Efficacy and Safety of Huachansu as an Adjuvant Therapy for Non-Small Cell Lung Cancer: An Overview of Systematic Reviews and Meta-Analyses.

OBJECTIVE: The purpose of this overview is to assess systematic reviews (SRs)/ meta-analyses (MAs) of Huachansu (HCS) combination chemotherapy for treating non-small cell lung cancer (NSCLC) and provide summarized evidence for clinical decision making. METHODS: From the creation of the database to JUNE 2023, 8 databases in English and Chinese were searched. SRs/MAs that met the inclusion and exclusion criteria were included. Two reviewers independently screened research, extracted data and assessed methodological quality, risk of bias, report quality and evidence quality by using relevant criteria from AMSTAR-2, ROBIS scale, PRISMA, and GRADE system. RESULTS: The short-term effect, long-term effect, quality of life improvement, safety and pain relief effect in 8 included SRs/MAs were assessed in this overview according to quantitative synthesis. Results assessed by AMSTAR-2, PRISMA, and ROBIS were generally unsatisfactory, with the results of the AMSTAR-2 assessment showing that all of them were of low or critically low quality; the number of items in the included research that were fully reported (compliance was 100%) by the PRISMA checklist was only 50%, while there were 38.10% of the research reporting less than 60% completeness; the ROBIS assessment showed a small number of systems to be low risk of bias. In addition, 26 items were rated as moderate quality, while 50.94% of items were rated as low or critically low quality by GRADE. CONCLUSION: HCS may be a promising adjuvant therapy for NSCLC. However, high-quality SRs/MAs and randomized control trials (RCTs) should be conducted to provide sufficient evidence so as to draw a definitive conclusion.

The chromatographic fingerprinting study and genotoxicity evaluation of aqueous extract from Cyclocarya paliurus leaves.

Cyclocarya paliurus leaf is a medicinal and edible homologous plant, which possess various bioactive components with significant health benefits. However, the quality and safety of the aqueous extract from Cyclocarya paliurus leaves (CPLAE) vary greatly due to the raw materials and preparation technology. At present, chromatographic fingerprinting has been widely used for qualitative and quantitative analysis of traditional Chinese medicine (TCM). In this study, a method combining high performance liquid chromatography (HPLC) fingerprint with quantitative analysis was established and successfully applied to the characterization and quality evaluation of the CPLAE. In addition, the genetic safety of the CPLAE was evaluated by genotoxicity tests, including Ames test, chromosomal aberration test of Chinese hamster lung (CHL) cell in vitro, and bone marrow micronucleus test in mice. The results showed that 10 batches of CPLAE samples were analyzed by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS), and the similarity of chromatographic fingerprint of each batch was above 0.961, indicating good similarity. At the same time, the 6 compounds with high absorption strength in the chromatogram were quantitatively analyzed. The results showed that all 6 compounds had good regression (R2=1.000) in the test range, and the recoveries ranged from 96.25% to 102.46%. The results of the 3 genotoxicity tests showed that the highest dose of CPLAE had no genotoxicity. In conclusion, the newly established chromatographic fingerprint and multi-component quantitative analysis method is stable and accurate, and can be used for the identification and quality evaluation of the CPLAE. Moreover, the CPLAE has the characteristics of safety and high quality as functional materials in food.

Network pharmacology and experimental verification reveal the mechanism of safranal against glioblastoma (GBM).

Introduction: Safranal is an active component of the traditional Tibetan medicine (TTM) saffron, which has potential anticancer activity. Methods and results: Here, we studied the therapeutic effect and mechanism of safranal on GBM. CCK-8, GBM-brain organoid coculture experiments and 3D tumour spheroid invasion assays showed that safranal inhibited GBM cell proliferation and invasion in vitro. Network pharmacology, RNA-seq, molecular docking analysis, western blotting, apoptosis, and cell cycle assays predicted and verified that safranal could promote GBM cell apoptosis and G2/M phase arrest and inhibit the PI3K/AKT/mTOR axis. In vivo experiments showed that safranal could inhibit GBM cell growth alone and in combination with TMZ. Conclusion: This study revealed that safranal inhibits GBM cell growth in vivo and in vitro, promotes GBM cell apoptosis and G2/M phase arrest, inhibits the PI3K/AKT/mTOR axis and cooperate with TMZ.

