, NaPi-IIb, PiT-1, and PiT-2) increased by 0.57-1.74 folds by adding 1,000-2,000 IU/kg VD3. These data suggest that intestinal Ca and P transporters are mainly expressed in the duodenum of broilers. Moreover, the addition of VD3 stimulates the two mineral transporter transcription in broiler intestines.

Efficacy of the Integrative Acupuncture and Moxibustion Treatment in Patients With Major Depressive Disorder: The Study Protocol for a Multicenter, Single-Blinded, Randomized Trial in China.

Introduction: Antidepressants are the front-line treatments for major depressive disorder (MDD), but remain unsatisfactory in outcome. An increasing number of patients are interested in acupuncture and moxibustion treatment as complementary therapies. This study aims to evaluate the efficacy and safety of integrative acupuncture and moxibustion (iAM) treatment in patients with MDD. Methods and Analysis: This multicenter, single-blind, 2 × 2 factorial randomized trial will enroll 592 patients with MDD of moderate severity from nine hospitals. All patients will be randomized, in a ratio of 2:2:2:1, through a computerized central randomization system, into four groups (the combined, iAM-only, sertraline-only, and placebo groups). Participants will undergo a 12-week intervention with either 50 mg of sertraline or a placebo once a day and active/sham iAM treatment three times per week. The primary outcome is depression severity, assessed using the Hamilton Depression Scale-17. The secondary outcomes include self-rated depression severity, anxiety, and sleep quality. The primary and secondary outcomes will be measured at weeks 0, 4, 8, 12, and the 8th week posttreatment. Safety will be evaluated through liver and kidney function tests conducted before and after treatment and through monitoring of daily adverse events. An intent-to-treat principle will be followed for the outcome analyses. Conclusion: This trial will provide sufficient evidence to ascertain whether iAM is effective and safe for treating MDD and provides a suitable combination strategy for treating MDD. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2100042841].

Emotional well-being, spiritual well-being and resilience of advanced clinical practitioners in the United Kingdom during COVID-19: an exploratory mixed method study.

AIM: To investigate the emotional and spiritual well-being and resilience of advanced clinical practitioners during COVID. BACKGROUND: Resilience is a protective factor for emotional and spiritual well-being. The pandemic has taken a toll on health professionals due to significant physical and psychological pressures. The impact of COVID-19 on well-being and resilience of advanced clinical practitioners is not known. METHOD: Three validated scales assessed resilience, emotional and spiritual well-being. Seven hundred and thirty-four responses were analysed. RESULTS: Participants have low levels of emotional and spiritual well-being. Participants with higher levels of spirituality reported greater resilience and those with higher levels of resilience reported greater well-being. CONCLUSION: Advanced clinical practitioners' emotional and spiritual well-being and resilience has been impacted significantly during the pandemic. Interventions are needed at team, service and systems levels to enhance well-being and resilience. IMPLICATIONS FOR NURSING MANAGEMENT: Worryingly low levels of well-being and resilience in advanced clinical practitioners have been found; support to increase well-being and resilience is needed. Our findings can inform policies, resources and interventions aimed at enabling positive adaptation and enhanced resilience. Understanding and responding to the scale and impact of COVID-19 on health care workers has become a key government recommendation following the pandemic.

Emodin-Mediated Treatment of Acute Kidney Injury.

Acute kidney injury (AKI), a common condition associated with a high mortality rate, is characterized by declined glomerular filtration rate, retention of nitrogen products, and disturbances in balance of water, electrolyte, and acid-base. Up to date, there is no effective treatment for AKI. Despite the continuous improvement in blood purification techniques, a considerable proportion of patients with AKI still progress to end-stage renal disease. These patients with advanced stage of end-stage renal disease will require long-term renal replacement therapy, which places a heavy burden on the family and the society. In recent years, the use of traditional Chinese medicine (TCM) in AKI management has been gradually increasing. Clinical evidence has demonstrated that three-month treatment with TCM produced better clinical outcomes in terms of clinical effectiveness rate and improvement in renal function (serum creatinine, neutrophil gelatinase-associated lipocalin, and cystatin C) compared with Western medicine. Rhubarb is a commonly used herb in TCM for the treatment of AKI. The main active component of rhubarb is emodin, which was first recorded in Shennong's Classic of Materia Medica. It has been shown that emodin has a variety of pharmacological activities including antibacterial, anti-inflammatory, antiulcer, and immunosuppressive effects. Emodin has been found to be effective against renal fibrosis and has been widely studied for its effects on kidney diseases such as diabetic nephropathy, renal fibrosis, and AKI. Moreover, promising results have been obtained from these studies. In this study, the results obtained from research on the use of emodin for AKI treatment has been reviewed.

