Tangshen formula protects against podocyte apoptosis via enhancing the TFEB-mediated autophagy-lysosome pathway in diabetic nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease and currently there are no specific and effective drugs for its treatment. Podocyte injury is a detrimental feature and the major cause of albuminuria in DN. We previously reported Tangshen Formula (TSF), a Chinese herbal medicine, has shown therapeutic effects on DN. However, the underlying mechanisms remain obscure. AIM OF THE STUDY: This study aimed to explore the protective effect of TSF on podocyte apoptosis in DN and elucidate the potential mechanism. MATERIALS AND METHODS: The effects of TSF were assessed in a murine model using male KKAy diabetic mice, as well as in advanced glycation end products-stimulated primary mice podocytes. Transcription factor EB (TFEB) knockdown primary podocytes were employed for mechanistic studies. In vivo and in vitro studies were performed and results assessed using transmission electron microscopy, immunofluorescence staining, and western blotting. RESULTS: TSF treatment alleviated podocyte apoptosis and structural impairment, decreased albuminuria, and mitigated renal dysfunction in KKAy mice. Notably, TSF extracted twice showed a more significant reduction in proteinuria than TSF extracted three times. Accumulation of autophagic biomarkers p62 and LC3, and aberrant autophagic flux in podocytes of DN mice were significantly altered by TSF therapy. Consistent with the in vivo results, TSF prevented the apoptosis of primary podocytes exposed to AGEs and activated autophagy. However, the anti-apoptosis capacity of TSF was countered by the autophagy-lysosome inhibitor chloroquine. We found that TSF increased the nuclear translocation of TFEB in diabetic podocytes, and thus upregulated transcription of its several autophagic target genes. Pharmacological activation of TFEB by TSF accelerated the conversion of autophagosome to autolysosome and lysosomal biogenesis, further augmented autophagic flux. Conversely, TFEB knockdown negated the favorable effects of TSF on autophagy in AGEs-stimulated primary podocytes. CONCLUSIONS: These findings indicate TSF appears to attenuate podocyte apoptosis and promote autophagy in DN via the TFEB-mediated autophagy-lysosome system. Thus, TSF may be a therapeutic candidate for DN.

Investigation of the transport and metabolic patterns of oil-displacing bacterium FY-07-G in the microcosm model using X-CT technology.

AIMS: Microbial enhanced oil recovery (MEOR) is dedicated to enhancing oil recovery by harnessing microbial metabolic activities and their byproducts within reservoir rocks and fluids. Therefore, the investigation of microbial mobility and their extensive distribution within crude oil is of paramount importance in MEOR. While microscale models have been valuable for studying bacterial strain behavior in reservoirs, they are typically limited to 2D representations of porous media, making them inadequate for simulating actual reservoir conditions. Consequently, there is a critical need for 3D models and dependable visualization methods to observe bacterial transport and metabolism within these complex reservoir environments. METHODS AND RESULTS: Bacterial cellulose (bc) is a water-insoluble polysaccharide produced by bacteria that exhibits biocompatibility and biodegradability. It holds significant potential for applications in the field of MEOR as an effective means for selective plugging and spill prevention during oil displacement processes. Conditionally cellulose-producing strain, FY-07-G, with green fluorescent labeling, was engineered for enhanced oil recovery. 3D micro-visualization model was constructed to directly observe the metabolic activities of the target bacterial strain within porous media and to assess the plugging interactions between cellulose and the medium. Additionally, X-ray computed tomography (X-CT) technology was employed for a comprehensive analysis of the transport patterns of the target strain in oil reservoirs with varying permeabilities. The results indicated that FY-07-G, as a microorganism employing biopolymer-based plugging principles to enhance oil recovery, selectively targets and seals regions characterized by lower permeability and smaller pore spaces. CONCLUSIONS: This work provided valuable insights into the transport and metabolic behavior of MEOR strains and tackled the limitation of 2D models in faithfully replicating oil reservoir conditions, offering essential theoretical guidance and insights for the further application of oil-displacing bacterial strains in MEOR processes.

