Dendrobium officinale phenolic extract maintains proteostasis by regulating autophagy in a Caenorhabditis elegans model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and accumulating evidence suggested that proteostatic imbalance is a key feature of the disease. Traditional Chinese medicine exhibits a multi-target therapeutic effect, making it highly suitable for addressing protein homeostasis imbalance in AD. Dendrobium officinale is a traditional Chinese herbs commonly used as tonic agent in China. In this study, we investigated protection effects of D. officinale phenolic extract (SH-F) and examined its underlying mechanisms by using transgenic Caenorhabditis elegans models. We found that treatment with SH-F (50 µg/mL) alleviated Aß and tau protein toxicity in worms, and also reduced aggregation of polyglutamine proteins to help maintain proteostasis. RNA sequencing results showed that SH-F treatment significantly affected the proteolytic process and autophagy-lysosomal pathway. Furthermore, we confirmed that SH-F showing maintainance of proteostasis was dependent on bec-1 by qRT-PCR analysis and RNAi methods. Finally, we identified active components of SH-F by LC-MS method, and found the five major compounds including koaburaside, tyramine dihydroferulate, N-p-trans-coumaroyltyramine, naringenin and isolariciresinol are the main bioactive components responsible for the anti-AD activity of SH-F. Our findings provide new insights to develop a treatment strategy for AD by targeting proteostasis, and SH-F could be an alternative drug for the treatment of AD.

Pitavastatin induces autophagy-dependent ferroptosis in MDA-MB-231 cells via the mevalonate pathway.

Triple-negative breast cancer (TNBC) is more prone to recurrence and metastasis relative to other subtypes of breast cancer, leading to an extremely poor prognosis. The increasing potential chemoresistance of TNBC patients is mainly due to that tumor cells escape from apoptosis. In recent years, statins have demonstrated extensive anti-tumor effects. It is worth noting that statins have more effective anti-tumor effects on TNBC cells and drug-resistant breast cancer cells. Therefore, this study examines the superior cytotoxic effects of statins on TNBC cell lines and further explores their potential therapeutic mechanisms. We detected different cell phenotypes and found that statins significantly reduced the cell viability of TNBC cells. Specifically, pitavastatin showed an obvious induction in cell death, cell cycle arrest and oxidative stress in TNBC MDA-MB-231 cells. The reversal effect of iron chelator desferrioxamine (DFO) on the morphological and molecular biological changes induced by pitavastatin has revealed a new mode of cell death induced by pitavastatin: ferroptosis. This ferroptotic effect was strengthened by the decreased expression of glutathione peroxidase 4 (GPx4) as well as newly discovered ferroptosis suppressor protein 1 (FSP1). The data showed that ferroptotic death of MDA-MB-231 cells is autophagy-dependent and mediated by the mevalonate pathway. Finally, we found that therapeutic oral doses of statins can inhibit the growth of transplanted tumors, which establishes statins as a potential treatment for TNBC patients. In conclusion, we found pitavastatin could induce autophagy-dependent ferroptosis in TNBC cells via the mevalonate pathway which may become a potential adjuvant treatment option for TNBC patients.

Development and application of the practical training instrument of warming needle moxibustion with quantifiable evaluation. / ä¸€ç§å¯é‡åŒ–è¯„ä»·çš„æ¸©é’ˆç¸å®žè®­æ•™å­¦ä»ªçš„ç ”åˆ¶ä¸Žå®žè·µ.

Based on summarizing the essential procedures and elements of traditional manipulation techniques of warming needle moxibustion and determining the quantitative parameters and indicators for evaluating the operation of this acupuncture technique, a training instrument of warming needle moxibustion was developed and adopted in the curriculum teaching of practice. It showed that this instrument could quantify the speed of fixing mugwort ball on the needle handle, the number of the prepared mugwort ball, the duration for anti-vibration, the frequency of anti-vibration and the burning time of mugwort ball. The instrument could objectively evaluate the skills of warming needle moxibustion and the effects of fixing mugwort ball. Besides, it may provide the references to improve the protocol of the future research. The development and application of the practical training instrument of warming needle moxibustion is conductive to cultivate the standardization and accuracy of the technique operation in students, and it is significant for objectif-ying the teaching course of warming needle and teaching assessment, as well as for diversifying the teaching modes. Moreover, it plays an exemplary role in the practical training of other acupuncture and moxibustion techniques.

