Iron Oxide Nanoparticles Inhibit Tumor Progression and Suppress Lung Metastases in Mouse Models of Breast Cancer.

Systemic exposure to starch-coated iron oxide nanoparticles (IONPs) can stimulate antitumor T cell responses, even when little IONP is retained within the tumor. Here, we demonstrate in mouse models of metastatic breast cancer that IONPs can alter the host immune landscape, leading to systemic immune-mediated disease suppression. We report that a single intravenous injection of IONPs can inhibit primary tumor growth, suppress metastases, and extend survival. Gene expression analysis revealed the activation of Toll-like receptor (TLR) pathways involving signaling via Toll/Interleukin-1 receptor domain-containing adaptor-inducing IFN-ß (TRIF), a TLR pathway adaptor protein. Requisite participation of TRIF in suppressing tumor progression was demonstrated with histopathologic evidence of upregulated IFN-regulatory factor 3 (IRF3), a downstream protein, and confirmed in a TRIF knockout syngeneic mouse model of metastatic breast cancer. Neither starch-coated polystyrene nanoparticles lacking iron, nor iron-containing dextran-coated parenteral iron replacement agent, induced significant antitumor effects, suggesting a dependence on the type of IONP formulation. Analysis of multiple independent clinical databases supports a hypothesis that upregulation of TLR3 and IRF3 correlates with increased overall survival among breast cancer patients. Taken together, these data support a compelling rationale to re-examine IONP formulations as harboring anticancer immune (nano)adjuvant properties to generate a therapeutic benefit without requiring uptake by cancer cells.

Effects of Electroacupuncture on Gut Microbiota and Fecal Metabolites in Rats with Poststroke Depression.

Background: Poststroke depression (PSD) is the most frequent neuropsychiatric consequence of stroke. Electroacupuncture (EA) has been found to be an effective therapy for treating PSD. However, the underlying mechanisms of EA's efficacy remain unclear. This research aimed to investigate the effects of EA on alterations in gut microbiota and fecal metabolome in PSD rats. Methods: Analyses of gut microbiome and fecal metabolome were performed to identify gut microbes and their functional metabolites in a sham group, PSD group, and EA group. We conducted enrichment analysis to identify the differential metabolic pathways in three groups. Correlations between altered gut microbes and differential metabolites after EA treatment were studied. Results: PSD showed decreased species-richness/diversity indices of microbial composition, characterized by an increase in Muribaculaceae, Peptostreptococcaceae, Oscillospiraceae, Ruminococcaceae, and Clostridiaceae and a decrease in Lactobacillaceae, Lachnospiraceae, and Bacteroidaceae. Of these, the abundance of Muribaculaceae, Lactobacillaceae, Lachnospiraceae, Peptostreptococcaceae, and Clostridiaceae were reversed by EA. Furthermore, PSD was associated with 34 differential fecal metabolites, mainly belonging to steroid hormone biosynthesis, that could be regulated by EA. Conclusion: Regulation of gut microbiome and lipid metabolism could be one of the potential mechanisms for EA treatment for alleviating the depressive behaviors of PSD.

Quality and Reliability of Liver Cancer-Related Short Chinese Videos on TikTok and Bilibili: Cross-Sectional Content Analysis Study.

BACKGROUND: Liver cancer incidence has been increasing in China in the recent years, leading to increased public concern regarding the burden of this disease. Short videos on liver cancer are disseminated through TikTok and Bilibili apps, which have gained popularity in recent years as an easily accessible source of health information. However, the credibility, quality, and usefulness of the information in these short videos and the professional knowledge of the individuals uploading health information-based videos in these platforms have not yet been evaluated. OBJECTIVE: Our study aims to assess the quality of the information in Chinese short videos on liver cancer shared on the TikTok and Bilibili short video-sharing platforms. METHODS: In March 2023, we assessed the top 100 Chinese short videos on liver cancer in TikTok and Bilibili (200 videos in total) for their information quality and reliability by using 2 rating tools, namely, global quality score (GQS) and the DISCERN instrument. Correlation and Poisson regression analyses were applied to discuss the factors that could impact video quality. RESULTS: Compared to Bilibili, TikTok is more popular, although the length of the videos on TikTok is shorter than that of the videos on Bilibili (P<.001). The quality of the short videos on liver cancer in TikTok and Bilibili was not satisfactory, with median GQS of 3 (IQR 2-4) and 2 (IQR 1-5) and median DISCERN scores of 5 (IQR 4-6) and 4 (IQR 2-7), respectively. In general, the quality of videos sourced from professional institutions and individuals was better than that of those sourced from nonprofessionals, and videos involving disease-related knowledge were of better quality than those covering news and reports. No significant differences were found in the quality of videos uploaded by individuals from different professions, with the exception of those uploaded by traditional Chinese medicine professionals, which demonstrated poorer quality. Only video shares were positively correlated with the GQS (r=0.17, P=.01), and no video variables could predict the video quality. CONCLUSIONS: Our study shows that the quality of short videos on health information related to liver cancer is poor on Bilibili and TikTok, but videos uploaded by health care professionals can be considered reliable in terms of comprehensiveness and content quality. Thus, short videos providing medical information on TikTok and Bilibili must be carefully considered for scientific soundness by active information seekers before they make decisions on their health care management.