Kaempferol promotes non-small cell lung cancer cell autophagy via restricting Met pathway.

BACKGROUND: Kaempferol is extracted from Hedyotis diffusa, exerting an obvious anti-cancer effect. Here in the present study, we explored the anti-cancer effects and mechanism of kaempferol in non-small cell lung cancer cell (NSCLC). PURPOSE: Our objective is to figure out the molecular mechanism by which kaempferol promotes autophagy in NSCLC cells. STUDY DESIGN: A549 and H1299 NSCLC cell lines were used for in vitro experiments. And BALB/c nude mice of NSCLC were used to perform in vivo experiments. METHODS: For in vitro experiments, CCK-8 and EdU assay was used to observe the effect of kaempferol on NSCLC cell proliferation. Confocal microscopy of mCherry-EGFR-LC3 assay and electron microscopy assay were used to detect NSCLC cell autophagy. Protein expression was determined using Western blot, and mRNA expression was determined using qRT-PCR. Flow cytometry was performed to detect the cell apoptosis. For in vivo experiments, a subcutaneously implanted tumor model in BALB/C nude mice was performed using human NSCLC cell line A549-Luc. The kaempferol effect on NSCLC mice model was detected by measuring the tumor weight and bioluminescence intensity. Immunohistochemistry was done to measure the key protein expression from mice tumor tissues. RESULTS: Our results confirmed that kaempferol inhibited NSCLC cell proliferation significantly. And it promoted NSCLC cell autophagy, leading to NSCLC cell death. Interestingly, Met-was greatly inhibited at both protein and mRNA levels. Meanwhile, PI3K/AKT/mTOR signaling pathway was inhibited accordingly. Furthermore, overexpressing Met-reversed the effect of kaempferol on NSCLC cell viability and cell autophagy with significance. Finally, the above effect and pathway were validated using the xenograft model. CONCLUSION: Kaempferol may exert its anti-NSCLC effect by promoting NSCLC cell autophagy. Mechanistically, Met-and its downstream PI3K/AKT/mTOR signaling pathway were involved in the process, which provides a novel mechanism how kaempferol functions in inhibiting NSCLC.

Identification of the therapeutic mechanism of the saffron crocus on glioma through network pharmacology and bioinformatics analysis.

Saffron crocus is a herbal medicine of traditional Tibetan medicine (TTM). Saffron extract has been indicated to inhibit tumor cell growth and promote tumor cell apoptosis in a variety of cancers, including glioma, but the specific mechanism is not clear. To study the possible mechanism of saffron action on glioma, network pharmacology and bioinformatics analysis methods were used in this study. We used the online database to obtain the active ingredients of saffron and their targets. Glioma-related targets were also acquired from online database. We intersected drug targets with glioma-related targets and conducted PPI network analysis to obtain network core genes. Then, we obtained RNA-seq data from The Cancer Genome Atlas (TCGA) database for glioma patients. Through different expression analysis and lasso regression, further screening of core genes in the network was conducted, and a prognostic model was established. The sample was divided into two groups with high and low risk using this model. The RNA-seq data from the Chinese Glioma Genome Atlas (CGGA) database were used to further validate our prediction model. Then, we explored the difference in pathways enrichment between high-risk patients and low-risk patients and calculated the difference in immune microenvironment between the two groups. Finally, we used scRNA-seq data in the CGGA database to analyze the cell types in which the model gene is mainly enriched and predicted the cell types which saffron effected on.

Structure Characterization and Anti-Rheumatoid Arthritis Activity of a Polysaccharide from Notopterygium incisum.

