Acupoint Thread Embedding Combined With Wenshen Bugu Decoction for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptom Among Postmenopausal Breast Cancer Patients: Study Protocol of a Randomized Controlled Trial.

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.

FHL3 promotes the formation of fast glycolytic muscle fibers by interacting with YY1 and muscle glycolytic metabolism.

The proportions of the various muscle fiber types are important in the regulation of skeletal muscle metabolism, as well as animal meat production. Four-and-a-half LIM domain protein 3 (FHL3) is highly expressed in fast glycolytic muscle fibers and differentially regulates the expression of myosin heavy chain (MyHC) isoforms at the cellular level. Whether FHL3 regulates the transformation of muscle fiber types in vivo and the regulatory mechanism is unclear. In this study, muscle-specific FHL3 transgenic mice were generated by random integration, and lentivirus-mediated gene knockdown or overexpression in muscles of mice or pigs was conducted. Functional analysis showed that overexpression of FHL3 in muscles significantly increased the proportion of fast-twitch myofibers and muscle mass but decreased muscle succinate dehydrogenase (SDH) activity and whole-body oxygen consumption. Lentivirus-mediated FHL3 knockdown in muscles significantly decreased muscle mass and the proportion of fast-twitch myofibers. Mechanistically, FHL3 directly interacted with the Yin yang 1 (YY1) DNA-binding domain, repressed the binding of YY1 to the fast glycolytic MyHC2b gene regulatory region, and thereby promoted MyHC2b expression. FHL3 also competed with EZH2 to bind the repression domain of YY1 and reduced H3K27me3 enrichment in the MyHC2b regulatory region. Moreover, FHL3 overexpression reduced glucose tolerance by affecting muscle glycolytic metabolism, and its mRNA expression in muscle was positively associated with hemoglobin A1c (HbA1c) in patients with type 2 diabetes. Therefore, FHL3 is a novel potential target gene for the treatment of muscle metabolism-related diseases and improvement of animal meat production.

Preparation of Monascus-fermented ginkgo seeds: optimization of fermentation parameters and evaluation of bioactivity.

In this study, a high monacolin K yield was achieved through solid-state fermentation of Ginkgo biloba seeds. Monascus purpureus suspension made from red yeast rice was used as spore inoculum. Fermentation conditions in solid-state fermentation were optimized using response surface methodology, and the optimal conditions for the maximum monacolin K yield (17.71 ± 1.57 mg/g) were 0.22% ammonium sulfate, 0.34% ammonium chloride, 0.05% magnesium sulfate, fermentation time of 12 days, inoculation volume of 11%, and temperature of 27 °C. The total phenolic content of Monascus-fermented ginkgo seeds attained 9.67 mg GAE/g, 4.88-fold higher than that of unfermented ginkgo seeds. The scavenging abilities of DPPH and ABTS free radicals increased to 9.79 mg TE/g and 13.92 mg TE/g, respectively. These findings highlight the importance of investigating the optimal fermentation conditions for maximum monacolin K yield and the utilization value of ginkgo seed as fermentation substrate for higher bioactivities. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01078-z.

Mechanisms of Gegen Qinlian Pill to ameliorate irinotecan-induced diarrhea investigated by the combination of serum pharmacochemistry and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine suggests the use of natural extracts and compounds is a promising strategy to prevent irinotecan (CPT-11)-induced gut toxicity and resulting diarrhea. Previous work from our lab indicated the protective effect of Gegen Qinlian decoction; given this, we further speculated that Gegen Qinlian Pill (GQP) would exhibit similar therapeutic effects. The effective material basis as well as potential mechanisms underlying the effect of GQP for the treatment of CPT-11-induced diarrhea have not been fully elucidated. AIM OF THE STUDY: The application of natural extracts or compounds derived from Chinese medicine is deemed to a promising strategy to prevent irinotecan (CPT-11)-induced gut toxicity. The aim of this study was to investigated the beneficial effects of GQP on CPT-11-induced gut toxicity and further explored its anti-diarrheal mechanism. METHODS: First, the beneficial effect of GQP in alleviating diarrhea in mice following CPT-11 administration was investigated. We also obtained the effective ingredients in GQP from murine serum samples using HPLC-Q-TOF-MS analysis. Based on these active components, we next established an interaction network linking "compound-target-pathway". Finally, a predicted mechanism of action was obtained using in vivo GQP validation based on Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RESULTS: A total of 19, GQP-derived chemical compounds were identified in murine serum samples. An interaction network linking "compound-target-pathway" was then established to illuminate the interaction between the components present in serum and their targets that mitigated diarrhea. These results indicated GQP exerted a curative effect on diarrhea and diarrhea-related diseases through different targets, which cumulatively regulated inflammation, oxidative stress, and proliferation processes. CONCLUSION: Taken together, this study provides a feasible strategy to elucidate the effective constituents in traditional Chinese medicine formulations. More specifically, this work detailed the basic pharmacological effects and underlying mechanism behind GQP's effects in the treatment of CPT-11-induced gut toxicity.