Efficacy of acupuncture on cognitive function in poststroke depression: study protocol for a randomized, placebo-controlled trial.

INTRODUCTION: Poststroke depression (PSD) is the most common mental complication after stroke and has a serious impact on functional outcomes and quality of life. Antidepressants are the first-line treatment for PSD, but many reported side effects remain. Clinical research has shown that acupuncture has a positive effect on PSD. This trial aims to study the efficacy and safety of acupuncture for PSD and to explore its effect on cognitive function. It is hypothesized that acupuncture treatment improves depressive symptoms, cognitive behavior, and negative emotion processing bias in PSD. METHODS: In this randomized, placebo-controlled, single-blinded trial, fifty-six people with PSD will be randomly allocated into the intervention (n=28) or control (n=28) groups. The intervention group will receive acupuncture treatment, and the control group will receive sham acupuncture treatment, in 20 sessions over 4 weeks. The primary outcome is the change from baseline in the Hamilton Depression Scale-17 (HAMD-17) scores at week 4. Secondary outcomes include the Wisconsin Card Sorting Test (WCST) and latency and amplitude of P1, N170, and P3 of the event-related potentials (ERPs) components to assess the changes in cognitive function and electroencephalography. Outcomes are assessed at baseline and post intervention. DISCUSSION: Acupuncture therapy could become an alternative treatment for PSD, and it is expected that this trial will provide reliable clinical evidence for the future use of acupuncture for the treatment of PSD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900026948 . Registered on 27 October 2019.

Madelung's disease with alcoholic liver disease and acute kidney injury: A case report.

BACKGROUND: Madelung's disease (MD) is a rare disorder of lipid metabolism, characterized by the growth of unencapsulated masses of adipose tissue symmetrically deposited around the neck, shoulders, or other sites around the body. Its pathological mechanism is not yet known. One of the most common comorbidities in MD patients is liver disease, especially chronic alcoholic liver disease (CALD); however, no reports exist of acute kidney injury (AKI) with MD. CASE SUMMARY: We report a 60-year-old man who presented with complaint of edema in the lower limbs that had persisted for 3 d. Physical examination showed subcutaneous masses around the neck, and history-taking revealed the masses to have been present for 2 years and long-term heavy drinking. Considering the clinical symptoms, along with various laboratory test results and imaging characteristics, a diagnosis was made of MD with acute exacerbation of CALD and AKI. The patient was treated with liver function protection and traditional Chinese medicine, without surgical intervention. He was advised to quit drinking. After 10 d, the edema had subsided, renal function indicators returned to normal, liver function significantly improved, and size of subcutaneous masses remained stable. CONCLUSION: In MD, concomitant liver or kidney complications are possible and monitoring of liver and kidney functions can be beneficial.

Qian Yang Yu Yin Granule Improves Renal Injury of Hypertension by Regulating Metabolic Reprogramming Mediated by HIF-1α/PKM2 Positive Feedback Loop.

Protection against hypoxia injury is an important therapeutic strategy for treating hypertensive nephropathy. In this study, the effects of Qian Yang Yu Yin granule (QYYY) on spontaneously hypertensive rats fed with high salt diet and HEK293T cells exposed to hypoxia were investigated. After eight weeks' treatment of QYYY, blood pressure, serum creatinine, serum cystatin C, blood urea nitrogen, urinary ß2-microglobulin, urinary N-acetyl-ß-glucosaminidase, and urinary microalbumin were assessed. The changes of hypoxia-inducible factor-1α (HIF-1α), pyruvate kinase M2 (PKM2), glucose transport 1 (GLUT1), lactate dehydrogenase A (LDH-A), connective tissue growth factor (CTGF), transforming growth factor-ß1 (TGF-ß1), ATP, lactate, pyruvate, and pathology were also assessed in vivo. HEK293T cells pre-treated with QYYY and/or HIF-1α over expressing cells were cultured in a three gas hypoxic incubator chamber (5% CO2, 1% O2, 94% N2) for 12 h and then the expressions of HIF-1α, PKM2, GLUT1, LDH-A, CTGF, TGF-ß1, ATP, lactate, and pyruvate were detected. Our results showed that QYYY promoted the indicators of renal inflammation and fibrosis mediated by HIF-1α/PKM2 positive feedback loop in vivo and vitro. Our findings indicated that QYYY treated hypertensive nephropathy by regulating metabolic reprogramming mediated by HIF-1α/PKM2 positive feedback loop.