Therapeutic application of traditional Chinese medicine in kidney disease: Sirtuins as potential targets.

Sirtuins are a family of NAD+ III-dependent histone deacetylases that consists of seven family members, Sirt1-Sirt7, which regulate various signalling pathways and are involved in many critical biological processes of kidney diseases. Traditional Chinese medicine (TCM), as an essential part of the global healthcare system, has multi-component and multi-pathway therapeutic characteristics and plays a role in preventing and controlling various diseases. Through ongoing collaboration with modern medicine, TCM has recently achieved many remarkable advancements in theoretical investigation, mechanistic research, and clinical applications related to kidney diseases. Therefore, a comprehensive and systematic summary of TCM that focuses on sirtuins as the intervention target for kidney diseases is necessary. This review introduces the relationship between abnormal sirtuins levels and common kidney diseases, such as diabetic kidney disease and acute kidney injury. Based on the standard biological processes, such as inflammation, oxidative stress, autophagy, mitochondrial homeostasis, and fibrosis, which are underlying kidney diseases, comprehensively describes the roles and regulatory effects of TCM targeting the sirtuins family in various kidney diseases.

Fabrication of bacterial cellulose composites with antimicrobial properties by in situ modification utilizing the specific function-suspension containing water-insoluble magnolol.

In situ modification is commonly employed for Bacterial cellulose (BC) functionalization. However, water-insoluble modifiers are usually deposited at the bottom of the medium, therefore cannot be used for in situ modification of BC. Herein, a novel strategy for in situ modification of insoluble modifiers after suspension by a suspending agent was proposed. The BC-producing strain Kosakonia oryzendophytica FY-07, not Gluconacetobacter xylinus, was selected to prepare BC products with antibacterial activity because of its tolerance to natural antibacterial products. The experimental results showed that xanthan gum as a suspending agent can uniformly and stably disperse water-insoluble plant extracts magnolol in the culture medium to prepare the in situ modified BC products. Characterization of the properties showed that the in situ modified BC products have reduced crystallinity, significantly increased swelling ratio and strong inhibition on Gram-positive bacteria and fungi and weak inhibition on Gram-negative bacteria. Furthermore, the in situ modified BC products had no toxicity to cells. This study provided a feasible strategy for in situ modification of BC using water-insoluble modifiers to extend BC functionality and has significant implications for the biopolymer industry.

Therapeutic potential of artemisinin and its derivatives in managing kidney diseases.

Artemisinin, an antimalarial traditional Chinese herb, is isolated from Artemisia annua. L, and has shown fewer side effects. Several pieces of evidence have demonstrated that artemisinin and its derivatives exhibited therapeutic effects on diseases like malaria, cancer, immune disorders, and inflammatory diseases. Additionally, the antimalarial drugs demonstrated antioxidant and anti-inflammatory activities, regulating the immune system and autophagy and modulating glycolipid metabolism properties, suggesting an alternative for managing kidney disease. This review assessed the pharmacological activities of artemisinin. It summarized the critical outcomes and probable mechanism of artemisinins in treating kidney diseases, including inflammatory, oxidative stress, autophagy, mitochondrial homeostasis, endoplasmic reticulum stress, glycolipid metabolism, insulin resistance, diabetic nephropathy, lupus nephritis, membranous nephropathy, IgA nephropathy, and acute kidney injury, suggesting the therapeutic potential of artemisinin and its derivatives in managing kidney diseases, especially the podocyte-associated kidney diseases.

Amino acids-targeted metabolomics reveals novel diagnostic biomarkers for ulcerative colitis and Crohn's disease.

