[Application of "eliminating stagnation and bloodletting/fire needling" in treatment of jingjin diseases].

Based on the development of conditions, the etiology and pathogenesis of jingjin (muscle region of meridian) diseases are summarized as 3 stages, i.e. stagnation due to over-exertion at early stage, manifested by tendon-muscle contracture and tenderness; cold condition due to stagnation, interaction of stasis and cold, resulting in clustered nodules at the middle stage; prolonged illness and missed/delayed treatment, leading to tendon-muscle contracture and impairment of joint function at the late stage. It is proposed that the treatment of jingjin diseases should be combined with the characteristic advantages of fire needling and bloodletting technique, on the base of "eliminating stagnation and bloodletting/fire needling". This combined therapy warming yang to resolve stasis and dispels cold to remove nodules, in which, eliminating the stagnation is conductive to the tissue regeneration, and the staging treatment is delivered in terms of the condition development at different phases.

Efficacy of acupuncture for pain relief in patients receiving extracorporeal shock wave lithotripsy: a meta-analysis of randomized controlled studies.

Background: This meta-analysis aimed at investigating the efficacy of acupuncture for pain relief in patients receiving extracorporeal shock wave lithotripsy (ESWL). Methods: Randomized controlled trials comparing the efficacy of acupuncture with conventional treatments were retrieved from major electronic databases (e.g., MEDLINE, EMBASE, and Cochrane Library) until August 28, 2022. The primary outcome was the response rate (i.e., rate of pain relief), while secondary outcomes included stone-free rate, satisfaction rate, duration of ESWL, peri-/post-procedural pain score, and risk of adverse events. Results: Thirteen eligible studies involving 1,220 participants published between 1993 and 2022 were analyzed. Pooled results indicated that acupuncture had a better response rate compared to conventional treatments (RR = 1.17, 95% CI: 1.06-1.3, p = 0.003, seven trials, n = 832). Despite no difference in ESWL duration (MD = 0.02 min, 95% CI: -1.53 to 1.57, p = 0.98, three trials, n = 141), stone-free rate (RR = 1.11, 95% CI: 1-1.25, p = 0.06, six trials, n = 498), and satisfaction rate (RR = 1.51, 95% CI: 0.92-2.47, p = 0.1, three trials, n = 334) between the two groups, the acupuncture group had a lower risk of adverse events (RR = 0.51, 95% CI: 0.33-0.79, p = 0.003, five trials, n = 327), peri- (MD = -1.91 points, 94% CI: -3.53 to -0.28, p = 0.02, four trials, n = 258 patient) and post-procedural (MD = -1.07, 95% CI: -1.77 to -0.36, p = 0.003, four trials, n = 335) pain score. Conclusion: The results of this meta-analysis showed that the use of acupuncture in patients receiving ESWL was associated with a higher pain relief rate and a lower risk of adverse events, suggesting feasibility of its use in this clinical setting. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022356327.

Effect of neutralization treatment on properties of chitosan/bamboo leaf flavonoids/nano-metal oxide composite films and application of films in antioxidation of rapeseed oil.

Neutralization treatment improved the slow-release antioxidant food packaging function of chitosan (CS)/bamboo leaf flavone (BLF)/nano-metal oxides composite films. The film cast from the CS composite solution neutralized by KOH solution had good thermal stability. The elongation at break of the neutralized CS/BLF film was increased by about 5 times, which provided the possibility for its packaging application. After 24 h of soaking in different pH solutions, the unneutralized films swelled severely and even dissolved, while the neutralized films maintained the basic structure with a small degree of swelling, and the release trend of BLF conformed to the logistic function (R2 ≥ 0.9186). The films had a good ability to resist free radicals, which was related to the release amount of BLF and the pH of the solution. The antimicrobial neutralized CS/BLF/nano-ZnO film, like the nano-CuO and Fe3O4 films, were effective in inhibiting the increase in peroxide value and 2-thiobarbituric acid induced by thermal oxygen oxidation of rapeseed oil and had no toxicity to normal human gastric epithelial cells. Therefore, the neutralized CS/BLF/nano-ZnO film is likely to become an active food packaging material for oil-packed food, which can prolong the shelf life of packaged food.

