Fufang Luohanguo Qingfei granules reduces influenza virus susceptibility via MAVS-dependent type I interferon antiviral signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Luohanguo Qingfei granules (LQG) is a Chinese patent medicine, clinically used to treat flu-like symptoms including cough with yellow phlegm, impeded phlegm, dry throat and tongue. However, the protective activity of LQG against influenza infection is indeterminate. AIM OF THE STUDY: This study is to investigate the therapeutic effect of LQG on influenza infection and elucidate its underlying mechanism. MATERIALS AND METHODS: In vivo: A viral susceptible mouse model induced by restraint stress was established to investigate LQG's beneficial effects on influenza susceptibility. MAVS knockout (Mavs-/-) mice were used to verify the potential mechanism of LQG. In vitro: Corticosteroid (CORT)-treated A549 cells were employed to identify the active ingredients in LQG. Mice morbidity and mortality were monitored daily for 21 days. Histopathologic changes and inflammatory cytokines in lung tissues were examined by H&E staining and ELISA. RNA-seq was used to explore the signaling pathway influenced by LQG and further confirmed by qPCR. Immunoblotting and immunohistochemistry (IHC) were used to determine the protein levels. CO-IP and DARTS were applied to detect protein-protein interaction and compound-protein interaction, respectively. RESULTS: LQG effectively attenuated the susceptibility of restrained mice to H1N1 infection. LQG significantly boosted the production of IFN-ß transduced by mitochondrial antiviral-signaling protein (MAVS), while MAVS deficiency abrogated its protective effects on restrained mice infected with H1N1. Moreover, in vitro studies further revealed that mogroside Ⅱ B, amygdalin, and luteolin are potentially active components of LQG. CONCLUSION: These results suggested that LQG inhibited the mitofusin 2 (Mfn2)-mediated ubiquitination of MAVS by impeding the E3 ligase synoviolin 1 (SYVN1) recruitment, thereby enhancing IFN-ß antiviral response. Overall, our work elaborates a potential regimen for influenza treatment through reduction of stress-induced susceptibility.

Effect of acupuncture combined with antidepressants on post-stroke depression: A network meta-analysis of nine acupuncture therapy.

Background: Post-stroke depression (PSD) is a common psychiatric complication of mental disorders after stroke. Acupuncture for PSD is effective and has few adverse effects. As a classical complementary and alternative therapy, acupuncture is often used in combination with antidepressants for PSD. However, there is a wide variety of acupuncture therapies, and the efficacy of different acupuncture varies. In this study, a network meta-analysis (NMA) was used to assess the clinical efficacy of different acupuncture combined with antidepressants for the treatment of PSD. Methods: A comprehensive search of PubMed, The Cochrane Library, EMbase, Web of Science, CNKI, CBM, VIP, and Wan-Fang databases for published randomized controlled trials of acupuncture combined with antidepressants for the treatment of PSD was conducted. The time frame for the literature search was from the date of database creation to April 30, 2022. The Cochrane risk of bias tool for randomized trials (RoB 2.0) was used to evaluate the bias risk of the included studies. Data analysis was performed by STATA 14.0 software. Results: A total of 38 literatures with 2,898 patients involving nine acupuncture therapies were included. NMA results were as follows: moxibustion plus antidepressants had the best efficacy in terms of improving total effective rate. Conventional acupuncture plus antidepressants was the most effective in improving HAMD scores. In terms of improving SDS scores, acupressure plus antidepressants was the most effective. In terms of improving NIHSS scores, moxibustion plus antidepressants showed the best results. Conclusion: A comparison of the efficacy indicators of the nine different acupuncture therapies combined showed that moxibustion plus antidepressants, conventional acupuncture plus antidepressants and acupressure plus antidepressants were superior in the treatment of PSD. Based on the shortcomings of the existing studies, this conclusion needs to be validated by additional high-quality randomized controlled trials.

