Higher ratio of plasma omega-6/omega-3 fatty acids is associated with greater risk of all-cause, cancer, and cardiovascular mortality: A population-based cohort study in UK Biobank.

Background: Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality. Methods: We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors. Results: Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15-38%) higher total mortality, 14% (95% CI, 0-31%) higher cancer mortality, and 31% (95% CI, 10-55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects. Conclusions: Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality. Funding: Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Fatty acids play an essential role in health. Studies have shown that diets high in omega-3 fatty acids found in foods like fish, fish oil, flaxseed and walnuts may be beneficial. Yet some studies have raised concern that too many omega-6 fatty acids in Western diets rich in vegetable oils may be harmful. Some scientists have proposed that the balance of omega-3 and omega-6 in diets is vital to health. They hypothesize that a higher omega-6 to omega-3 fatty acids ratio is detrimental. But, proving that a higher ratio of omega-6 to omega-3 fatty acids is harmful has been difficult. Many studies have found conflicting results. Scientists have struggled to accurately measure fatty acid intake as tracking an individual's dietary intake is challenging and self-reported dietary intake may be incorrect. Additionally, scientists must follow individuals for many years to determine if a high ratio of omega-6 to omega-3 is linked with cancer, heart disease, or death. But, measuring circulating fatty acids in an individual's blood may offer an easier and more reliable approach to studying the health impacts of these vital nutrients. Zhang et al. show that people with higher ratios of omega-6 to omega-3 fatty acids in their blood are at greater risk of dying from cancer, heart disease, or any cause than those with lower ratios. The experiments measured omega-6 and omega-3 fatty acid levels in more than 85,000 participants in the UK Biobank who scientists followed for an average of about 13 years. Participants with the highest ratios of omega-6 to omega-3 fatty acids were 26% more likely to die of any cause, 14% more likely to die of cancer, and 31% more likely to die of heart disease than individuals with the lowest ratios. Individually, high levels of omega-6 fatty acids and high levels of omega-3 fatty acids were both associated with a lower risk of dying. But the protective effects of omega-3 were greater. For example, individuals with the highest levels of omega-6 fatty acids were 23% less likely to die of any cause. By comparison, those with the highest levels of omega-3s were 31% less likely to die. The stronger protection offered by high levels of omega-3s likely explains why having a high ratio of omega-6s to omega-3s was linked to harm. Both are protective. But the protection provided by omega-3s is more robust. The experiments support dietary interventions to raise omega-3 fatty acid levels and maintain a low omega-6 to omega-3 fatty acid ratio to prevent early deaths from cancer, heart disease or other causes. More research is needed to understand the impact of dietary fatty acid intake on other diseases and how genetics may influence the health impact of fatty acids.

[Intervention effect of Erchen Decoction on methionine and choline deficient diet-induced non-alcoholic steatohepatitis in mice].

This study investigated the effect of Erchen Decoction(ECD) on the prevention of non-alcoholic steatohepatitis(NASH) in mice and explored its possible mechanism, so as to provide scientific data for the clinical application of ECD in the prevention of NASH. C57BL/6 male mice were randomly divided into normal group(methionine and choline supplement, MCS), model group(methionine and choline deficient, MCD), low-dose ECD group(ECD＿L, 6 g·kg~(-1)), medium-dose ECD group(ECD＿M, 12 g·kg~(-1)), and high-dose ECD group(ECD＿H, 24 g·kg~(-1)), with eight mice in each group. The MCS group was fed with an MCS diet, and the other groups were fed with an MCD diet. The mice in each group were given corresponding diets, but the drug intervention group was given low-, medium-, and high-dose ECD(10 mL·kg~(-1)·d~(-1)) by intragastric administration for six weeks on the basis of MCD diet feeding, and the mice could eat and drink freely during the whole experiment. At the end of the experiment, mice were fasted overnight(12 h) and were anesthetized with 20% urethane. Thereafter, the blood and liver tissue were collected. The serum was used to detect the levels of alanine aminotransferase(ALT), aspartate aminotransaminase(AST), interleukin-1ß(IL-1ß), interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Liver tissue was processed by hematoxylin-eosin(HE) staining and used for hepatic histological analysis and detection of the expression levels of genes and proteins related to nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4(Nrf2/GPX4) pathway by real-time quantitative reverse transcriptase-polymerase chain reaction(RT-qPCR) and Western blot analysis, respectively. The results showed that compared with the MCS group, the MCD group showed higher serum ALT and AST levels; the HE staining exhibited fat vacuoles and obvious inflammatory cell infiltration in liver tissue; serum IL-1ß, IL-6, and TNF-α levels were significantly increased, and the serum IL-10 level was significantly decreased. The mRNA expressions of fatty acid synthase(FASN), monocyte chemoattractant protein-1(MCP-1), and IL-1ß in liver tissue were significantly up-regulated, while those of GPX4, Nrf2, and NAD(P)H:quinine oxidoreductase(NQO1) were significantly down-regulated. Compared with the MCD group, the serum ALT and AST levels of ECD＿M and ECD＿H groups were significantly decreased, and the AST level in the ECD＿L group was significantly decreased. The number of fat vacuoles and the degree of inflammatory cell infiltration in liver tissue were improved; serum IL-1ß, IL-6, and TNF-α levels were significantly decreased, but the serum IL-10 level was significantly increased only in the ECD＿H group. The mRNA expressions of FASN, MCP-1, and IL-1ß in liver tissue were significantly down-regulated, and those of GPX4 and NQO1 were significantly up-regulated. The mRNA expressions of Nrf2 in ECD＿M and ECD＿H groups were significantly up-regulated. Western blot results showed that compared with the MCD group, the protein expression levels of Nrf2 and GPX4 in each group were significantly increased after ECD administration, and the protein expression level of FASN was significantly decreased; the protein expression of NQO1 was increased in ECD＿M and ECD＿H groups. In summary, ECD can reduce hepatic lipid accumulation, oxidative stress, liver inflammation, and liver injury in NASH mice, which may be related to the activation of the Nrf2/GPX4 pathway.