Functional characterization and transcriptional activity analysis of Dryopteris fragrans farnesyl diphosphate synthase genes.

Farnesyl diphosphate synthase (FPS), a key enzyme of the terpene metabolic pathway, catalyzes the precursor of sesquiterpene compounds farnesyl diphosphate (FPP) synthesis, and plays an important role in regulating plant growth and development. Dryopteris fragrans is a medicinal plant rich terpenoids. In this study, the function of the gene was verified in vitro and in vivo, the promoter of the gene was amplified and its transcriptional activity was analyzed. In the present study, we report the molecular cloning and functional characterization of DfFPS1 and DfFPS2, two FPS genes from D. fragrans. We found that the two genes were evolutionarily conserved. Both DfFPS genes were highly expressed in the gametophyte and mature sporophyte leaves, and their expression levels increased in response to methyl jasmonate (MeJA) and high temperature. Both DfFPS proteins were localized in the cytoplasm and could catalyze FPP synthesis in vitro. We also found that the overexpression of DfFPS genes in tobacco plants promoted secondary metabolite accumulation but exhibited negligible effect on plant growth and development. However, the transgenic plants exhibited tolerance to high temperature and drought. The promoters of the two genes were amplified using fusion primer and nested integrated polymerase chain reaction (FPNI-PCR). The promoter sequences were truncated and their activity was examined using the ß-glucuronidase (GUS) gene reporter system in tobacco leaves, and we found that both genes were expressed in the stomata. The transcriptional activity of the promoters was found to be similar to the expression pattern of the genes, and the transcriptional core regions of the two genes were mainly between -943 bp and -740 bp of proDfFPS1. Therefore, we present a preliminary study on the function and transcriptional activity of the FPS genes of D. fragrans and provide a basis for the regulation of terpene metabolism in D. fragrans. The results also provide a novel basis for the elucidation of terpene metabolic pathways in ferns.

Biometrics Data Visualization of Ginsenosides in Anticancer Investigations.

Ginsenoside extracts have been shown to have anticancer effects by a growing number of studies and have thus become a hot topic in cancer research. Our study used VOSviewer and CiteSpace softwares to conduct a bibliometric approach to co-citation and co-occurrence analysis of countries, institutions, authors, references, and keywords in the field of cancer research to investigate the current status and trends of ginsenosides research in cancer. The web of science core collection (WoSCC) contained a total of 1102 papers. China made the most contributions in this area, with the most publications (742, 67.3%), and collaborated closely with Korea and the USA. The Journal of Ginseng Research, with the most total citations (1607) and an IF of 6.06, is the leading journal in the field of ginsenoside and cancer research, publishing high quality articles. Saponin and its extracts inhibit oxidative stress, promote apoptosis, and inhibits chemotherapy resistance by ginsenosides, all of which are hot research areas in this field. In the coming years, it is expected that the combination of ginsenosides and nanoparticles, in-depth mechanisms of cancer inhibition, and targeted therapy will receive widespread attention.

Andrographolide ameliorates hepatic steatosis by suppressing FATP2-mediated fatty acid uptake in mice with nonalcoholic fatty liver disease.

