Boosting the immunogenicity of the CoronaVac SARS-CoV-2 inactivated vaccine with Huoxiang Suling Shuanghua Decoction: a randomized, double-blind, placebo-controlled study.

Introduction: In light of the public health burden of the COVID-19 pandemic, boosting the safety and immunogenicity of COVID-19 vaccines is of great concern. Numerous Traditional Chinese medicine (TCM) preparations have shown to beneficially modulate immunity. Based on pilot experiments in mice that showed that supplementation with Huoxiang Suling Shuanghua Decoction (HSSD) significantly enhances serum anti-RBD IgG titers after inoculation with recombinant SARS-CoV-2 S-RBD protein, we conducted this randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the potential immunogenicity boosting effect of oral HSSD after a third homologous immunization with Sinovac's CoronaVac SARS-CoV-2 (CVS) inactivated vaccine. Methods: A total of 70 participants were randomly assigned (1:1 ratio) to receive a third dose of CVS vaccination and either oral placebo or oral HSSD for 7 days. Safety aspects were assessed by recording local and systemic adverse events, and by blood and urine biochemistry and liver and kidney function tests. Main outcomes evaluated included serum anti-RBD IgG titer, T lymphocyte subsets, serum IgG and IgM levels, complement components (C3 and C4), and serum cytokines (IL-6 and IFN-γ). In addition, metabolomics technology was used to analyze differential metabolite expression after supplementation with HSSD. Results: Following a third CVS vaccination, significantly increased serum anti-RBD IgG titer, reduced serum IL-6 levels, increased serum IgG, IgM, and C3 and C4 levels, and improved cellular immunity, evidenced by reduce balance deviations in the distribution of lymphocyte subsets, was observed in the HSSD group compared with the placebo group. No serious adverse events were recorded in either group. Serum metabolomics results suggested that the mechanisms by which HSSD boosted the immunogenicity of the CVS vaccine are related to differential regulation of purine metabolism, vitamin B6 metabolism, folate biosynthesis, arginine and proline metabolism, and steroid hormone biosynthesis. Conclusion: Oral HSSD boosts the immunogenicity of the CVS vaccine in young and adult individuals. This trial provides clinical reference for evaluation of TCM immunomodulators to improve the immune response to COVID-19 vaccines.

Antioxidation and Hepatoprotection of Selenium Mycelium Polysaccharides Against Alcoholic Liver Diseases from the Cultivated Morel Mushroom Morchella esculenta (Ascomycota).

The liver was regarded as the most important metabolic and detoxification organ in vivo, and Morchella esculenta had been reported as the admittedly rare edible fungus belonging to Ascomycetes contributing to the abundant bioactivities. The objective of this study aimed to confirm the potential antioxidant activities of selenium mycelium polysaccharides (Se-MIP) from M. esculenta against alcoholic liver diseases (ALD) in mice. The results indicated that a selenium concentration of 25 µg/mL exhibited potential in vitro antioxidant capacities of Se-MIP. The in vivo mice results demonstrated that Se-MIP showed potential anti-ALD effects by improving the antioxidant activities and alleviating the hepatic dysfunctions. The present conclusions suggested that Se-MIP could be used as a candidate on improving ALD and its complications for further clinical investigations.

Real-World Efficacy and Safety of Amivantamab for EGFR-Mutant NSCLC.