A Phytophthora infestans RXLR effector AVR8 suppresses plant immunity by targeting a desumoylating isopeptidase DeSI2.

The potato's most devastating disease is late blight, which is caused by Phytophthora infestans. Whereas various resistance (R) genes are known, most are typically defeated by this fast-evolving oomycete pathogen. However, the broad-spectrum and durable R8 is a vital gene resource for potato resistance breeding. To support an educated deployment of R8, we embarked on a study on the corresponding avirulence gene Avr8. We overexpressed Avr8 by transient and stable transformation, and found that Avr8 promotes colonization of P. infestans in Nicotiana benthamiana and potato, respectively. A yeast-two-hybrid (Y2H) screen showed that AVR8 interacts with a desumoylating isopeptidase (StDeSI2) of potato. We overexpressed DeSI2 and found that DeSI2 positively regulates resistance to P. infestans, while silencing StDeSI2 downregulated the expression of a set of defense-related genes. By using a specific proteasome inhibitor, we found that AVR8 destabilized StDeSI2 through the 26S proteasome and attenuated early PTI responses. Altogether, these results indicate that AVR8 manipulates desumoylation, which is a new strategy that adds to the plethora of mechanisms that Phytophthora exploits to modulate host immunity, and StDeSI2 provides a new target for durable resistance breeding against P. infestans in potato.

Pulmonary artery catheter usage in diagnosis of Shoshin beriberi presented with unexplained lactic acidosis.

Wet beriberi is a rare but fatal disease in modern society. The nonspecific clinical manifestations, including symptoms of heart failure and recalcitrant lactic acidosis, can prevent timely diagnosis. The use of a pulmonary artery catheter can promptly confirm a high cardiac output state and plays a crucial role in rapidly deteriorating cases. Appropriate treatment with intravenous administration of thiamine leads to dramatic recovery within hours. We present two cases of Shoshin beriberi, a fulminant variant of wet beriberi, diagnosed in 2016 and 2022 at our institute. The patients experienced haemodynamic collapse and refractory lactic acidosis, which were successfully diagnosed with the use of a pulmonary artery catheter and reversed by thiamine supplementation. We also reviewed 19 cases of wet beriberi reported between 2010 and 2022.

Evaluation of Taraxacum mongolicum flavonoids in diets for Channa argus based on growth performance, immune responses, apoptosis and antioxidant defense system under lipopolysaccharide stress.

To ascertain the effects of Taraxacum mongolicum flavonoids (TMF) on the growth performance, digestive enzyme activity, immune indices, inflammatory response and antioxidant capacity of Channa argus, 400 C. argus with an average body weight of (8.08 ± 0.21) g were selected and divided randomly into four groups. They were fed with four experimental diets supplemented with TMF of 0 (control), 25, 50 and 100 mg/kg for 56 d, and then challenged with lipopolysaccharide (LPS) for 96 h, afterwards indices were detected. The results manifested that the addition of TMF above 50 mg/kg in the dietary could significantly improve the final body weight, WGR, SGR and PER of C. argus, while decreased FCR (P < 0.05). Similarly, the 50 mg/kg group had the highest activity of digestive enzymes (protease, lipase, amylase) in intestine and hepatopancreas, which were notably higher than those in the control group (P < 0.05). Nevertheless, 100 mg/kg group could effectively inhibit the liver and gut injury caused by LPS and reduce the contents of ALT and AST, LPS and LBP in serum. In the immune (LY, AKP, ACP, IgM, C3) and antioxidant (T-AOC, SOD, CAT, GSH-PX, GR, ASA, MDA) systems, 100 mg/kg groups were the optimal group, which were remarkably higher than those of the control group (P < 0.05). Additionally, the expression of genes revealed that 100 mg/kg group could noteworthy restrain the expression of pro-inflammatory factors (tnf-α, il-1ß, il-8) and pro-apoptosis (cas-3,8,9, p53, bax, bcl-2) related genes, up-regulate the expression of anti-inflammatory (il-10, tgf-ß) factors, antioxidant-related (nrf2, gpx, gst, cat) genes and heat shock proteins (hsp70, hsp90). Simultaneously, the survival rate of C. argus in the 100 mg/kg TMF-supplemented group was the highest after LPS challenge. Our results elucidate that dietary supplementation TMF protects C. argus from LPS-induced inflammatory injury, to ameliorate digestion, immune response, antioxidant status and apoptosis, implying that TMF could be regarded as an anti-inflammatory and antioxidant agent adding to aquatic animal feed.