Inflammatory bowel disease (IBD), which mainly comprises ulcerative colitis (UC) and Crohn's disease (CD), is a common chronic intestinal inflammatory disease that affects the ileum, rectum, and colon. Currently, the diagnosis of IBD is based on clinical history, physical examination and complementary diagnostic tests. It is challenging for physicians to make a definitive diagnosis. This study aimed to analyze the variation in amino acid metabolites in IBD serum and to identify potential predictive biomarkers of IBD diagnosis and progression. Serum samples were collected from 158 UC patients, 130 CD patients and 138 healthy controls (HCs). The 37 amino acids in serum were determined by ultra-high-pressure liquid chromatography coupled to a mass spectrometer. A panel of three-amino-acid metabolites (taurine, homocitrulline and kynurenine) was identified as a specific biomarker panel of IBD. Receiver operating characteristic analysis (ROC) showed that the panel had a sensitivity of 88.4% with a specificity of 84.6% for discriminating CD patients from UC patients. The biomarkers identified are increased in CD compared to UC. Our approach demonstrated a strong relationship between serum amino acid levels and IBD. We successfully identified serum amino acid biomarkers associated with CD and UC. The biomarker panel has potential in clinical practice for IBD diagnosis and will provide new insights into IBD pathogenesis.

Baitouweng decoction alleviates dextran sulfate sodium-induced ulcerative colitis by suppressing leucine-related mTORC1 signaling and reducing oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Baitouweng decoction (BTW) has been used for hundreds of years to treat ulcerative colitis (UC) in China and has produced remarkable clinical results. However, the knowledge in protective mechanism of BTW against UC is still unclear. AIM OF THE STUDY: The present study was designed to investigate the anti-UC effects of BTW and the underlying mechanisms involved. METHODS: 3.5% dextran sulfate sodium (DSS)-induced experimental colitis was used to simulate human UC and the mice were treated with BTW (6.83 g/kg), leucine (200 mg/kg, Leu) or rapamycin (2 mg/kg, RAPA) as a positive control for 7 days. The clinical symptoms, serum myeloperoxidase (MPO) and malondialdehyde (MDA) levels were evaluated. Biological samples were collected to detect the effects of BTW on mechanistic target of rapamycin complex 1 (mTORC1) pathway and Leu metabolism. RESULTS: In our study, BTW notably improved the clinical symptoms and histopathological tissue damage and reduced the release of proinflammatory cytokines, including IL-6, IL-1ß and TNF-α in UC mice. BTW also alleviated oxidative stress by decreasing serum MPO and MDA levels. Additionally, BTW significantly suppressed mTORC1 activity in the colon tissues of UC mice. Serum metabolomics analysis revealed that the mice receiving BTW had lower Leu levels, which was in line with the decreased expression of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in the colon tissues. Furthermore, oral administration of Leu aggravated DSS-induced acute colitis and enhanced mTORC1 activity in the colon. CONCLUSION: These data strongly demonstrated that BTW could ameliorate DSS-induced UC by regulating the Leu-related mTORC1 pathway and reducing oxidative stress.

The characterization and expression analysis under stress conditions of PCST1 in Arabidopsis.

Analysis of PCST1 expression characteristics and the role of PCST1 in response to osmotic stress in Arabidopsis thaliana. The structure of PCST1 was analyzed using Bioinformatics method. Real-time PCR, GUS tissue localization and subcellular localization were adopted to analyze the expression pattern of PCST1 in Arabidopsis. To validate the transgenic positive strain of PCST1 using Real-time PCR, overexpression experiments were performed in wild type. Full-length cDNA was cloned and connected into a binary vector with 35S promoter, and the construction was transformed into wild type. With NaCl and mannitol treatments, the germination rate, green leaves rate, physiological indexes were carried out and counted in Arabidopsis with overexpression of PCST1 and T-DNA insertion mutants. The molecular mechanism of PCST1 in response to osmotic stress in Arabidopsis was analyzed. Based on the bioinformatic analysis, PCST1 is a hydrophobin with 403 amino acids, and the molecular weight is 45.3236 KDa. It contains only the START (the lipid/sterol - binding StAR - related lipid transfer protein domains) conservative domain. PCST1 possesses phosphatidylcholine binding sites and transmembrane region. Expression pattern analysis showed that expression of PCST1 increased with time. The PCST1 widely expressed in Arabidopsis, including roots, axils of stem leaves, flowers (sepal, conductive tissue of the petal, thrum, anther and stigmas), and the top and basal parts of the siliquas. It mainly localized in cell membrane. The overexpression of PCST1 enhanced the sensitivity to osmotic stress in Arabidopsis based on the germination rate. While expression of PCST1 decreased, and the sensitivity to osmotic stress had no obvious change in Arabidopsis. Its molecular mechanism study showed, that PCST1 response to osmotic stress resistance by regulating the proline, betaine synthesis, as well as the expression of key genes SOS, NCED, CIPK. PCST1 is composed of 403 amino acids. The START conservative domain, a transmembrane structure, the phosphatidyl choline binding sites are contained in PCST1. It is localized in cytoplasmic membrane. The PCST1 widely expressed in the root, leaf, flower and siliquas. NaCl and mannitol suppressed the expression of PCST1 and PCST1 can negatively control action of Arabidopsis in the osmotic stress. PCST1 regulates the synthetic pathway of proline, betaine and the expression of SOS, NCED and CIPK in response to the osmotic stress resistance.

