Is it more effective for anhedonia and avolition? A systematic review and meta-analysis of non-invasive brain stimulation interventions for negative symptoms in schizophrenia.

BACKGROUND: Noninvasive brain stimulation (NIBS) techniques are a promising tool for treating the negative symptoms of schizophrenia. Growing evidence suggests that different dimensions of negative symptoms have partly distinct underlying pathophysiological mechanisms. Previous randomized controlled trials (RCTs) have shown inconsistent impacts of NIBS across dimensions. OBJECTIVE: This systematic review and meta-analysis evaluated the effects of NIBS on general negative symptoms, and on specific domains, including blunted affect, alogia, asociality, anhedonia, and avolition. DATA SOURCES: PubMed, Web of Science, Embase, Cochrane CENTRAL, PsycINFO, OpenGrey, and Clinicaltrials.gov from the first date available to October, 2023. RESULTS: Among 1049 studies, we identified eight high-quality RCTs. NIBS significantly affects general negative symptoms (SMD = -0.54, 95% CI [-0.88, -0.21]) and all five domains (SMD = -0.32 to -0.63). Among dimensions, better effects have been shown for improvement of avolition (SMD = -0.47, 95% CI [-0.81, -0.13]) and anhedonia (SMD = -0.63, 95% CI [-0.98, -0.28]). Subgroup analyses of studies that applied once daily stimulation or >10 sessions showed significantly reduced negative symptom severity. CONCLUSION: NIBS exerts distinct effects across multiple dimensions of negative symptom, with treatment effects related to stimulation frequency and total sessions. These results need to be confirmed in dedicated studies.

Cucurbitacin B suppresses hepatocellular carcinoma progression through inducing DNA damage-dependent cell cycle arrest.

BACKGROUND: The mortality rate of liver cancer ranks third in the world, and hepatocellular carcinoma (HCC) is a malignant tumor of the digestive tract. Cucurbitacin B (CuB), a natural compound extracted from Cucurbitaceae spp., is the main active component of Chinese patent medicine the Cucurbitacin Tablet, which has been widely used in the treatment of various malignant tumors in clinics, especially HCC. PURPOSE: This study explored the role and mechanism of CuB in the suppression of liver cancer progression. METHODS: Cell Counting Kit-8 (CCK-8) and colony formation assays were used to detect the inhibitory function of CuB in Huh7, Hep3B, and Hepa1/6 hepatoma cells. Calcein-AM/propidium iodide (PI) staining and lactate dehydrogenase (LDH) measurement assays were performed to determine cell death. Mitochondrial membrane potential (Δψm) was measured, and flow cytometry was performed to evaluate cell apoptosis and cell cycle. Several techniques, such as proteomics, Western blotting (WB), and ribonucleic acid (RNA) interference, were utilized to explore the potential mechanism. The animal experiment was performed to verify the results of in vitro experiments. RESULTS: CuB significantly inhibited the growth of Huh7, Hep3B, and Hepa1/6 cells and triggered the cell cycle arrest in G2/M phage without leading to cell death, especially apoptosis. Knockdown of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a target of CuB, did not reverse CuB elicited cell cycle arrest. CuB enhanced phosphorylated ataxia telangiectasia mutated (p-ATM) and phosphorylated H2A histone family member X (γ-H2AX) levels. Moreover, CuB increased p53 and p21 levels and decreased cyclin-dependent kinase 1 (CDK1) expression, accompanied by improving phosphorylated checkpoint kinase 1 (p-CHK1) level and suppressing cell division cycle 25C (CDC25C) protein level. Interestingly, these phenomena were partly abolished by a deoxyribonucleic acid (DNA) protector methylproamine (MPA). Animal studies showed that CuB also significantly suppressed tumor growth in BALB/c mice bearing Hepa1/6 cells. In tumor tissues, CuB reduced the expression levels of proliferating cell nuclear antigen (PCNA) and γ-H2AX but did not change the terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) level. CONCLUSION: This study demonstrated for the first time that CuB could effectively impede HCC progression by inducing DNA damage-dependent cell cycle arrest without directly triggering cell death, such as necrosis and apoptosis. The effect was achieved through ataxia telangiectasia mutated (ATM)-dependent p53-p21-CDK1 and checkpoint kinase 1 (CHK1)-CDC25C signaling pathways. These findings indicate that CuB may be used as an anti-HCC drug, when the current findings are confirmed by independent studies and after many more clinical phase 1, 2, 3, and 4 testings have been done.