Excessive intrahepatocellular lipid accumulation or steatosis is caused by abnormal lipid metabolism and a common character of nonalcoholic fatty liver disease (NAFLD), which may progress into cirrhosis and hepatocellular cancer. Andrographolide (Andro) is the primary active ingredient extracted from Andrographis paniculata, showing a protective role against dietary steatosis with the mechanism not fully understood. In this study, we showed that administration of Andro (50, 100, and 200 mg/kg/day for 8 weeks, respectively) attenuated obesity and metabolic syndrome in high-fat diet (HFD)-fed mice with improved glucose tolerance, insulin sensitivity, and reduced hyperinsulinemia, hyperglycemia, and hyperlipidemia. HFD-fed mice presented hepatic steatosis, which was significantly prevented by Andro. In vitro, Andro decreased the intracellular lipid droplets in oleic acid-treated LO2 cells. The selected RT-PCR array revealed a robust expression suppression of the fatty acid transport proteins (FATPs) by Andro treatment. Most importantly, we found that Andro consistently reduced the expression of FATP2 in both the oleic acid-treated LO2 cells and liver tissues of HFD-fed mice. Overexpression of FATP2 abolished the lipid-lowering effect of Andro in oleic acid-treated LO2 cells. Andro treatment also reduced the fatty acid uptake in oleic acid-treated LO2 cells, which was blunted by FATP2 overexpression. Collectively, our findings reveal a novel mechanism underlying the anti-steatosis effect of Andro by suppressing FATP2-mediated fatty acid uptake, suggesting the potential therapeutic application of Andro in the treatment of NAFLD.

Mechanism of traditional Chinese medicine in treating overactive bladder.

Overactive bladder syndrome (OAB) has made increasing progress in mechanism and treatment research. Traditional Chinese medicine (TCM) is a common complementary therapy for OAB, and it has been found to be effective. However, the intervention mechanism of TCM in the treatment of OAB is still unclear. The aim of this review is to consolidate the current knowledge about the mechanism of TCM: acupuncture, moxibustion, herbs in treating OAB, and the animal models of OAB commonly used in TCM. Finally, we put forward the dilemma of TCM treatment of OAB and discussed the insufficiency and future direction of TCM treatment of OAB.

Sishen Pill Ameliorates Dextran Sulfate Sodium (DSS)-Induced Colitis with Spleen-Kidney Yang Deficiency Syndromes: Role of Gut Microbiota, Fecal Metabolites, Inflammatory Dendritic Cells, and TLR4/NF-κB Pathway.

Sishen pill (SSP) is an old Chinese medicine used to treat colitis with spleen-kidney-yang deficiency (SKYD) syndromes. However, its exact mechanism of action has not yet been fully elucidated. The aim of this study was to evaluate the effects and potential mechanisms of SSP on colitis with SKYD syndromes in mice. Colitis with SKYD syndromes was induced by rhubarb, hydrocortisone, and dextran sulfate sodium (DSS), and treatment was provided with SSP. Flow cytometry was performed to examine the inflammatory dendritic cell (infDC) regulations of SSP. The changes in the gut microbiota (GM) and fecal metabolites post-SSP treatment were investigated using the combination of 16S rRNA sequencing and untargeted metabolomics. Additionally, we also examined whether SSPs could regulate the infDCs by modifying TLR4/NF-κB signaling pathways. Compared with the DSS group, the disease activity index, colonic weight, index of colonic weight, and colonic injury scores, as well as the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-12p70 decreased significantly in the DSS + SSP group, while free triiodothyronine (FT3), free tetraiodothyronine (FT4), testosterone (TESTO), body weight change, colonic length, and the levels of IL-10 increased. Also, SSP decreased the amounts of CD103+CD11c+iNOS+, CD103+CD11c+TNF-α +, CD11c+CD103+CD324+, CD103+CD11c+MHC-II+, and CD103+CD11c+CD115+. Interestingly, 16S rRNA sequencing and untargeted metabolomics showed that SSP treatment restored the dysbiosis of GM and improved the dysfunction in fecal metabolism in colitis mice with SKYD syndromes. Correlation analysis indicated that the modulatory effects of SSP on FT3, FT4, IL-10, colonic weight index, CD103+CD11c+TNF-α +, CD103+CD11c+MHC-II+, and 13 common differential metabolites were related to alterations in the abundance of Parvibacter, Aerococcus, norank_f_Lachnospiraceae, Lachnospiraceae_UCG-006, Akkermansia, and Rhodococcus in the GM. In addition, SSP markedly inhibited the activation of the TLR4, MyD88, TRAF6, TAB2, and NF-κBp65 proteins and activated IκB. These results indicate that SSP can effectively alleviate colitis mice with SKYD syndrome by regulating infDCs, GM, fecal metabolites, and TLR4/NF-κB signaling pathways.