Shikonin promotes ubiquitination and degradation of cIAP1/2-mediated apoptosis and necrosis in triple negative breast cancer cells.

BACKGROUND: Shikonin (SKO) is a natural naphthoquinone derived from Chinese herbal medicine Arnebiae Radix with high development potentials due to its anti-inflammatory and anti-tumor activities. Overwhelming evidences have indicated that SKO can induce both necrosis and apoptosis in cancer cells, while the mechanisms for triple negative breast cancer cells is still need to be disclosed. METHODS: In this study, kinds of molecular biological technologies, including flow-cytometry, Western blot, immunoprecipitation, enzyme-linked immunosorbent assay (ELISA) as well as real-time quantitative PCR (RT-qPCR), were applied for investigation on the underlying mechanisms of SKO induced necrosis and apoptosis for MDA-MB-231 cells. Inhibitors were also used for validation ofthe key signaling pathways involved in SKO triggered necrosis and apoptosis. RESULTS: We found that SKO significantly triggered necrosis and apoptosis of MDA-MB-231 cells in both a concentration- and time-dependent manner. Mechanism studies demonstrated that SKO significantly promoted the autoubiquitination levels and facilitated the proteasome dependent degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) and cIAP2 in MDA-MB-231 cells. Autoubiquitination and degradation of cIAP1 and cIAP2 induced by SKO further led to significant decreased ubiquitination and inactivation of RIP1, which played an important role in inhibition of pro-survival and accelerating of necrosis of MDA-MB-231 cells. Treatment with proteasome inhibitor lactacystin significantly rescued the cell viability induced by treatment of SKO. CONCLUSIONS: Our results demonstrate that SKO promotes the autoubiquitination and degradation of cIAP1 and cIAP2, which further induces the decrease of the ubiquitination of RIP1 to inhibit the activation of pro-survival signaling pathways and accelerate the necrosis of MDA-MB-231 cells. The disclosed mechanisms of SKO induced necrosis and apoptosis in our study is firstly reported, and it is believed that SKO could be considered as a potential candidate and further developed for the treatment of triple negative breast cancer.