AR/PCC herb pair inhibits osteoblast pyroptosis to alleviate diabetes-related osteoporosis by activating Nrf2/Keap1 pathway.

Osteoporosis is a prevalent complication of diabetes, characterized by systemic metabolic impairment of bone mass and microarchitecture, particularly in the spine. Anemarrhenae Rhizoma/Phellodendri Chinensis Cortex (AR/PCC) herb pair has been extensively employed in Traditional Chinese Medicine to manage diabetes; however, its potential to ameliorate diabetic osteoporosis (DOP) has remained obscure. Herein, we explored the protective efficacy of AR/PCC herb pair against DOP using a streptozotocin (STZ)-induced rat diabetic model. Our data showed that AR/PCC could effectively reduce the elevated fasting blood glucose and reverse the osteoporotic phenotype of diabetic rats, resulting in significant improvements in vertebral trabecular area percentage, trabecular thickness and trabecular number, while reducing trabecular separation. Specifically, AR/PCC herb pair improved impaired osteogenesis, nerve ingrowth and angiogenesis. More importantly, it could mitigate the aberrant activation of osteoblast pyroptosis in the vertebral bodies of diabetic rats by reducing increased expressions of Nlrp3, Asc, Caspase1, Gsdmd and IL-1ß. Mechanistically, AR/PCC activated antioxidant pathway through the upregulation of the antioxidant response protein Nrf2, while concurrently decreasing its negative feedback regulator Keap1. Collectively, our in vivo findings demonstrate that AR/PCC can inhibit osteoblast pyroptosis and alleviate STZ-induced rat DOP, suggesting its potential as a therapeutic agent for mitigating DOP.

Natural products targeting macrophages in tumor microenvironment are a source of potential antitumor agents.

BACKGROUND: Macrophages are one of the major cell types in the immune system and are closely related to tumor development, which can be polarized into M1 type with anti-tumor activity or M2 type with pro-tumor activity. The infiltration of more macrophages into tumor predicts poorer prognosis due to their more exhibition of M2 phenotype under the influence of many factors in the tumor microenvironment (TME). Therefore, reverse of M2 macrophage polarization in TME is conducive to the suppression of tumor deterioration and understanding the influencing factors of macrophage polarization is helpful to provide new ideas for the subsequent targeting macrophages for tumor therapy. PURPOSE: This review summarizes the effects of TME on macrophage polarization and natural products against M2 macrophage polarization, which may provide some directions for tumor therapy. METHODS: The search of relevant literature was conducted using the PubMed, Science Direct, CNKI and Web of Science databases with the search terms "macrophage", "tumor microenvironment", "natural product" and "tumor". RESULTS: The mutual transformation of M1 and M2 phenotypes in macrophages is influenced by many factors. Tumor cells affect the polarization of macrophages by regulating the expression of genes and proteins and the secretion of cytokines. The expression of some genes or proteins in macrophages is also related to their own polarization. Many natural products can reverse M2 polarization of macrophages which has been summarized in this review. CONCLUSION: Regulation of macrophage polarization in TME can inhibit tumor development, and natural products have the potential to impede tumor development by regulating macrophage polarization.

Zinc dynamics regulate early ovarian follicle development.