SCOPE: Notopterygium incisum is a traditional Chinese medicine that is commonly used to treat rheumatoid arthritis. Polysaccharides from N. incisum can be one of its main active components. However, there have been little investigations on N. incisum polysaccharides. METHODS AND RESULTS: A novel polysaccharide named NIP is extracted from N. incisum with a molecular weight of 2.34 × 106  Da. NIP, composed of arabinose, galactose, glucose, and galacturonic acid, is linked by methyl esterified 1,4-linked α-galacturonic acid, 1,6-linked ß-galactose, 1,5-linked α-arabinose, and 1,4,6-linked ß- glucose. In vitro, NIP can inhibit the NO production of LPS-stimulated RAW264.7 cells. In vivo, NIP relieves toe redness and swelling of AIA rats, reduces the release of inflammatory factors in the serum, and inhibits the activation of NF-κB and JAK/STAT3 signaling pathways. In addition, NIP can effectively decrease oxidative stress, reverse intestinal flora imbalance, and promote butyric acid-producing bacteria's proliferation to exert anti-RA activity. CONCLUSION: NIP may be recommended as a functional food that can alleviate the damage of rheumatoid arthritis.

Fuzheng Kang-Ai inhibits NSCLC cell proliferation via regulating hsa_circ_0048091/hsa-miR-378g/ARRDC3 pathway.

BACKGROUND: Current treatments for lung cancer have their own deficiencies, such as severe adverse effect. Therefore, more safe and effective drugs are needed. PURPOSE: Fuzheng Kang-Ai (FZKA for short) has been applied as an adjuvant treatment in advanced Non-Small Cell Lung Cancer (NSCLC) patients for decades in China, showing a definitive effect with minimal toxicities. However, the underlying mechanism is yet to be identified. STUDY DESIGN: Both in vitro and in vivo experiments were performed in this study to identify the exact mechanism by which FZKA inhibits NSCLC cell proliferation. METHODS: MTT and CCK-8 assays were used to detect cell viability. Xenograft model was performed for in vivo experiments. CircRNA and miRNA sequencing were used to find the differentially expressed circRNAs and miRNAs, respectively. qRT-PCR was performed to check the expression levels of circRNA, miRNA and mRNA. BaseScope was carried out to observe the expression of circRNA in situ. Actinomycin D and RNase R experiments were done to show the stability of circRNA. Nuclear-cytoplasmic fractionation and FISH were used to identify the localization of circRNA and miRNA. Pull-down, RIP, and luciferase activity assays were performed to show the biding ability of circRNA, miRNA and target proteins. Flow cytometry was done to observe cell apoptosis. Western blot and IHC were done to detect the protein expression. TCGA database was used to analyze the survival rate. RESULTS: FZKA inhibits NSCLC cell proliferation both in vitro and in vivo. Hsa_circ_0048091 and hsa-miR-378g were the most differentially expressed circRNA and miRNA, respectively, after FZKA treatment. Silencing hsa_circ_0048091 and overexpressing hsa-miR-378g promoted cell proliferation and reversed the inhibition effect of FZKA on NSCLC, respectively. Hsa-miR-378g was sponged by hsa_circ_0048091, and the overexpression of miR-378g reversed the inhibition effect of hsa_ circ_0048091 on NSCLC. ARRDC3, as a target of hsa-miR-378g, was increased by FZKA treatment. Silencing ARRDC3 reversed both the inhibition effect of FZKA and miR-378g inhibitor on NSCLC. CONCLUSION: This study, for the first time, has established the function of hsa_circ_0048091, hsa- miR-378g, and ARRDC3 in lung cancer. It also shows that FZKA inhibits NSCLC cell proliferation through hsa_circ_0048091/hsa-miR-378g/ARRDC3 pathway, uncovering a novel mechanism by which FZKA controls human NSCLC cell growth.

Efficacy and safety of Brucea javanica oil emulsion injection as adjuvant therapy for cancer: An overview of systematic reviews and meta-analyses.