Myricetin inhibits interferon-γ-induced PD-L1 and IDO1 expression in lung cancer cells.

Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints induced by interferon-γ (IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. In this study, MY was identified to inhibit IFN-γ-induced PD-L1 expression in human lung cancer cells. It also reduced the expression of IDO1 and the production of kynurenine which is the product catalyzed by IDO1, while didn't show obvious effect on the expression of major histocompatibility complex-I (MHC-I), a crucial molecule for antigen presentation. In addition, the function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line overexpressing PD-1. MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. Together, our research revealed a new mechanism of MY mediated anti-tumor activity and highlighted the potential implications of MY in tumor immunotherapy.

Identification of AHSA1 as a Potential Therapeutic Target for Breast Cancer: Bioinformatics Analysis and in vitro Studies.

BACKGROUND: Shenling Baizhu Powder (SBP), a famous Traditional Chinese Medicine (TCM) formulation, has been widely used in the adjuvant treatment of cancers, including breast cancer. This study aims to identify potential new targets for breast cancer treatment based on the network pharmacology of SBP. METHODS: By analyzing the relationship between herbs and target proteins, potential targets of multiple herbs in SBP were identified by network pharmacology analysis. Besides, by comparing the data of breast cancer tissue with normal tissue, upregulated genes in two breast cancer expression profiles were found. Thereafter, the expression level and prognosis of activator of heat shock protein 90 (HSP90) ATPase activity 1 (AHSA1) were further analyzed in breast cancer by bioinformatics analysis, and the network module of AHSA1 binding protein was constructed. Furthermore, the effect of knocking down AHSA1 on the proliferation, migration, and invasion of breast cancer cells was verified by MTT, clone formation assay, and transwell assay. RESULTS: Vascular endothelial growth factor A (VEGFA), intercellular adhesion molecule 1 (ICAM1), chemokine (C-X-C motif) ligand 8 (CXCL8), AHSA1, and serpin family E member 1 (SERPINE1) were associated with multiple herbs in SBP. AHSA1 was remarkably upregulated in breast cancer tissues and positively correlated with poor overall survival and disease metastasis- free survival. Furthermore, knockdown of AHSA1 significantly inhibited the migration and invasion in MCF-7 and MDA-MB-231 breast cancer cells but had no obvious effect on proliferation. In addition, among the proteins that bind to AHSAl, the network composed of proteasome, chaperonin, and heat shock proteins is closely connected, and these proteins are associated with poor prognosis in a variety of cancers. CONCLUSION: AHSA1 is positively correlated with breast cancer progression and might act as a novel therapeutic target for breast cancer.

Polysaccharide from dandelion enriched nutritional composition, antioxidant capacity, and inhibited bioaccumulation and inflammation in Channa asiatica under hexavalent chromium exposure.