Cardioprotection effect of Yiqi-Huoxue-Jiangzhuo formula in a chronic kidney disease mouse model associated with gut microbiota modulation and NLRP3 inflammasome inhibition.

BACKGROUND: The pathogenesis and treatment of cardiovascular disease mediated by chronic kidney disease (CKD) are key research questions. Specifically, the mechanisms underlying the cardiorenal protective effect of Yiqi-Huoxue-Jiangzhuo formula (YHJF), a traditional Chinese herbal medicine, have not yet been clarified. METHODS: A classical CKD mouse model was constructed by 5/6 nephrectomy (Nx) to study the effects of YHJF intervention on 5/6 Nx mice cardiorenal function, gut microbial composition, gut-derived metabolites, and NLRP3 inflammasome pathways. RESULTS: YHJF improved cardiac dysfunction and reversed left ventricular hypertrophy, myocardial hypertrophy, and interstitial fibrosis in 5/6 Nx mice. In addition, YHJF inhibited activation of the NLRP3 inflammasome and downregulated the expression of TNF-α and IL-1ß both in the heart and serum; reconstitution of the intestinal flora imbalance was also found in 5/6 Nx mice treated with YHJF. Spearman's correlation and redundancy analyses showed that changes in the intestinal flora of 5/6 Nx mice were related to clinical phenotype and serum inflammatory levels. CONCLUSIONS: Treatment with YHJF effectively protected the heart function of 5/6 Nx mice; this effect was attributed to inhibition of NLRP3 inflammasome activation and regulation of intestinal microbial composition and derived metabolites. YHJF has potential for improving intestinal flora imbalance and gut-derived toxin accumulation in patients with CKD, thereby preventing cardiovascular complications.

Comparative efficacy of 10 Chinese herbal injections combined with GP regimen chemotherapy for patients with advanced NSCLC a systematic review and network meta-analysis.

Background: Numerous studies have indicated that some Chinese herbal injections (CHIs) might have a beneficial treatment effect when used in combination with chemotherapy. However, the results of these studies have been inconsistent. The aim of this network meta-analysis (NMA) was to evaluate and compare the clinical efficacy and safety of different CHIs combined with gemcitabine plus cisplatin (GP) regimen chemotherapy with that of GP regimen chemotherapy alone in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Eight databases were systematically searched to identify randomized clinical trials (RCTs) from the date of inception of the database to August 11, 2021. The primary outcome measures were the objective response rate (ORR) and adverse reactions (including nausea and vomiting, and leukopenia). The secondary outcome measures were median survival time (MST) and quality of life (QOL). The quality of the included studies was assessed using the Cochrane risk of bias tool. Standard pair-wise and Bayesian NMAs were carried out to compare the effectiveness and safety of different CHIs combined with GP regimen chemotherapy using WinBUGS 14 and Stata 15.1 software. Sensitivity analysis and Egger's test were also performed to check robust. Results: A total of 92 eligible RCTs involving 7,728 patients and 10 CHIs were included. The results showed that Kangai injection (KAI), Kanglaite injection (KLT), Aidi injection and Compound Kushen (CKSI) injection displayed obvious advantages in both efficacy and safety. Aidi+GP (79.0%) showed great advantages of ORR, and KAI+GP and KLT+GP had the lowest probability in terms of leukopenia (4.4%) and nausea and vomiting (24.2%). Besides, KLT+GP was shown to positively affect MST. According to the subgroup analyses, CHIs might have a limited effect in reducing adverse reactions, and have a similar effect in squamous cell carcinoma and adenocarcinoma. Conclusions: KAI+GP of adjuvant drugs, Aidi+GP and CKSI+GP of anticancer drugs appeared to be the advantageous treatment options for patients with advanced NSCLC, owing to its superior therapeutic performance and reduced adverse reactions. KLT+GP might prolong survival. Nevertheless, additional results from multicenter trials and high-quality studies will be pivotal in supporting our findings.