INTRODUCTION: Amivantamab-vmjw (amivantamab) is a bispecific EGFR/MET antibody approved for patients with advanced NSCLC with EGFR exon 20 insertion mutations, after prior therapy. Nevertheless, the benefits and safety of amivantamab in other EGFR-mutant lung cancer, with or without osimertinib, and with concurrent radiation therapy, are less known. METHODS: We queried the MD Anderson Lung Cancer GEMINI, Fred Hutchinson Cancer Research Center, University of California Davis Comprehensive Cancer Center, and Stanford Cancer Center's database for patients with EGFR-mutant NSCLC treated with amivantamab, not on a clinical trial. The data analyzed included initial response, duration of treatment, and concomitant radiation safety in overall population and prespecified subgroups. RESULTS: A total of 61 patients received amivantamab. Median age was 65 (31-81) years old; 72.1% were female; and 77% were patients with never smoking history. Median number of prior lines of therapies was four. On the basis of tumor's EGFR mutation, 39 patients were in the classical mutation cohort, 15 patients in the exon 20 cohort, and seven patients in the atypical cohort. There were 37 patients (58.7%) who received amivantamab concomitantly with osimertinib and 25 patients (39.1%) who received concomitant radiation. Furthermore, 54 patients were assessable for response in the overall population; 19 patients (45.2%) had clinical response and disease control rate (DCR) was 64.3%. In the classical mutation cohort of the 33 assessable patients, 12 (36.4%) had clinical response and DCR was 48.5%. In the atypical mutation cohort, six of the seven patients (85.7%) had clinical response and DCR was 100%. Of the 13 assessable patients in the exon 20 cohort, five patients (35.7%) had clinical response and DCR was 64.3%. Adverse events reported with amivantamab use were similar as previously described in product labeling. No additional toxicities were noted when amivantamab was given with radiation with or without osimertinib. CONCLUSIONS: Our real-world multicenter analysis revealed that amivantamab is a potentially effective treatment option for patients with EGFR mutations outside of exon 20 insertion mutations. The combination of osimertinib with amivantamab is safe and feasible. Radiation therapy also seems safe when administered sequentially or concurrently with amivantamab.

Explore the use of complementary and alternative medicine among Chinese gynaecological patients with cancer undergoing chemotherapy: a qualitative phenomenological study.

OBJECTIVES: To explore the use of complementary and alternative medicine (CAM) by Chinese gynaecological oncology patients undergoing chemotherapy and discuss measures to address the existing gaps. DESIGN: Qualitative phenomenology. Semistructured in-depth interview. Colaizzi's method data analysis. SETTING: A tertiary general hospital. PARTICIPANTS: 16 gynaecological oncology patients (mean age 51.7) having undergone ≥1 chemotherapy cycle were recruited by purposive sampling. RESULTS: Six themes were generated. The participants were under-informed about CAM concept and options. They were open to explore various modalities after chemotherapy as long as it could alleviate symptoms. The gynaecological patients with cancer sought information about CAM from diverse sources, with professional expertise being the most desirable way to seek information. They used CAM as a strategy to support continued chemotherapy and for symptom alleviation. Financial burden was not stressed but they had concerns about sustainability of some therapies. Their attitudes toward different CAM types varied. Some were sceptical about the efficacy. CONCLUSIONS: The Chinese gynaecological oncology patients may be under-informed about CAM. They are open to use various CAM therapies for symptom relief and as a support strategy. However, their attitudes toward specific therapies may vary. Some may host scepticism about certain CAM modalities. The patients actively seek information on CAM and treatment resources but prefer professional expertise to other sources. Financial burden due to continued CAM use is inconclusive due to possible sampling bias. Sustainability of CAM therapies is a common concern because of limited resources and access. Education on CAM should be incorporated into the curriculum of healthcare professionals. Oncologists and nurses should educate gynaecological patients with cancer on the concept and options of CAM, preferably with information tailored to patient's individual needs. Health authorities should advocate provisions of diverse CAM services and develop the necessary technologies such as network of local care resources.

Arabidopsis 3ß-Hydroxysteroid Dehydrogenases/C4-Decarboxylases Are Essential for the Pollen and Embryonic Development.