Sevoflurane Inhalation Anesthesia in Lower Limb Fracture Surgery in Children.

To investigate the effect of sevoflurane inhalation anesthesia on hemodynamics in children undergoing lower limb fracture surgery. Between January 2019 and December 2021, 187 kids at our hospital were randomly divided into two distinct categories: the experimental category (95 cases) and the control category (92 cases). Sevoflurane inhalation anesthesia was administered to the experimental cohort whereas Ketamine basic anesthesia was administered to the control cohort. Comparisons were made among the two categories' hemodynamic indices, anesthetic quality, and VAS ratings. When the eyelash reflex vanished, immediately after skin incision, as well as 5 min after skin incision, the SaO2, as well as MAP in the experimental group, were higher than those in the control category, while HR, SBP, as well as DBP were less than those in the control category. These variations were statistically noteworthy (P < .05). The onset of the experimental group's sensory blocks and the awakening of patients was faster than the control category, and the variations were of statistical importance (P < .05). At 24 hours, 48 hours, and 72 hours, the VAS score in the experimental category was substantially distinct from that in the control category (P < .05). In addition to lowering postoperative discomfort and stabilizing hemodynamics, sevoflurane inhalation anesthesia helps speed up the onset and recovery of anesthesia block in children having lower extremity fracture surgery.

[Current status and trend of acupuncture-moxibustion for myofascial pain syndrome: a visual analysis of knowledge graph based on CiteSpace and VOSviewer].

Bibliometric and scientific knowledge graph methods were used to analyze the research status and hot spots of acupuncture-moxibustion in treatment of myofascial pain syndrome (MPS) and explore its development trend. The articles of both Chinese and English versions relevant to MPS treated by acupuncture-moxibustion were searched in CNKI, VIP, Wanfang, SinoMed and WOS from the database inception to March 20, 2023. Using Excel2016, CiteSpace6.2.R2 and VOSviewer1.6.18, the visual analysis was conducted by means of the cooperative network, keyword co-occurrence, keyword timeline, keyword emergence, etc. From Chinese databases and WOS database, 910 Chinese articles and 300 English articles were included, respectively. The annual publication volume showed an overall rising trend. Literature output of English articles was concentrated in Spain, China, and the United States, of which, there was less cross-regional cooperation. In the keyword analysis, regarding acupuncture-moxibustion therapy, Chinese articles focused on "acupuncture", "electroacupuncture" and "acupotomy"; while, "dry needling" and "injection" were dominated for English one. Clinical study was the current hot spot in Chinese databases, in comparison, the randomized controlled double-blind clinical trial was predominant in WOS. Both Chinese and English articles were limited in the report of mechanism research. The cooperation among research teams should be strengthened to conduct comparative research, dose-effect research and effect mechanism research with different methods of acupuncture-moxibustion involved so that the evidences can be provided for deeper exploration.

[Development and application of visual analysis teaching software for acupoint compatibility laws].

A user-friendly teaching software for visual analysis of acupoint compatibility laws has been developed based on the principles of partial order mathematics. This software is designed to provide auxiliary teaching of structured organization and visualization of law knowledge of compatibility data of acupuncture and moxibustion prescriptions from ancient texts, textbooks, and clinical case records. The software is installed as a plugin in the Microsoft Office Excel, allowing the generation of visually appealing graphs and associated rules that align with the cognitive patterns of teachers and students majoring in acupuncture and moxibustion. Its aim is to facilitate the discovery and analysis of underlying patterns and structured knowledge embedded in acupoint compatibility data, thus contributing to the enhancement of teaching effectiveness in acupoint compatibility.