Effect of phenolic extracts from Camellia oleifera seed cake on the formation of polar compounds, core aldehydes, and monoepoxy oleic acids during deep-fat frying.

The frying process is an excellent way to obtain food with desirable sensory. However, some harmful substances, such as aldehydes and monoepoxy oleic acids, could also be produced. This study mainly explores the inhibition of polyphenols from the Camellia oleifera seed cake extract (CSCE) on the formation of polar compounds, core aldehydes, and monoepoxy oleic acids during deep-fat frying. The results showed that the CSCE could significantly decrease peroxide, p-anisidine, total polar, and monoepoxy oleic acids compared with other groups. In addition, the CSCE could significantly inhibit the generation of oxidized triacylglycerol polymer (TGP) and oxidized triacylglycerol (ox-TG), indicating its anti-polymerization activity. The total amount of core aldehydes and glycerol ester core aldehydes (9-oxo) in soybean oil was significantly reduced. Furthermore, CSCE had a better inhibitory effect on monoepoxy fatty acids than TBHQ. Our results might be helpful to provide a basis for the search for new natural antioxidants.

Insight into the effect of fatty acid composition on the texture of French fries.

BACKGROUND: Several researchers have reported that the texture of fries is affected by the fatty acid composition of oil, although the mechanism of this effect is not clear. In this regard, fries were fried in refined rapeseed oil and fully hydrogenated rapeseed oil with diverse proportions (0%, 20%, 40%, 60%, 80% and 100%) and were analyzed based on the content of moisture and oil, texture, thermal properties, crystalline properties and microstructure. RESULTS: The outcomes presented that fries fried in fully hydrogenated oil had less oil absorption and moisture loss than those fried in refined oil. The results from the texture analyzer, differential scanning calorimetry and X-ray diffraction showed that hardness, enthalpy and relative crystallinity increased with an increase in the proportion of fully hydrogenated oil. However, the peaks of starch-lipid complexes were hardly observed during frying. Furthermore, scanning electron microscopy results displayed that some physically trapped fat was observed in fries fried in mixed hydrogenated oil. Stereomicroscope images showed that the crust thickness of the fries increased slightly with an increase in the proportion of fully hydrogenated oil. CONCLUSION: Overall, the upsurge in crust thickness and oil crystals was responsible for an increase in the hardness of the fries. This indicated that the texture of fries can be manipulated by altering the fatty acid composition of the oil. © 2021 Society of Chemical Industry.

Polycythemia Vera With Multiple Cerebral Infarctions Complicated By Cerebral Microhemorrhage: A Report of Two Cases.

Polycythemia vera (PV) has multiple vascular risk factors and gradual onset and is an important risk factor for stroke. The first manifestation in some patients with PV is thrombotic cerebrovascular events. However, there are few reports on polycythemia vera with multiple cerebral infarctions and cerebral microhemorrhage. The clinical and imaging features of two PV patients with multiple cerebral infarctions complicated by cerebral microhemorrhage were analyzed retrospectively in order to improve the clinical understanding of the disease.

Knowledge Domain and Emerging Trends in Podocyte Injury Research From 1994 to 2021: A Bibliometric and Visualized Analysis.