Taraxacum mongolicum polysaccharide (TMP) exhibits anti-inflammatory and antioxidant activity, making it an attractive candidate for aquatic-product-safety applications. Here, this study was aimed to investigate the effects of dietary TMP on the growth, nutritional composition, antioxidant capacity, bioaccumulation and inflammation in Channa asiatica under hexavalent chromium stress. The C. asiatica was randomly distributed into five groups: The first group served as the blank control group (CK), the subsequent groups were fed TMP-supplemented feed (0, 0.5, 1.0 and 2.0 g/kg), respectively, and exposed to waterborne Cr6+ for 28 days. Our results indicated that the TMP effectively increased (P < 0.05) C. asiatica muscle flavour amino acid, total free amino acids, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and EPA + DHA contents, enhanced positively antioxidant enzyme activity (GPX, SOD, CAT, T-AOC), reduced oxidative stress parameters (MDA, PC), and up-regulated antioxidant-related genes mRNA expression. Meanwhile, the appropriate amount of TMP supplementation also inhibited the bioaccumulation of Cr6+ in tissues and alleviated the inflammatory response (P < 0.05). Furthermore, sensory evaluation implied that the overall score of sashimi and cooked fillet in the 2.0 g/kg TMP group was the highest in the experimental group, second only to CK. In brief, these results elucidate that TMP-supplemented diets excellently ameliorated the growth, enriched nutritional composition and antioxidant capacity, and inhibited bioaccumulation and inflammation in C. asiatica exposed to waterborne Cr6+.

Delineating the Decussating Dentato-rubro-thalamic Tract and Its Connections in Humans Using Diffusion Spectrum Imaging Techniques.

The objective of this study was to identify the decussating dentato-rubro-thalamic tract (d-DRTT) and its afferent and efferent connections in healthy humans using diffusion spectrum imaging (DSI) techniques. In the present study, the trajectory and lateralization of the d-DRTT was explored using data from subjects in the Massachusetts General Hospital-Human Connectome Project adult diffusion dataset. The afferent and efferent networks that compose the cerebello-thalamo-cerebral pathways were also reconstructed. Correlation analysis was performed to identify interrelationships between subdivisions of the cerebello-dentato-rubro-thalamic and thalamo-cerebral connections. The d-DRTT was visualized bilaterally in 28 subjects. According to a normalized quantitative anisotropy and lateralization index evaluation, the left and right d-DRTT were relatively symmetric. Afferent regions were found mainly in the posterior cerebellum, especially the entire lobule VII (crus I, II and VIIb). Efferent fibers mainly are projected to the contralateral frontal cortex, including the motor and nonmotor regions. Correlations between cerebello-thalamic connections and thalamo-cerebral connections were positive, including the lobule VIIa (crus I and II) to the medial prefrontal cortex (MPFC) and the dorsolateral prefrontal cortex and lobules VI, VIIb, VIII, and IX, to the MPFC and motor and premotor areas. These results provide DSI-based tratographic evidence showing segregated and parallel cerebellar outputs to cerebral regions. The posterior cerebellum may play an important role in supporting and handling cognitive activities through d-DRTT. Future studies will allow for a more comprehensive understanding of cerebello-cerebral connections.

Effects of dietary Astragalus Propinquus Schischkin polysaccharides on growth performance, immunological parameters, antioxidants responses and inflammation-related gene expression in Channa argus.

The present study investigated the effects of dietary Astragalus Propinquus schischkin polysaccharides on growth, immune responses, antioxidants responses and inflammation-related genes expression in Channa argus. Channa argus were randomly divided into 5 groups and fed 5 levels diets of A. propinquus schischkin polysaccharides (0, 250, 500, 1000 and 2000 mg/kg) for 56 days. The results showed, dietary A. propinquus schischkin polysaccharides addition can increase the final body weight, weight gain and specific growth rate, decrease the feed conversion ratio of Channa argus. And dietary A. propinquus schischkin polysaccharides supplementation can increase the levels of serum superoxide dismutase, catalase, glutathione peroxidase, lysozyme, complement 3, complement 4, immunoglobulin M and alkaline phosphatase, decrease the levels of serum malondialdehyde, cortisol, aspartate aminotransferase and glutamic-pyruvic transaminase. Furthermore, dietary A. propinquus schischkin polysaccharides can decrease the gene expression levels of interleukin-1ß, interleukin-, tumor necrosis factor-α and nuclear factor-κB, increase the gene expression levels of glucocorticoid receptor in liver, spleen, kidney, intestine. To sum up, dietary A. propinquus schischkin polysaccharides can accelerate growth, enhance immune responses and antioxidants responses, regulate inflammation-related genes expression in Channa argus and the optimum amount is 1000 mg/kg.