Combined therapy of hypertensive nephropathy with ginkgo leaf extract and dipyridamole injection and antihypertensive drugs: A systematic review and meta-analysis.

BACKGROUND: In recent years, the incidence rate of hypertensive nephropathy has been increasing quickly, which has been a major threat to people's health. Renin-angiotensin-aldosterone system blockers have certain curative effects. However, there are some patients having serious adverse reactions, and the benefit population is limited, so the treatment of hypertensive renal damage is necessary to have beneficial supplement. More and more clinical studies have shown that ginkgo leaf extract and dipyridamole injection (GDI) combined with antihypertensive drugs has achieved good results in the treatment of hypertensive renal damage. It is supposed to be a supplementary treatment in hypertensive nephropathy. OBJECTIVES: To systematically assess the efficacy and safety of GDI combined with antihypertensive drugs on hypertensive renal injury. METHODS: Seven databases including PubMed, Cochrane Library, Embase, Wanfang database, China biomedical literature service system (Sino Med), VIP Chinese Sci-tech journal database (VIP), and China national knowledge internet (CNKI) were retrieved to collect randomized controlled trials (RCTs) in the experimental group containing combined therapy of hypertensive nephropathy with GDI and antihypertensive drugs. The retrieval time was from the establishment of database to July 8, 2020. Two researchers independently selected literature, extracted data, and evaluated the risk of bias in the study. The methodological quality was evaluated with Cochrane handbook and meta-analysis was performed with Stata 14.0 software. RESULTS: Eight studies were included in this study which involved 556 patients. The meta-analyses indicated that, compared with using antihypertensive drugs alone, combined treatment of GDI with antihypertensive drugs can decrease 24-hour urinary total protein (weighted mean difference [WMD] -0.61, 95% confidence interval [CI]: -0.82, -0.39; k = 6, P ≤ .001), blood urea nitrogen (WMD -1.27, 95% CI: -2.45, -0.10; k = 6, P = .033, serum creatinine (WMD -29.50, 95% CI: -56.44, -2.56; number of estimates [k] = 6, P = .032). CONCLUSIONS: Our meta-analyses showed that GDI combined with antihypertensive drugs can improve the renal function of hypertensive patients with renal injury.

Efficacy and safety of traditional Chinese medicinal enemas for treatment of chronic renal failure: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic renal failure (CRF) is a common kidney disease characterized by a slow and progressive decline in kidney function. Clinical practice suggests that traditional Chinese medicinal enemas have a therapeutic effect on CRF. To assess the therapeutic efficacy and safety of traditional Chinese medicinal enemas in treating CRF, we created a protocol for a systematic review to inform future clinical applications. METHODS: We completed a literature search of all clinical randomized controlled trials evaluating traditional Chinese medicinal enemas on CRF in the following five English and four Chinese databases completed before August 2020: Medline, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Library database, Chinese National Knowledge Infrastructure (CNKI), WANFANE Database, Chinese Scientific and Technological Periodical Database (VIP) and Chinese Biomedical Database (CBM). The primary outcomes evaluated blood urea nitrogen levels, uric acid levels, endogenous creatinine clearance rate, and serum creatinine, and the secondary outcomes included clinical efficacy and adverse effects of treatment. Two independent researchers performed data extraction and quality assessment. RevMan5.3 software was used to assess data quality and bias. This protocol was conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis Protocol (PRISMA-P) statement. RESULTS: This study will provide a rational synthesis of current evidence for traditional Chinese medicinal enemas for the treatment of CRF. CONCLUSION: This study presents evidence on whether traditional Chinese medicinal enemas are an effective and safe intervention for CRF patients. REGISTRATION NUMBER: INPLASY202080052.

Danhong Injection for the Treatment of Hypertensive Nephropathy: A Systematic Review and Meta-Analysis.