Bushen Tongluo formula ameliorated testosterone propionate-induced benign prostatic hyperplasia in rats.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in older men worldwide. However, there is currently no effective treatment for BPH. Bushen Tongluo Formula (Kidney-supplementing and collaterals-unblocking formula [KCF]) is a traditional Chinese medicine formula commonly used to ameliorate the symptoms of BPH, although the specific molecular mechanisms remain unclear. PURPOSE: We aimed to discover the effects and potential mechanisms of KCF against BPH. METHODS: Sixty male SD rats were randomly assigned to one of six group (n = 10): control, low-dosage KCF, medium-dosage KCF, high-dosage KCF, BPH model, and finasteride. A rat model of BPH was established by surgical castration followed by subcutaneous injection of testosterone propionate (TP) for 4 weeks. After treatment, the prostate index, histopathological staining, serum levels of estradiol (E2) and dihydrotestosterone (DHT), protein/mRNA levels of E-cadherin, TGF-ß1, caspase-3, Ki67, and vimentin, abundances of serum metabolites, and the proliferation, cell cycle, and apoptosis of BPH-1 cells were documented. RESULTS: KCF treatment for 4 weeks reduced the prostate volume and prostate index, alleviated histopathological changes to the prostate of rats with TP-induced BPH, decreased serum levels of E2 and DHT, reduced protein/mRNA levels of TGF-ß1 and vimentin, and increased E-cadherin levels. Moreover, KCF-spiked serum inhibited proliferation of BPH-1 cells, blocked the cell cycle, and promoted apoptosis. KCF was also found to regulate the contents of three metabolites (D-maltose, citric acid, and fumaric acid). CONCLUSION: The present study was the first to report that KCF exhibited therapeutic effects against BPH by regulating energy metabolism and inhibiting epithelial-mesenchymal transition in prostate tissues. Hence, KCF presents a viable treatment option for BPH.

Green extraction and purification of chondroitin sulfate from jumbo squid cartilage by a novel procedure combined with enzyme, ultrasound and hollow fiber dialysis.

Chondroitin sulfate (ChS) from marine sources is gaining attention. The purpose of this study was to extract ChS from jumbo squid cartilage (Dosidicus gigas) using ultrasound-assisted enzymatic extraction (UAEE). An ultrasound with protease assistance, including either alcalase, papain or Protin NY100 was used to extract ChS. The results showed that alcalase had the best extraction efficiency. The response surface methodology was employed to evaluate the relationship between extraction conditions and extraction yield of ChS. The ridge max analysis revealed a maximum extraction yield of 11.9 mg ml- 1 with an extraction temperature of 59.40 °C, an extraction time of 24.01 min, a pH of 8.25, and an alcalase concentration of 3.60%. Compared to ethanol precipitation, purification using a hollow fiber dialyzer (HFD) had a higher extraction yield of 62.72% and purity of 85.96%. The structure characteristics of ChS were identified using FTIR, 1 H-NMR, and 13 C-NMR to confirm that the purified ChS structure was present in the form of chondroitin-4-sulfate and chondroitin-6-sulfate. The results of this study provide a green and efficient process for extraction and purification of ChS and are essential for the use of ChS for the development and production of nutrient food products or pharmaceuticals. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05701-7.

New cyclic C-geranylflavanones isolated from Paulownia fortunei fruits with their anti-proliferative effects on three cancer cell lines.