Characterization and anti-aging activities of polysaccharide from Rana dybowskii Guenther.

Introduction: Rana dybowskii Guenther (RDG), as a traditional Chinese medicine, has been shown to have antioxidant effects. However, studies on the anti-aging effect of RDG are still limited. Methods: In this study, we prepared polysaccharides from the skin of RDG (RDGP) by hot water extraction, alcohol precipitation, ion-exchange chromatography and gel chromatography. The proteins were removed using the Sevage method in combination with an enzymatic method. The structural features were analyzed using high-performance gel permeation chromatography, ß-elimination reaction and Fourier transform infrared spectra. The anti-aging effect of RDGP was investigated by using D-Gal to establish an aging model in mice, and pathological changes in the hippocampus were observed under a microscope. Results: We obtained the crude polysaccharide DGP from the skin of RDG, with a yield of 61.8%. The free protein was then removed by the Sevage method to obtain DGPI and deproteinated by enzymatic hydrolysis combined with the Sevage method to further remove the bound protein to obtain the high-purity polysaccharide DGPII. Then, DGPIa (1.03 × 105 Da) and DGPIIa (8.42 × 104 Da) were obtained by gel chromatography, monosaccharide composition analysis showed that they were composed of Man, GlcA, GalNAc, Glc, Gal, Fuc with molar ratios of 1: 4.22 : 1.55: 0.18 : 8.05: 0.83 and 0.74 : 1.78: 1: 0.28: 5.37 : 0.36, respectively. The results of the ß-elimination reaction indicated the presence of O-glycopeptide bonds in DGPIa. The Morris water maze test indicated that mice treated with DGPIIa exhibited a significantly shorter escape latency and increased time spent in the target quadrant as well as an increase in the number of times they traversed the platform. Pathologic damage to the hippocampus was alleviated in brain tissue stained with hematoxylin-eosin. In addition, DGPIIa enhanced the activities of SOD, CAT, and GSH-Px and inhibited the level of MDA in the serum and brain tissues of aging mice. Discussion: These results suggest that RDGP has potential as a natural antioxidant and provide useful scientific information for anti-aging research.

Understanding Sorafenib-Induced Cardiovascular Toxicity: Mechanisms and Treatment Implications.

Tyrosine kinase inhibitors (TKIs) have been recognized as crucial agents for treating various tumors, and one of their key targets is the intracellular site of the vascular endothelial growth factor receptor (VEGFR). While TKIs have demonstrated their effectiveness in solid tumor patients and increased life expectancy, they can also lead to adverse cardiovascular effects including hypertension, thromboembolism, cardiac ischemia, and left ventricular dysfunction. Among the TKIs, sorafenib was the first approved agent and it exerts anti-tumor effects on hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) by inhibiting angiogenesis and tumor cell proliferation through targeting VEGFR and RAF. Unfortunately, the adverse cardiovascular effects caused by sorafenib not only affect solid tumor patients but also limit its application in curing other diseases. This review explores the mechanisms underlying sorafenib-induced cardiovascular adverse effects, including endothelial dysfunction, mitochondrial dysfunction, endoplasmic reticulum stress, dysregulated autophagy, and ferroptosis. It also discusses potential treatment strategies, such as antioxidants and renin-angiotensin system inhibitors, and highlights the association between sorafenib-induced hypertension and treatment efficacy in cancer patients. Furthermore, emerging research suggests a link between sorafenib-induced glycolysis, drug resistance, and cardiovascular toxicity, necessitating further investigation. Overall, understanding these mechanisms is crucial for optimizing sorafenib therapy and minimizing cardiovascular risks in cancer patients.