Zinc fluctuations regulate key steps in late oocyte and preimplantation embryo development; however, roles for zinc in preceding stages in early ovarian follicle development, when cooperative interactions exist between the oocyte and somatic cells, are unknown. To understand the roles of zinc during early follicle development, we applied single cell X-ray fluorescence microscopy, a radioactive zinc tracer, and a labile zinc probe to measure zinc in individual mouse oocytes and associated somatic cells within early follicles. Here, we report a significant stage-specific increase and compartmental redistribution in oocyte zinc content upon the initiation of early follicle growth. The increase in zinc correlates with the increased expression of specific zinc transporters, including two that are essential in oocyte maturation. While oocytes in follicles exhibit high tolerance to pronounced changes in zinc availability, somatic survival and proliferation are significantly more sensitive to zinc chelation or supplementation. Finally, transcriptomic, proteomic, and zinc loading analyses reveal enrichment of zinc targets in the ubiquitination pathway. Overall, these results demonstrate that distinct cell type-specific zinc regulations are required for follicle growth and indicate that physiological fluctuation in the localization and availability of this inorganic cofactor has fundamental functions in early gamete development.

Determination of Five Coumarins in Angelicae Pubescentis Radix from Different Origins by HPTLC-Scanning.

The HPTLC method is widely used in the field of quality evaluation and component analysis of traditional Chinese medicine (TCM). This work developed an HPTLC method to determine the five effective components of osthole, columbianadin, isoimperatorin, oxypeucedanin, and imperatorin in Angelicae Pubescentis Radix (APR) from twelve different origins, and the quality difference was analyzed by comprehensive factor analysis and cluster analysis. The results showed that the calibration curves of five components exhibited good linearity within the linear ranges (0.8-4.0 µg). The RSD of precision was 1.06%-1.21%, and the repeatability and stability tests were good. The results of cluster analysis showed that the APR from 12 different areas was divided into two categories, and at the same time, it was found that the quality of Dazhou in Sichuan and Huating in Gansu was better than in other areas. In this study, a simple, rapid, and efficient method for quality evaluation of TCM was established by the HPTLC method.

Embryonic exposure to selenium nanoparticles delays growth and hatching in the freshwater snail Lymnaea stagnalis.

Selenium nanoparticles (SeNPs) have been applied in the biomedical and biocidal domain which may have potential environmental risks for aquatic systems. However, the knowledge of its toxicity and the role of functionalization on aquatic invertebrates are scarce. Thus, the present study aimed to analyze the embryotoxicity of two types of SeNPs coated with Sodium carboxymethyl cellulose (CMC-SeNPs) and Chitosan (CS-SeNPs) to the freshwater snail Lymnaea stagnalis in lake water, focusing on embryonic development. The influence of surface coatings and ions release, on the embryonic development of SeNPs to freshwater snail L. stagnalis was investigated. For this end, the snails were exposed to different concentrations of SeNPs and Se ions (0.05-1 mg L-1) during 7 days and multiple endpoints were analyzed, including developmental stage frequency, morphological alterations, embryos mortality and hatching success. The results showed that both Se forms promoted the developmental delay, mortality, morphological changes, and hatching inhibition in snail embryos in a concentration-dependent manner. CMC-SeNPs are 2.6 times more embryotoxic compared to CS-SeNPs indicating the importance of surface coating on the embryotoxicity. Moreover, the results revealed that although both forms of Se inhibited the embryo development and reduced the hatching of L. stagnalis, the mode of action on the embryogenesis was different. SeNPs had a higher toxicity to snails' embryos compared to their dissolved counterparts. Despite significant dissolution, by comparing the SeNPs with their dissolved fraction, the results suggest SeNPs inhibition effect on the snail development could be caused by both SeNPs and Se4+, and SeNPs might be the major development retardation driver rather than Se ions. The present study evidenced by the first time the toxicity effects of SeNPs on the snail embryogenesis, and highlighted how SeNPs intrinsic properties influence their transformation and toxicity in environmental relevant scenarios.

The Dynamic Accumulation Rules of Chemical Components in Different Medicinal Parts of Angelica sinensis by GC-MS.