PANoptosis-based molecular subtyping and HPAN-index predicts therapeutic response and survival in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a highly prevalent and fatal cancer. The role of PANoptosis, a novel form of programmed cell death, in HCC is yet to be fully understood. This study focuses on identifying and analyzing PANoptosis-associated differentially expressed genes in HCC (HPAN_DEGs), aiming to enhance our understanding of HCC pathogenesis and potential treatment strategies. Methods: We analyzed HCC differentially expressed genes from TCGA and IGCG databases and mapped them to the PANoptosis gene set, identifying 69 HPAN_DEGs. These genes underwent enrichment analyses, and consensus clustering analysis was used to determine three distinct HCC subgroups based on their expression profiles. The immune characteristics and mutation landscape of these subgroups were evaluated, and drug sensitivity was predicted using the HPAN-index and relevant databases. Results: The HPAN_DEGs were mainly enriched in pathways associated with the cell cycle, DNA damage, Drug metabolism, Cytokines, and Immune receptors. We identified three HCC subtypes (Cluster_1, SFN+PDK4-; Cluster_2, SFN-PDK4+; Cluster_3, SFN/PDK4 intermediate expression) based on the expression profiles of the 69 HPAN_DEGs. These subtypes exhibited distinct clinical outcomes, immune characteristics, and mutation landscapes. The HPAN-index, generated by machine learning using the expression levels of 69 HPAN_DEGs, was identified as an independent prognostic factor for HCC. Moreover, the high HPAN-index group exhibited a high response to immunotherapy, while the low HPAN-index group showed sensitivity to small molecule targeted drugs. Notably, we observed that the YWHAB gene plays a significant role in Sorafenib resistance. Conclusion: This study identified 69 HPAN_DEGs crucial to tumor growth, immune infiltration, and drug resistance in HCC. Additionally, we discovered three distinct HCC subtypes and constructed an HPAN-index to predict immunotherapeutic response and drug sensitivity. Our findings underscore the role of YWHAB in Sorafenib resistance, presenting valuable insights for personalized therapeutic strategy development in HCC.

Moxibustion ameliorates cerebral ischemia-reperfusion injury by regulating ferroptosis in rats.

Moxibustion is an effective treatment for the clinical management of acute cerebral infarction. However, its exact mechanism of action is still not fully understood. This study aimed to investigate the protective effect of moxibustion on cerebral ischemia-reperfusion injury (CIRI) in rats. Middle cerebral artery occlusion/reperfusion (MCAO/R) was used to construct a CIRI rat model, all animals were randomly divided into four groups including sham operation group, MCAO/R group (MCAO/R), moxibustion therapy + MCAO/R (Moxi) and ferrostatin-1 + MCAO/R (Fer-1) group. In the Moxi group, moxibustion treatment was initiated 24 h after modeling, once a day for 30 mins each time for 7 days. Moreover, the Fer-1 group received intraperitoneal injections of Fer-1 12 h after modeling, once a day for a total of 7 days. The results showed that moxibustion could reduce nerve function damage and neuronal death. Additionally, moxibustion could reduce the production of lipid peroxides such as lipid peroxide, malondialchehyche and ACSL4 to regulate lipid metabolism, promote the production of glutathione and glutathione peroxidase 4 and reduce the expression of hepcidin by inhibiting the production of inflammatory factor interleukin-6, therefore, downregulating the expression of SLC40A1, reducing the iron level in the cerebral cortex, reducing the accumulation of reactive oxygen species and inhibiting ferroptosis. Based on our studies, it can be concluded that moxibustion has the ability to inhibit ferroptosis of nerve cells post CIRI and plays a protective role in the brain. This protective role can be attributed to the regulation of iron metabolism of nerve cells, reduction of iron deposition in the hippocampus and lowering the level of lipid peroxidation.

