Combining cisplatin with Pinellia pedatisecta Schott lipid-soluble extract induces tumor immunogenic cell death in cervical cancer.

BACKGROUND: Pinellia pedatisecta Schott extract (PE) is extracted from Pinellia pedatisecta Schott (PPS), a traditional Chinese medicinal plant with the potential for direct anticancer effects or eliciting an anti-tumor response by activating the immune system. PURPOSE: To explore PE's ability and mechanism to reconstruct cisplatin's immunogenicity. METHODS: Cervical cancer cells were treated with cisplatin (CDDP) and/or PE. The exposure of calreticulin (CRT) on cell membrane was investigated by flow cytometry. The extracellular of ATP and HMGB1 was investigated by Western blot analysis, immunofluorescence and ELISA assay. Changes in immune profiles were using flow cytometry in vaccination and anti-tumor assays in vivo. Lastly, the mechanism of PE influenced the ROS/ERS pathway was examined by ROS assay kit, flow cytometry and Western blotting. RESULTS: PE treatment induced translocation of CRT from the endoplasmic reticulum to the cell membrane of tumor cells, concomitantly triggering immunogenic cell death (ICD). In terms of mechanisms, endoplasmic reticulum (ER) stress relievers could impede the ability of PE to induce immunogenicity. This indicates that PE is activated by ER stress, leading to subsequent induction of ICD. Upon analyzing RNA-seq data, it was observed that PE primarily induces programmed cell death in tumors by impeding upstream antioxidant mechanisms. Additionally, it transforms dying tumor cells into vaccines, activating a series of immune responses. CONCLUSIONS: This study observed for the first time that PE-induced CRT exposure on the membrane of cervical cancer cells compensates for the defect of nonimmunogenic cell death inducer CDDP thereby stimulating potent ICD. This ability restores the immunogenicity of CDDP through ER stress induced by the ROS signal. ROS played a role in PE's ability to induce ICD, leading to increased expression of ER stress-related proteins, including ATF3 and IRE-1α. PE exerted anti-cancer effects by increasing the ROS levels, and ROS/ERS signaling may be a potential avenue for cervical cancer treatment. Hence, the synergistic use of PE and CDDP holds potential for enhancing immunochemotherapy in cancer treatment.

Different responses of marine microalgae Phaeodactylum tricornutum upon exposures to WAF and CEWAF of crude oil: A case study coupled with stable isotopic signatures.

Increasing use of chemical dispersants for oil spills highlights the need to understand their adverse effects on marine microalgae and nutrient assimilation because the toxic components of crude oil can be more bioavailable. We employed the crude oil water-accommodated fraction (WAF) and chemically enhanced WAF (CEWAF) to compare different responses in marine microalgae (Phaeodactylum tricornutum) coupled with stable isotopic signatures. The concentration and proportion of high-molecular-weight polycyclic aromatic hydrocarbons (HMW PAHs), which are key toxic components in crude oil, increased after dispersant addition. CEWAF exposure caused higher percent growth inhibition and a lower chlorophyll-a level of microalgae than those after WAF exposure. Compared with WAF exposure, CEWAF led to an enhancement in the self-defense mechanism of P. tricornutum, accompanied by an increased content of extracellular polymeric substances. 13C-depletion and carbon assimilation were altered in P. tricornutum, suggesting more HMW PAHs could be utilized as carbon sources by microalgae under CEWAF. CEWAF had no significant effects on the isotopic fractionation or assimilation of nitrogen in P. tricornutum. Our study unveiled the impact on the growth, physiological response, and nutrient assimilation of microalgae upon WAF and CEWAF exposures. Our data provide new insights into the ecological effects of dispersant applications for coastal oil spills.

Revealing the clinical effect and biological mechanism of acupuncture in COPD: A review.