The chemical components and medicinal properties of different medicinal parts of Angelica sinensis are often used as medicine after being divided into the head, body and tail of Angelica sinensis. In this study, the chemical components of different medicinal parts in different periods were analyzed by GC-MS for the first time, and the differences of the accumulation rules of chemical components in different medicinal parts of Angelica sinensis were obtained. This study demonstrated that the differences of composition accumulation in different medicinal parts of Angelica sinensis were mainly reflected in the types and relative contents of compounds. The study found that the number of compounds in different medicinal parts of Angelica sinensis in each period were different and the change rules of the same compound in different medicinal parts were also different. The number of compounds in the tail of Angelica sinensis was the least in April, and the largest in October. The content of ligustilide in the body of Angelica sinensis was higher in April and was the highest in the tail in October. The relative content of butylidenephthalide in the head was the highest in October. The relative contents of senkyunolide A and butylphthalide in the head were decreased in October, while the contents in the body and tail increased, indicating that the compounds that accumulate in the head may transfer to the body and tail in later stages of growth. This study clarified the differences in the accumulation of chemical components in different medicinal parts of Angelica sinensis, which could provide a theoretical basis for the reasons for the differences of chemical components in the different medicinal parts.

Trifluoperazine Synergistically Potentiates Bortezomib-Induced Anti-Cancer Effect in Multiple Myeloma via Inhibiting P38 MAPK/NUPR1.

Multiple myeloma (MM) is a common hematological malignancy. Bortezomib (BTZ) is a traditional medicine for MM treatment, but there are limitations for current treatment methods. Trifluoperazine (TFP) is a clinical drug for acute and chronic psychosis therapy. Lately, researchers have found that TFP can suppress tumor growth in many cancers. We attempted to study the effects of BTZ and TFP on MM in vivo and in vitro. We concentrated on the individual and combined impact of BTZ and TFP on the proliferation and apoptosis of MM cells via Cell Counting kit-8 assay, EdU assay, western blot, and flow cytometry. We found that combination therapy has a strong synergistic impact on MM cells. Combination therapy could induce cell arrest during G2/M phase and induce apoptosis in MM cells. Meanwhile, BTZ combined with TFP could play a better role in the anti-MM effect in vivo through MM.1s xenograft tumor models. Furthermore, we explored the mechanism of TFP-induced apoptosis in MM, and we noticed that TFP might induce MM apoptosis by inhibiting p-P38 MAPK/NUPR1. In summary, our findings suggest that TFP could synergistically enhance the BTZ-induced anti-cancer effect in multiple myeloma, which might be a promising therapeutic strategy for MM treatment.

Stability and surface properties of selenium nanoparticles coated with chitosan and sodium carboxymethyl cellulose.

The effect of polysaccharide coatings on the stability and release characteristics of selenium nanoparticles (SeNPs) was evaluated by comparing the characteristics of chitosan-coated SeNPs (CS-SeNPs) and sodium carboxymethyl cellulose-coated SeNPs (CMC-SeNPs). The release characteristics of SeNPs were investigated in storage conditions, gastrointestinal conditions, and free radical systems. CMC-SeNPs formed dimers or trimers, whereas CS-SeNPs were monodispersed but formed large aggregates in a pH range of 7.4-8.25. Upon 50 days of storage at 30 °C, both CMC-SeNPs and CS-SeNPs were converted to Se4+. SeNPs exhibited a lower release rate in simulated gastrointestinal conditions than in free radical systems. SeNPs release in ABTS and superoxide anion free radical systems followed the first-order and Korsmeyer-Peppas models, respectively, indicating that SeNP release is mainly governed by dissolution mechanisms. Additional studies are needed to examine the potential environmental effects and biological activity of the Se4+ released from SeNPs.

Simultaneous Determination of Five Coumarins in Peucedanum Decursivum Radix by UPLC.