Overexpression of DfRaf from Fragrant Woodfern (Dryopteris fragrans) Enhances High-Temperature Tolerance in Tobacco (Nicotiana tabacum).

Heat stress seriously affects medicinal herbs' growth and yield. Rubisco accumulation factor (Raf) is a key mediator regulating the activity of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), which plays important roles in carbon assimilation and the Calvin cycle in plants. Raf has been studied in many plants, but has rarely been studied in the important medicinal plant fragrant woodfern (Dryopteris fragrans). The aim of this study was to analyze the effects of Raf on carbohydrate metabolism and the response to heat stress in medicinal plants. In this study, high temperature treatment upregulated the expression of DfRaf, which was significantly higher than that of phosphoribokinase (DfPRK), Rubisco small subunits (DfRbcS), Rubisco large subunits (DfRbcL) and Rubisco activase (DfRCA). The subcellular localization showed that the DfRaf proteins were primarily located in the nucleus; DfPRK, DfRbcS, DfRbcL and DfRCA proteins were primarily located in the chloroplast. We found that overexpression of DfRaf led to increased activity of Rubisco, RCA and PRK under high-temperature stress. The H2O2, O2- and MDA content of the DfRaf-OV-L2 and DfRaf-OV-L6 transgenic lines were significantly lower than those of WT and VC plants under high-temperature stress. The photosynthetic pigments, proline, soluble sugar content and ROS-scavenging ability of the DfRaf-OV-L2 and DfRaf-OV-L6 transgenic lines were higher than those of WT and VC plants under high-temperature stress. The results showed that overexpression of the DfRaf gene increased the Rubisco activity, which enhanced the high-temperature tolerance of plants.

Antiepileptic Therapy of Abrus cantoniensis: Evidence from Network Pharmacology.

The present study explores the mechanism of antiepileptic treatment of Abrus cantoniensis through network pharmacology. During this process, several databases were recruited, e.g., the TCMSP database, HERB database, and SwissTargetPrediction database were used to retrieve the active components and targets of Abrus cantoniensis; GeneCards database and OMIM database were used to retrieve the targets of epilepsy. The targets of epilepsy and Abrus cantoniensis were subjected to target intersection in venny2.1, and protein interaction analysis of Abrus cantoniensis in the String database. We set the Cyto NCA plug-in condition as betweenness; selected the first 8 genes of betweenness as the core genes; performed the integrative bioinformatics of candidates by GO analysis and KEGG analysis. Moreover, AutoDockTools and AutoDockVina software were used to perform the molecular docking; Pymol was used to perform the docking visualization. We obtained three active components of Abrus cantoniensis, which are mainly related to ß-sitosterol and stigmasterol; 92 intersection targets of epilepsy of Abrus cantoniensis, including 9 core targets such as AKT1, ESR1, MMP9, CES1, SRC, HIF1A, ABCB1, CASP3, and SNCA; 8 core targets were flavanone constituent proteins. Define p value less than 0.05; according to the screening principle, the first 20 GO pathways and KEGG pathways were selected. We found that Abrus cantoniensis was mainly connected with epilepsy through the neuroactive ligand-receptor interaction signaling pathway, the neurodegeneration pathway, and multiple disease signaling pathway; the docking between ESR1 and components is the most stable among the core targets. Besides, the binding energies of the core targets were all less than -5 kcal mol-1. Taken together, the current research provides a new strategy for the antiepileptic treatment of Abrus cantoniensis.

Contrasting Responses of Multispatial Soil Fungal Communities of Thuja sutchuenensis Franch., an Extremely Endangered Conifer in Southwestern China.