BACKGROUND: To provide new ideas for the clinical and mechanism research of acupuncture in the treatment of chronic obstructive pulmonary disease (COPD), this study systematically reviews clinical research and the progress of basic research of acupuncture in the treatment of COPD. METHODS: PubMed and Web of Science databases were searched using acupuncture and COPD as keywords in the last 10 years, and the included literature was determined according to exclusion criteria. FINDINGS: Acupuncture can relieve clinical symptoms, improve exercise tolerance, anxiety, and nutritional status, as well as hemorheological changes (blood viscosity), reduce the inflammatory response, and reduce the duration and frequency of COPD in patients with COPD. Mechanistically, acupuncture inhibits M1 macrophage activity, reduces neutrophil infiltration, reduces inflammatory factor production in alveolar type II epithelial cells, inhibits mucus hypersecretion of airway epithelial cells, inhibits the development of chronic inflammation in COPD, and slows tissue structure destruction. Acupuncture may control pulmonary COPD inflammation through the vagal-cholinergic anti-inflammatory, vagal-adrenomedullary-dopamine, vagal-dual-sensory nerve fiber-pulmonary, and CNS-hypothalamus-orexin pathways. Furthermore, acupuncture can increase endogenous cortisol levels by inhibiting the HPA axis, thus improving airway antioxidant capacity and reducing airway inflammation in COPD. In conclusion, the inhibition of the chronic inflammatory response is the key mechanism of acupuncture treatment for COPD.

Insights into Pyrroloquinoline Quinone (PQQ) Effects on Soil Nutrients and Pathogens from Pepper Monocropping Soil under Anaerobic and Aerobic Conditions.

Imbalances of soil available nutrients and soilborne diseases have seriously restricted the productivity of crops and jeopardized food security worldwide. Pyrroloquinoline quinone (PQQ), a redox cofactor in some bacteria involved in glucose metabolism and phosphorus mineralization, could be anticipated to alter soil ecosystems to a certain extent. However, there is limited information on PQQ defending soilborne pathogens and regulating soil main nutrients. Here, a pot experiment based on mono-cropping soils of pepper was conducted to examine the effects of PQQ amendment on reconstructing soil microbial communities and soil nutrients under aerobic/anaerobic conditions comprising three treatments, namely, control, PQQ (aerobic), and FL-PQQ (anaerobic). The results revealed that soil microbial community composition and soil nutrients were distinctly altered by PQQ regimes. Compared to control, PQQ treatment significantly increased the content of soil available phosphorus (AP), while FL_PQQ treatment strongly improved the content of soil available nitrogen (AN). In terms of pathogens, relative to control, both PQQ treatments suppressed the abundances of pathogens, of which FL_PQQ treatment significantly decreased the abundance of the pathotrophic fungal by 64% and the abundance of Fusarium oxysporum by 57%, largely attributed to the increase of organic acid generators (Oxobacter, Hydrogenispora) and potential antagonists (Bacillus, Talaromyces). Structural equation modeling (SEM) showed that PQQ regimes suppressed pathogens by indirectly regulating soil physicochemical properties and microbial communities. Overall, we proposed that PQQ application both in aerobic/anaerobic conditions could improve soil available nutrients and suppress soil pathogens in pepper monocropping soils. IMPORTANCE The attention to PQQ (pyrroloquinoline quinone) effect on soil nutrients and pathogens was less paid in monocropping soils. However, the underlying microbial interacting mechanism remains unclear. Adopting a novel external bio-additive, the effects of PQQ on soil main nutrients and the pathotrophic fungal under aerobic and anaerobic regimes will be investigated, which would help to improve soil quality health. Our main conclusion was that PQQ would help to remediate monocropping obstacle soils in terms of soil nutrients and soil pathogens by associating with the microbial community, and anaerobic PQQ application more favored amelioration of continuous obstacle soils. These results will benefit the health and sustainable development of pepper production as well as other greenhouse vegetable production.