OBJECTIVE: To establish an ultra-high performance liquid chromatography (UPLC) method for simultaneous determination of umbelliferonel, nodakenin, psoralen, xanthotoxin and bergapten contents in Peucedanum decursivum Radix. METHODS: The analysis was achieved on a Symmetry®C18 column (4.6 mm × 250 mm, 5 µm), with acetonitrile and water as the mobile phase in gradient elution mode. The column temperature was maintained at 30°C, with flow rate 1.0 mL·min-1. The injection volume of sample was 10 µL. The ultraviolet detection wavelength was set at the maximum absorption wavelength 325 nm for umbelliferonel and nodakenin, 259 nm for psoralen, xanthotoxin and bergapten, respectively. RESULTS: The five kinds of coumarins in Peucedanum decursivum Radix were separated well and the linear relation was obtained (R2 ≥ 0.9998). The average recoveries were 101.31, 105.27, 90.85, 106.42 and 90.19%, respectively, with Relative standard deviation (RSD) 3.07, 3.17, 1.62, 2.53 and 4.54%, respectively. CONCLUSIONS: The established method was accurate and feasible, which could be used as the basis of quality control of Peucedanum decursivum Radix.

Ginsenoside Rd: A promising natural neuroprotective agent.

BACKGROUND: Neurological diseases seriously affect human health, which are arousing wider attention, and it is a great challenge to discover neuroprotective drugs with minimal side-effects and better efficacies. Natural agents derived from herbs or plants have become unparalleled resources for the discovery of novel drug candidates. Panax ginseng C. A. Meyer, a well-known herbal medicine in China, occupies a very important position in traditional Chinese medicines (TCMs) with a long history of clinical application. Ginsenoside Rd is the active compound in P. ginseng known to have broad-spectrum pharmacological effects to reduce neurological damage that can lead to neurological diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, depression, cognitive impairment, and cerebral ischemia. PURPOSE: To review and discuss the effects and mechanisms of ginsenoside Rd in the treatment of neurological diseases. STUDY DESIGN & METHODS: The related information was compiled by the major scientific databases, such as Chinese National Knowledge Infrastructure (CNKI), Elsevier, ScienceDirect, PubMed, SpringerLink, Web of Science, and GeenMedical. Using 'Ginsenoside Rd', 'Ginsenosides', 'Anti-inflammation', 'Antioxidant', 'Apoptosis' and 'Neuroprotection' as keywords, the correlated literature was extracted and conducted from the databases mentioned above. RESULTS: Through summarizing the existing research progress, we found that the general effects of ginsenoside Rd are anti-inflammatory, antioxidant, anti-apoptosis, inhibition of Ca2+ influx and protection of mitochondria, and through these pathways, the compound can inhibit excitatory toxicity, regulate nerve growth factor, and promote nerve regeneration. CONCLUSION: Ginsenoside Rd is a promising natural neuroprotective agent. This review would contribute to the future development of ginsenoside Rd as a novel clinical candidate drug for treating neurological diseases.

Toxicity of selenium nanoparticles on Poterioochromonas malhamensis algae in Waris-H culture medium and Lake Geneva water: Effect of nanoparticle coating, dissolution, and aggregation.

Understanding the algal toxicity of selenium nanoparticles (SeNPs) in aquatic systems by considering SeNPs physicochemical properties and environmental media characteristics is a concern of high importance for the evaluation and prediction of risk assessment. In this study, chitosan (CS) and sodium carboxymethyl cellulose (CMC) coated SeNPs are considered using Lake Geneva water and a Waris-H cell culture medium to investigate the effect of SeNPs on the toxicity of algae Poterioochromonas malhamensis, a widespread mixotrophic flagellate. The influence of surface coating, z-average diameters, ζ-potentials, aggregation behavior, ions release, and medium properties on the toxicity of SeNPs to algae P. malhamensi was investigated. It is found that SeNPs are 5-10 times more toxic in Lake Geneva water compared to the culture medium, suggesting that the traditional algal tests in Waris-H culture medium currently underestimate the toxicity of NPs in a natural water environment. Despite significant dissolution, it is also found that SeNPs themselves are the toxicity driver, and dissolved ions have only a marginal influence on toxicity. SeNPs diameter is found a minor factor in toxicity. Based on a principal component analysis (PCA) it is found that in Lake Geneva water, the nature of the surface coating (CMC versus CS) is the most influential factor controlling the toxicity of SeNPs. In the culture medium, surface coating, ζ-potential, and aggregation are found to contribute at the same level. These results highlight the importance of considering in details both NPs intrinsic and media properties in the evaluation of NPs biological effects.

Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Liuwei Dihuang Decoction Against Intervertebral Disc Degeneration.

PURPOSE: To explore the pharmacological mechanisms of Liuwei Dihuang Decoction (LWDHD) against intervertebral disc (IVD) degeneration (IVDD) via network pharmacology analysis combined with experimental validation. METHODS: First, active ingredients and related targets of LWDHD, as well as related genes of IVDD, were collected from public databases. The protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed to predict the core targets and pathways of LWDHD against IVDD. Secondly, the IVDD model of mice treated with LWDHD was selected to validate the major targets predicted by network pharmacology. RESULTS: By searching the intersection of the active ingredient targets and IVDD targets, a total of 110 targets matched the related targets of 30 active ingredients in LWDHD and IVDD were retrieved. PPI network analysis indicated that 17 targets, including Caspase-3, IL-1ß, P53, etc., were hub targets. GO and KEGG enrichment analyses showed that the apoptosis pathway was enriched by multiple targets and served as the target for in vivo experimental study validation. The results of animal experiments revealed that LWDHD administration not only restored the decrease in disc height and abnormal degradation of matrix metabolism in IVDD mice but also reversed the high expression of Bax, Caspase-3, IL-1ß, P53, and low expression of Bcl-2, thereby inhibiting the apoptosis of IVD tissue and ameliorating the progression of IVDD. CONCLUSION: Using a comprehensive network pharmacology approach, our findings predicted the active ingredients and potential targets of LWDHD intervention for IVDD, and some major target proteins involved in the predictive signaling pathway were validated experimentally, which gave us a new understanding of the pharmacological mechanism of LWDHD in treating IVDD at the comprehensive level.

Natural products are an important source for proteasome regulating agents.

BACKGROUND: Natural medicines have a long history in the prevention and treatment of various diseases in East Asian region, especially in China. Modern research has proved that the pharmacological effects of numerous natural medicines involve the participation of ubiquitin proteasome system (UPS). UPS can degrade the unwanted and damaged proteins widely distributed in the nucleus and cytoplasm of various eukaryotes. PURPOSE: The objective of the present study was to review and discuss the regulatory effects of natural products and extracts on proteasome components, which may help to find new proteasome regulators for drug development and clinical applications. METHODS: The related information was compiled using the major scientific databases, such as CNKI, Elsevier, ScienceDirect, PubMed, SpringerLink, Wiley Online, and GeenMedical. The keywords "natural product" and "proteasome" were applied to extract the literature. Nature derived extracts, compounds and their derivatives involved in proteasome regulation were included, and the publications related to synthetic proteasome agents were excluded. RESULTS: The pharmacological effects of more than 80 natural products and extracts derived from phytomedicines related to the proteasome regulation were reviewed. These natural products were classified according to their chemical properties. We also summarized some laws of action of natural products as proteasome regulators in the treatment of diseases, and listed the action characteristics of the typical natural products. CONCLUSION: Natural products derived from nature can induce the degradation of damaged proteins through UPS or act as regulators to directly regulate the activity of proteasome. But few proteasome modulators are applied clinically. Summary of known rules for proteasome modulators will contribute to discover, modify and synthesize more proteasome modulators for clinical applications.

Multi-intervention integrated deworming strategy for sustained control of soil-transmitted helminths infections: a case study in Jiangsu Province, China.