Tracking evidences of Coptis chinensis for the treatment of inflammatory bowel disease from pharmacological, pharmacokinetic to clinical studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptis chinensis (C. chinensis, Huanglian in Chinese), a famous traditional herbal medicine used for clearing heat and detoxification since thousands of years ago, is widely and traditionally used for clinical treatment of stomach inflammation, duodenum and digestive tract ulcers alone or through combing with other herbs in compound formulations. AIM OF THE REVIEW: Through literature reviews of C. chinensis and berberine (one of the most important bioactive compounds derived from this plant) for the treatment of inflammatory bowel disease (IBD), this review aims to provide beneficial information for further exploration of the potent bioactive constituents from C. chinensis, deep investigation on the molecular mechanisms for the treatment of IBD, as well as further research and development of brand new products from C. chinensis for clinical therapy of IBD. METHODS: "C. chinensis" and "IBD" were selected as the main keywords, and various online search engines, such as Google Scholar, PubMed, Web of Science, China National Knowledge Infrastructure database (CNKI) and other publication resources, were used for searching literatures. RESULTS: To present, C. chinensis together with other herbs are involved in plenty of Chinese herbal prescriptions for the treatment of IBD, but little research focused on the single therapeutic effects of C. chinensis or extracts from this herb for the treatment of this disease. Berberine, one of important and representative bioactive compound isolated from C. chinensis, was reported to treat IBD effectively at a big arising speed in recent years. However, systematically and comprehensively reviews on the research of C. chinensis and berberine for the treatment of IBD from the aspects of chemical constituents, pharmacological effects, pharmacokinetics as well as clinical studies are seldom accomplished by researchers. Bioactive components from C. chinensis exert therapeutic effects for the treatment of IBD mainly through the inhibition of oxidative stress, antinociception, protection of intestinal mucosal epithelial barrier, regulation of T helper cells, as well as antibacterial activity. Although numerous studies on bioactive compounds from C. chinense have been performed by clinical investigators in recent years, most of them should be performed in a more strict and standard way to ensure the safety and efficacy of these compounds. CONCLUSIONS: Berberine is considered as the representative and effective component from C. chinensis, but many other chemical components isolated from C. chinensis also have therapeutic effects for the treatment of IBD, which need deep research and further exploration. To accelerate research and development of C. chinensis and its bioactive components for the treatment of IBD, clinical trials are needed to clarify the effectiveness and safety of these chemical components from C. chinensis, as well as their molecular mechanisms for IBD treatment in vitro and in vivo. It is believed that continuous research and exploration on C. chinensis together with its bioactive compounds will bring great hope to the treatment of IBD.

[Review of chemical constituents, pharmacological effects and clinical applications of Jiaotai Pills and predictive analysis of its quality marker(Q-marker)].

Jiaotai Pills is a traditional medical prescription to treat the incompatibility of heart and kidney. It has the distinctive functions of heart and kidney communication, sedation and hypnosis, anti-anxiety and depression, as well as the improvement of insulin resistance. However, this pill is broadly used to cure insomnia, anxiety, depression, and diabetes in the contemporary clinical trials. Based on the article, it illustrates the research progress of the chemical ingredients, pharmacological actions, and clinical applications of Jiaotai Pills. With respect to the "five principles" of Q-marker in Chinese medicine, the Q-marker of Jiaotai Pills is comprehensively predicted and analyzed, noting that berberine, epiberberine, coptisine chloride, palmatine chloride, berberine chloride, berberrubine chloride, ferulic acid, cinnamic acid, cinnamaldehyde, proanthocyanidin B2 can be treated as the Q-marker of Jiaotai Pills. In addition, these components of Q-marker have been selected as indicators to provide a significant reference for the quality control and surveillance research of Jiaotai Pills.

Traditional uses, phytochemistry and pharmacological activities of the genus Cinnamomum (Lauraceae): A review.

Species of Cinnamomum exhibit excellent economic and medicinal value, and have found use in traditional medicine, are consumed as a spice, as well as being cultivated as landscape plants. Investigations into the pharmacological activities of the genus Cinnamomum revealed that it manifested a wide range of pharmacological properties including antimicrobial, antioxidant, anti-inflammatory and analgesic, antitumor, anti-diabetic and anti-obesity, immunoregulation, insecticidal and acaricidal, cardiovascular protective, cytoprotective, as well as neuroprotective properties both in vivo and in vitro. In the past five years, approximately 306 chemical constituents have been separated and identified from the genus Cinnamomum, covering 111 terpenes, 44 phenylpropanoids, 51 lignans, 17 flavonoids, 53 aromatic compounds, 17 aliphatic compounds, four coumarins, two steroids. This article highlights the traditional uses, phytochemistry and pharmacological properties of the few studied taxa of Cinnamomum through searching for the pieces of literature both at home and abroad, which would provide a reference for the pharmaceutical research and clinical application of this genus.