Efficacy and Safety of Chinese Medicine in Treating Arrhythmia: Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the clinical efficacy of traditional Chinese medicine in the treatment of arrhythmia. METHODS: The researchers searched CNKI, VIP, WF, PubMed, Web of Science, and Cochrane Library with the set-up themes as randomized controlled trials (RCTs) on the clinical efficacy of traditional Chinese medicine in the treatment of arrhythmia. This research evaluated all the retrieve literature and conducted selection based on the evaluation. Stata software was applied for meta-analysis. RESULTS: 23 articles were retrieved with a total patient number of 2846. The results observed from the meta-analysis indicated the following: (1) compared with the result showed in placebo group, the traditional Chinese medicine group presented to have good efficacy, especially in the treatment of premature ventricular contractions. (2) In comparison with the western medicine group, the curative effect of Chinese medicine could approximately equal the therapeutic effect as western medicine. (3) Compared with the application of sole western medicine group, the combination of both traditional Chinese medicine and western medicine could have a better curative effect. CONCLUSION: In the treatment of arrhythmia disease, the application of traditional Chinese medicine can be considered as an effective method. In addition to that, the therapeutic effect obtained from the combination of both Chinese traditional medicine and western medicine is clinically better than that of the sole use of western medicine.

Annotation of genes involved in high level of dihydromyricetin production in vine tea (Ampelopsis grossedentata) by transcriptome analysis.

BACKGROUND: Leaves of the medicinal plant Ampelopsis grossedentata, which is commonly known as vine tea, are used widely in the traditional Chinese beverage in southwest China. The leaves contain a large amount of dihydromyricetin, a compound with various biological activities. However, the transcript profiles involved in its biosynthetic pathway in this plant are unknown. RESULTS: We conducted a transcriptome analysis of both young and old leaves of the vine tea plant using Illumina sequencing. Of the transcriptome datasets, a total of 52.47 million and 47.25 million clean reads were obtained from young and old leaves, respectively. Among 471,658 transcripts and 177,422 genes generated, 7768 differentially expressed genes were identified in leaves at these two stages of development. The phenylpropanoid biosynthetic pathway of vine tea was investigated according to the transcriptome profiling analysis. Most of the genes encoding phenylpropanoid biosynthesis enzymes were identified and found to be differentially expressed in different tissues and leaf stages of vine tea and also greatly contributed to the biosynthesis of dihydromyricetin in vine tea. CONCLUSIONS: To the best of our knowledge, this is the first formal study to explore the transcriptome of A. grossedentata. The study provides an insight into the expression patterns and differential distribution of genes related to dihydromyricetin biosynthesis in vine tea. The information may pave the way to metabolically engineering plants with higher flavonoid content.

Evaluation of antioxidant properties of the different tissues of vine tea (Ampelopsis grossedentata) in stripped canola oil and sunflower oil.

The leaves of Ampelopsis grossedentata have a long history of use as a health tea and herbal medicine. Data on the distribution of active metabolites in, and antioxidant capacities of, different vine tea tissues remain incomplete. The aim of this work was to investigate the content of metabolites from A. grossedentata different tissues and evaluate the antioxidant capacities of the extraction of the species in vitro and in oil systems: canola oil and sunflower oil. To evaluate the degree of lipid oxidation, the peroxide value (POV) and thiobarbituric acid-reactive substance value (TBARS) were determined, and proton nuclear magnetic resonance (1 H-NMR) was performed. The results revealed a high total flavonoid content in each of the four extractions (>580 mg/g dried weigh). Leaf extractions exhibited higher antioxidant ability, followed by fruit extract and butylated hydroxytoluene (BHT). The POVs of oils bearing extracts of A. grossedentata and BHT maintained less than 21.08 meq/kg oil against to control with 1,406.33 ± 52.63 meq/kg oil on day 32 in canola oil, and 27.87 meq/kg oil comparing to 1,892.96 ± 48.63 meq/kg oil in control on day 24 in sunflower oil. Concurring results were also obtained in TBARS and 1 H-NMR analysis. Our results indicated that these different tissues of A. grossedentata could be a potential antioxidant resource, and this work may contribute to the comprehensive utilization of this species. PRACTICAL APPLICATION: Leaf extracts of Ampelopsis grossedentata showed effective antioxidant properties, followed by the fruit extract, which showed similar activity to that of the synthetic antioxidant of BHT. Moreover, the investigation of different tissues within the plant may contribute to the comprehensive utilization of this species.

Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L.

Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world. The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf. Methanolic extract of A. vera leaves was fractionated using column chromatography and ten fractions (AV1-AV10) were obtained. Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities were evaluated using standard protocols. Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results. Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities. AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6µg GAE/mg and total antioxidant activity 150.4 ± 25.815µg AAE/mg determined by phosphomolybdenum complex assay. Fraction AV6 showed 95% antileishmanial effect as well as the lowest LD50 value of 0.5305µg/mL in brine shrimp lethality assay. The Protein Kinase inhibition potential in A. vera leaves was determined for the first time and three fractions AV1, AV6, and AV7 depicted activity with the highest zone of inhibition up to 21±0.5mm (AV7). Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant. Therefore, with more studies, A. vera could probably have the potential to be used for drug development against leishmaniasis.

Immune modulation of a lipid-soluble extract of Pinellia pedatisecta Schott in the tumor microenvironment of an HPV+ tumor-burdened mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Pinellia pedatisecta Schott extract (PE), a traditional Chinese medicine, has been used to reduce swelling, dry dampness and suppress cervical tumors. AIMS: To evaluate the roles of PE in the regulation of anti-tumor effects and the cellular immune response in the tumor microenvironment. METHODS: The immune microenvironment of HPV+TC-1 tumors was examined by immunohistochemistry, real-time PCR and flow cytometry. RESULTS: Our study demonstrated that PE in vitro could significantly increase the percentage of apoptosis and necrosis in HPV+TC-1 cells and block the cell cycle phase. In vivo treatment with PE eradicated established subcutaneous HPV+TC-1 tumors in wild-type C57BL/6 mice by infiltrating CD8+ T cells and CD4+ T cells and by directly suppressing tumor growth and resistance to avascular necrosis. The key factors in the canonical Wnt signaling pathway in the experimental group (PE+mDC+naive CD4+T cells) were challenged, and the levels of beta-catenin, C-myc, cyclin D1 and PPAR1 were significantly enhanced at the 5th day. In particular, the subset proportion of Th1 cells (characterized by IFNγ production and the transcription factor Tbet) increased significantly, and both Th2 cells (characterized by IL-4 production and the transcription factor GATA3) and Th17 cells (characterized by IL-17 production and the transcription factor RoRγt) decreased profoundly. CONCLUSIONS: These findings linked the anti-tumor properties of PE with the immune microenvironment to present a reliable basis for the future practical application of PE in cervical cancer as a novel and pharmacologically safe immunotherapy strategy.

Effect of long-term electroacupuncture stimulation on recovery of sensorimotor function after peripheral nerve anastomosis.

BACKGROUND: Recently, application of electroacupuncture (EA) to stimulate nerve regeneration has become a mainstream treatment in clinical rehabilitation and related basic research, but the efficacy of long-term stimulation has not been confirmed. OBJECTIVE: To evaluate the influence of long term EA on peripheral nerve injury (PNI) from multiple angles. METHOD: Twenty-four rats were divided into three groups: control, PNI and PNI+EA. In the latter two groups, PNI was modelled by transection followed by re-anastomosis of thesciatic nerve. In the PNI+EA group only,EA was delivered using a discontinuous wave with frequency 5 Hz, pulse width 2 ms, and intensity approximately 2 mA, until the affected limb was observed to twitch slightly. The treatment was given for 15 min each time, six times a week (continuously for 6 days followed by a 1-day break) for a total of 8 weeks. The effects of EA on anastomotic sciatic nerve regeneration were evaluated using the sciatic function index (SFI), mechanical withdrawal thresholds, thermo-nociceptive thresholds, conduction velocity of the sciatic nerve and bilateral gastrocnemius wet weight. RESULTS: From weeks 2 to 4 after modelling, the SFI recovery rate in the PNI+EA group was faster than that in the PNI group. In week 4, the SFI of the PNI+EA group was significantly higher than that of the PNI group (p<0.05). However, a significant effect of EA was no longer evident from weeks 5 to 8. There was no effect of acupuncture on anti-amyotrophy and conduction velocity of the sciatic nerve at 8 weeks after modelling. EA did not shorten the paw withdrawal threshold time, but appeared to alleviate thermo-nociceptive sensitivity. CONCLUSION: Long term repeated stimulation of the same site with EA does not appear to be conducive to the functional recovery of an injured sciatic nerve in rats.