Neuroimaging research progress of acupuncture treatment for patients with functional dyspepsia. / é’ˆåˆºæ²»ç–—åŠŸèƒ½æ€§æ¶ˆåŒ–ä¸è‰¯çš„ç¥žç»å½±åƒå­¦ç ”ç©¶è¿›å±•.

Neuroimaging technology provides objective and visualized research tool to study the mechanisms of acupuncture effects. Building on a systematic review of previous clinical studies on acupuncture treatment for functional dyspepsia using neuroimaging technology, this paper summarizes and synthesizes past researches from 4 aspects： acupoint-specific effects, factors influencing the effects, different physiological responses, and predictive factors for acupuncture efficacy. It suggests that acupuncture treatment for FD involves central integration with disease-targeted (acupuncture treatment can target and regulate abnormal brain functional activity patterns in patients with FD), meridian-specific (stimulation of specific acupuncture points along the stomach meridian can significantly regulate abnormal brain functional activity patterns in FD patients), and dynamic conditional features(the effects of acupuncture treatment for FD are influenced by multiple factors). Lastly, considering the current research status, this paper outlines prospects in terms of research subjects, influencing factors, and result validation, aiming to provide references for future in-depth research.

[Systematic review and Meta-analysis of efficacy and safety of Bidouyan Oral Liquid in treatment of rhinosinusitis].

This study aimed to systematically review the efficacy and safety of Bidouyan Oral Liquid in the treatment of rhinosinu-sitis(RS). CNKI, Wanfang, SinoMed, VIP, Cochrane Library, PubMed, EMbase, Web of Science, and Ovid were searched for the randomized controlled trial(RCT) of Bidouyan Oral Liquid for the treatment of RS patients. Moreover, the reference lists and the grey literature were searched manually. Two researchers independently screened the literature and extracted data. The Cochrane collaboration's tool for assessing risk of bias(RoB 2.0) in randomized trial was used to assess the methodological quality of the included stu-dies. Meta-analysis was performed in RevMan 5.3 and Stata 12.0, and the grades of recommendation, assessment, development and evaluation(GRADE) was employed to evaluate the quality of evidence. A total of 54 RCTs(35 with drug combinations and 19 with single drugs) comprising 7 511 patients(3 973 in the observation group and 3 538 in the control group) were included. Meta-analysis showed that Bidouyan Oral Liquid + conventional treatment was superior to conventional treatment alone in increasing the total response rate(RR=1.19, 95%CI[1.15, 1.24], P<0.000 01) and decreasing the Lund-Kennedy scores(MD=-1.94, 95%CI[-2.61,-1.26], P<0.000 01), Lund-Mackay scores(MD=-2.14, 95%CI[-2.98,-1.31], P<0.000 01), and visual analogue scale(VAS) scores(MD_(total VAS scores)=-1.28, 95%CI[-1.56,-1.01], P<0.000 01; MD_(nasal congestion VAS scores)=-0.58, 95%CI[-0.89,-0.27], P=0.000 2; MD_(runny nose VAS scores)=-0.61, 95%CI[-0.93,-0.29], P=0.000 2; MD_(olfactory dysfunction VAS scores)=-0.43, 95%CI[-0.52,-0.34], P<0.000 01; MD_(head and facial pain VAS scores)=-0.41, 95%CI[-0.57,-0.26], P<0.000 01). Furthermore, the combined treatment outperformed conventional treatment alone in improving the mucociliary transport rate(MTR)(MD=1.64, 95%CI[1.08, 2.20], P<0.000 01) and lowering the levels of inflammatory cytokines{tumor necrosis factor-α(TNF-α)(SMD=-1.95, 95%CI[-2.57,-1.33], P<0.000 01), interleukin-6(IL-6)(SMD=-2.64, 95%CI[-4.08,-1.21], P=0.000 3)} in RS patients. In addition, the combined treatment did not increase the incidence of adverse reactions(RR=0.83, 95%CI[0.44, 1.57], P=0.57). Bidouyan Oral Liquid was superior to conventional treatment in increasing total response rate(RR=1.25, 95%CI[1.18, 1.32], P<0.000 01), decreasing the Lund-Kennedy(P<0.01) and Lund-Mackay scores(P<0.05), alleviating major symptoms(P_(total VAS scores)<0.01; P_(nasal congestion VAS scores)<0.01; P_(runny nose VAS scores)<0.01; P_(olfactory dysfunction VAS scores)<0.05; P_(head and facial pain VAS scores)<0.01), and decreasing adverse reactions(P=0.03). The results showed that either Bidouyan Oral Liquid or Bidouyan Oral Liquid + conventional treatment can increase the total response rate, decrease the Lund-Kennedy and Lund-Mackay scores, and mitigate major symptoms. In addition, Bidouyan Oral Liquid + conventional treatment improved MTR and reduced the expression of TNF-α and IL-6 without causing serious adverse events. However, due to the limited methodological quality of the included studies, large-sample and high-quality RCTs are needed to provide evidence support.