The biosynthesis of C27-29 sterols from their C30 precursor squalene involves C24-alkylation and the removal of three methyl groups, including two at the C4 position. The two C4 demethylation reactions require a bifunctional enzyme known as 3ß-hydroxysteroid dehydrogenase/C4-decarboxylase (3ßHSD/D), which removes an oxidized methyl (carboxylic) group at C4 while simultaneously catalyzing the 3ß-hydroxyl→3-keto oxidation. Its loss-of-function mutations cause ergosterol-dependent growth in yeast and congenital hemidysplasia with ichthyosiform erythroderma and limb defect (CHILD) syndrome in humans. Although plant 3ßHSD/D enzymes were well studied enzymatically, their developmental functions remain unknown. Here we employed a CRISPR/Cas9-based genome-editing approach to generate knockout mutants for two Arabidopsis 3ßHSD/D genes, HSD1 and HSD2, and discovered the male gametophytic lethality for the hsd1 hsd2 double mutation. Pollen-specific expression of HSD2 in the heterozygous hsd1 hsd2/+ mutant not only rescued the pollen lethality but also revealed the critical roles of the two HSD genes in embryogenesis. Our study thus demonstrated the essential functions of the two Arabidopsis 3ßHSD/D genes in male gametogenesis and embryogenesis.

[Properties of new exotic traditional Chinese medicinal Vernonia amygdalina leaves:a literature research].

The leaves of Vernonia amygdalina Delile of the family Asteraceae(also known as "bitter leaf"), rich in biological activities, are used as both medicine and food for a long time in West tropical Africa. They have been introduced into Southeast Asia and Fujian and Guangdong provinces of China in recent years. However, little is known about the properties of the plant in traditional Chinese medicine(TCM), which limits its combination with other Chinese medicinal herbs. In this study, 473 articles on V. amygdalina leaves were selected from PubMed, Web of Science, CNKI, Wanfang Data and VIP to summarize their components, pharmacological effects and clinical research. V. amygdalina leaves presented anti-microbial, hypoglycemic, anti-hypertensive, lipid-lowering, anti-tumor, anti-inflammatory, antioxidant, and other pharmacological effects. On the basis of the theory of TCM properties, the leaves were inferred to be cold in property and bitter and sweet in flavor, acting on spleen, liver, stomach and large intestine and with the functions of clearing heat, drying dampness, purging fire, removing toxin, killing insects and preventing attack of malaria. They can be used to treat dampness-heat diarrhea, interior heat and diabetes, malaria, insect accumulation and eczema(5-10 g dry leaves by decoction per day and an appropriate amount of crushed fresh leaves applying to the affected area for external use). Due to the lack of TCM properties, V. amygdalina leaves are rarely used medicinally in China. The determination of medicinal properties of the leaves is conducive to the introduction of new exotic medicinal herbs and the development of new TCM resources, which facilitated further clinical application and research and development of Chinese medicinal herbs.

Predicting benefit from immune checkpoint inhibitors in patients with non-small-cell lung cancer by CT-based ensemble deep learning: a retrospective study.

BACKGROUND: Only around 20-30% of patients with non-small-cell lung cancer (NCSLC) have durable benefit from immune-checkpoint inhibitors. Although tissue-based biomarkers (eg, PD-L1) are limited by suboptimal performance, tissue availability, and tumour heterogeneity, radiographic images might holistically capture the underlying cancer biology. We aimed to investigate the application of deep learning on chest CT scans to derive an imaging signature of response to immune checkpoint inhibitors and evaluate its added value in the clinical context. METHODS: In this retrospective modelling study, 976 patients with metastatic, EGFR/ALK negative NSCLC treated with immune checkpoint inhibitors at MD Anderson and Stanford were enrolled from Jan 1, 2014, to Feb 29, 2020. We built and tested an ensemble deep learning model on pretreatment CTs (Deep-CT) to predict overall survival and progression-free survival after treatment with immune checkpoint inhibitors. We also evaluated the added predictive value of the Deep-CT model in the context of existing clinicopathological and radiological metrics. FINDINGS: Our Deep-CT model demonstrated robust stratification of patient survival of the MD Anderson testing set, which was validated in the external Stanford set. The performance of the Deep-CT model remained significant on subgroup analyses stratified by PD-L1, histology, age, sex, and race. In univariate analysis, Deep-CT outperformed the conventional risk factors, including histology, smoking status, and PD-L1 expression, and remained an independent predictor after multivariate adjustment. Integrating the Deep-CT model with conventional risk factors demonstrated significantly improved prediction performance, with overall survival C-index increases from 0·70 (clinical model) to 0·75 (composite model) during testing. On the other hand, the deep learning risk scores correlated with some radiomics features, but radiomics alone could not reach the performance level of deep learning, indicating that the deep learning model effectively captured additional imaging patterns beyond known radiomics features. INTERPRETATION: This proof-of-concept study shows that automated profiling of radiographic scans through deep learning can provide orthogonal information independent of existing clinicopathological biomarkers, bringing the goal of precision immunotherapy for patients with NSCLC closer. FUNDING: National Institutes of Health, Mark Foundation Damon Runyon Foundation Physician Scientist Award, MD Anderson Strategic Initiative Development Program, MD Anderson Lung Moon Shot Program, Andrea Mugnaini, and Edward L C Smith.