Vitamin D and Polycystic Ovary Syndrome: a Narrative Review.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders of reproductive age women and contributes to metabolic dysfunctions including insulin resistance (IR) and dyslipidemia. Vitamin D is a steroid hormone, which is involved in calcium metabolism and bone structure and has a potential role in the prevention of many illnesses, including cancers, autoimmune disorders, hypertension, diabetes, and obesity. Recently, it has been reported that vitamin D deficiency was a common complication of PCOS and vitamin D status was associated with reproductive ability, metabolic alterations, and mental health of PCOS patients. This review summarizes the advances between vitamin D status and the pathophysiological process of PCOS. Vitamin D level was negatively associated with serum androgen level. Vitamin D treatment could reduce serum androgen and anti-MüllerianHormone (AMH) levels, and decrease endometrial thickness, which resulted in improvement of menstrual cycle and folliculogenesis of PCOS patients. Moreover, vitamin D concentrations were negatively correlated with parameters of IR and body fat mass. Vitamin D supplementation has beneficial effects on IR and lipid metabolism. In addition, a positive of vitamin D on mental health of PCOS patients was proposed. Understanding the relationship between vitamin D status and the symptoms of PCOS patients is of great clinical significance to treat and prevent the progression of PCOS.

Licochalcone A inhibits interferon-gamma-induced programmed death-ligand 1 in lung cancer cells.

BACKGROUND: Programmed death-ligand 1 (PD-L1), which can be induced by interferon-gamma (IFN-γ) in the tumor microenvironment, is a critical immune checkpoint in cancer immunotherapy. Natural products which reduce IFN-γ-induced PD-L1 might be exert immunotherapy effect. Licochalcone A (LCA), a natural compound derived from the root of Glycyrrhiza inflata Batalin. (Fabaceae), was found to interfere IFN-γ-induced PD-L1. PURPOSE: The aim of this study is to further clarify the effect and the mechanism of LCA on inhibiting IFN-γ-induced PD-L1 in lung cancer cells. METHODS: The expression levels of PD-L1 were evaluated by flow cytometry, western blot and qRT-PCR. Click-iT protein synthesis assay and luciferase assay were used to identify the effect of LCA on protein synthesis. Jurkat T cell proliferation and apoptosis in the co-culture system were detected by flow cytometry. Flow cytometry was also applied to evaluate reactive oxygen species (ROS) generation. RESULTS: LCA downregulated IFN-γ-induced PD-L1 protein expression and membrane localization in human lung cancer cells, regardless of inhibiting PD-L1 mRNA level or promoting its protein degradation. LCA decreased apoptosis and proliferative inhibition of Jurkat T cells caused by IFN-γ-induced PD-L1-expressing in A549 cells in the co-culture system. Strikingly, LCA was verified as a protein synthesis inhibitor, which reduced both cap-dependent and -independent translation. LCA inhibited PD-L1 translation, likely due to inhibition of 4EBP1 phosphorylation (Ser 65) and activation of PERK-eIF2α pathway. Furthermore, LCA induced ROS generation in a time-dependent manner in lung cancer cells. N-acetyl-L-cysteine (NAC) not only revered ROS generation triggered by LCA but also restored IFN-γ-induced expression of PD-L1. Both the inhibition of 4EBP1 phosphorylation (Ser 65) and activation of PERK-eIF2α axis triggered by LCA was restored by co-treatment with NAC. CONCLUSION: LCA abrogated IFN-γ-induced PD-L1 expression via ROS generation to abolish the protein translation, indicating that LCA has the potential to be applied in cancer immunotherapy.