Thuja sutchuenensis Franch. is an endangered species in southwest China, distributed sporadically in mountainous areas. Soil property and soil fungal community play a crucial role in plant growth and survival. Nevertheless, understanding soil properties and the soil fungal community in the areas where T. sutchuenensis is distributed is extremely limited. Hence, this study collected a total of 180 soil samples from five altitudinal distribution areas (altitudinal gradients) and three vertical depths throughout four horizontal distances from the base of each tree. The results found that altitudinal gradients and vertical depths altered soil properties, including pH, organic matter content, water content, total nitrogen, phosphorus, and potassium, and available nitrogen, phosphorus, and potassium. The fungal alpha diversity indexes (Chao1 and Shannon) and beta diversity were dramatically decreased with elevation. In addition, high altitudes (2,119 m) harbored the highest relative abundance of ectomycorrhizal fungi (27.57%) and the lowest relative abundance of plant-pathogenic fungi (1.81%). Meanwhile, we identified a series of fungal communities, such as Tomentella, Piloderma, Cortinarius, Sebacina, and Boletaceae, that play an essential role in the survival of T. sutchuenensis. The correlation analysis and random forest model identified that water content and total phosphorus showed strong relationships with fungal characteristics and were the primary variables for Zygomycota and Rozellomycota. Collectively, the findings of this integrated analysis provide profound insights into understanding the contrasting responses of T. sutchuenensis soil fungal communities and provide a theoretical basis for T. sutchuenensis habitat restoration and species conservation from multispatial perspectives. IMPORTANCE The present study highlights the importance of fungal communities in an endangered plant, T. sutchuenensis. Comparative analysis of soil samples in nearly all extant T. sutchuenensis populations identified that soil properties, especially soil nutrients, might play critical roles in the survival of T. sutchuenensis. Our findings prove that a series of fungal communities (e.g., Tomentella, Piloderma, and Cortinarius) could be key indicators for T. sutchuenensis survival. In addition, this is the first time that large-scale soil property and fungal community investigations have been carried out in southwest China, offering important values for exploring the distribution pattern of regional soil microorganisms. Collectively, our findings display a holistic picture of soil microbiome and environmental factors associated with T. sutchuenensis.

Integrated mRNA and miRNA Transcriptome Analysis Suggests a Regulatory Network for UV-B-Controlled Terpenoid Synthesis in Fragrant Woodfern (Dryopteris fragrans).

Fragrant woodfern (Dryopteris fragrans) is a medicinal plant rich in terpenoids. Ultraviolet-B (UV-B) light could increase concentration of terpenoids. The aim of this study was to analyze how UV-B regulates the terpenoid synthesis of the molecular regulatory mechanism in fragrant woodfern. In this study, compared with the control group, the content of the terpenes was significantly higher in fragrant woodfern leaves under UV-B treatment for 4 days (d). In order to identify how UV-B regulates the terpenoid metabolic mechanism in fragrant woodfern, we examined the mRNAs and small RNAs in fragrant woodfern leaves under UV-B treatment. mRNA and miRNA-seq identified 4533 DEGs and 17 DEMs in the control group compared with fragrant woodfern leaves under UV-B treatment for 4 d. mRNA-miRNA analysis identified miRNA target gene pairs consisting of 8 DEMs and 115 miRNAs. The target genes were subjected to GO and KEGG analyses. The results showed that the target genes were mainly enriched in diterpene biosynthesis, terpenoid backbone biosynthesis, plant hormone signal transduction, MEP pathway and MVA pathway, in which miR156 and miR160 regulate these pathways by targeting DfSPL and DfARF, respectively. The mRNA and miRNA datasets identified a subset of candidate genes. It provides the theoretical basis that UV-B regulates the terpenoid synthesis of the molecular regulatory mechanism in fragrant woodfern.

Families of Patients With Cancer: Responses and Actions to People With Cancer Who Use Complementary and Alternative Medicine: A Qualitative Study in Taiwan.

This study aims to explore how the families of patients with cancer respond to and act toward complementary and alternative medicine (CAM) use. A qualitative research design based on grounded theory was adopted in this study. Semistructured and face-to-face in-depth interviews were conducted. Each participant was involved in a one-to-one individual interview. Five categories emerged regarding how the families of patients with cancer responded to and acted toward CAM use: purposes of using CAM, CAM use between patients and families, role of family caregivers, actions when using CAM, and seeking religious practice. The core category following coding emphasized the paramount importance of patients' comfort. The findings revealed that the families of patients with cancer may respond and act differently regarding patients' use of CAM. During this process, patients may not inform family members that they are using CAM. Health care professionals should consider this in their interactions with family members.