Astragali Radix (Huangqi): A promising edible immunomodulatory herbal medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragali Radix (AR, Huangqi in Chinese), the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or A. membranaceus (Fisch.) Bge., possesses diverse therapeutic effects against fatigue, dyspepsia, diarrhea, heart diseases, hepatitis, and anemia. In recent years, increasing evidence has indicated the multiple immunomodulatory activities of AR in preclinical and clinical studies. AIM OF THE REVIEW: This review attempts to elaborate the immunomodulatory effects of AR and its potential application in the treatment of immune related diseases. MATERIALS AND METHODS: A comprehensive literature search AR was carried out using multiple internationally recognized databases (including Web of Science, Google Scholar, PubMed, ScienceDirect, Wiley, ACS, Springer, Taylor & Francis, and CNKI). RESULTS: The immunomodulatory effects of AR are closely attributed to its active constituents such as polysaccharides, saponins, and flavonoids. We also demonstrate that AR can be used as a potential therapeutic intervention for immune related diseases through regulating immune organs, mucosal immune, and immune system (innate immunity and acquired immunity). CONCLUSION: AR promotes the development of immune organs, enhances mucosal immune function, increases the quantity and phagocytic capacity of innate immunity, promotes the maturation and differentiation of acquired immunity cells, and improves the expression of antibodies in acquired immunity. We believe that AR has a broad research space in the adjuvant treatment of immune related diseases, which could be a breakthrough point to improve the application value of AR.

[Establishment of rat heart-kidney insomnia model consistent with traditional Chinese medicine syndrome and its serum metabolomics].

Enzyme-linked immunosorbent assay(ELISA) and metabolomics were used to analyze and compare two animal models of heart-kidney insomnia, in order to explore a more ideal animal model and preliminarily explore the essence of heart-kidney insomnia. Based on the clinical symptoms and disease characteristics of heart-kidney insomnia, the animal model of heart-kidney insomnia was reproduced through intraperitoneal injection with p-chlorophenylalanine(PCPA) and multi-factor interaction. The animal model of disease-syndrome combination was evaluated by behavioral observation, ELISA and metabolomics. Wistar rats were randomly divided into normal group, PCPA group and compound model group(FH). The rats' behavior, body weight, adrenal index and spleen index were recorded. The levels of corticotropin releasing hormone(CRH) and adrenocorticotropin(ACTH) in serum were detected by ELISA, and the differential metabolites in serum were detected by UPLC-QE-MS. The body weight and adrenal index in FH group were significantly lower than those in PCPA group(P<0.05); whereas ACTH and CRH in FH group were significantly higher than those in PCPA group by ELISA; nine potential biomarkers were identified by serum sample statistics. There were four main metabolic pathways in cardiorenal insomnia: pentose phosphate metabolism, alanine, aspartic acid and glutamic acid metabolism, histidine metabolism, and taurine and subtaurine metabolism. PCPA and multi-factor interaction method can successfully replicate the insomnia model, but multi-factor modeling method is more similar to clinical traditional Chinese medicine syndrome. Animal behavior, ELISA and metabolomics were used to evaluate the rat model of cardiorenal insomnia from in vitro to in vivo, from macro to micro, and from individual to the whole.

Synthesis and biological evaluation of novel tanshinone IIA derivatives for treating pain.

Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound III-3 (IC50 120 nmol·L-1) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA.

Adsorption and reaction mechanism of arsenic vapors over γ-Al2O3 in the simulated flue gas containing acid gases.

Arsenic emission from fuel combustion and metal smelting flue gas causes serious pollution. Addition of sorbents is a promising way for the arsenic capture from high temperature flue gas. However, it is difficult to remove arsenic from SO2/HCl-rich flue gas due to the competitive reaction of the sorbents with arsenic and these acid gases. To solve this problem, arsenic adsorption over γ-Al2O3 was studied in this work to evaluate its adsorption mechanism, resistance to acid gases as well as regeneration behavior. The results show that γ-Al2O3 had good resistance to acid gases and the arsenic adsorption by γ-Al2O3 could be effectively carried out at a wide temperature range between 573 and 1023 K. Nevertheless, adsorption at higher-temperature (like 1173 K) leaded to the decrease of surface area and the rearrangement of crystal structure of γ-Al2O3, reducing the active sites for arsenic adsorption. The adsorption of arsenic was confirmed to occur at different active sites in γ-Al2O3 by forming various adsorbed species. Increasing temperature facilitated arsenic transformation into more stable chemisorbed As3+ and As5+ which were difficult to remove through thermal treatment regeneration. Fortunately, the regeneration of spent γ-Al2O3 could be well performed using NaOH solution.