Myricetin inhibits interferon-γ-induced programmed death ligand-1 and indoleamine 2, 3-dioxygenase 1 expression in lung cancer cells / 中国药理学与毒理学杂志

OBJECTIVE Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints which can be induced by interferon-γ(IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells. METHODS Expressions of PD-L1 and major histocompatibility complex-I (MHC-I) were evaluated by flow cytometry and Western blotting, and the expression of IDO1 was measured by Western blotting. qRT-PCR was used to detect their mRNA levels. The function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line that overexpressing PD-1. Molecular docking analysis, Western blotting and immunofluorescence were used for mechanism study. RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells, while didn't show obvious effect on the expression of MHC-I. In addition, MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells in the co-culture system. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression, supporting the potential of MY in anti-tumor immunotherapy.

Amelioration of hexavalent chromium-induced bioaccumulation, oxidative stress, tight junction proteins and immune-related signaling factors by Allium mongolicum Regel flavonoids in Ctenopharyngodon idella.

Chromium (Cr) is the most common heavy metal and that becomes toxic when present at higher concentrations in aquatic environments. Allium mongolicum Regel flavonoids (AMRF) has been documented to possess detoxification, antioxidant and anti-inflammatory properties. The aim of this study was to explore the potential of dietary AMRF and Cr exposure on bioaccumulation, oxidative stress, and immune response in Ctenopharyngodon idella. After acclimation, 360 fish were randomly distributed into six groups. The fish were fed with diets supplemented with Cr and/or AMRF for 4 weeks (28 days), the Cr concentrations were 0, 120, and 240 mg/kg and the concentrations of AMRF were 0 or 40 mg/kg, respectively. The results shown that Cr accumulation in the kidney, liver, spleen, intestine and gill were significantly increased following Cr exposure, dietary AMRF supplementation attenuated the increased in Cr accumulation. Dietary AMRF supplementation significantly reduced the levels of malondialdehyde (MDA) and protein carbonyl (PC) in liver, spleen and gill compared with the same Cr dose groups. When fish were supplemented with AMRF significantly increased lysozyme activity (LZM), complement 3 (C3) in kidney and intestine compared with the same Cr dose groups. Serum glutamic oxalate transaminase (GOT) and glutamic pyruvate transaminase (GPT) were significantly increased following exposure to Cr. Dietary AMRF supplementation significantly decreased GOT and GPT activity in the serum. In addition, AMRF supplementation can decrease the expression of inflammatory (NF-κB p65, TNF-α and IL-1ß) and increased the expression of tight junction proteins (occludin and ZO-1) following Cr exposure in C. idella. These results indicate that AMRF has the potential to alleviate the effects of Cr toxicity in C. idella.

The effectiveness of cupping therapy on chronic fatigue syndrome: A single-blind randomized controlled trial.