Seven new C-geranylated flavanones, fortunones F - L (1-7), were isolated from the fresh mature fruits of Paulownia fortunei (Seem.) Hemsl. Their structures were determined by extensive spectroscopic data interpretation (UV, IR, HRMS, NMR, and CD). These new isolated compounds were all with a cyclic side chain modified from the geranyl group. Among them, compounds 1-3 all possessed a dicyclic geranyl modification, which was described firstly for Paulownia C-geranylated flavonoids. All the isolated compounds were subjected to the cytotoxic assay on human lung cancer cell A549, mouse prostate cancer cell RM1 and human bladder cancer cell T24, respectively. Results indicated A549 cell line was more sensitive to C-geranylated flavanones than the other two cancer cell lines and compounds 1, 7 and 8 exhibited potential anti-tumor effects (IC50 ˂ 10 µM). Further research revealed the effective C-geranylated flavanones could exert their anti-proliferative activity on A549 cells by inducing apoptosis and blocking cells in G1 phase.

[Effect of Morus alba extract sanggenon C on growth and proliferation of glioblastoma cells].

Glioblastoma is the most common primary cranial malignancy, and chemotherapy remains an important tool for its treatment. Sanggenon C(San C), a class of natural flavonoids extracted from Morus plants, is a potential antitumor herbal monomer. In this study, the effect of San C on the growth and proliferation of glioblastoma cells was examined by methyl thiazolyl tetrazolium(MTT) assay and 5-bromodeoxyuridinc(BrdU) labeling assay. The effect of San C on the tumor cell cycle was examined by flow cytometry, and the effect of San C on clone formation and self-renewal ability of tumor cells was examined by soft agar assay. Western blot and bioinformatics analysis were used to investigate the mechanism of the antitumor activity of San C. In the presence of San C, the MTT assay showed that San C significantly inhibited the growth and proliferation of tumor cells in a dose and time-dependent manner. BrdU labeling assay showed that San C significantly attenuated the DNA replication activity in the nucleus of tumor cells. Flow cytometry confirmed that San C blocked the cell cycle of tumor cells in G_0/G_1 phase. The soft agar clone formation assay revealed that San C significantly attenuated the clone formation and self-renewal ability of tumor cells. The gene set enrichment analysis(GSEA) implied that San C inhibited the tumor cell division cycle by affecting the myelocytomatosis viral oncogene(MYC) signaling pathway. Western blot assay revealed that San C inhibited the expression of cyclin through the regulation of the MYC signaling pathway by lysine demethylase 4B(KDM4B), which ultimately inhibited the growth and proliferation of glioblastoma cells and self-renewal. In conclusion, San C exhibits the potential antitumor activity by targeting the KDM4B-MYC axis to inhibit glioblastoma cell growth, proliferation, and self-renewal.

Manual acupuncture for neuromusculoskeletal disorders: The selection of stimulation parameters and corresponding effects.

As a minimally invasive method of physical stimulation, manual acupuncture (MA) is used globally as a sort of therapy for neuromusculoskeletal disorders. In addition to selecting appropriate acupoints, acupuncturists should also determine the stimulation parameters of needling, such as the manipulation (lifting-thrusting or twirling), needling amplitude, velocity, and stimulation time. At present, most studies focus on acupoint combination and mechanism of MA, the relationship between stimulation parameters and their therapeutic effects, as well as the influence on mechanism of action are relatively scattered, and lack of systematic summary and analysis. This paper reviewed the three types of stimulation parameters of MA, their common options and values, corresponding effects and potential mechanisms of action. The purpose of such efforts is to provide a useful reference for the dose-effect relationship of MA and the quantification and standardization of its clinical treatment of neuromusculoskeletal disorders to further promote the application of acupuncture in the world.

Effects of intercropping on Se accumulation and growth of pakchoi, lettuce and radish.