Is Ancient Medical Treatment an Option for Curating Osteosarcoma Combined with Chemotherapy? A Basic Analysis of Clinic Pharmacy.

BACKGROUND: As a malignant tumor, osteosarcoma (OS) ranks first place among adolescent cancers and is susceptible to developing resistance to chemotherapeutic agents. Differently, traditional Chinese medicine (TCM) has multiple pharmacodynamic targets and complex biological components, which can inhibit tumor survival and drug resistance and gradually play an important role in the treatment of sarcoma. METHODS: This study is to systematically evaluate the safety and efficacy of TCM combined with chemotherapy performed in the clinical treatment of OS. Based on multiple mainstream databases, eleven articles on the relationship between natural products and chemotherapy involving 656 patients were selected from all the literature published as of June 2022. Revman 5.4 software was used for a comprehensive search analysis, supplemented by established exclusion criteria, the Jadad scale, and the evaluation methods provided by Cochrane. RESULTS: The efficiency of TCM combined with chemotherapy was significantly increased compared with chemical drugs alone [OR=2.56, 95% CI (1.36,4.79), Z=2.92, P=0.003]. Meanwhile, the adverse reactions such as nausea and vomiting, hepatotoxicity, and hematological changes caused by chemical drugs were alleviated correspondingly. CONCLUSION: This study indicates that the mode of TCM combined with chemotherapy sheds light on the clinical treatment of OS, which is much better than the one-way mode.

The Efficacy and Safety of Shashen-Maidong Decoction Combined with Western Medicine in the Treatment of Omicron Infected Individuals Over 85 Years Old: A Retrospective Study.

Background: During the Omicron variant outbreak of COVID-19 (2022-2023), Chinese healthcare institutions combined traditional Chinese medicine (TCM) with Western medical practices to treat COVID-19 patients, especially the elderly. The efficacy and safety of this approach, especially for individuals aged over 85, need further investigation. Methods: In this retrospective study, a cohort of 62 patients aged over 85 years, diagnosed with COVID-19 infection, was examined. Among them, 34 patients were administered Shashen-Maidong decoction in conjunction with Western medicine (SMD+WM group), while the remaining 28 patients received only Western medicine (WM group). Comparative analysis was conducted between the two groups, encompassing parameters such as the duration for the nucleic acid test to turn negative, length of intensive care unit (ICU) stay, mortality rate, utilization of high-flow nasal cannula oxygen (HFNC), occurrence of endo-tracheal intubation, frequency of recurrent respiratory infections within three months, and various laboratory indicators. Results: There were no significant differences observed between the two groups in terms of the duration for the nucleic acid test to turn negative, the length of ICU stay, mortality rate, utilization of HFNC, performance of endo-tracheal intubation, or the frequency of recurrent respiratory infections within three months (P > 0.05). However, in comparison to the WM group, the SMD+WM group exhibited notably lower growth rates in white blood cell (WBC) and neutrophil (NEUT) values. Additionally, the SMD+WM group demonstrated superior improvement in cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP) values. Conclusion: In contrast to the administration of Western medicine alone, the combined use of Shashen-Maidong decoction with Western medicine significantly suppresses the increase in WBC count, particularly in NEUT levels, in elderly patients diagnosed with COVID-19. Moreover, this combined treatment exhibits a protective effect on cardiac function and demonstrates a relatively safe profile.

Recent advances in caspase-3, breast cancer, and traditional Chinese medicine: a review.

Caspases (cysteinyl aspartate-specific proteinases) are a group of structurally similar proteases in the cytoplasm that can be involved in cell differentiation, programmed death, proliferation, and inflammatory generation. Experts have found that caspase-3 can serve as a terminal splicing enzyme in apoptosis and participate in the mechanism by which cytotoxic drugs kill cancer cells. Breast cancer (BC) has become the most common cancer among women worldwide, posing a severe threat to their lives. Finding new therapeutic targets for BC is the primary task of contemporary physicians. Numerous studies have revealed the close association between caspase-3 expression and BC. Caspase-3 is essential in BC's occurrence, invasion, and metastasis. In addition, Caspase-3 exerts anticancer effects by regulating cell death mechanisms. Traditional Chinese medicine acting through caspase-3 expression is increasingly used in clinical treatment. This review summarizes the biological mechanism of caspase-3 and research progress on BC. It introduces a variety of traditional Chinese medicine related to caspase-3 to provide new ideas for the clinical treatment of BC.

[Quality evaluation of Compound Cheqian Tablets based on UPLC-Q-TOF-MS/MS, network pharmacology and "double external standards" QAMS].