OBJECTIVE: Danhong Injection (DHI) has been widely used to treat various diseases in China for many years. The objective of this systematic review was to evaluate the efficacy of DHI combined with antihypertensive drugs for treatment of hypertensive nephropathy. METHODS: Seven databases were searched from inception to September 21st, 2019. Randomized controlled trials comparing DHI combined with antihypertensive drugs versus antihypertensive drugs alone were extracted. The primary outcome was microalbuminuria (mALB). Secondary outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum creatinine (SCr). RESULTS: Fifteen studies were included in the meta-analysis, which indicated that DHI combined with antihypertensive drugs has advantages compared with antihypertensive drugs alone for reducing mALB [weighted mean difference (WMD) = -12.86, 95% confidence interval (CI) (-14.72, -11.0), P < 0.01], lowering SBP [WMD = -2.84, 95% CI (-4.56, -1.12), P = 0.001] and DBP [WMD = -2.38, 95% CI (-4.34, -0.43), P = 0.017], and decreasing SCr [WMD = -40.45, 95% CI (-55.69, -25.21), P < 0.01]. CONCLUSION: The combination of DHI with antihypertensive drugs appears to be more effective than antihypertensive drugs alone for treatment of hypertensive nephropathy. A moderate duration (≤4 weeks) of DHI administration is reasonable, and longer treatment with DHI should be avoided, according to the results of subgroup analysis.

Hirsutella sinensis inhibits NLRP3 inflammasome activation to block aristolochic acid-induced renal tubular epithelial cell transdifferentiation.

In recent years, kidney damage caused by ingestion of Chinese medicinal herbs containing Aristolochic acid (AA) has attracted extensive attention. However, whether the nephrotoxicity of AA is related to NLRP3 inflammasome has not been reported. Hirsutella sinensis (HS) has a certain therapeutic effect on aristolochic acid nephropathy (AAN) and is related to NLRP3 inflammasome. Therefore, this study explores whether HS plays a role in renal injury induced by AA through NLRP3 inflammasome pathway. AA-stimulated renal tubular epithelial cells showed that AA could promote the expression of NLRP3, ASC, and α-SMA, increase the secretion and expression of caspase-1, IL-1ß, and IL-18, and inhibit the expression of E-cadherin in a dose- and time-dependent manner. When NLRP3 was down-regulated, the expression of α-SMA and E-cadherin did not change significantly, but significantly blocked the regulation of α-SMA and E-cadherin expression by AA. When AA and HS were added to renal tubular epithelial cells at the same time, the effects of AA on the expression of NLRP3, ASC, caspase-1, IL-1ß, IL-18, and α-SMA gradually decreased to the level of control group with the increase of HS dosage. At the same time, HS can reduce the transdifferentiation of renal tubular epithelial cells by inhibiting the activation of NLRP3 inflammasome. These findings will provide important pharmacological references for the treatment of AAN and the clinical application of HS.

S-Locus F-Box Proteins Are Solely Responsible for S-RNase-Based Self-Incompatibility of Petunia Pollen.

Self-incompatibility (SI) in Petunia is regulated by a polymorphic S-locus. For each S-haplotype, the S-locus contains a pistil-specific S-RNase gene and multiple pollen-specific S-locus F-box (SLF) genes. Both gain-of-function and loss-of-function experiments have shown that S-RNase alone regulates pistil specificity in SI. Gain-of-function experiments on SLF genes suggest that the entire suite of encoded proteins constitute the pollen specificity determinant. However, clear-cut loss-of-function experiments must be performed to determine if SLF proteins are essential for SI of pollen. Here, we used CRISPR/Cas9 to generate two frame-shift indel alleles of S2 -SLF1 (SLF1 of S2 -haplotype) in S2S3 plants of P. inflata and examined the effect on the SI behavior of S2 pollen. In the absence of a functional S2-SLF1, S2 pollen was either rejected by or remained compatible with pistils carrying one of eight normally compatible S-haplotypes. All results are consistent with interaction relationships between the 17 SLF proteins of S2 -haplotype and these eight S-RNases that had been determined by gain-of-function experiments performed previously or in this work. Our loss-of-function results provide definitive evidence that SLF proteins are solely responsible for SI of pollen, and they reveal their diverse and complex interaction relationships with S-RNases to maintain SI while ensuring cross-compatibility.

Combined Therapy of Hypertensive Nephropathy with Breviscapine Injection and Antihypertensive Drugs: A Systematic Review and a Meta-Analysis.