Selenium is one of the most basic trace elements in the human body. It is necessary to improve the selenium content in agricultural products through agricultural planting technology to ensure that human nutrition and health need selenium. Therefore, our research passed the effect of intercropping on the growth and selenium accumulation of pakchoi, lettuce and radish were studied through pot experiments to determine whether intercropping of the three crop species can improve their selenium accumulation ability. The results showed that intercropping increased the root and shoot biomass of pakchoi and radish compared with the monocultures, while the biomass of roots and shoots decreased in other intercropping combinations. Intercropping also affected the photosynthetic pigment content of the three crop species. Specifically, the photosynthetic pigments increased in pakchoi and decreased in radish after intercropping. Notably, intercropping the three crop species together increased the SOD (superoxide dismutase) activities of the three crops compared with the monocultures. Meanwhile, intercropping radish with lettuce significantly increased the activities of SOD and CAT (catalase) in radish. Intercropping also increased the soluble sugar content in pakchoi and soluble protein content of radish relative to the monocultures. Furthermore, intercropping decreased the selenium content and the bioconcentration factor of the roots of the three vegetable crops, but improved the shoot selenium content, the bioconcentration factor and the transport factor of Se in pakchoi and radish. In conclusion, intercropping combination of pakchoi and radish can improve selenium accumulation in the edible parts of the crops, which is significant for efficient production of selenium-enriched vegetables.

This research is significant because this study provides some basis for improving the selenium content of plants and efficient production of pakchoi and radish. Under the condition of selenium application in soil, the intercropping of pakchoi and lettuce can promote the growth of both and improve their selenium enrichment ability.

Enhanced stability and clinical absorption of a form of encapsulated vitamin A for food fortification.

Food fortification is an effective strategy to address vitamin A (VitA) deficiency, which is the leading cause of childhood blindness and drastically increases mortality from severe infections. However, VitA food fortification remains challenging due to significant degradation during storage and cooking. We utilized an FDA-approved, thermostable, and pH-responsive basic methacrylate copolymer (BMC) to encapsulate and stabilize VitA in microparticles (MPs). Encapsulation of VitA in VitA-BMC MPs greatly improved stability during simulated cooking conditions and long-term storage. VitA absorption was nine times greater from cooked MPs than from cooked free VitA in rats. In a randomized controlled cross-over study in healthy premenopausal women, VitA was readily released from MPs after consumption and had a similar absorption profile to free VitA. This VitA encapsulation technology will enable global food fortification strategies toward eliminating VitA deficiency.

Systematic realist synthesis of health-related and lifestyle interventions designed to decrease overweight, obesity and unemployment in adults.

BACKGROUND: Obesity and unemployment are complex social and health issues with underlying causes that are interconnected. While a clear link has been established, there is lack of evidence on the underlying causal pathways and how health-related interventions could reduce obesity and unemployment using a holistic approach. OBJECTIVES: The aim of this realist synthesis was to identify the common strategies used by health-related interventions to reduce obesity, overweight and unemployment and to determine for whom and under what circumstances these interventions were successful or unsuccessful and why. METHODS: A realist synthesis approach was used. Systematic literature searches were conducted in Cochrane library, Medline, SocIndex, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and PsychInfo. The evidence from included studies were synthesised into Context-Mechanism-Outcome configurations (CMOcs) to better understand when and how programmes work, for which participants and to refine the final programme theory. RESULTS: A total of 83 articles met the inclusion criteria. 8 CMOcs elucidating the contexts of the health-related interventions, underlying mechanisms and outcomes were identified. Interventions that were tailored to the target population using multiple strategies, addressing different aspects of individual and external environments led to positive outcomes for reemployment and reduction of obesity. CONCLUSION: This realist synthesis presents a broad array of contexts, mechanisms underlying the success of health-related interventions to reduce obesity and unemployment. It provides novel insights and key factors that influence the success of such interventions and highlights a need for participatory and holistic approaches to maximise the effectiveness of programmes designed to reduce obesity and unemployment. TRIAL REGISTRATION: PROSPERO 2020 CRD42020219897 .

Effects of Sophora flavescens aiton and the absorbed bioactive metabolite matrine individually and in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cells in nude mice.