The Compound Cheqian Tablets are derived from Cheqian Power in Comprehensive Recording of Divine Assistance, and they are made by modern technology with the combination of Plantago asiatica and Coptis chinensis. To investigate the material basis of Compound Cheqian Tablets in the treatment of diabetic nephropathy, in this study, the chemical components of Compound Cheqian Tablets were characterized and analyzed by UPLC-Q-TOF-MS/MS, and a total of 48 chemical components were identified. The identified chemical compounds were analyzed by network pharmacology. By validating with previous literature, six bioactive compounds including acteoside, isoacteoside, coptisine, magnoflorine, palmatine, and berberine were confirmed as the index components for qua-lity evaluation. Furthermore, the content of the six components in the Compound Cheqian Tablets was determined by the "double external standards" quantitative analysis of multi-components by single marker(QAMS), and the relative correction factor of isoacteoside was calculated as 1.118 by using acteoside as the control; the relative correction factors of magnoflorine, palmatine, and berberine were calculated as 0.729, 1.065, and 1.126, respectively, by using coptisine as the control, indicating that the established method had excellent stability under different conditions. The results obtained by the "double external standards" QAMS approximated those obtained by the external standard method. This study qualitatively characterized the chemical components in the Compound Cheqian Tablets by applying UPLC-Q-TOF-MS/MS and screened the pharmacodynamic substance basis for the treatment of diabetic nephropathy via network pharmacology, and primary pharmacodynamic substance groups were quantitatively analyzed by the "double external stan-dards" QAMS method, which provided a scientific basis for clarifying the pharmacodynamic substance basis and quality control of Compound Cheqian Tablets.

Active ingredients Isorhamnetin of Croci Srigma inhibit stomach adenocarcinomas progression by MAPK/mTOR signaling pathway.

Gastric cancer (GC) remains the third leading cause of cancer-related mortality in the world, and ninety-five percent of GC are stomach adenocarcinomas (STAD). The active ingredients of Croci Stigma, such as Isorhamnetin, Crocin, Crocetin and Kaempferol, all have antitumor activity. However, their chemical and pharmacological profiles remain to be elusive. In this study, network pharmacology was used to characterize the action mechanism of Croci Stigma. All compounds were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database, and active ingredients were selected by their oral bioavailability and drug-likeness index. The targets of Croci Stigma active ingredients were obtained from the traditional Chinese medicine integrated database (TCMID), whereas the related genes of STAD were obtained from DisGeNET platform. Cytoscape was used to undertake visual analyses of the Drug Ingredients-Gene Symbols-Disease (I-G-D) network, and 2 core genes including MAPK14, ERBB3 were obtained, which are the predicted targets of isorhamnetin (IH) and quercetin, respectively. Data analysis from TCGA platform showed that MAPK14 and ERBB3 all upregulated in STAD patients, but only the effect of MAPK14 expression on STAD patients' survival was significant. Molecular docking showed that IH might affect the function of MAPK14 protein, and then the underlying action mechanisms of IH on STAD were experimentally validated using human gastric cancer cell line, HGC-27 cells. The results showed that IH can inhibit cell proliferation, migration, clonal formation, and arrest cell cycle, but promote the apoptosis of HGC-27 cells. qRT-PCR data demonstrated that IH downregulated the MAPK14 mRNA expression and EMT related genes. WB results showed that IH regulates MAPK/mTOR signaling pathway. These findings suggest that IH has the therapeutic potential for the treatment of STAD.

Polysaccharides Extracted from Dendrobium officinale Grown in Different Environments Elicit Varying Health Benefits in Caenorhabditis elegans.

Dendrobium officinale is one of the most widely used medicinal herbs, especially in Asia. In recent times, the polysaccharide content of D. officinale has garnered attention due to the numerous reports of its medicinal properties, such as anticancer, antioxidant, anti-diabetic, hepatoprotective, neuroprotective, and anti-aging activities. However, few reports of its anti-aging potential are available. Due to high demand, the wild D. officinale is scarce; hence, alternative cultivation methods are being employed. In this study, we used the Caenorhabditis elegans model to investigate the anti-aging potential of polysaccharides extracted from D. officinale (DOP) grown in three different environments; tree (TR), greenhouse (GH), and rock (RK). Our findings showed that at 1000 µg/mL, GH-DOP optimally extended the mean lifespan by 14% and the maximum lifespan by 25% (p < 0.0001). TR-DOP and RK-DOP did not extend their lifespan at any of the concentrations tested. We further showed that 2000 µg/mL TR-DOP, GH-DOP, or RK-DOP all enhanced resistance to H2O2-induced stress (p > 0.05, p < 0.01, and p < 0.01, respectively). In contrast, only RK-DOP exhibited resistance (p < 0.01) to thermal stress. Overall, DOP from the three sources all increased HSP-4::GFP levels, indicating a boost in the ability of the worms to respond to ER-related stress. Similarly, DOP from all three sources decreased α-synuclein aggregation; however, only GH-DOP delayed ß-amyloid-induced paralysis (p < 0.0001). Our findings provide useful information on the health benefits of DOP and also provide clues on the best practices for cultivating D. officinale for maximum medicinal applications.

Decreased acetylation of HDGF improves oviduct production in Rana dybowskii, Rana amurensis, and Rana huanrenensis.