BACKGROUND: In China, Brucea javanica oil emulsion injection (BJOEI) has been used as adjuvant therapy to treat cancer for many years. Many systematic reviews (SRs) or meta-analyses (MAs) were published to evaluate its efficacy and safety. Nevertheless, uneven quality made it difficult to reach a consensus and there has been no specific review to integrate the evidence of BJOEI for cancer at present. Therefore, a comprehensive evidence map is needed to guide clinicians. PURPOSE: We, for the first time, conducted an overview to assess the SRs/MAs of BJOEI, and provided a comprehensive evidence map to guide clinicians. Besides, this study provided a promising direction for future research to promote the generation of advanced evidence. STUDY DESIGN: An overview of SRs or MAs. METHODS: The pre-defined search strategies were applied to 8 databases. Suitable SRs/MAs were included according to the inclusion and exclusion criteria. Methodological quality, reporting quality, and risk of bias were assessed. An evidence map was conducted to show the situation of clinical evidence. RESULTS: 27 SRs/MAs in 7 cancer types were included in this overview. The main problems of SRs/MAs were concentrated on the following aspects: without registration or protocol, lacking gray literature retrieval and a list of excluded studies, incomplete description in the literature retrieval strategy or the methods of merging results, the bias of each synthetic result, less exploration in heterogeneity or publication bias, deficiencies in assessing evidence quality and less description in conflict, funding or access to relevant information. Based on the rules of GRADE, the evidence quality of 154 items in 27 SRs/MAs was defined as moderate quality (103 items), low-quality (44 items), and very low-quality (7 items). Especially, risk of bias (154 items), imprecision (27 items), inconsistency (20 items), and publication bias (9 items) were the main downgrading factors. CONCLUSION: BJOEI may be a promising adjuvant therapy for treating cancer, especially in the digestive system. However, high-quality SRs/MAs are expected to be carried out to improve the reliability of the above conclusion in the future.

Plasma Membrane H+-ATPase SmPHA4 Negatively Regulates the Biosynthesis of Tanshinones in Salvia miltiorrhiza.

Salvia miltiorrhiza Bunge has been widely used in the treatment of cardiovascular and cerebrovascular diseases, due to the pharmacological action of its active components such as the tanshinones. Plasma membrane (PM) H+-ATPase plays key roles in numerous physiological processes in plants. However, little is known about the PM H+-ATPase gene family in S. miltiorrhiza (Sm). Here, nine PM H+-ATPase isoforms were identified and named SmPHA1-SmPHA9. Phylogenetic tree analysis showed that the genetic distance of SmPHAs was relatively far in the S. miltiorrhiza PM H+-ATPase family. Moreover, the transmembrane structures were rich in SmPHA protein. In addition, SmPHA4 was found to be highly expressed in roots and flowers. HPLC revealed that accumulation of dihydrotanshinone (DT), cryptotanshinone (CT), and tanshinone I (TI) was significantly reduced in the SmPHA4-OE lines but was increased in the SmPHA4-RNAi lines, ranging from 2.54 to 3.52, 3.77 to 6.33, and 0.35 to 0.74 mg/g, respectively, suggesting that SmPHA4 is a candidate regulator of tanshinone metabolites. Moreover, qRT-PCR confirmed that the expression of tanshinone biosynthetic-related key enzymes was also upregulated in the SmPHA4-RNAi lines. In summary, this study highlighted PM H+-ATPase function and provided new insights into regulatory candidate genes for modulating secondary metabolism biosynthesis in S. miltiorrhiza.

A Mycochemical Investigation of the Black Lingzhi Mushroom, Amauroderma rugosum (Agaricomycetes), Reveals Several Lipidic Compounds with Anti-Inflammatory and Antiproliferative Activities.

A mycochemical investigation on the medicinal mushroom Amauroderma rugosum led to the isolation of 30 compounds, including 14 sterols, 6 phenolic constituents, 5 unsaturated fatty acids, and 5 other compounds. The structures of these compounds were elucidated by comparison of their nuclear magnetic resonance spectroscopic and mass spectrometry data with literature data. Among them, compound 27 was obtained as a new natural compound, and compounds 2-4, 7-13, and 15-30 were isolated from the genus Amauroderma for the first time. Sterols and unsaturated fatty acids showed anti-inflammatory and antiproliferative activities in vitro. Compounds 5 and 6 showed the highest inhibitory effect on nitric oxide production in lipopolysaccharide-induced murine macrophage RAW264.7 cells, with half maximal inhibitory concentration (IC50) values of 27.6 ± 2.1 µM and 15.3 ± 2.0 µM respectively. Compound 17 exhibited the strongest inhibition against HepG2 and MDA-MB-231 cell lines, with IC50 values < 25 µM. This study not only enriches the understanding of the diversity of chemical constituents in A. rugosum, but it also provides a basis for further development and utilization of A. rugosum as a source of new potential antitumor or anti-inflammatory chemotherapy agents.