BACKGROUND: and purpose: We investigated the effectiveness of cupping therapy with three different pressures in patients with chronic fatigue syndrome (CFS). MATERIALS AND METHODS: The participants were randomly assigned to three groups, as follows: cupping pressure of -0.02 mpa (n = 38), -0.03 mpa (n = 38), or -0.05 mpa (n = 36). Each group received cupping treatment that consisted of 10 sessions over 5 weeks (2 sessions per week). The primary outcomes were Fatigue Scale (FS-14) score and Fatigue Assessment Instrument (FAI) score after 5 and 10 sessions. The secondary outcomes were the Self-Rating Anxiety Scale (SAS) score, the Self-Rating Depression Scale (SDS) score, and the Pittsburgh Sleep Quality Index (PSQI) score. RESULTS: There were 91 participants who completed the trial. After five sessions of treatment, the primary outcome of FS-14 score decreased by 3.20 (2.19, 4.21) in the -0.02 mpa group, by 2.39 (1.51, 3.27) in the -0.03 mpa group, and by 3.40 (2.28, 4.52) in the -0.05 mpa group (P = 0.667). After 10 sessions of treatment, the outcome of FS-14 score decreased by 5.00 (3.79, 6.21) in the -0.02 mpa group, by 4.06 (3.07, 5.05) in the -0.03 mpa group, and by 4.77 (3.52, 5.94) in the -0.05 mpa group (P = 0.929). And, the results were statistically different between 5 sessions and 10 sessions of treatment (P < 0.01). However, there were no statistical differences in FAI, SAS, SDS, and PSQI scores between the three groups after 5 sessions and 10 sessions of treatment. CONCLUSIONS: In conclusion, cupping therapy has significantly relieved fatigue symptoms and improved emotion and sleep condition of CFS patients, and 10 sessions of treatment had superior results compared with 5 sessions in each group. Moreover, in 5 sessions of treatment, cupping with high pressure showed better improvement in fatigue syndromes and sleep condition according to effective rates. TRIAL REGISTRATION: Chinese clinical trial registry (ChiCTR1800017590); Ethical approval number: ChiECRCT-20180085.

Alleviative effects of dietary microbial floc on copper-induced inflammation, oxidative stress, intestinal apoptosis and barrier dysfunction in Rhynchocypris lagowski Dybowski.

The heavy metal poisoning in humans and fish represents a significant global problem. Copper (Cu), as an essential micronutrient in human and animal metabolism, often accumulates excessively in aquatic environment. The microbial floc is rich in a variety of probiotics and bioactive compounds, which has been documented to have the functions of antioxidant and immunoenhancement. A 64-day experiment was conducted to investigate the protective effects and potential mechanisms of dietary supplementation of microbial floc and Cu exposure on inflammatory response, oxidative stress, intestinal apoptosis and barrier dysfunction in Rhynchocypris lagowski Dybowski. A total of four hundred fifty R. lagowski were fed five experimental diets containing graded levels of microbial floc from 0% to 16% (referred to as B0, B4, B8, B12 and B16, respectively) in the first 60 days, and 96 h of acute copper exposure test was carried out in the last four days. The results showed that microbial floc exerted significant alleviative effects by preventing alterations in the levels of bioaccumulation, caspase3, caspase8, caspase9, malondialdehyde and interleukin-6, improving the activities of lysozyme, complement C3, complement C4, immunoglobulin M, alkaline phosphatase, heat shock protein 70, heat shock protein 90 and glutathione peroxidase, catalase, superoxide dismutase, total antioxidant capacity. In addition, microbial floc assisted in regulating the expression of NF-κB/Nrf2 signaling molecule genes, including NF-κB, TNF-α, IL-1ß, IL-8, IL-10, TGF-ß, Keap1, Nrf2, Maf, HO-1, CAT, CuZn-SOD, GCLC and GPX. Overall, our results suggest that dietary supplementation with of microbial floc can alleviate copper-induced inflammation, oxidative stress, intestinal apoptosis and barrier dysfunction in R. lagowski. A suitable supplementation level of approximately 12% microbial floc is recommended in the present study.

Nagilactone E increases PD-L1 expression through activation of c-Jun in lung cancer cells.

Nagilactone E (NLE), a natural product with anticancer activities, is isolated from Podocarpus nagi. In this study, we reported that NLE increased programmed death ligand 1 (PD-L1) expressions at both protein and mRNA levels in human lung cancer cells, and enhanced its localization on the cell membrane. Mechanistically, NLE increased the phosphorylation and expression of c-Jun, and promoted the localization of c-Jun in the nucleus, while silencing of c-Jun by small interfering RNA (siRNA) reduced NLE-induced PD-L1. Further study showed that NLE activated the c-Jun N-terminal kinases (JNK), the upstream of c-Jun, and its inhibitor SP600125 reversed the NLE-increased PD-L1. Moreover, NLE-induced PD-L1 increased the binding intensity of PD-1 on the cell surface. In summary, NLE upregulates the expression of PD-L1 in lung cancer cells through the activation of JNK-c-Jun axis, which has the potential to combine with the PD-1/PD-L1 antibody therapies in lung cancer.