Cell Apoptosis Mechanism and Traditional Chinese Medicine Intervention in Diabetic Peripheral Neuropathy： A Review / 中国实验方剂学杂志

Diabetic peripheral neuropathy is a common complication of diabetes， and its pathogenesis is complex. Its high morbidity can result in disability， teratogenesis， and death in diabetic patients. At present， the pathogenesis of diabetic peripheral neuropathy has not been clearly elucidated， which may be related to oxidative stress， inflammatory response， microcirculation dysfunction， metabolic abnormalities， etc. Recent studies have found that apoptosis plays an important role in the pathogenesis of diabetic peripheral neuropathy. The three pathways， i.e.， mitochondrial pathway， death receptor pathway， and endoplasmic reticulum pathway， jointly regulate the cell apoptosis in the body. Traditional Chinese medicine， with definite efficacies in the treatment of diabetic peripheral neuropathy， is advantageous in overall regulation and multi-target and multi-pathway treatment. As reported， the active ingredients in Chinese medicine and Chinese medicinal compounds can alleviate diabetic peripheral neuropathy by regulating apoptosis signaling pathways. Furthermore， apoptosis pathways are expected to be potential targets for new drugs against diabetic peripheral neuropathy following oxidative stress. Therefore， this paper， taking apoptosis as the entry point， reviewed the research progress on TCM intervention in diabetic peripheral neuropathy in recent years to provide references for the clinical prevention and treatment of diabetic peripheral neuropathy and the development of new drugs.

A meta-analysis of randomized clinical trials on the impact of oral vitamin C supplementation on first-year outcomes in orthopedic patients.

This meta-analysis aimed at investigating the impact of oral vitamin C supplementation on the post-procedural recovery of orthopedic patients, including functional outcomes and complex regional pain syndrome type I (CRPS I). Literature search using the Medline, Cochrane Library, and Embase databases from inception till March 2021 identified seven eligible randomized controlled trials with 1,361 participants. Forest plot revealed no significant difference in the functional outcomes at 6-12 months [standardized mean difference (SMD) = -0.00, 95% CI - 0.19 to 0.18, 467 patients], risk of overall complications (RR = 0.98, 95% CI 0.68 to 1.39, 426 patients), and pain severity at 3-6 months (SMD = - 0.18, 95% CI - 0.49 to 0.12, 486 patients) between patients with and without oral vitamin C supplementation. Pooled analysis showed that vitamin C treatment reduced the risk of CRPS I regardless of dosage (RR = 0.46, 95% CI 0.25 to 0.85, 1143 patients). In conclusion, the current meta-analysis demonstrated that oral vitamin C supplementation may reduce the risk of complex regional pain syndrome type I but did not improve the functional outcomes in orthopedic patients. Nevertheless, because of the small number of trials included in the present study, further large-scale clinical studies are warranted to support our findings.

Effect of music therapy on improving sleep quality in older adults: A systematic review and meta-analysis.

OBJECTIVES: Poor sleep quality is a common issue among older adults; it can lead to a poor quality of life and impairments in cognitive function and physical health. This study aimed to conduct a systematic review and meta-analysis of the effect of listening to music on sleep quality in older adults. DESIGN: Systematic review and meta-analyses. SETTING: Five databases, including Embase, Ovid Medline, Cochrane Library, Scopus, and the Index to Taiwan Periodical Literature System, were searched to identify studies assessing the efficacy of music therapy in older adults aged 60 years and older published through February 20, 2021. PARTICIPANTS: Adults aged 60 years and older. MEASUREMENTS: We searched English- and Chinese-language studies of randomized control trials. All studies were reviewed by two independent investigators. The primary sleep outcome was the Pittsburgh sleep quality index. The Cochrane Collaboration tool was used to assess the risk of bias, and Review Manager 5.3 software was used to conduct the meta-analysis. RESULTS: Five randomized control trials were included in the meta-analysis. Older adults who listened to music experienced significantly better sleep quality than those who did not listen to music [mean difference (MD): -1.96, 95% CI -2.23 to -1.73, P = 0.003]. The subgroup analysis revealed that older adults who listened to sedative music obtained a more effective improvement in sleep quality than those who listened to rhythm-centered music (MD: -2.35, 95% CI -3.59 to -1.10, P = 0.0002). Furthermore, listening to music for longer than 4 weeks (MD: -2.61, 95% CI -4.72 to -0.50, P = 0.02) was to be effective at improving sleep quality. CONCLUSIONS: Music therapy is safe and easy to administer and can effectively improve sleep quality among older adults, particularly those listening to more sedative music for at least a four-week duration.