Ethanol Extract of Brucea javanica Seed Inhibit Triple-Negative Breast Cancer by Restraining Autophagy via PI3K/Akt/mTOR Pathway.

Triple-negative breast cancer (TNBC) is an aggressive disease with worst prognosis than other subtypes of breast cancer. Owing to the lack of hormone receptors and HER2 expression on TNBC cells, patients do not have targeted therapy options available with other breast cancer subtypes. Extensive efforts have been made to identify novel therapeutics against TNBC. Interestingly, recent studies had shown that plant-derived natural products could modulate the autophagy and induce the breast cancer cells death. Seed of Brucea javanica has been used as an important traditional Chinese medicine against cancers. In the present study, the anti-breast cancer potential of ethanol crude extracts from B. javanica seed (BJE) was explored. Data demonstrated that BJE could inhibit the TNBC cell line MDA-MB-231 proliferation and induced apoptosis. In the cells exposed to BJE, protein expressions of UNC-51-like kinase-1 (ULK1) and Beclin-1 and the ratio of light chain 3 II/I (LC3 II/I) were reduced, while the expression of p62 was increased, indicating an inhibition on autophagy. Moreover, BJE promoted the phosphorylation of mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and Akt in MDA-MB-231. BJE also suppressed the MDA-MB-231 tumor growth in vivo. Coincide with the results in vitro, autophagy in the tumor tissue was weakened as indicated by decreased ratio of LC 3 II/I and Beclin-1 accompanied by enhanced phosphorylation of mTOR, which confirmed that autophagy restraint via the PI3K/Akt/mTOR signaling pathway contributes to the suppression by BJE. Notably, no noticeable toxicity in non-targeted organs was found, including small intestine, liver, and kidney. Taken together, this study revealed anti-breast cancer activity of BJE based on autophagy restraint, highlighting its clinical importance as a novel natural agent against TNBC.

Alleviating effects of noni fruit polysaccharide on hepatic oxidative stress and inflammation in rats under a high-fat diet and its possible mechanisms.

Non-alcoholic fatty liver disease is associated with gut microbiota, oxidative stress, and inflammation. We aimed to investigate the possible mechanism by which noni fruit polysaccharide (NFP) improved hepatic oxidative stress and inflammation in rats under a high-fat diet (HFD) by modulating short-chain fatty acids (SCFAs), the intestinal barrier, and gut microbiota. Hepatic oxidative stress, inflammation, and gut dysbiosis in rats were induced through HFD feeding for 4 weeks, followed by intervention with NFP treatment (100 mg per kg bw) for 5 weeks. The results showed that NFP reduced body weight gain and improved lipid metabolism, hepatic oxidative stress, and inflammation in rats under a HFD. Aside from these beneficial effects, NFP positively affected the SCFA production and reversed the HFD-induced gut dysbiosis as indicated by improved microbiota diversity and composition. The levels of Lactobacillus, Ruminococcaceae_UCG_014, Parasutterella, [Eubacterium]_coprostanoligenes_group, and Ruminococcus_1 improved, whereas the levels of Prevotella_9, Collinsella, Bacteroides, and Turicibacter decreased. Furthermore, NFP maintained the colonic barrier integrity (increased the mRNA relative expression of CCL5, ZO-1, and occludin in the colon, and decreased the serum CCL5 level), and decreased the serum lipopolysaccharide level. Thus, NFP may modulate the gut microflora and SCFA production and reduce the permeability of the colonic barrier and metabolic endotoxemia, thereby alleviating hepatic oxidative stress and inflammation in rats under a HFD.

[Effect of hypnosis on pain and fear in the acupuncture subjects].