Wnt/ß-catenin signalling pathway in breast cancer cells and its effect on reversing tumour drug resistance by alkaloids extracted from traditional Chinese medicine.

Breast cancer is a high-risk disease with a high mortality rate among women. Chemotherapy plays an important role in the treatment of breast cancer. However, chemotherapy eventually results in tumours that are resistant to drugs. In recent years, many studies have revealed that the activation of Wnt/ß-catenin signalling is crucial for the emergence and growth of breast tumours as well as the development of drug resistance. Additionally, drugs that target this pathway can reverse drug resistance in breast cancer therapy. Traditional Chinese medicine has the properties of multi-target and tenderness. Therefore, integrating traditional Chinese medicine and modern medicine into chemotherapy provides a new strategy for reversing the drug resistance of breast tumours. This paper mainly reviews the possible mechanism of Wnt/ß-catenin in promoting the process of breast tumour drug resistance, and the progress of alkaloids extracted from traditional Chinese medicine in the targeting of this pathway in order to reverse the drug resistance of breast cancer.

[Application and development of systems biology in computer-aided drug design].

With the advances in medicine, people have deeply understood the complex pathogenesis of diseases. Revealing the mechanism of action and therapeutic effect of drugs from an overall perspective has become the top priority of drug design. However, the traditional drug design methods cannot meet the current needs. In recent years, with the rapid development of systems biology, a variety of new technologies including metabolomics, genomics, and proteomics have been used in drug research and development. As a bridge between traditional pharmaceutical theory and modern science, computer-aided drug design(CADD) can shorten the drug development cycle and improve the success rate of drug design. The application of systems biology and CADD provides a methodological basis and direction for revealing the mechanism and action of drugs from an overall perspective. This paper introduces the research and application of systems biology in CADD from different perspectives and proposes the development direction, providing reference for promoting the application.

Does acupuncture treatment have satisfactory clinical efficacy for late-life depression? A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to assess the clinical efficacy of acupuncture in late-life depression (LLD). METHODS: A comprehensive search of seven electronic databases was conducted from inception to November 2022, including the Cochrane Library, PubMed, Embase, CNKI, VIP, CBM and the Wan Fang database. All data analysis were conducted by Revman 5.3. RESULTS: A total of nine RCTs involving 603 participants were included. The meta-analysis results showed that acupuncture combined with antidepressants significantly reduced HAMD scores (MD, -3.69 [95% CI, -5.11 to -2.27], I2 =74%) and a significantly higher cure rate (RR, 1.11 [95% CI, 1.01 to 1.22], I2 = 0%) compared with antidepressants alone. However, no significant difference was found between acupuncture and antidepressants in reducing HAMD scores and improving clinical outcomes. CONCLUSIONS: Acupuncture combined or not combined with antidepressants is an effective and safe treatment for LLD.

Light-Triggered Nitric Oxide Nanogenerator with High l-Arginine Loading for Synergistic Photodynamic/Gas/Photothermal Therapy.

The development of nanomedicines that combine photothermal therapy (PTT) with photodynamic therapy (PDT) is considered promising for cancer treatment, but still faces the challenge of enhancing tumoricidal efficiency. Fortunately, apart from the well-acknowledged effect on direct tumor cell-killing, nitric oxide (NO) is also considered to be effective for the enhancement of both PTT and PDT. However, both the low loading efficiency of NO precursor and the short half-life time and diffusion distance of NO hamper the synergistic therapeutic efficacy of NO. Taking the aforementioned factors into account, a mitochondria-targeted nitric oxide nanogenerator, EArgFe@Ce6, is constructed to achieve high loading of the NO donor l-Arginine (l-Arg) for synergistic photodynamic/gas/photothermal therapy upon single 660 nm light irradiation. The coordination of epigallocatechin gallate (EGCG) and ferric ions (Fe3+ ) provides EArgFe@Ce6 supreme photothermal capability to perform low-temperature PTT (mPTT). EGCG endows EArgFe@Ce6 with mitochondria-targeting capability and meanwhile favors hypoxia alleviation for enhanced PDT. The PDT-produced massive reactive oxygen species (ROS) further catalyzes l-Arg to generate a considerable amount of NO to perform gas therapy and sensitize both mPTT and PDT. In vitro and in vivo studies demonstrate that the synergistic photodynamic/gas/photothermal therapy triggered by single 660 nm light irradiation is highly effective for tumor treatments.