Background: Sophora flavescens aiton (SFA) and its main bioactive metabolite matrine are widely used in traditional Chinese medicine (TCM) preparations and have achieved good curative effects for the treatment of various tumors. However, the mechanisms underlying SFA and matrine individually and in combination with chemotherapeutic drugs for treatment of gastric cancer (GC) remain unclear. Aim of the study: To elucidate the mechanisms underlying the ability of SFA and matrine individually and in combination with chemotherapeutic drugs to inhibit proliferation and promote apoptosis of human GC cells. Materials and methods: Forty-eight nude mice were randomly divided into six groups that were treated with normal saline (model group), 5-fluorouracil (5-FU), SFA decoction (SFAD), matrine, SFAD+5-FU, or matrine+5-FU. A subcutaneous heterotopic tumor model was established in nude mice by implantation of human GC BGC-823 cells. All mice were treated for 28 days. Bioactive metabolites in SFA were determined by HPLC-MS/MS. The tumor volume, tumor weight, and tumor inhibition rate of mice were documented. Histopathology and ultramicroscopic pathology of tumor tissues were observed. The tumor cell cycle and apoptosis in vivo were detected. Serum levels of PCNA, BAX, Bcl-2, Caspase-9, Caspase-3 and cleaved Caspase-3 were measured. Protein levels of MS4A10, MS4A8, MS4A7, PCNA, BAX, Bcl-2, Caspase-3, and cleaved Caspase-3 were measured in tumor tissues. Results: Both SFAD and matrine inhibited the growth of transplanted GC cells, which was more effective when combined with 5-FU. The tumor inhibition rates of the 5-FU, SFAD, matrine, SFAD+5-FU, and matrine+5-FU groups were 53.85%, 33.96%, 30.44%, 59.74%, and 56.55%, respectively. The body weight of tumor-bearing nude mice was greater in the SFAD group than the normal saline and matrine groups. SFAD+5-FU and matrine+5-FU blocked BGC-823 cells in the G0-G1/S transition, promoted apoptosis, and significantly decreased the content of serum apoptosis-inhibitory proteins (PCNA and Bcl-2) as well as protein expression of MS4A8, MS4A10, Bcl-2, and PCNA in tumor tissues, while increasing serum levels of pro-apoptotic proteins (Caspase-9, Caspase-3 and cleaved-Caspase-3) and protein expression of BAX and cleaved-Caspase-3 in tumor tissues. Conclusion: SFAD and matrine both individually and in combination with 5-FU ameliorated malignancy of transplanted tumors by reducing proliferation and promoting apoptosis of BGC-823 cells. These findings confirm the anti-tumor synergistic effect of TCM and chemotherapeutic drugs.

[Study on the quantitative evaluation parameter system for basic acupuncture manipulations based on 3D motion tracking technology].

OBJECTIVE: To establish a quantitative evaluation parameter system for basic acupuncture manipulations based on 3D motion tracking technology, and to further analyze the characteristics of acupuncture manipulation. METHODS: The motion tracking system Simi Motion Ver.8.5 was used to collect parameters of acupuncture manipulations, so as to establish a quantitative evaluation system mainly in spatial control parameters, time control parameters and stability parameters. Based on the evaluation parameter system, data of acupuncture manipulations (even reinforcing-reducing manipulation using lifting-thrusting technique and twirling technique) were collected from 19 teachers majored in acupuncture-moxibustion, of which the characteristics were analyzed and were compared with the results tested by traditional ATP-Ⅱ acupuncture manipulation parameter determination apparatus (ATP-Ⅱ). RESULTS: The evaluation parameter system could quantitatively analyze the basic acupuncture manipulations in 3 aspects, i.e. space, time and stability. Acupuncture manipulations were performed by shifting the needle body in a certain range along X, Y and Z axes. The amplitude and speed of thumb movement were greater than those of index finger. The time-history of lifting was similar to thrusting, while the time-history of twirling to left was similar to twirling to right in even reinforcing-reducing manipulation. The coordinate-time curve of finger movement of the evaluation system had consistent wave pattern compared with the voltage-time curve generated by ATP-Ⅱ. CONCLUSION: The quantitative evaluation parameter system based on 3D motion tracking technology can objectively evaluate basic acupuncture manipulations, and show the characteristics of different manipulations and the movement details of finger joints.