Background: Podocyte injury has a direct causal relationship with proteinuria and glomerulosclerosis and, on a chronic level, can lead to irreversible disease progression. Podocyte injury plays a critically decisive role in the development of proteinuric kidney disease. In recent years, the research on podocyte injury has developed rapidly all over the world. However, no report has summarized the field of podocyte injury as a whole to date. Using bibliometric analysis, this study aimed to evaluate the current state of worldwide podocyte injury research in the last 30 years and identify important achievements, primary research fields, and emerging trends. Methods: Publications related to podocyte injury were retrieved from Web of Science Core Collection. HistCite, VOSviewer, CiteSpace, and the Bibliometrix Package were used for bibliometric analysis and visualization, including the analysis of the overall distribution of annual outputs, leading countries, active institutions and authors, core journals, co-cited references, and keywords. Total global citation score and total local citation score were used to assess the quality and impact of publications. Results: A total of 2,669 publications related to podocyte injury were identified. Publications related to podocyte injury tended to increase continuously. A total of 10,328 authors from 2,171 institutions in 69 countries published studies related to podocyte injury. China (39.46%) was the most prolific country, and the number of citations of studies in the United States (cited 36,896 times) ranked first. Moin A Saleem, John Cijiang He, and Zhihong Liu were the top three contributing authors, and Journal of the American Society of Nephrology and Kidney International were the most popular journals in the field. "Diabetic nephropathy" is the primary focus area of podocyte injury research, and "autophagy," "microRNA," and "inflammation" were the top keywords of emerging research hotspots, and traditional Chinese medicine monomer may be a neglected research gap. Conclusion: Our research found that global publications on podocyte injury have increased dramatically. Diabetic nephropathy is the main research field of podocyte injury, whereas autophagy, microRNA, and inflammation are the top topics getting current attention from scholars and which may become the next focus in podocyte injury research.

Protective Effects of Water Extract of Fructus Ligustri Lucidi against Oxidative Stress-Related Osteoporosis In Vivo and In Vitro.

Fructus Ligustri Lucidi (FLL) is the fruit of Ligustrum lucidum Ait and is a component of many kidney-tonifying traditional Chinese medicine formulae for treating osteoporosis. Accumulating evidence has linked oxidative stress with the progression of bone diseases. The present study aimed to identify the effects of FLL on oxidative stress-related osteoporosis in vivo and in vitro. To construct animal models, we utilized d-galactose (D-gal) injection to induce oxidative stress combined with a low calcium (the exact percentage in the diet was 0.1%) diet. Thirteen-week-old Kunming female mice were gavaged with water extract of FLL for 20 days. Then, eight-month-old Kunming female mice were treated with FLL under standard administration and diet as the aged group. In vitro, MC3T3-E1 cells stimulated by H2O2 were treated with FLL for 24 h. The micro-CT results showed that the modeling approach combining oxidative stress with a low calcium diet caused low conversion type osteoporosis in mice. FLL exerted a prominent effect on preventing osteoporosis by inhibiting oxidative stress, increasing bone mineral density (BMD), improving bone microstructure, and promoting osteoblast proliferation and osteoprotegerin (OPG) protein expression; however, FLL had no therapeutic effect on bone loss in aged mice. In conclusion, FLL showed outstanding anti-bone loss ability both in vivo and in vitro and could probably be developed as a prophylactic agent for osteoporosis.

Effect of Acupuncture on Neuroplasticity of Stroke Patients with Motor Dysfunction: A Meta-Analysis of fMRI Studies.