An efficient cocrystallization strategy for separation of dihydromyricetin from vine tea and enhanced its antibacterial activity for food preserving application.

The objective of this study was to optimize the separation and purification of dihydromyricetin (DMY) from vine tea to obtain high purity, antibacterial and antioxidant crystal forms. We developed a cocrystallization approach for separation of DMY from vine tea with easy operation and high efficiency. The type and concentration of co-formers as well as solvent for separation have been investigated in detail. Under the optimal conditions, DMY with a purity of 92.41% and its two co-crystal forms (purity >97%) can be obtained. Three DMY crystal forms had consistent and good antioxidant activities according to DPPH radical scavenging results. DMY had effective antibacterial activity against the two kinds of drug-resistant bacteria including CRAB and MRSA, and DMY co-crystals had a greater advantage than DMY itself on CRAB. This work implies that cocrystallization can be used for the DMY separation and enhanced its anti-drug-resistant bacteria activity in food preservation.

[Anti-fatigue effect of Lubian on kidney Yin deficiency and kidney Yang deficiency mice and mechanism based on PI3K-Akt pathway].

This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.

Monolithic integration of embedded III-V lasers on SOI.

Silicon photonic integration has gained great success in many application fields owing to the excellent optical device properties and complementary metal-oxide semiconductor (CMOS) compatibility. Realizing monolithic integration of III-V lasers and silicon photonic components on single silicon wafer is recognized as a long-standing obstacle for ultra-dense photonic integration, which can provide considerable economical, energy-efficient and foundry-scalable on-chip light sources, that has not been reported yet. Here, we demonstrate embedded InAs/GaAs quantum dot (QD) lasers directly grown on trenched silicon-on-insulator (SOI) substrate, enabling monolithic integration with butt-coupled silicon waveguides. By utilizing the patterned grating structures inside pre-defined SOI trenches and unique epitaxial method via hybrid molecular beam epitaxy (MBE), high-performance embedded InAs QD lasers with monolithically out-coupled silicon waveguide are achieved on such template. By resolving the epitaxy and fabrication challenges in such monolithic integrated architecture, embedded III-V lasers on SOI with continuous-wave lasing up to 85 °C are obtained. The maximum output power of 6.8 mW can be measured from the end tip of the butt-coupled silicon waveguides, with estimated coupling efficiency of approximately -6.7 dB. The results presented here provide a scalable and low-cost epitaxial method for the realization of on-chip light sources directly coupling to the silicon photonic components for future high-density photonic integration.

[Traditional Chinese medicine health care from "long term taking" drugs in Shen Nong's Classic of Materia Medica].