OBJECTIVE: To observe the effect of hypnosis on pain and fear in the healthy acupuncture subjects. METHODS: A total of 52 healthy subjects were randomized into an observation group and a control group, 26 cases in each one. In the observation group, the subjects received the first-time acupuncture under hypnosis. After wakened up and 30 min later, the subjects received the second-time acupuncture under clear consciousness condition. In the control group, the subjects received the first-time acupuncture under clear consciousness condition, 30 min later, received the second-time acupuncture under hypnosis. Likert scale was adopted to investigate the relaxation, pain sensation and the willingness in the subjects at the normal condition before acupuncture, after the first-time and the second-time acupuncture of the two groups separately. Using Boeran electronic blood pressure monitor, the pulse and blood pressure were measured in the subjects at the normal condition and after the first-time acupuncture of the two groups. RESULTS: Compared with the normal condition, the relaxation degree was increased, the pain sensation decreased and the willingness enhanced after acupuncture either after hypnosis or after wakened-up in the observation group (P<0.001). The difference was not significant in each index between acupuncture after hypnosis and acupuncture after wakened-up in the observation group (P>0.05). In the control group, compared with the normal condition, after the first-time acupuncture (acupuncture in clear consciousness), the relaxation degree was decreased, pain was alleviated and the willingness was increased when acupuncture was exerted once again (P<0.001, P<0.05); compared with the normal condition, after the second-time acupuncture (acupuncture after hypnosis), pain was alleviated and the willingness increased (P<0.001), but the difference in relaxation was not significant (P>0.05); compared with the first-time acupuncture, the relaxation degree was increased, pain alleviated and willingness enhanced after the second-time acupuncture (acupuncture after hypnosis) (P<0.05, P<0.001). Compared with the control group after the first-time acupuncture (acupuncture in clear consciousness), the relaxation degree and willingness were increased and the pain sensation was reduced in the observation group during acupuncture either after hypnosis or after wakened-up (P<0.001). Compared with the control group the second-time acupuncture (during acupuncture after hypnosis), the relaxation degree was increased and pain sensation reduced in the observation group during acupuncture either after hypnosis or after wakened-up (P<0.01, P<0.001), but the difference was not significant in willingness (P>0.05). In the control group, compared with the normal condition, the pulse was faster, both the diastolic pressure and systolic pressure were increased after the first-time acupuncture (P<0.05, P<0.01). In the observation group, compared with the normal condition, the pulse was getting slow and blood pressure was reduced after the first-time (acupuncture under hypnosis, P<0.01). Compared with the first-time acupuncture in the control group, pulse was getting slow and blood pressure was reduced in the observation group after acupuncture under hypnosis (P<0.001). CONCLUSION: During acupuncture, with hypnosis combined, the fear alleviates, pain reduces and the willingness of acupuncture increases in the subjects.

Therapeutic effects of noni fruit water extract and polysaccharide on oxidative stress and inflammation in mice under high-fat diet.

This study aims to compare the therapeutic effects of noni fruit water extract (NFW) and noni fruit polysaccharide (NFP) on oxidative stress and inflammation in mice under high-fat diet. In this study, mice were induced to develop oxidative stress and inflammation through high-fat diet. Treatment was performed via the administration of NFW (10 mL per kg bw) and NFP (50, 100, and 200 mg per kg bw) for 4 weeks. The results indicated that the NFW and NFP reduced the body weight gain, liver relative weight, and abdominal fat relative weight of mice under high-fat diet. Moreover, the NFW and NFP reduced the liver malondialdehyde level and increased the liver trolox equivalent antioxidant capacity level. The NFP effectively increased the liver superoxide dismutase and glutathione peroxidase activities, and the administration of NFP at 100 and 200 mg per kg bw effectively increased the hepatic nuclear factor erythroid-2 related factor level, thus presenting improved antioxidant activity. The NFW and NFP restrained the elevation of tumor necrosis factor alpha, interleutin-6, and nitric oxide levels in the liver and serum. All NFP doses prominently decreased the hepatic nuclear factor kappa B level, and the NFP at 100 and 200 mg per kg bw presented high anti-inflammatory activity. These results suggested that the NFW and NFP alleviated oxidative stress and inflammation in mice under high-fat diet, and the NFP at 100 mg per kg bw had a better effect than NFW with a similar polysaccharide dosage, illustrating that NFP may be an important component in the NFW.