Objective: To analyze the pattern of intrinsic brain activity variability that is altered by acupuncture compared with conventional treatment in stroke patients with motor dysfunction, thus providing the mechanism of stroke treatment by acupuncture. Methods: Chinese and English articles published up to May 2020 were searched in the PubMed, Web of Science, EMBASE, and Cochrane Library databases, China National Knowledge Infrastructure, Chongqing VIP, and Wanfang Database. We only included randomized controlled trials (RCTs) using resting-state fMRI to observe the effect of acupuncture on stroke patients with motor dysfunction. R software was used to analyze the continuous variables, and Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) was used to perform an analysis of fMRI data. Findings. A total of 7 studies comprising 143 patients in the treatment group and 138 in the control group were included in the meta-analysis. The results suggest that acupuncture treatment helps the healing process of motor dysfunction in stroke patients and exhibits hyperactivation in the bilateral basal ganglia and insula and hypoactivation in motor-related areas (especially bilateral BA6 and left BA4). Conclusion: Acupuncture plays a role in promoting neuroplasticity in subcortical regions that are commonly affected by stroke and cortical motor areas that may compensate for motor deficits, which may provide a possible mechanism underlying the therapeutic effect of acupuncture.

A network-based analysis and experimental validation of traditional Chinese medicine Yuanhu Zhitong Formula in treating neuropathic pain.

ETHNOPHARMACOLOGICAL RELEVANCE: The Yuanhu Zhitong Formula (YZF) consists of traditional Chinese herbs Corydalis Rhizoma (Corydalis yanhusuo (Y.H.Chou & Chun C.Hsu) W.T.Wang ex Z.Y.Su & C.Y.Wu; Chinese name, Yanhusuo) and Angelicae Dahuricae Radix (Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav.; Chinese name, Baizhi), which is usually administrated for painful conditions. It is well acknowledged that YZF has pharmacological effects on pain relief; nevertheless, limited data are available on its mechanism. AIM OF THE STUDY: This study aimed to explore the potential mechanism underlying YZF on nociception of rats. Also, the comprehensive mechanism of YZF was preliminarily determined based on network pharmacology on neuropathic pain. MATERIALS AND METHODS: A spared nerve injury (SNI) model was established to reveal the effects of YZF administration on nociceptive behavior in rats. Von-Frey tests were used to evaluate the paw withdrawal mechanical thresholds in rats administrated with YZF or vehicle. The "drug-ingredients" and "disease-drug-target" networks were established with a network pharmacology approach. The analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) profiles were performed based on the common targets between the herbs and neuropathic pain. Hub genes, identified with CytoHubba, were validated by Western blotting analysis. RESULTS: SNI rats developed significant nociceptive behavior as soon as 3 days after nerve injury, which was reversed by consecutive treatment with 300 mg/kg YZF for 7 days. Besides, 50 potential bioactive components in YZF with 1074 targets were identified. Then, 217 putative common genes related to YZF and neuropathic pain were identified for further study. After established a protein-protein interaction network, 12 subnetworks with CytoHubba and 10 predictive hub genes were obtained based on the maximal clique centrality model. Western blotting analysis indicated that SNI rats exhibited increased APP (Amyloid-beta precursor protein), SRC (Proto-oncogene tyrosine-protein kinase Src), and phosphorylation of JNK1 (Mitogen-activated protein kinase 8, JNK) and ERK1/2 (Mitogen-activated protein kinase 3/1). Obviously, continuous administration of YZF robustly reversed such changes. CONCLUSIONS: This study revealed that YZF modulates the nociceptive behavior in SNI rats. Moreover, the drug may be useful in the treatment of neuropathic pain through multi-components, multi-targets, and multi-pathways. Nevertheless, more attention should be paid to discriminating the potential ingredients in YZF contributing to its analgesic effects in the treatment of neuropathic pain.

A Network Pharmacology-Based Strategy for Unveiling the Mechanisms of Tripterygium Wilfordii Hook F against Diabetic Kidney Disease.