Targeting triple-negative breast cancer with an aptamer-functionalized nanoformulation: a synergistic treatment that combines photodynamic and bioreductive therapies.

BACKGROUND: Areas of hypoxia are often found in triple-negative breast cancer (TNBC), it is thus more difficult to treat than other types of breast cancer, and may require combination therapies. A new strategy that combined bioreductive therapy with photodynamic therapy (PDT) was developed herein to improve the efficacy of cancer treatment. Our design utilized the characteristics of protoporphyrin IX (PpIX) molecules that reacted and consumed O2 at the tumor site, which led to the production of cytotoxic reactive oxygen species (ROS). The low microenvironmental oxygen levels enabled activation of a bioreductive prodrug, tirapazamine (TPZ), to become a toxic radical. The TPZ radical not only eradicated hypoxic tumor cells, but it also promoted therapeutic efficacy of PDT. RESULTS: To achieve the co-delivery of PpIX and TPZ for advanced breast cancer therapy, thin-shell hollow mesoporous Ia3d silica nanoparticles, designated as MMT-2, was employed herein. This nanocarrier designed to target the human breast cancer cell MDA-MB-231 was functionalized with PpIX and DNA aptamer (LXL-1), and loaded with TPZ, resulting in the formation of TPZ@LXL-1-PpIX-MMT-2 nanoVector. A series of studies confirmed that our nanoVectors (TPZ@LXL-1-PpIX-MMT-2) facilitated in vitro and in vivo targeting, and significantly reduced tumor volume in a xenograft mouse model. Histological analysis also revealed that this nanoVector killed tumor cells in hypoxic regions efficiently. CONCLUSIONS: Taken together, the synergism and efficacy of this new therapeutic design was confirmed. Therefore, we concluded that this new therapeutic strategy, which exploited a complementary combination of PpIX and TPZ, functioned well in both normoxia and hypoxia, and is a promising medical procedure for effective treatment of TNBC.

Albicanol Alleviates D-Galactose-Induced Aging and Improves Behavioral Ability Via by Alleviating Oxidative Stress-Induced Damage.

Albicanol is a natural terpenoid derived from Dryopteris fragrans. Herein, we assessed the ability of Albicanol to protect against oxidative stress-induced senescence. Using a murine model of D-galactose (D-gal)-induced aging, we determined that Albicanol treatment can reverse D-gal-mediated learning impairments and behavioral changes, while also remediating brain tissue damage in treated mice. We found that serum SOD, CAT, GSH-Px, and T-AOC levels were significantly decreased in aging mice, and that Albicanol treatment significantly increased the serum levels of these antioxidant enzymes. We additionally evaluated the impact of Albicanol treatment on the Keap1/Nrf2/ARE signaling pathway, and found that it was able to decrease Keap1 expression while increasing the expression of Nrf2, thereby activating this signaling pathway, suppressing oxidative damage, and enhancing the expression of downstream target genes including SOD, GSH, GST, HO-1, and NQO1 in this murine aging model system. Albicanol treatment also inhibited the secretion of inflammatory TNF-a and IL-1b. Together, these data indicated that Albicanol can activate Nrf2 pathway-related genes, thereby inhibition of delayed aging by alleviating oxidative stress-induced damage.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5-3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg. MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER: NCT02063100 on ClinicalTrials.gov.