Sarmentosin promotes USP17 and regulates Nrf2-mediated mitophagy and cellular oxidative stress to alleviate APAP-induced acute liver failure.

BACKGROUND: An overdose of acetaminophen (APAP), the main cause of acute liver failure (ALF), induces oxidative stress that ultimately causes mitochondrial impairment and hepatotoxicity. The nuclear factor erythroid 2-related factor 2 (Nrf2) was widely recognized as an anti-oxidative stress mechanism. The present study was aimed at investigating whether sarmentosin, extract from traditional Chinese medicine, protects the liver against APAP-induced injury via activating Nrf2 and subsequently decreasing oxidative stress. METHODS: Male ICR mice were treated with sarmentosin oral administration for 1 week and injected APAP (300 mg/kg. i.p.) for acute liver injury model. The liver and serum of mice for histological and biochemistry analysis. AML12 and LO2 cells were used in vitro assays. RESULTS: We found that sarmentosin moderately increased accumulation of Nrf2 via upregulating USP17-mediated ubiquitin inhibition at the early stage of hepatocytes damage. The Nrf2 separating from bonding protein Keap1 translocated into nucleus and activated downstream gene of antioxidants. Mitophagy, a unique autophagy can remove Reactive Oxygen Species (ROS) damaged mitochondria, was elevated in this progress to maintain mitochondria function and ROS homeostasis. CONCLUSION: In summary, our research revealed that sarmentosin could alleviate APAP-induced liver acute injury through USP17-mediated Nrf2 overexpression and PINK1-dependent mitophagy.

Diverse polyacetylenes from Atractylodes chinensis and their anti-osteoclastogenesis activity.

The phytochemical investigation on Atractylodes chinensis afforded 15 polyacetylenes 1-15 and one meroterpenoid 16. Of the 16 isolates, compounds 4 and 9 are new ones, and compounds 8 and 16 are first reported from nature. In addition, the relative configuration of 1 and the available NMR data of compounds 1, 8, and 16 were first provided. Their structures were elucidated by extensive analysis of MS, UV, IR, and NMR spectroscopic data. Besides, all isolated compounds were evaluated for their effects on RANKL-induced osteoclastogenesis in BMMs. Among them, polyacetylenes 12-14 showed potent inhibitory activity with IC50 values of 0.67 ± 0.05 µM, 0.72 ± 0.31 µM, and 2.40 ± 0.41 µM, respectively. The current work demonstrates the polyacetylenes are the main active constituents of A. chinensis against osteoclastogenesis.

Expert consensus on clinical application of GBE50 Dispersible Tablets for ischemic cardiovascular and cerebrovascular diseases / 中国中药杂志

Ginkgo biloba Extract( GBE50) Dispersible Tablets is a new standardized prescription,which is widely used in the treatment of ischemic cardiovascular and cerebrovascular diseases. However,there are still many problems in its clinical application.Rational and safe use of GBE50 Dispersible Tablets is pivotal to the medication safety and clinical prognosis of patients. This consensus has been jointly formulated by clinical experts of traditional Chinese medicine and western medicine in cardiovascular and cerebrovascular diseases and followed the Manual for the Clinical Experts Consensus of Chinese Patent Medicine published by the China Association of Chinese Medicine. The present study identified clinical problems based on clinical investigation,searched the research papers according to PICO clinical problems,carried out evidence evaluation,classification,and recommendation by GRADE system,and reached the expert consensus with nominal group technique. The consensus combines evidence with expert experience. Sufficient evidence of clinical problems corresponds to " recommendations",while insufficient evidence to " suggestions". Safety issues of GBE50 Dispersible Tablets,such as indications,usage and dosage,and medication for special populations,are defined to improve clinical efficacy,promote rational medication,and reduce drug risks. This consensus needs to be revised based on emerging clinical issues and evidencebased updates in practical applications in the future.