The Immunomodulatory Activity of Polysaccharides from the Medicinal Mushroom Amauroderma rude (Agaricomycetes) Is Mediated via the iNOS and PLA2-AA Pathways.

Our earlier work indicated that the polysaccharides of Amauroderma rude (AR) appear to have an effect on immunoregulation. However, the pathways are not clear. In this paper, we discuss the immunomodulatory mechanisms of A. rude to provide a scientific basis for its possible use as a food. Amauroderma rude increased the expression of iNOS and P38 in the Raw246.7 cell line. When the AR concentration reached 150 µg/mL, the expressions of iNOS and P38 increased 23.0% and 191.7%, respectively. When the AR concentrations were 50 µg/mL, the concentrations of cytokines IL-2, TNF-α, and IFN-γ were 33.65 pg/mL, 12.53 pg/mL and 42.56 pg/mL. When AR reached 200 µg/mL, the lgA and lgM levels were 0.73 µg/mL and 1.5 µg/mL. When AR reached 400 µg/mL, the lgG level reached 1.65 µg/mL by ELISA assay. When 4.8 mg AR were orally administered, IL-2, TNF-α, IFN-γ, PGE2, and LTB4 increased dramatically, to 0.17 pg/mL, 0.16 pg/mL, 0.15 pg/mL, 30.71 pg/mL, and 18.68 pg/mL, respectively. The concentrations of lgA, lgM, and lgG, AA, and PLA2 also increased significantly to 2.62 pg/mL, 2.14 pg/mL, 2.06 pg/mL, 5.23 µg/mL and 3.68 ng/mL, respectively. With 4.8 mg AR p.o., iNOS protein expression increased 16.8% and P38 increased 234.0%. These results indicate that A. rude polysaccharides stimulate cytokine production and activate the iNOS, PLA2-AA, and MAPK pathways during the immunomodulatory process.

Activation of the AKT/FOXO3a Signaling Pathway during Breast Cancer Inhibition In Vivo and In Vitro by Amauroderma rude (Agaricomycetes).

We previously reported that Amauroderma rude polysaccharides (AR) displayed strong immunomodulatory tumor-suppressive effects in mice. The current study was designed to explore the potential mechanism by which AR polysaccharides inhibit tumor growth. We found that AR could effectively induce cell death in 4T1 and MDA-MB-231 breast cancer cells. AR could also inhibit tumor cell migration and invasion, significantly promote apoptosis in 4T1 cells, and significantly increase CDK4, CDK6, cylinD1, and P27 mRNA expression in mice. Additionally, AR was able to significantly increase FOXO3a expression and decrease p-AKT expression both in vitro and in vivo, indicating that the AKT/FOXO3a signaling pathway had been activated during the inhibitory process.

Shenmai injection for the treatment of cancer-related fatigue in advanced non-small cell lung cancer patients undergoing chemotherapy: study protocol for a randomized controlled trial.

BACKGROUND: Cancer-related fatigue (CRF) is the most common symptom in patients with advanced non-small cell lung cancer (NSCLC) undergoing treatment with chemotherapy. However, evidence upon which to base management strategies is scarce. Traditional Chinese Medicine (TCM) has been shown to be beneficial to patients with CRF. Chinese herbal injections should be administered under an evidence-based approach. This trial aims to assess the efficacy and safety of the addition of the Shenmai injection (SMI) to conventional therapy for CRF in NSCLC patients undergoing chemotherapy. METHODS/DESIGN: The study is a two-group, prospective, randomized controlled trial (RCT) designed to evaluate the efficacy and safety of SMI for CRF NSCLC patients undergoing chemotherapy. Eligible participants will be randomized to either a treatment group receiving a 5-day Shenmai injection regimen plus conventional therapy or a control group receiving only conventional therapy. The primary outcome is fatigue, assessed using severity scores from the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F) measurement system. Secondary outcomes include symptom distress scores, depression, sleep disorders, quality of life, and levels of immunologic indicators. Assessments will be carried out at baseline and on day 5 (the end of the intervention). DISCUSSION: This study can provide evidence to support clinical decision-making in the management of CRF in NSCLC patients undergoing chemotherapy in a way that can be scaled up and used throughout China. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( chictr.org.cn ), ChiCTR-INR-17013737 . Registered on 6 December 2017.