The oviduct of female Rana dybowskii is a functional food and can be used as a component of Traditional Chinese medicine. The differentially expressed genes enriched was screened in cell growth of three Rana species. We quantitatively analyzed 4549 proteins using proteomic techniques, enriching the differentially expressed proteins of Rana for growth and signal transduction. The results showed that log2 expression of hepatoma-derived growth factor (HDGF) was increased. We further verified 5 specific differential genes (EIF4a, EIF4g, HDGF1, HDGF2 and SF1) and found that HDGF expression was increased in Rana dybowskii. Through acetylation modification analysis, we identified 1534 acetylation modification sites in 603 proteins, including HDGF, and found that HDGF acetylation expression was significantly reduced in Rana dybowskii. Our results suggest that HDGF is involved in the development of oviductus ranae, which is regulated by acetylation modification.

Vitamin B12 alleviates myocardial ischemia/reperfusion injury via the SIRT3/AMPK signaling pathway.

AIM: To examine the protective effect of vitamin B12 against myocardial ischemia/reperfusion (I/R) injury and elucidate its underlying mechanism of action. METHODS: Mice were subjected to myocardial I/R injury by left anterior descending coronary artery (LAD) occlusion followed by 24 h reperfusion. Cardiac function and injury were evaluated by echocardiography, triphenyl tetrazolium chloride (TTC) and cardiac troponin T (cTnT) staining, and measuring lactate dehydrogenase (LDH) levels. In addition, various molecular and biochemical methods, as well as RNA sequencing were used to determine the effects and mechanism of action of vitamin B12 on I/R injury. RESULTS: We found that high doses of vitamin B12 inhibited myocardial I/R injury. Furthermore, our data indicated that vitamin B12 supplementation alleviated cardiac dysfunction and injury by mitigating oxidative stress and apoptosis through downregulation of Nox2, the Ac-SOD2/SOD2 and Bax/Bcl-2 ratios and cleaved caspase-3 expression, and upregulation of SIRT3 expression and AMPK activity. However, these effects were largely reversed following treatment with the SIRT3 inhibitor, 3-TYP. Our RNA-sequencing data further demonstrated that vitamin B12 supplementation reduced inflammation during I/R injury. CONCLUSION: High doses of vitamin B12 supplements improved myocardial I/R injury by suppressing the accumulation of reactive oxygen species and apoptosis of myocardial tissue through modulation of the SIRT3/AMPK signaling pathway, while reducing inflammation. Our findings suggested that vitamin B12 administered at high doses could be a potential therapy for myocardial I/R damage.

Phytoecdysteroids from Dianthus superbus L.: Structures and anti-neuroinflammatory evaluation.

Six undescribed C27-phytoecdysteroid derivatives, named superecdysones A-F, and ten known analogs were extracted from the whole plant of Dianthus superbus L. Their structures were identified by extensive spectroscopy, mass spectrometric methods, chemical transformations, chiral HPLC analysis, and the single-crystal X-ray diffraction analysis. Superecdysones A and B possess a tetrahydrofuran ring in the side chain and superecdysones C-E are rare phytoecdysones containing a (R)-lactic acid moiety, whereas superecdysone F is an uncommon B-ring-modified ecdysone. Notably, based on the variable temperature (from 333 K to 253 K) NMR experiments of superecdysone C, the missing carbon signals were visible at 253 K and assigned. The neuroinflammatory bioassay of all compounds were evaluated, and 22-acetyl-2-deoxyecdysone, 2-deoxy-20-hydroxyecdysone, 20-hydroxyecdysone, ecdysterone-22-O-benzoate, 20-hydroxyecdysone-20,22-O-R-ethylidene, and acetonide derivative 20-hydroxyecdysterone-20, 22-acetonide significantly suppressed the LPS-induced nitric oxide generation in microglia cells (BV-2), with IC50 values ranging from 6.9 to 23.0 µM. Structure-activity relationships were also discussed. Molecular docking simulations of the active compounds confirmed the possible mechanism of action against neuroinflammations. Furthermore, none compounds showed cytotoxicity against HepG2 and MCF-7. It is the first report about the occurrence and anti-neuroinflammatory activity of the phytoecdysteroids in the genus Dianthus. Our findings demonstrated that ecdysteroids may be used as potential anti-inflammatory drugs.