Overview of systematic reviews of Shufeng Jiedu Capsules / 中国中药杂志

At present, there have been many clinical trials and systematic reviews/Meta-analysis proving the good clinical efficacy of Shufeng Jiedu Capsules in the treatment of respiratory diseases, while comprehensive discussion is still required. This article overviews and analyzes the systematic reviews/Meta-analysis of Shufeng Jiedu Capsules to provide evidence support for clinical practice. The systematic reviews/Meta-analysis of Shufeng Jiedu Capsules were searched from CBM, Wanfang, CNKI, VIP, PubMed, EMbase and Cochrane Library. The AMSTAR 2 scale and GRADE system were respectively employed for the evaluation of methodological quality and the grading of evidence quality. Finally, 8 systematic reviews/Meta-analysis published during 2018-2021 were included for analysis. The diseases involved include acute exacerbation of chronic obstructive pulmonary disease, community-acquired pneumonia, acute tonsillitis, acute exacerbation of chronic bronchitis and acute upper respiratory tract infection. The number of included RCTs studies ranged from 8 to 25. The results showed that Shufeng Jiedu Capsules combined with western medicine routine had better therapeutic effect than the latter alone in the treatment of the above five diseases. The reported adverse reactions caused by Shufeng Jiedu Capsules were mainly gastrointestinal discomforts such as mild nausea, diarrhoea and vomiting, with low incidence and mild symptoms, which can be relieved by drug withdrawal. The methodological quality of the included studies was extremely low, and the outcome indicators were mainly of low and very low grades. The efficacy and safety of Shufeng Jiedu Capsules in the clinical treatment of diseases still need to be verified based on more high-quality studies. The relevant clinical research and systematic review/Meta-analysis should pay more attention to methodological quality and reporting standards and strengthen the scientificity of research.

Vitamin D supplementation for the treatment of migraine: A meta-analysis of randomized controlled studies.

INTRODUCTION: It is not well established to use vitamin D supplementation for migraine, and this meta-analysis aims to explore the efficacy of vitamin D for migraine patients. METHODS: PubMed, EMbase, Web of science, EBSCO and Cochrane library databases were systematically searched up to May 2021, and we included randomized controlled trials (RCTs) exploring the effect of vitamin D for migraine patients. RESULTS: Six RCTs and 301 patients were included in the meta-analysis. Compared with control group in migraine patients, vitamin D supplementation could remarkably decrease headache attacks per month (MD = -2.74; 95% CI = -3.82 to -1.67; P < 0.00001), headache days per month (MD = -1.56; 95% CI = -2.44 to -0.68; P = 0.0005) and MIDAS score (MD = -5.72; 95% CI = -10.90 to -0.54; P = 0.03), but demonstrated no obvious influence on attack duration (MD = -2.20; 95% CI = -7.38 to 2.97; P = 0.40) or headache severity (MD = -0.56; 95% CI = -1.18 to 0.06; P = 0.08). CONCLUSIONS: Vitamin D supplementation provided additional benefits to treat migraine.

An overview of kinase downregulators and recent advances in discovery approaches.

Since the clinical approval of imatinib, the discovery of protein kinase downregulators entered a prosperous age. However, challenges still exist in the discovery of kinase downregulator drugs, such as the high failure rate during development, side effects, and drug-resistance problems. With the progress made through multidisciplinary efforts, an increasing number of new approaches have been applied to solve the above problems during the discovery process of kinase downregulators. In terms of in vitro and in vivo drug evaluation, progress was also made in cellular and animal model platforms for better and more clinically relevant drug assessment. Here, we review the advances in drug design strategies, drug property evaluation technologies, and efficacy evaluation models and technologies. Finally, we discuss the challenges and perspectives in the development of kinase downregulator drugs.

Postoperative Chemoradiotherapy With Capecitabine and Oxaliplatin vs Capecitabine for Stage II to III Rectal Cancer: A Randomized Clinical Trial.