BACKGROUND: Diabetic kidney disease (DKD) poses a major public-health burden globally. Tripterygium wilfordii Hook F (TwHF) is a widely employed herbal medicine in decreasing albuminuria among diabetic patients. However, a holistic network pharmacology strategy to investigate the active components and therapeutic mechanism underlying DKD is still unavailable. METHODS: We collected TwHF ingredients and their targets by traditional Chinese Medicine databases (TCMSP). Then, we obtained DKD targets from GeneCards and OMIM and collected and analyzed TwHF-DKD common targets using the STRING database. Protein-protein interaction (PPI) network was established by Cytoscape and analyzed by MCODE plugin to get clusters. In addition, the cytoHubba software was used to identify hub genes. Finally, all the targets of clusters were subjected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses via DAVID. RESULTS: A total of 51 active ingredients in TwHF were identified and hit by 88 potential targets related to DKD. Compounds correspond to more targets include kaempferol, beta-sitosterol, stigmasterol, and Triptoditerpenic acid B, which appeared to be high-potential compounds. Genes with higher degree including VEGFA, PTGS2, JUN, MAPK8, and HSP90AA1 are hub genes of TwHF against DKD, which are involved in inflammation, insulin resistance, and lipid homeostasis. Kaempferol and VEGFA were represented as the uppermost active ingredient and core gene of TwHF in treating DKD, respectively. DAVID results indicated that TwHF may play a role in treating DKD through AGE-RAGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, insulin resistance, and calcium signaling pathway (P < 0.05). CONCLUSION: Kaempferol and VEGFA were represented as the uppermost active ingredient and core gene of TwHF in treating DKD, respectively. The key mechanisms of TwHF against DKD might be involved in the reduction of renal inflammation by downregulating VEGFA.

Comparative efficacy of Chinese herbal injections combined with GP regimen chemotherapy for patients with advanced NSCLC: A protocol for systematic review and network meta-analysis.

BACKGROUND: Many research has indicated that some Chinese herb injections (CHIs) might be beneficial in combination with chemotherapy, however, with inconsistent results. Hence, the purpose of this network meta-analysis is to evaluate different CHIs plus cisplatin and gemcitabine (GP) with GP alone in terms of clinical efficacy and safety for treating patients with advanced NSCLC. METHODS: A comprehensive systematic search of clinical randomized controlled trials (RCTs) published in the PubMed, Embase, Web of Science (ISI), Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Database and China Biological Medicine Database (CBM) databases will be conducted to identify eligible studies up to the date of May 2020. The primary outcome measures objective response rate and adverse reactions (nausea and vomiting, leukopenia). The secondary outcome measures median survival time (MST), disease control rate, and quality of life. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The network meta-analysis will be performed using WinBUGS 14 and Stata 15.1 software. RESULTS: Based on the current evidence, the potential rank of the efficacy and safety of CHIs plus GP chemotherapy for advanced NSCLC will be assessed, and a prioritization regimen will be summarized. CONCLUSION: Evidence from this systematic review could be useful for patients, clinical practitioners, and guideline-makers to select an optimum proposal of CHIs plus GP for advanced NSCLC. ETHICS AND DISSEMINATION: It is not necessary for ethical approval because it is based on published studies. The protocol will be disseminated in a peer-reviewed journal or presented at a topic-related conference. PROSPERO REGISTRATION NUMBER: CRD42020167142.

Purple acid phosphatase 10c encodes a major acid phosphatase that regulates plant growth under phosphate-deficient conditions in rice.

Whilst constitutive overexpression of particular acid phosphatases (APases) can increase utilization of extracellular organic phosphate, negative effects are frequently observed in these transgenic plants under conditions of inorganic phosphate (Pi) sufficiency. In this study, we identified rice purple acid phosphatase 10c (OsPAP10c) as being a novel and major APase that exhibits activities associated both with the root surface and with secretion. Two constructs were used to generate the OsPAP10c-overexpression plants by driving its coding sequence with either a ubiquitin promoter (UP) or the OsPAP10c-native promoter (NP). Compared with the UP transgenic plants, lower expression levels and APase activities were observed in the NP plants. However, the UP and NP plants both showed a similar ability to degrade extracellular ATP and both promoted root growth. The growth performance and yield of the NP transgenic plants were better than the wild-type and UP plants in both hydroponic and field experiments irrespective of the level of Pi supply. Overexpression of APase by its native promoter therefore provides a potential way to improve crop production that might avoid increased APase activity in untargeted tissues and its inhibition of the growth of transgenic plants.