"Taking drugs for a long term" is a qualitative expression of medication method based on the efficacy and safety of Chinese medicine, and the study on it is conducive to the full utilization of the efficacy and rational use of drugs. There are 148 drugs that can be taken for a long time recorded in Shen Nong's Classic of Materia Medica, accounting for 41% of the total drugs. This paper analyzed three-grade classification, natural qualities, four properties and five flavors, and efficacy features of the "long-term taking" drugs(LTTD), thus exploring the herbal source of traditional Chinese medicine health care and the rationality of effect accumulation by long-term taking. It was found that there were more than 110 top-grade LTTD in Shen Nong's Classic of Materia Medica, most of which were herbs, with sweet flavor, flat property, and no toxicity. The efficacies were mainly making body feel light and agile(Qingshen) and prolonging life. Eighty-three LTTD were included in the Chinese Pharmacopoeia(2020 edition). In the modern classification, tonic LTTD accounted for the most, followed by damp-draining diuretic LTTD and exterior-releasing LTTD. Twenty LTTD were included in the "List of Medicinal and Edible Products" and 21 were in the "List of Products Used for Health-care Food", involving in various modern health care effects, such as enhancing immunity, assisting in reducing blood lipids, and anti-oxidation. Shen Nong's Classic of Materia Medica is the classic source of traditional Chinese medicine health care, and its medication thought of taking drugs for a long term to accumulate effects has guiding significance for the regulation of sub-health and chronic diseases nowadays. The efficacy and safety of LTTD have been examined in practice for a long time, and some of the drugs are edible, which is unique in the whole cycle of health-care service, especially in line with the health-care needs in the aging society under the concept of Big Health. However, some records in the book are limited by the understanding of the times, which should be scientifically studied according to the Chinese Pharmacopoeia and the related regulations and technical requirements, under the attitude of eliminating falsifications and preserving the truth and keeping the right essence, so as to achieve further improvement, innovation, and development.

Ganoderma lucidum polysaccharides improve lipid metabolism against high-fat diet-induced dyslipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: As a kind of traditional medicinal fungi, Ganoderma lucidum has been employed as folk medicine in China against multiple metabolic diseases on account of its superior bioactivities. Recently, accumulated reports have investigated the protective effects of G. lucidum polysaccharides (GLP) on ameliorating dyslipidemia. However, the specific mechanism by which GLP improves dyslipidemia is not completely clear. AIMS OF THE STUDY: This study aimed to investigate the protective effects of GLP on high-fatdiet-induced hyperlipidemia and exploring its underlying mechanism. MATERIALS AND METHODS: The GLP was successfully obtained from G. lucidum mycelium. The mice were conducted with high-fatdiet to establish the hyperlipidemia model. Biochemical determination, histological analysis, immunofluorescence, western blot and real-time qPCR were used to assess the alterations in high-fatdiet-treated mice after the GLP intervention. RESULTS: It was found that GLP administration significantly decreased body weight gain and the excessive lipid levels, and partly alleviated tissue injury. Oxidative stress and inflammations were efficiently ameliorated after the treatment of GLP by activing Nrf2-Keap1 and inhibiting NF-κB signal pathways. GLP promoted cholesterol reverse transport by LXRα-ABCA1/ABCG1 signaling, increased the expressions of CYP7A1 and CYP27A1 responsible for bile acids production, accompanied by inhibition of intestinal FXR-FGF15 levels. Besides, multiple target proteins involved in lipid metabolism were also significantly modulated under the intervention of GLP. CONCLUSION: Taken together, our results suggested that GLP showed potential lipid-lowering effects and its possible mechanism was involved in improving oxidative stress and inflammation response, modulating bile acids synthesis and lipid regulatory factors, and promoting reverse cholesterol transport, thereby suggesting that GLP may possibly used as a dietary supplement or medication for the adjuvant therapy for hyperlipidemia.

Improvement influenza vaccine immune responses with traditional Chinese medicine and its active ingredients.