Importance: Several studies have explored the efficacy and toxic effects of concurrent 5-fluorouracil (5-FU)- or capecitabine-based chemoradiotherapy (CRT) with or without oxaliplatin in the neoadjuvant setting. Addition of oxaliplatin to 5-FU or capecitabine elicited similar outcomes but with significantly increased toxic effects; however, there is a need for randomized clinical trials comparing 2 CRT regimens for patients receiving CRT in the adjuvant setting. Objective: To explore the efficacy and toxic effects of oxaliplatin combined with postoperative concurrent capecitabine and radiotherapy (RT) for pathological stage II and III rectal cancer. Design, Setting, and Participants: This multicenter randomized clinical trial enrolled patients from 7 centers in China between April 1, 2008, and December 30, 2015. Patients with pathologically confirmed stage II and III rectal cancer were randomized (1:1) to receive concurrent CRT with capecitabine or capecitabine plus oxaliplatin. Analysis was conducted from December 31, 2019, to March 15, 2020. Interventions: RT comprised 45 to 50 Gy in 25 fractions of 1.8 to 2.0 Gy over 5 weeks. In the capecitabine with RT group, concurrent chemotherapy included 2 cycles of capecitabine (1600 mg/m2) on days 1 to 14 and 22 to 35. The capecitabine and oxaliplatin with RT group received identical postoperative RT to that in the capecitabine with RT group combined with capecitabine (1300 mg/m2) on days 1 to 14 and 22 to 35 and a 2-hour infusion of oxaliplatin (60 mg/m2) on weeks 1, 2, 4, and 5. Patients in both groups received adjuvant chemotherapy (capecitabine or fluorouracil and oxaliplatin) after CRT. Main Outcomes and Measures: The primary end point was 3-year disease-free survival (DFS). Results: A total of 589 patients (median [IQR] age, 55 [47-52] years; 375 [63.7%] men and 214 [36.3%] women) were enrolled, including 294 patients randomized to the capecitabine with RT group and 295 patients randomized to the capecitabine and oxaliplatin with RT group. Median (IQR) follow-up was 68 (45-96) months. Most patients had stage III disease (574 patients [75.9%]). Three-year DFS was 76.3% for the capecitabine with RT group and 74.1% for the capecitabine and oxaliplatin with RT group, and 5-year DFS was 72.0% for the capecitabine with RT group and 71.1% for the capecitabine and oxaliplatin with RT group (hazard ratio [HR], 1.07; 95% CI, 0.79-1.44; P = .68). There was no significant difference between groups in overall survival (HR, 0.93; 95% CI, 0.64-1.34; P = .70) or local recurrence (HR, 0.61; 95% CI, 0.31-1.22; P = .16). More grade 3 and 4 acute toxic effects were observed in the capecitabine and oxaliplatin with RT group than in the capecitabine with RT group (114 patients [38.6%] vs 84 patients [28.6%]; P = .01). Conclusions and Relevance: This randomized clinical trial found that addition of oxaliplatin to capecitabine-based postoperative CRT did not improve the efficacy of treatment but increased the risk of severe acute toxic effects. This finding highlights the basic role of postoperative capecitabine with RT for patients with locally advanced rectal cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT00714077.

Purification and Structural Characterization of Dendrobium officinale Polysaccharides and Its Activities.

In this study, Dendrobium officinale polysaccharide (named DOPS-1) was isolated from the stems of Dendrobium officinale by hot-water extraction and purified by using Sephadex G-150 column chromatography. The structural characterization, antioxidant and cytotoxic activity were carried out. Based on the results of HPLC, GC, Congo red experiment, together with periodate oxidation, Smith degradation, SEM, FT-IR, and NMR spectral analysis, it expressed that DOPS-1 was largely composed of mannose, glucose and galacturonic acid in a molar ratio of 3.2 : 1.3 : 1. The molecular weight of DOPS-1 was 1530 kDa and the main chain was composed of (1→4)-ß-D-Glcp, (1→4)-ß-D-Manp and 2-O-acetyl-(1→4)-ß-D-Manp. The measurement results of antioxidant activity showed that DOPS-1 had the strong scavenging activities on hydroxyl radicals, DPPH radicals and superoxide radicals and the high reducing ability in vitro. Moreover, DOPS-1 was cytotoxic to all three human cancer cells of MDA-MB-231, A549 and HepG2.