OBJECTIVE: To evaluate the beneficial and adverse effects of breviscapine injection in combination with antihypertensive drugs for treating hypertensive nephropathy in clinical practice. METHODS: We searched PubMed, the Cochrane Library, Embase, CNKI, Sino Med, VIP, and Wanfang Data for relevant literature. The timeframe of retrieval was set from the founding date of each database to September 28, 2018. RESULTS: Fourteen papers were included in this study. The quality of all the studies included was determined to be low. All studies were conducted with Chinese populations. Meta-analysis showed that, compared with single-use antihypertensive drugs, using breviscapine injection in combination with antihypertensive drugs to treat hypertensive nephropathy can reduce serum creatinine (Scr) [WMD = -35.16, 95% CI(-50.01, -20.31), P ≤ 0.001], blood urea nitrogen (BUN) [WMD = -2.00, 95% CI(-3.07, -0.94), P ≤ 0.001], 24-hour urinary total protein (24 h UTP) [WMD = -0.04, 95% CI(-0.05, -0.02), P ≤ 0.001], and the beta-2-microglobulin (B2M) [WMD = -0.09, 95% CI(-0.11, -0.07), P ≤ 0.001], improve creatinine clearance rate (Ccr) [WMD = 7.84, 95% CI(5.20, 10.49), P ≤ 0.001], and increase the clinical efficacy [RR = 1.27, 95% CI(1.05, 1.53), P = 0.014], but does not lower systolic blood pressure (SBP) [WMD = -1.02, 95% CI(-2.88, 0.84), P = 0.281]. There was no significant difference in adverse events between experimental groups and control groups. CONCLUSION: Breviscapine injection in combination with antihypertensive drugs can improve clinical efficacy and Ccr and reduce Scr, BUN, 24 h UTP, and B2M in patients with hypertensive nephropathy. The present meta-analysis indicated that breviscapine injection can serve as a renal protective effect to patients with hypertensive nephropathy. However, the evidence of methodological quality and sample sizes is weak, and thus, further standardized research is required.

Use of Domain-Swapping to Identify Candidate Amino Acids Involved in Differential Interactions between Two Allelic Variants of Type-1 S-Locus F-Box Protein and S3-RNase in Petunia inflata.

Petunia inflata possesses a self-incompatibility (SI) mechanism, which involves S-RNase and multiple S-locus F-box (SLF) genes at the polymorphic S-locus. For a given S-haplotype, each SLF is thought to interact with some of its non-self S-RNases, but not with its self S-RNase. In this work, we studied an allelic pair of SLF1, S2-SLF1 and S3-SLF1, which differ in 44 amino acids and show differential interactions with S3-RNase. We first used an in vivo transgenic assay to determine whether four chimeric proteins of S2-SLF1 and S3-SLF1, each with one of the three functional domains swapped, interact with S3-RNase. The results narrowed the candidate amino acids for specific interaction of S2-SLF1 with S3-RNase to the 16 in domain FD3. We then examined seven additional chimeric proteins by dividing FD3 into two subdomains and four mini-domains (A, B, C and D). The results further narrowed the candidate amino acids to four in mini-domain A and four in mini-domain D. Molecular modeling of interactions between S3-RNase and S2-SLF1 revealed that three of these eight are at the interaction surface, and all three are conserved in S1-SLF1 and S6a-SLF1, both of which interact with S3-RNase based on the in vivo transgenic assay. Three of the chimeric proteins were used for the in vivo transgenic assay to determine whether FD3 alone contains the amino acids required for S2-SLF1 to interact with S7-RNase and S13-RNase. The results revealed the diversity and complexity of interactions between SLF proteins and S-RNases.

Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription.

The biogenesis of ribosomes in vivo is an essential process for cellular functions. Transcription of ribosomal RNA (rRNA) genes is the rate-limiting step in ribosome biogenesis controlled by environmental conditions. Here, we investigated the role of folate antagonist on changes of DNA double-strand breaks (DSBs) landscape in mouse embryonic stem cells. A significant DSB enhancement was detected in the genome of these cells and a large majority of these DSBs were found in rRNA genes. Furthermore, spontaneous DSBs in cells under folate deficiency conditions were located exclusively within the rRNA gene units, representing a H3K4me1 hallmark. Enrichment H3K4me1 at the hot spots of DSB regions enhanced the recruitment of upstream binding factor (UBF) to rRNA genes, resulting in the increment of rRNA genes transcription. Supplement of folate resulted in a restored UBF binding across DNA breakage sites of rRNA genes, and normal rRNA gene transcription. In samples from neural tube defects (NTDs) with low folate level, up-regulation of rRNA gene transcription was observed, along with aberrant UBF level. Our results present a new view by which alterations in folate levels affects DNA breakage through epigenetic control leading to the regulation of rRNA gene transcription during the early stage of development.

Arbutin, an intracellular hydroxyl radical scavenger, protects radiation-induced apoptosis in human lymphoma U937 cells.