Bioactive platycodins from Platycodonis Radix: Phytochemistry, pharmacological activities, toxicology and pharmacokinetics.

Platycodonis Radix, the root of Platycodon grandiflorum (Jacq.) A. DC., is a well-known edible herbal medicine. It is a common vegetable used for the preparation of side dish, kimchi, dessert, and tea. Besides, it has been used to treat respiratory disease including cough, excessive phlegm, and sore throat for a long history. In the past decades, the bioactive components and the pharmacological activities of Platycodonis Radix have been widely investigated. Thereinto, platycodins, the oleanane-type triterpenoid saponins were demonstrated to be the main bioactive components in Platycodonis Radix, and more than 70 platycodins have been identified up to date. This paper mainly reviewed the phytochemistry, pharmacological activities (apophlegmatic, anti-tussive, anti-inflammatory, anti-cancer, anti-obesity, anti-diabetic, immunomodulatory, cardiovascular protective, and hepatoprotective activities, etc.), toxicology and pharmacokinetics of platycodins isolated from Platycodonis Radix, aiming to promote further investigation on therapeutic potential of these platycodins.

Effect of sub-chronic exposure to selenium and astaxanthin on Channa argus: Bioaccumulation, oxidative stress and inflammatory response.

Selenium (Se) is the most common micronutrient and that becomes toxic when present at higher concentrations in aquatic environments. Astaxanthin (AST) has been documented to possess antioxidant and anti-inflammatory properties. The aim of this study was to explore the potential of dietary AST and Se exposure on oxidative stress, and inflammatory response in Channa argus. After acclimation, 540 fish were randomly distributed into nine groups housed in twenty-seven glass tanks. The fish were exposed for 8 weeks to waterborne Se at 0, 100 and 200 µg L-1 or dietary AST at 0, 50 and 100 mg kg-1. The results shown that Se accumulation in the kidney, liver, spleen, intestine and gill were significantly increased following Se exposure, dietary 50 and 100 mg kg-1 AST supplementation decreased the accumulation of Se in the kidney, liver, spleen, and intestine. In addition, AST supplementation can decrease oxidative stress and inflammatory response in the liver and spleen following exposure to waterborne Se. These results indicate that AST has the potential to alleviate the effects of Se toxicity in C. argus.

Platycodin D triggers the extracellular release of programed death Ligand-1 in lung cancer cells.

Programmed death ligand-1 (PD-L1) is an important immune checkpoint for cancer immunotherapy in clinic. In this study, we reported that platycodin D, a natural product isolated from an edible and medicinal plant Platycodon grandiflorus (Jacq.) A. DC., down-regulated the protein level of PD-L1 in lung cancer cells. Flow cytometry and immunofluorescence assay showed a weaker surface PD-L1 signal in NCI-H1975 cells after the incubation with platycodin D (10 µM) for 15 min compared to the control group. Jurkat T cells showed enhancive interleukin-2 secretion when co-cultured with platycodin D-treated NCI-H1975 cells, suggesting that platycodin D-induced PD-L1 reduction increases the activation of Jurkat T cells. An augmentation of PD-L1 protein was detected in the cell culture medium from platycodin D treatment group. Chlorpromazine (60 µM) almost abolished the platycodin D-mediated PD-L1 extracellular release and restored the membrane PD-L1. Finally, hemolysis assay exhibited that platycodin D-triggered PD-L1 extracellular release was independent of the hemolytic mechanism. Taken together, our study demonstrates that platycodin D reduces the protein level of PD-L1 in lung cancer cells via triggering its release into the cell culture medium, which sheds new light for the application of natural products in cancer immunotherapy.