The current influenza vaccines are unable to provide effective protection in many cases, like influenza viruses strain antigenic drift or shift, and the influenza continues to cause significant annual morbidity and mortality. Improving the immune response to influenza vaccination is an unmet need. Traditional Chinese medicine (TCM) and its active ingredients are commonly known to have immunomodulatory properties. We therefore compared influenza vaccination alone or formulated with Astragali Radix (Huangqi in Chinese), and several representative ingredients of TCM, including lentinan (polysaccharide), panax notoginseng saponins (saponin), breviscapine (flavone), andrographolide (terpenoid), and a Chinese herbal compound (kangai) for their potential to enhance immune responses to influenza vaccine in mice. We found that all these TCM-adjuvants were able to increase hemagglutination inhibition (HAI) antibody titers, splenocyte proliferation, splenic T cell differentiation, bone marrow dendritic cell maturity, and both Th1 and Th2 cytokine secretion of influenza vaccine to varying degrees, and that had the characteristics of no excessive inflammatory responses and bidirectional regulation simultaneously. Taken together, our findings show that Astragali Radix exerts a more comprehensive effect on vaccine immunity, on both innate and adaptive immunity. The effects of lentinan and andrographolide on adaptive immunity were more significant, while the effects of breviscapine on innate immunity were stronger, and the other two TCM adjuvants were weaker. As the first report of a comprehensive evaluation of TCM adjuvants in influenza vaccines, the results suggest that TCM and their active ingredients are good candidates for enhancing the immune response of influenza vaccines, and that suitable TCMs can be selected based on the adjuvant requirements of different vaccines.

A clinical study to observe the efficacy and safety of Besunyen Detox Tea for constipation.

INTRODUCTION: Functional constipation (FC) is a common functional gastrointestinal disease and is one of the most common outpatient diseases. The purpose of this study was to investigate the efficacy and safety of the traditional Chinese medicine Besunyen Detox Tea (BDT) for FC and to compare the effect of BDT between constipation patients with and non-dryness-heat syndrome. METHODS AND ANALYSIS: This multicenter, prospective, observational registry study included 1000 participants diagnosed with FC. This study will collaborate with 3 comprehensive hospitals and 15 community hospitals and recruit patients into the registry between July 2022 and July 2023. After enrollment, we will collect the individual characteristics of each patient, anthropometric data and general condition, bowel movement, patient assessment of constipation symptoms, patient assessment of constipation quality of life, TCM syndrome scale, and time to take the laxative product again after treatment. We will also record adverse events and economic indicators at each visit. DISCUSSION: This is the first registry-based study to collect real-world data of participants diagnosed with FC receiving BDT treatment. The results of this registry may also reflect these characteristics and provide direct clinical evidence to verify the importance of syndrome differentiation and treatment for the use of TCM health care products.

Effect of Noni on Memory Impairment Induced by Hydrocortisone in Mice.

Background: Oxidative stress and memory impairment have been implicated as common functional brain diseases. Nuclear factor E2-related factor 2 (Nrf2) is highly induced in oxidative stress, indicating that Nrf2 is an emerging target of memory therapy. This study aimed to investigate the effect of noni on brain memory impairment induced by hydrocortisone and its protective mechanism in mice. Methods: Male Kunming mice (n = 8/group) were given hydrocortisone by gastric gavage for 14 consecutive days to establish the memory impairment model, except for those in the control group. On the same day, the corresponding drugs were given by gastric gavage. The changes in ethology were examined. The brains were extracted and subjected to western blot analysis and biochemical analyses to assess the activities of antioxidative stress. Results: The middle- and high-dose noni groups exhibited ameliorated ethology, and the high-dose noni group exhibited increased cerebral protein expression of Nrf2, Kelch-like ECH-associated protein 1 (KEAP1), and haem oxygenase-1 (HO-1) compared to the model group. The arrangement of CA3 vertebral cells in the hippocampus of mice was slightly compact, and hyperchromasia and pyknosis were alleviated. Furthermore, biochemical analyses showed that the activities of enzymes related to oxidative stress in the high-dose noni group were increased. Conclusions: Noni might be a powerful antioxidant that can protect nerve cells and may possess potential benefits for the treatment of memory impairment.

Immunomodulatory Effects of Lepidium meyenii Walp. Polysaccharides on an Immunosuppression Model Induced by Cyclophosphamide.