Danggui Buxue decoction ameliorates mitochondrial biogenesis and cognitive deficits through upregulating histone H4 lysine 12 acetylation in APP/PS1 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue decoction (DBD) is a classic herbal decoction consisting of Astragali Radix (AR) and Angelica Sinensis Radix (ASR) with a 5:1 wt ratio, which can supplement 'blood' and 'qi' (vital energy) for the treatment of clinical diseases. According to Traditional Chinese Medicine (TCM) theory, dementia is induced by Blood deficiency and Qi weakness, which causes a decline in cognition. However, the underlying mechanisms of DBD improving cognition deficits in neurodegenerative disease are no clear. AIM OF THE STUDY: This study aims at revealing the underlying mechanisms of DBD plays a protective role in the cognitive deficits and pathology process of Alzheimer's disease (AD). MATERIALS AND METHODS: The APP/PS1 (Mo/HuAPP695swe/PS1-dE9) double transgenic mice were adopted as an experimental model of AD. Qualitative and quantitative analysis of 3 compounds in DBT was analyzed by HPLC. Morris water maze test, Golgi staining and electrophysiology assays were used to evaluate the effects of DBD on cognitive function and synaptic plasticity in APP/PS1 mice. Western blot, immunofluorescence and Thioflavin S staining were used for the pathological evaluation of AD. Monitoring the level of ATP, mitochondrial membrane potential, SOD and MDA to evaluate the mitochondrial function, and with the usage of qPCR and CHIP for the changes of histone post-translational modification. RESULTS: In the current study, we found that DBD could effectively attenuate memory impairments and enhance long-term potentiation (LTP) with concurrent increased expression of memory-associated proteins. DBD markedly decreased Aß accumulation in APP/PS1 mice by decreasing the phosphorylation of APP at the Thr668 level but not APP, PS1 or BACE1. Further studies demonstrated that DBD restored mitochondrial biogenesis deficits and mitochondrial dysfunction. Finally, the restored mitochondrial biogenesis and cognitive deficits are under HADC2-mediated histone H4 lysine 12 (H4K12) acetylation at the peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) and N-methyl-D-aspartate receptor type 2B (GluN2B) promoters. CONCLUSIONS: These findings reveal that DBD could ameliorate mitochondrial biogenesis and cognitive deficits by improving H4K12 acetylation. DBD might be a promising complementary drug candidate for AD treatment.

Purification and identification of xanthine oxidase inhibitory peptides from enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein.

The development of food-derived Xanthine Oxidase (XO) inhibitors is critical to the treatment of hyperuricemia and oxidative stress-related disease. Few studies report on milk protein hydrolysates' XO inhibitory activity, with the mechanism of their interaction remaining elusive. Here, different commercial enzymes were used to hydrolyze α-lactalbumin and bovine colostrum casein. The two proteins hydrolyzed by alkaline protease exhibited the most potent XO inhibitory activity (bovine casein: IC50 = 0.13 mg mL-1; α-lactalbumin: IC50 = 0.28 mg mL-1). Eight potential XO inhibitory peptides including VYPFPGPI, GPVRGPFPIIV, VYPFPGPIPN, VYPFPGPIHN, QLKRFSFRSFIWR, LVYPFPGPIHN, AVFPSIVGR, and GFININSLR (IC50 of 4.67-8.02 mM) were purified and identified from alkaline protease hydrolysates by using gel filtration, LC-MS/MS and PeptideRanker. The most important role of inhibiting activity of peptides is linked to hydrophobic interactions and hydrogen bonding based on the results of molecular docking and molecular dynamics simulation. The enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein could be a competitive candidates for hyperuricemia-resisting functional food.

17ß-oestradiol inhibits ferroptosis in the hippocampus by upregulating DHODH and further improves memory decline after ovariectomy.

Ovariectomy (OVX) conducted before the onset of natural menopause is considered to bringing forward and accelerate the process of ageing-associated neurodegeneration. However, the mechanisms underlying memory decline and other cognitive dysfunctions following OVX are unclear. Given that iron accumulates during ageing and after OVX, we hypothesized that excess iron accumulation in the hippocampus would cause ferroptosis-induced increased neuronal degeneration and death associated with memory decline. In the current study, female rats that underwent OVX showed decreased dihydroorotate dehydrogenase (DHODH) expression and reduced performance in the Morris water maze (MWM). We used primary cultured hippocampal cells to explore the ferroptosis resistance-inducing effect of 17ß-oestradiol (E2). The data supported a vital role of DHODH in neuronal ferroptosis. Specifically, E2 alleviated ferroptosis induced by erastin and ferric ammonium citrate (FAC), which can be blocked by brequinar (BQR). Further in vitro studies showed that E2 reduced lipid peroxidation levels and improved the behavioural performance of OVX rats. Our research interprets OVX-related neurodegeneration with respect to ferroptosis, and both our in vivo and in vitro data show that E2 supplementation exerts beneficial antiferroptotic effects by upregulating DHODH. Our data demonstrate the utility of E2 supplementation after OVX and provide a potential target, DHODH, for which hormone therapy has not been available.

[Acupuncture relieves pain by inhibiting expression of Cx43 in astrocytes and release of interfe-ron-γ in neurons of trigeminal spinal nucleus in rats with migraine].