BACKGROUND: Soil-transmitted helminths (STH) infections still present a global health problem. Mass drug administration (MDA) is a widely applied strategy to reduce morbidity and mortality caused by STH. Yet, this approach has some shortcomings. In this study, we analyzed the impact of a multi-intervention integrated deworming approach including MDA, health education (HE), and environmental sanitation improvements (ESI) for sustained STH control in Jiangsu Province of China that was applied from 1989 to 2019. METHODS: Data, including infection rate of STH, medications used, coverage of the medication, non-hazardous lavatory rate, and household piped-water access rate in rural areas, and actions related to HE and ESI were collected (from archives) and analyzed in this retrospective descriptive study. Pearson's correlation analysis was applied to test correlations. RESULTS: There was a dramatic decline in the infection rate of STH from 1989 (59.32%) to 2019 (0.12%). From 1995 to 1999, MDA and HE were recommended in rural areas. A negative correlation was observed between infection rate and medication from 1994 to 1998 (r = - 0.882, P = 0.048). From 2000 to 2005, targeted MDA was given to high-risk populations with HE continuously promoting good sanitation behaviors. From 2006 to 2014, targeted MDA + HE and ESI were used to consolidate the control effect. ESI was strengthened from 2006, and a negative correlation was observed between the coverage rate of the non-hazardous lavatory and the infection rate from 2006 to 2019 (r = - 0.95, P < 0.001). The targeted MDA was interrupted in 2015, while continuous efforts like HE and ESI contributed in sustaining STH control. CONCLUSIONS: Multi-intervention integrated deworming strategy contributes to the reduction of STH infections. This approach is a valuable example of how different interventions can be integrated to promote durable STH control.

The Role of Autophagy in Anti-Cancer and Health Promoting Effects of Cordycepin.

Cordycepin is an adenosine derivative isolated from Cordyceps sinensis, which has been used as an herbal complementary and alternative medicine with various biological activities. The general anti-cancer mechanisms of cordycepin are regulated by the adenosine A3 receptor, epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs), and glycogen synthase kinase (GSK)-3ß, leading to cell cycle arrest or apoptosis. Notably, cordycepin also induces autophagy to trigger cell death, inhibits tumor metastasis, and modulates the immune system. Since the dysregulation of autophagy is associated with cancers and neuron, immune, and kidney diseases, cordycepin is considered an alternative treatment because of the involvement of cordycepin in autophagic signaling. However, the profound mechanism of autophagy induction by cordycepin has never been reviewed in detail. Therefore, in this article, we reviewed the anti-cancer and health-promoting effects of cordycepin in the neurons, kidneys, and the immune system through diverse mechanisms, including autophagy induction. We also suggest that formulation changes for cordycepin could enhance its bioactivity and bioavailability and lower its toxicity for future applications. A comprehensive understanding of the autophagy mechanism would provide novel mechanistic insight into the anti-cancer and health-promoting effects of cordycepin.

Extraction and Analysis of Six Effective Components in Glycyrrhiza uralensis Fisch by Deep Eutectic Solvents (DES) Combined with Quantitative Analysis of Multi-Components by Single Marker (QAMS) Method.

Deep eutectic solvents (DESs) are green organic solvents that have broad prospects in the extraction of effective components of traditional Chinese medicine. This work employed the quantitative analysis of multi-components by a single marker (QAMS) method to quantitatively determine the six effective components of glycyrrhizic acid, liquiritin, isoliquiritin apioside, liquiritigenin, isoliquiritin, and glycyrrhetinic acid in Glycyrrhiza uralensis, which was used for comprehensive evaluation of the optimal extraction process by DESs. First, Choline Chloride: Lactic Acid (ChCl-LA, molar ratio 1:1) was selected as the most suitable DES by comparing the extraction yields of different DESs. Second, the extraction protocol was investigated by extraction time, extraction temperature, liquid-to-material ratio, molar ratio, and ultrasonic power. The Box-Behnken design (BBD) combined with response surface methodology (RSM) was used to investigate the optimal DES conditions. The result showed that the best DES system was 1.3-butanediol/choline chloride (ChCl) with the molar ratio of 4:1. The optimal extraction process of licorice was 20 mL/g, the water content was 30%, and the extraction time was 41 min. The comprehensive impact factor (z) was 0.92. At the same time, it was found that the microstructure of the residue extracted by the eutectic solvent was more severely damaged than the residue after the traditional solvent extraction through observation under an electron microscope. The DES has the characteristics of high efficiency and rapidity as an extraction solution.