Conjugated fatty acid-rich oil from Gynostrmma pentaphyllum seed can ameliorate lipid and glucose metabolism in type 2 diabetes mellitus mice.

Gynostrmma pentaphyllum seed oil (GPSO), extracted from G. pentaphyllum seeds, is rich in conjugated linolenic acid, which is a special fatty acid consisting of cis-9, trans-11, trans-13 isomers. Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia resulting from insulin resistance, and is usually accompanied by hypertension, hyperlipidemia, atherosclerosis (i.e., the metabolic syndrome, or syndrome X), and polycystic ovarian disease. This study aimed to investigate the effect of GPSO on T2DM hepatic lipid metabolism and the underlying mechanism involving level of protein expression. In the experiment, the model of T2DM was established. Kunming male mice were fed with a high-fat diet and injected with streptozocin, in which the exploration of detailed mechanism in the therapy of T2DM was targeted. The results showed that the ability of oral glucose tolerance was improved in the GPSO group. Biochemical indices also revealed that GPSO had a positive effect on hypoglycemic activity, suggesting that GPSO could promote the expression of glucose transporter 4 in liver and skeletal muscle.

Synergistic cytotoxic effects of a combined treatment of a Pinellia pedatisecta lipid-soluble extract and cisplatin on human cervical carcinoma in vivo.

Herbal medicines are known to have numerous benefits, including lower toxicity and fewer side effects than traditional chemotherapeutic drugs. In traditional Chinese medicine, the rhizome of Pinellia pedatisecta (PE) Schott has long been used to treat cancer, undiagnosed swelling and erythema toxicum. However, its medical benefits lack support from scientific evidence. A novel lipid-soluble extract from PE has been previously verified to enhance the cytotoxicity of cis-dichlorodiammineplatinum-II (CDDP) against human cervical cancer cells in vitro. The present study evaluated the synergistic cytotoxic effects of PE and CDDP against human cervical cancer. Combination therapy of PE with CDDP exhibited synergistic cytotoxicity towards CaSki cell growth in mouse xenograft tumors. PE exhibited a cytotoxic effect on tumor size and weight, although the inhibitory ratio of tumor weight was only 26.3% in the PE-treated group. However, when mice were co-treated with PE and CDDP, the inhibitory ratio was higher than that of mice treated with CDDP alone (50.8 vs. 68.4%, respectively). The potential synergistic mechanism was likely via inhibiting the signaling E6/p53 pathway, restoring p53 function and inducing downstream tumor suppressor chain effects on apoptosis. Western blot analysis and immunohistochemistry indicated thatE6protein expression was significantly decreased upon treatment with combined PE and CDDP. The expression of p53 was increased in the combined PE and CDDP treatment group. Upregulation of p53-dependent apoptosis-associated proteins, including Bcl-2-associated X protein and cleaved caspases-9 and -3, was observed in the combined PE and CDDP treatment group. Our results present a molecular basis for the future application of the combination of PE and CDDP in the treatment of cervical cancer as a novel and pharmacologically safe chemotherapeutic strategy.

Synthesis and bioactivity of novel coumarin derivatives.

A series of coumarin derivatives (6-8) containing (E)-methyl 2-(methoxyimino)-2-phenylacetate, (E)-2-(methoxyimino)-N-methyl-2-phenylacetamide and methyl methoxy(phenyl)carbamate were synthesized from substituted resorcinols (1) and substituted beta-keto esters (2) as starting material via cyclization and condensation reactions. The test results indicated that (E)-methyl 2-{2-[(3-hexyl-4-methyl-coumarin-7-yloxy)methyl]phenyl}-2-(methoxyimino)acetate (6f) was the optimal structure with good fungicidal activity against cucumber grey mold (CGM) giving 100% control at 100 mg L(-1) concentration, much higher than that of coumoxystrobin. Methyl 2-[(3,4-dimethyl-coumarin -7-yloxy)methyl]phenyl(methoxy)carbamate (8a) was another optimal structure with good fungicidal activity against wheat powdery mildew (WPM) showing 100% control at 50 mg L(-1) concentration, at the same level as that of the commercial kresoxim-methyl, and very significantly higher than that of coumoxystrobin (no control against WPM at 400 mg L(-1)).