Background: Lepidium meyenii Walp. (Maca) has emerged as a functional plant food and traditional herb owing to its biological activities; Maca polysaccharides as an important active component of Maca have good immunomodulatory effect; however, studies on the immunomodulatory effect of Maca polysaccharides are mainly focused on macrophages; little attention has been devoted to the mechanisms and other immune cells. This study is aimed at investigating the immunomodulatory effects and mechanisms of Maca polysaccharides. Methods: Sixty mice were divided into five groups, and the mice were injected with cyclophosphamide to establish an immunosuppression model except for those in the common group. The body weights were measured, as well as immune-related indices, such as organ indices, haematological parameters, lymphocyte cycle, and proliferation, cytokine, and protein expression levels. Results: The weight loss and immune organ index decline caused by cyclophosphamide could be reversed by MP. Furthermore, MP increased WBC and HGB counts and reduced the ratio of G0/G1 phase obviously, increased the proportion of S phase and G2/M phase in peripheral blood lymphocytes, increased the counts of CD4+ T cells and the ratio of CD4+/CD8+, and reduced the inhibition rate of splenic lymphocytes. MP affected the production of cytokines by increasing IFN-γ, TNF-α, and IL-2 levels and by decreasing IL-4 levels. MP increased the mRNA expression of T-bet and the protein expression of Bcl-2 in the spleen and decreased the protein expression of caspase-3 and Bax. Conclusions: Maca polysaccharides might be the basic material for Maca's immunomodulatory effect. The mechanism was perhaps related to inhibiting lymphocyte apoptosis and promoting the balance of Th1/Th2 cell subsets.

Exploring Molecular Mechanisms of Aloe barbadmsis Miller on Diphenoxylate-Induced Constipation in Mice.

Aloe barbadensis Miller (Aloe) known as a common succulent perennial herb had been traditionally used in constipation for more than 1,000 years. Aloe contained anthraquinones and other active compounds which had laxative effect and could modulate constipation. However, the therapeutic effects and mechanisms of aloe in constipation were still unclear. To explore the therapeutic effects and mechanisms of aloe in treating constipation, we employed network pharmacology, molecular docking, and mice experiments in this study. Our network pharmacology indicated that beta-carotene, sitosterol, campest-5-en-3beta-ol, CLR, arachidonic acid, aloe-emodin, quercetin, and barbaloin were the main active ingredients of aloe in treating constipation. Besides, the MAPK signaling pathway was the principal pathway utilized by aloe in treating constipation. Molecular docking results revealed that beta-carotene and sitosterol were acting as interference factors in attenuating inflammation by binding to an accessory protein of ERK, JNK, AKT, and NF-κB p65. Otherwise, in vivo experiments, we used diphenoxylate-induced constipation mice model to explore the therapeutic effects and mechanisms of aloe. Results showed that aloe modulated the constipation mice by reducing the discharge time of first melena, improving the fecal conditions, increasing the gastric intestinal charcoal transit ratio, and improving the intestinal secretion in small intestine. Besides, aloe played an important regulation in promoting intestinal motility sufficiency and the levels of neurotransmitters balance with 5-HT, SP, and VIP on constipation mice. Moreover, aloe significantly inhibited the mRNA and proteins expressions of ERK, JNK, AKT and NF-κB p65 in colon. Our study proved that aloe could reverse diphenoxylate-induced changes relating to the intestinal motility, intestinal moisture, and inhibition of the MAPK (ERK, JNK)/AKT/NF-κB p65 inflammatory pathway. Our study provided experimental evidences of the laxative effect of aloe, which was beneficial to the further research and development of aloe.

From metabolomic analysis to quality assessment and biosynthetic insight in traditional Chinese medicine: Mulberry tree as a case study.