OBJECTIVE: To observe the effect of acupuncture on the expression of connexin 43 (Cx43), glial fibrillary acidic protein (GFAP), interferon-γ (IFN-γ) in the trigeminal spinal nucleus (TNC) of rats with migraine, so as to explore its mechanisms underlying amelioration of migraine. METHODS: A total of 44 SD rats were randomly divided into control, model, acu-puncture, and sham acupuncture groups (n=11 in each group). Acupuncture was applied to bilateral "Shuaigu"(GB8) and "Yanglingquan"(GB34) or non-acupoint Ⅰ (the spot about 10 mm superior to the iliac spine and 20 mm lateral to the post-median line) and non-acupoint Ⅱ (behind the iliac spine, the ending-spot of the posterior superior iliac spine at the muscles) on both sides for 20 min, once daily for 9 days. Paw withdrawal latency (mechanical pain threshold,PWMT) and thermal tail flick latency (TFL) were measured using a VonFrey detector and photothermal tail pain meter, respectively. The content of IFN-γ of TNC tissue was detected by ELISA. The expression levels of Cx43 and IFN-γ proteins of TNC tissue were detected by Western blot. The immunofluorescence dual labeling method was used to detect the positive expression of GFAP and Cx43, IFN-γR and NeuN in TNC tissue, for displaying the activity of Cx43 in astrocytes and IFN-γ in neurons, respectively. RESULTS: Compared with the control group, both PWMT and TFL at 3, 5, 7 and 9 days after modeling were significantly decreased (P<0.01), while the expression of Cx43 and IFN-γ proteins, the immunofluorescence intensity of GFAP, Cx43, IFN-γR, and the content of IFN-γ were considerably up-regulated in the model group (P<0.01). In comparison with the model group, both PWMT and TFL at 3, 5, 7 and 9 days after modeling were obviously increased (P<0.01), whereas the expression of Cx43 and IFN-γ proteins, the immunofluorescence intensity of GFAP, Cx43, IFN-γR, and the content of IFN-γ in the acupuncture group, as well as the protein expression of IFN-γR in the sham acupuncture group were also remarkably decreased (P<0.05, P<0.01). The effect of acupuncture was significantly superior to that of sham acupuncture in down-regulating the expression of Cx43 and IFN-γ proteins, and the immunofluorescence intensity of GFAP, Cx43, and IFN-γR (P<0.05, P<0.01). Immunofluorescence dual labeling outcomes showed that in the model group, a large number of GFAP and Cx43 co-expressed astrocytes were found, and the cell body and protrusion of GFAP-labelled astrocytes were evidently increased, and Cx43 was mainly expressed on the surface of astrocyte membrane and the protrusion site, and the proportion of IFN-γR and NeuN co-expressing neurons in the model group was significantly increased, suggesting an activation of astrocytes and neurons after modeling. Whereas in the acupuncture group, the bright green clustered particles on the cell membrane and protrusion of astrocytes, and the proportion of IFN-γR and NeuN co-expressing neurons were significantly reduced, suggesting a suppression of activities of Cx43, astrocytes and neurons and IFN-γ release from TNC after acupuncture intervention. CONCLUSION: Acupuncture can relieve the pain response in rats with migraine, which may be associa-ted with its functions in inhibiting the expression of Cx43 and activation of astrocytes and neurons, and reducing release of pro-inflammatory factor IFN-γ in TNC.

[Rapid health technology assessment of four oral Chinese patent medicines in treatment of functional gastrointestinal disorders].

To provide proof of the evidence-based medicine and decision-making information for the clinical decision of functional gastrointestinal disorders(FGIDs), this study evaluated and compared the efficacy, safety, and economy of four oral Chinese patent medicines(CPMs) in the treatment of FGIDs using the method of rapid health technology assessment. The literature was systematically retrieved from CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, Cochrane Library and ClinicalTrials.gov from the establishment of the databases to May 1, 2022. Two evaluators screened out the literature, extracted data, evaluated the quality of the literature, and descriptively analyzed the results according to the prepared standard. Eventually, 16 studies were included, all of which was rando-mized controlled trial(RCT). The results showed that Renshen Jianpi Tablets, Renshen Jianpi Pills, Shenling Baizhu Granules, and Buzhong Yiqi Granules all had certain effects on the treatment of FGIDs. Renshen Jianpi Tablets treated FGIDs and persistent diarrhea. Shenling Baizhu Granules treated diarrhea with irritable bowel syndrome and FGIDs. Buzhong Yiqi Granules treated diarrhea with irritable bowel syndrome, FGIDs, and chronic diarrhea in children. Renshen Jianpi Pills treated chronic diarrhea. The four oral CPMs all have certain effects on the treatment of FGIDs and have specific advantages for specific patients. Compared with other CPMs, Renshen Jianpi Tablets have higher clinical universality. However, there are problems such as insufficient clinical research evidence, generally low quality of evidence, lack of comparative analysis among medicines, and lack of academic evaluation. More high-quality clinical research and the economic research should be carried out in the future, so as to provide more evidence for the evaluation of the four CPMs.