Ionizing radiation (IR) can generate reactive oxygen species (ROS). Excessive ROS have the potential to damage cellular macromolecules including DNA, proteins, and lipids and eventually lead to cell death. In this study, we evaluated the potential of arbutin, a drug chosen from a series of traditional herbal medicine by measuring intracellular hydroxyl radical scavenging ability in X-irradiated U937 cells. Arbutin (hydroquinone-ß-D-glucopyranoside), a naturally occurring glucoside of hydroquinone, has been traditionally used to treat pigmentary disorders. However, there are no reports describing the effect of arbutin on IR-induced apoptosis. We confirmed that arbutin can protect cells from apoptosis induced by X-irradiation. The combination of arbutin and X-irradiation could reduce intracellular hydroxyl radical production and prevent mitochondrial membrane potential loss. It also could down-regulate the expression of phospho-JNK, phospho-p38 in whole cell lysate and activate Bax in mitochondria. Arbutin also inhibits cytochrome C release from mitochondria to cytosol. To verify the role of JNK in X-irradiation-induced apoptosis, the cells were pretreated with a JNK inhibitor, and found that JNK inhibitor could reduce apoptosis induced by X-irradiation. Taken together, our data indicate that arbutin plays an anti-apoptotic role via decreasing intracellular hydroxyl radical production, inhibition of Bax-mitochondria pathway and activation of the JNK/p38 MAPK pathway.

Isofraxidin, a potent reactive oxygen species (ROS) scavenger, protects human leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in p53-independent manner.

Ionizing radiation (IR) leads to oxidizing events such as excessive reactive oxygen species (ROS) in the exposed cells, resulting in further oxidative damage to lipids, proteins and DNA. To screen the potential radio-protective drug, the intracellular ROS was measured in irradiated U937 cells pretreated with 80 candidate traditional herbal medicine, respectively. Isofraxidin (IF) was one possible radio-protector in these 80 drugs. This study investigated the radio-protective role of IF, a Coumarin compound, in human leukemia cell lines, for the first time. Results indicate that IF protects against IR-induced apoptosis in U937 cells in the time- and concentration- dependent manner. IF decreases IR-induced intracellular ROS generation, especially hydroxyl radicals formation, inhibits IR-induced mitochondrial membrane potential loss and reduces IR-induced high intracellular Ca(2+) levels regardless of ER stress. IF down-regulates the expression of caspase-3, phospho-JNK, phospho-p38 and activates Bax in mitochondria. IF inhibits cytochrome c release from mitochondria to cytosol. IF also moderates IR-induced Fas externalization and caspase-8 activation. IF also exhibits significant protection against IR-induced cell death in other leukemia cell lines such as Molt-4 cells and HL60 cells regardless of p53. Taken together, the data demonstrate that IF protects leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in a p53-independent manner.

Isolation and screened neuroprotective active constituents from the roots and rhizomes of Valeriana amurensis.

In previous study, we have screened the effective fraction against Alzheimer's disease (AD-EF) from the extracts of roots and rhizomes of Valeriana amurensis, based on which neuroprotective active constituents from AD-EF were investigated. Six new compounds 1-6, including four iridoids (xiecaoside A-C and xiecaoline A), one pinane-type monoterpeneglucoside (xiecaoside D), and one phenylpropanoid glycoside (xiecaoside E) were isolated together with 11 known compounds 7-17. The structures of 1-6 were elucidated by their spectroscopic data. The protective effects of compounds 1-17 on PC12 cells with neurotoxicity induced by amyloid-beta 1-42 (Aß(1-42)) was also investigated, respectively. Consequently, compound 6 and lignans 11-17 were responsible for protecting against Aß-induced toxicity in PC12 cells.

A mini-review of chemical composition and nutritional value of edible wild-grown mushroom from China.

In China, many species of edible wild-grown mushrooms are appreciated as food and also found use in traditional Chinese medicine. In this mini-review, for the first time, is summarized and discussed data available on chemical components of nutritional significance for wild-grown mushrooms collected from China. We aimed to update and discuss the latest data published on ash, fat, carbohydrates, fibre, proteins, essential amino acids and nonessential amino acids, some essential (P, K, Na, Ca, Mg, Fe, Mn, Zn, Cu) and toxic elements (As, Hg, Cd, Pb), vitamins (thiamine, riboflavin, niacin, tocopherol, vitamin D), flavour and taste compounds, antioxidants and also on less studied organic compounds (lectin, adustin, ribonuclease and nicotine) contents of wild-grown mushrooms.