INTRODUCTION: Ramulus Mori (RM, Sangzhi) and Cortex Mori (CM, Sangbaipi) both come from the Chinese medicinal plant mulberry tree. CM is usually used to relieve cough, while RM is usually used to treat pain. There are no studies on the quality control of RM and CM based on their analgesic and anti-inflammatory constituents associated with their traditional use. The chemical profiles of CM and RM were confusing. Some CM had similar profiles to RM, but some did not. OBJECTIVE: We aimed to reveal the chemical differences between RM and CM and to evaluate their quality. MATERIALS AND METHODS: Their chemical differences were studied using metabolomic analysis based on UHPLC-ESI-MS data. The contents of five quality marker candidates were determined by UHPLC-PDA. The analgesic activities of morusin and kuwanon C were assessed by an acetic acid-induced writhing test. RESULTS: CM was characterized by chemical diversity, whereas RM had good homogeneity. Four groups of CM were classified based on their chemicals. The chemical profiles of CM group 4 were more similar to that of RM. Eighteen putative features were identified based on an MS-Finder search and fragmentation rules. Content limits for four quality markers with anti-inflammatory or analgesic activities were proposed for RM. Furthermore, a possible biosynthetic relationship between kuwanon C, kuwanon G, and morusin was hypothesized based on the high Pearson coefficient between kuwanon G and morusin. CONCLUSION: The obtained results may be useful in the evaluation of RM and CM and afford insight into the biosynthetic pathway of Diels-Alder adducts in Morus.

Ameliorative Effect of Ethanolic Echinacea purpurea against Hyperthyroidism-Induced Oxidative Stress via AMRK and PPAR Signal Pathway Using Transcriptomics and Network Pharmacology Analysis.

Echinacea purpurea (L.) Moench (EP) is a well-known botanical supplement with antioxidant characteristics. However, the effects of EP on oxidative stress induced by hyperthyroidism have not yet been studied. This study was designed to evaluate the antioxidative effect of ethanolic Echinacea Purpurea (EEP) on hyperthyroidism-induced oxidative stress mice using an integrated strategy combining transcriptomics with network pharmacology analysis. Firstly, a hyperthyroidism mice model was induced via thyroxine (160 mg/kg) and EEP (1, 2, or 4 g/kg) once daily for 2 weeks. Body weight, thyroid-stimulating hormones, and oxidative stress markers were tested. Secondly, EEP regulating the potential genes at transcript level were analyzed. Thirdly, a network pharmacology based on the constituents of EEP identified using UPLC-Q-TOF-MS analysis was adopted. Finally, a joint analysis was performed to identify the key pathway. The results showed that EEP significantly changed the thyroid-stimulating hormones and oxidative stress markers. Meanwhile, RT-qPCR and Western Blotting demonstrated that the mechanism of the antioxidant effect of EEP reversed the mRNA expression of EHHADH, HMGCR and SLC27A2 and the protein expression of FABP and HMGCR in AMPK and PPAR signaling pathways. This study integrates transcriptomics with network pharmacology to reveal the mechanism of ameliorative effect of EEP on hyperthyroidism-induced oxidative stress.

Intake of Calcium, Magnesium, and Phosphorus and Risk of Pancreatic Cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

ObjectiveFew epidemiological studies have investigated the associations between calcium, magnesium, and phosphorus intake and pancreatic cancer. We examined these associations in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.MethodsDiet was assessed using the Dietary Questionnaire (DQX) at baseline in the intervention arm and the Dietary History Questionnaire (DHQ) in 1999 or around the third anniversary of randomization in both the intervention and control arms. During a median follow-up of 12.2 years, 279 cases of pancreatic cancer occurred from 58,477 participants who completed DQX; 380 cases arose from 101,622 participants who responded to DHQ over a median follow-up of 8.9 years. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI).ResultsTotal calcium intake was inversely associated with pancreatic cancer [HR (95% CI) for the fourth vs. the first quartiles in the DHQ cohort: 0.67 (0.47, 0.96); p-trend: 0.035]. An inverse association was also observed for total magnesium intake [HR (95% CI) for the fourth vs. the first quartiles in the DQX cohort: 0.61 (0.37, 1.00); p-trend: 0.023]. Reduced risk associated with total calcium intake was confined to subjects with a high fat intake (>73 g/day) in the DHQ cohort (p-interaction: 0.16).ConclusionsThere was not a significant association between dietary phosphorus intake and pancreatic cancer risk in both cohorts. Total intake of calcium and magnesium are associated with a lower pancreatic cancer risk. The effect of total calcium intake was modified by fat intake.