Meta-analysis for clinical efficacy of traditional Chinese medicine in treating resistant hypertension / 中国中药杂志

To systematically evaluate the efficacy and safety of traditional Chinese medicine in treating patients with resistant hypertension. CNKI, Wanfang, VIP, CBM, PubMed, Web of Science, Cochrane Library, EMbase and other databases were retrieved by computers to screen out the randomized controlled trial of traditional Chinese medicine in treating resistant hypertension. Cochrane Handbook was used to evaluate the quality of the included literature, RevMan 5.3 and Stata 12.0 was used for Meta-analysis. Finally, 11 literatures meeting the criteria were included, involving 1 023 patients. The results of Meta-analysis showed that the combined therapy of standard triple antihypertensive regimen with traditional Chinese medicine could further reduce systolic blood pressure of patients with resistant hypertension(MD=-16.69, 95%CI[-22.21,-11.16], P<0.000 01), reduce diastolic blood pressure(MD=-7.51, 95%CI[-8.26,-6.76], P<0.000 01), improve the effective rate of anti-hypertension(OR=5.16, 95%CI[3.01, 8.84], P<0.000 01), improve the up-to-standard rate of blood pressure(OR=3.01, 95%CI[1.49, 6.09], P=0.002), and improve the effectiveness of clinical symptoms(OR=4.48, 95%CI[2.31, 8.68], P<0.000 01), with no significant effect on creatinine level(MD=-2.51, 95%CI[-6.91, 1.89], P=0.26). The results of this study indicated that the combined therapy of standard triple antihypertensive regimen with traditional Chinese medicine could further improve the clinical efficacy in patients with resistant hypertension with a good safety, but more high-quality clinical studies are still needed to verify this conclusion.

Network-based analysis with primary cells reveals drug response landscape of acute myeloid leukemia.

Acute myeloid leukemia (AML) is one of the most common, complex, and heterogeneous hematological malignancies in adults. Despite progresses in understanding the pathology of AML, the 5-year survival rates still remain low compared with CML, CLL, etc. The relationship between genomic features and drug responses is critical for precision medication. Herein, we depicted a picture for response of 145 drugs against 33 primary cell samples derived from AML patients with full spectrum of genomic features assessed by whole exon sequencing and RNA sequencing. In general, most of the samples were much more sensitive to the combinatorial chemotherapy regimens than the single chemotherapy drugs. Overall, these samples were moderately sensitive to the Traditional Chinese Medicine (TCM) and the targeted drugs. In the weighted gene coexpression network analysis (WGCNA), the TCM and targeted therapies displayed similar genetic signatures in the gene module correlation. Meanwhile, the expression of miRNAs, lncRNAs, and mRNAs did not display apparent gene module correlations among those different types of therapies. In addition, the combinatorial chemotherapy bear more module correlations than the single drugs. Interestingly, we found that the gene mutations and drug response were not enriched in any WGCNA module analysis. Most of the sensitive drug response biomarkers were enriched in the ribosome, endocytosis, cell cycle, and p53 associated signaling pathways. This study showed that gene expression modules might show better correlation than gene mutations for drug efficacy predictions.

Systemically delivered antibody-labeled magnetic iron oxide nanoparticles are less toxic than plain nanoparticles when activated by alternating magnetic fields.

OBJECTIVE: Toxicity from off-target heating with magnetic hyperthermia (MHT) is generally assumed to be understood. MHT research focuses on development of more potent heating magnetic iron oxide nanoparticles (MIONs), yet our understanding of factors that define biodistribution following systemic delivery remains limited. Preclinical development relies on mouse models, thus understanding off-target heating with MHT in mice provides critical knowledge for clinical development. METHODS: Eight-week old female nude mice received a single tail vein injection of bionized nanoferrite (BNF) MIONs or a counterpart labeled with a polyclonal human antibody (BNF-IgG) at 1 mg, 3 mg or 5 mg Fe/mouse on day 1. On day 3, mice were exposed to an alternating magnetic field (AMF) having amplitude of 32, 48 or 64 kA/m at ∼145 kHz for 20 min. Twenty-four hours later, blood, livers and spleens were harvested and analyzed. RESULTS: Damage to livers was apparent by histology and serum liver enzymes following MHT with BNF or BNF-IgG at doses ≥3 mg Fe and AMF amplitudes ≥48 kA/m. Differences between effects with BNF vs. BNF-IgG at a dose of 3 mg Fe were noted in all measures, with less damage and increased survival occurring in mice injected with BNF-IgG. Necropsies revealed severe damage to duodenum and upper small intestines, likely the immediate cause of death at the highest MHT doses. CONCLUSION: Results demonstrate that the MION coating affects biodistribution, which in turn determines off-target effects. Developments to improve heating capabilities of MIONs may be clinically irrelevant without better control of biodistribution.