Preclinical Pharmacokinetics and Bioavailability of Oxypeucedanin in Rats after Single Intravenous and Oral Administration.

Oxypeucedanin, a furanocoumarin extracted from many traditional Chinese herbal medicines, has a variety of pharmacological effects. However, the independent pharmacokinetic characteristics and bioavailability of this compound remains elusive. In this study, a rapid, sensitive, and selective method using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) was developed for evaluating the intravenous and oral pharmacokinetics of oxypeucedanin. After intravenous administration of oxypeucedanin (2.5, 5, and 10 mg/kg), and intragastric administration of oxypeucedanin (20 mg/kg), blood samples were collected periodically from the tail vein. The plasma concentration-time curves were plotted, and the pharmacokinetic parameters were calculated using a non-compartmental model analysis. After intravenous administration of oxypeucedanin (single dosing at 2.5, 5, and 10 mg/kg) to rats, the pharmacokinetics fit the linear kinetics characteristics, which showed that some parameters including average elimination half-life (T1/2Z of 0.61~0.66 h), mean residence time (MRT of 0.62~0.80 h), apparent volume of distribution (VZ of 4.98~7.50 L/kg), and systemic clearance (CLZ of 5.64~8.55 L/kg/h) are dose-independent and the area under concentration-time curve (AUC) increased in a dose-proportional manner. Single oral administration of oxypeucedanin (20 mg/kg) showed poor and slow absorption with the mean time to reach the peak concentration (Tmax) of 3.38 h, MRT of 5.86 h, T1/2Z of 2.94 h, and a mean absolute bioavailability of 10.26% in rats. These results provide critical information for a better understanding of the pharmacological effect of oxypeucedanin, which will facilitate its research and development.

Zengye Decoction Attenuated Severe Acute Pancreatitis Complicated with Acute Kidney Injury by Modulating the Gut Microbiome and Serum Amino Acid Metabolome.

Objective: To explore the effect and underlying mechanism of Zengye decoction (ZYD), a traditional formula from China, on the severe acute pancreatitis (SAP) rat model with acute kidney injury (AKI). Methods: The SAP-AKI model was induced by 3.5% sodium taurocholate. Rats were treated with normal saline or ZYD twice and sacrificed at 36 h after modeling. Amylase, lipase, creatinine, blood urea nitrogen, kidney injury molecule 1(KIM-1), and multiple organs' pathological examinations were used to assess the protective effect of ZYD. Gut microbiome detected by 16S rRNA sequencing analysis and serum amino acid metabolome analyzed by liquid chromatography-mass spectrometry explained the underlying mechanism. The Spearman correlation analysis presented the relationship between microflora and metabolites. Results: ZYD significantly decreased KIM-1(P < 0.05) and the pathological score of the pancreas (P < 0.05), colon (P < 0.05), and kidney (P < 0.05). Meanwhile, ZYD shifted the overall gut microbial structure (ß-diversity, ANOSIM R = 0.14, P=0.025) and altered the microbial compositions. Notably, ZYD reduced the potentially pathogenic bacteria-Bacteroidetes, Clostridiales vadin BB60 group, and uncultured_Clostridiales_bacterium, but promoted the short-chain fatty acid (SCFA) producers-Erysipelotrichaceae, Bifidobacterium, Lactobacillus, and Moryella (all P < 0.05). Moreover, principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and hierarchical clustering analysis (HCA) presented a remarkable change in amino acid metabolome after SAP-AKI induction and an apparent regulation by ZYD treatment (R2Y 0.878, P=0.01; Q2 0.531, P=0.01). Spearman's correlation analysis suggested that gut bacteria likely influenced serum metabolites levels (absolute r > 0.4 and FDR P < 0.02). Conclusions: ZYD attenuated SAP-AKI by modulating the gut microbiome and serum amino acid metabolome, which may be a promising adjuvant treatment.