Gefitinib plus Fuzheng Kang'ai Formula () in Patients with Advanced Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of Fuzheng Kang'ai Formula (, FZKA) plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations. METHODS: A randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage IIIB/IV non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib (250 mg/day orally) plus FZKA (250 mL, twice per day, orally); 35 cases] or G group (gefitinib 250 mg/day orally; 35 cases) according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival (PFS)] and secondary endpoints [median survival time (MST), objective response rate (ORR), disease control rate (DCR) and safety] were observed. RESULTS: No patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months (95% CI 3.30-21.69) vs. 8.4 months (95% CI 6.30-10.50; log-rank P<0.01), MST of 21.5 months (95% CI 17.28-25.73) vs. 18.3 months (95% CI 17.97-18.63; log-rank P<0.01). ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively (P>0.05). The most common toxic effects in the GF group and G group were rash or acne (42.8% vs. 57.1%, P>0.05), diarrhea (11.5% vs. 31.4%, P<0.05), and stomatitis (2.9% vs. 8.7%, P>0.05). CONCLUSION: Patients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.

Acute and Subchronic Toxicity of Dusky-Skinned Mushroom, Amauroderma rude (Agaricomycetes).

Our earlier work indicated that Amauroderma rude seems to have an effect on immunoregulation and tumor inhibition. However, its toxicity is not yet clear. The aim of this work is to demonstrate the acute and subchronic toxicity of A. rude in order to provide a scientific basis for its possible use as a food. The acute toxicity study (involving mice) showed that the median lethal dose of the A. rude extract was >15,000 mg/kg. In the repeated-dose 90-day oral toxicity study (involving rats), the administration of A. rude extract at 0.1 (AR0.1), 0.2 (AR0.2), and 0.4 g (AR0.4) per rat produced no significant difference in food or water consumption or changes in body weight, hematological parameters, biochemical parameters, relative organ weights, organ coefficients, or histopathology compared with the control group. Analyses of these results with data from monitoring the appearance, behavior, and health of the animals indicate that the oral administration of A. rude extract daily for 90 days does not cause subchronic toxicity.

Chinese Herbal Medicine Fuzheng Kang-Ai Decoction Inhibited Lung Cancer Cell Growth through AMPKα-Mediated Induction and Interplay of IGFBP1 and FOXO3a.

The aim of this study is to investigate the actions of Chinese herbal medicine, called "Fuzheng Kang-Ai" (FZKA for short) decoction, against non-small cell lung cancer (NSCLC) and its mechanisms in vitro and in vivo. We showed that the effect of FZKA decoction significantly inhibited growth of A549 and PC9 cells. Furthermore, FZKA increased phosphorylation of AMP-activated protein kinase alpha (AMPKα) and induced protein expression of insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and forkhead homeobox type O3a (FOXO3a). The specific inhibitor of AMPKα (Compound C) blocked FZKA-induced protein expression of IGFBP1 and FOXO3a. Interestingly, silencing of IGFBP1 and FOXO3a overcame the inhibitory effect of FZKA on cell growth. Moreover, silencing of IGFBP1 attenuated the effect of FZKA decoction on FOXO3a expression, and exogenous expression of FOXO3a enhanced the FZKA-stimulated phosphorylation of AMPKα. Accordingly, FZKA inhibited the tumor growth in xenograft nude mice model. Collectively, our results show that FZKA decoction inhibits proliferation of NSCLC cells through activation of AMPKα, followed by induction of IGFBP1 and FOXO3a proteins. Exogenous expression of FOXO3a feedback enhances FZKA decoction-stimulated IGFBP1 expression and phosphorylation of AMPKα. The reciprocal interplay of IGFBP1 and FOXO3a contribute to the overall responses of FAKA decoction.