Aidi injection induces apoptosis of hepatocellular carcinoma cells through the mitochondrial pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence and mortality rates of hepatocellular carcinoma are very high all over the world, which seriously threatens human life and health. Aidi injection as a Chinese medicine preparation has a positive curative effect on hepatocellular carcinoma, but its mechanism remains unclear. AIM OF THE STUDY: The purpose of this study is to evaluate the anti-hepatocellular carcinoma effects of Aidi injection and explore its mechanism of action vitro and vivo. MATERIALS AND METHODS: The main components of Aidi injection were determined by LC-MS/MS. The effects of Aidi injection on the viability of HepG2 and PLC/PRF/5 cells were detected via CCK-8 analysis and Calcein AM/PI staining. DAPI staining and flow cytometry were applied to analyze the apoptosis-induced effects of Aidi injection on hepatocellular carcinoma cells (HCCs). The growth inhibition of Aidi injection on hepatocellular carcinoma was observed in nude mice bearing PLC/PRF/5 cells. The related signal transduction and apoptosis pathways were investigated through assays for JC-1 mitochondrial membrane potential (MMP), RNA-seq, KEGG, PPI and WB. RESULTS: There were 12 main chemical components contained in Aidi injection, viz. cantharidin, syringin, calycosin-7-o-ß-Dglucoside, isozinpidine, ginsenosides Rd, Rc, Rb1, Re, and Rg1, astragalosides II and IV, and eleutheroside E. Aidi injection significantly inhibited the proliferation of HepG2 and PLC/PLF/5 cells with IC50 of 20.66 mg/ml and 27.5 mg/ml at 48h, respectively, increased the proportion of dead cells, induced cell apoptosis, suppressed the tumor growth of nude mice bearing PLC/PLF/5 cells, reduced MMP, activated PI3K/Akt and MAPK signal transduction pathways, down-regulated the expression of p-PI3K and Bcl-xL, and up-regulated the expression of p-JNK, p-p38 and Bim. CONCLUSION: Aidi injection inhibits the growth of liver cancer probably through regulating PI3K/Akt and MAPK signal transduction pathways, inducing MMP collapse to activate the mitochondrial apoptosis pathway, and then eliciting apoptosis of HCCs.

Mindfulness-based interventions for breast cancer patients in China across outcome domains: a systematic review and meta-analysis of the Chinese literature.

OBJECTIVE: This study aims to evaluate the treatment effect of a mindfulness-based intervention for Chinese breast cancer patients across outcome domains, including symptom-related, psychosocial, and quality of life outcomes. METHODS: Following the Cochrane Systematic Review guideline, we searched across five electronic databases, reference lists of eligible studies, professional websites, and major academic journals in Chinese. Publication bias was assessed using funnel plot and Vevea and Woods sensitivity analysis, and risk of bias was evaluated using the revised Cochrane risk of bias tool for randomized trials and risk of bias in non-randomized studies of interventions. A meta-analysis of Hedges' g was conducted using meta-regression with robust variance estimation. RESULTS: Final analysis included a total of 45 controlled trials containing 286 effect size estimates. Across outcome domains, studies reported an overall large and statistically significant treatment effect, d = 0.921, 95% CI (0.805, 1.040), p < 0.001. Subgroup analyses of specific domains of outcome reported overall significant treatment effects for (1) symptom-related outcomes, d = 0.885, 95% CI (0.657, 1.110), p < 0.001; (2) psychosocial wellness outcomes, d = 0.984, 95% CI (0.879, 1.090), p < 0.001; and (3) quality of life, d = 0.990, 95% CI (0.776, 1.200), p < 0.001. Moderator analysis did not identify any significant moderator. CONCLUSION: Chinese literature reported an overall statistically significant and large treatment effect of a mindfulness-based intervention for breast cancer patients in China. Except for physical symptom outcomes, e.g., nausea/vomiting and pain, a mindfulness-based intervention was effective across outcome domains among Chinese breast cancer patients.