Activation of mitochondrial-associated apoptosis signaling pathway and inhibition of PI3K/Akt/mTOR signaling pathway by voacamine suppress breast cancer progression.

BACKGROUND: Breast cancer is one of the malignant tumors with the highest morbidity and mortality rate. Numerous efficient anti-breast cancer drugs are being derived from the development of natural products. Voacamine (VOA), a bisindole alkaloid isolated from Voacanga africana Stapf, possesses various pharmacological and biological activities. PURPOSE: In this study, we investigated the efficacy of VOA against breast cancer cells and elucidated the underlying mechanisms in vitro and in vivo. METHODS: Human breast cancer cell line MCF-7 and mouse breast cancer cell line 4T1 were used to study the underlying anti-cancer mechanisms of VOA. The proliferation was detected by MTT, colony formation, cell proliferation and wound-healing migration assays. Flow cytometry was utilized to determine the level of reactive oxygen species (ROS) cell-cycle, apoptosis and mitochondrial membrane potential. The target proteins were analyzed by Western blot. Molecular docking was performed and scored by AutoDock. Subcutaneous cancer models in mice were established to evaluate the anticancer effects in vivo. RESULT: Our results demonstrated that VOA selectively suppressed breast cancer MCF-7 and 4T1 cells proliferation with IC50 values of 0.99 and 1.48 µM, and significantly inhibited the migration and colony formation of tumor cells. Furthermore, the cell cycle was arrested in the S phase with the decreased expression levels of CDK2, Cyclin A and Cyclin E. Additionally, exposure to VOA dose-dependently brought about dose-dependently the loss of mitochondrial membrane potential (Δψm) and amassment of reactive oxygen species (ROS), resulting in the initiation of the intrinsic apoptotic pathway. Western blot analysis unveiled that VOA significantly activated mitochondrial-associated apoptosis and obviously suppress the PI3K/Akt/mTOR pathway via modulation of related protein expression levels in both tumor cell lines. In tumor-bearing mouse models, administration of VOA dose-dependently inhibited the tumor growth without causing apparent toxicities. CONCLUSION: These findings revealed the novel properties of VOA in promoting apoptosis of breast cancer cells by activating mitochondrial-associated apoptosis signaling pathway and inhibiting PI3K/Akt/mTOR signaling pathway and significantly decreasing tumor size without detecting appreciable toxicity. In summary, the present results demonstrated VOA could be an encouraging drug candidate to cure breast cancer, exhibiting an effective method to exploit unique drugs from natural components.

Data mining-based detection of the clinical effect on motion style acupuncture therapy combined with conventional acupuncture therapy in chronic neck pain.

BACKGROUND: Neck pain is the most common symptom of cervical spondylosis. OBJECTIVE: To discuss the indications for conventional acupuncture therapy (CAT) and motion style acupuncture therapy (MSAT) combined with CAT in neck pain patients using data mining. METHOD: Seventy-six participants with neck pain were recruited and randomly divided into two paralleled groups. Participants in intervention group received two-course MSAT at Houxi (SI3) and CAT at local neck region, while the control group received CAT at neck only. Take the SF-36 score scale and pain pressure threshold (PPT) values as the raw data and use data-mining to evaluate the clinical effect of two treatments. RESULT: Both groups have the best effect after one-time and one-course treatment. The main factors influencing effect most are Role-Emotional (RE), Physical Functioning (PF) and Social Functioning (SF) in intervention group, while it transfers to General Health (GH), RE and SF in control group. To patients in intervention group who scores 41.70 to 68.70 in PF before treatment, MSAT can effectively improve the restriction of activities and play an analgesic effect; to patients in control group who score 56.09 to 66.09 in GH before treatment, CAT may have curative effect. CONCLUSION: Both MSAT and CAT can improve the life-quality of neck pain patients. Patients with high general health status before treatment can choose CAT, while patients who score mild to moderate decline in physiological function can choose MSAT combined with CAT.