Effects of Viscum coloratum (Kom.) Nakai on collagen-induced rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Viscum coloratum (Kom.) Nakai has been traditionally used in China for nearly a thousand years to treat rheumatic diseases. However, its efficacy and mechanisms in treating rheumatoid arthritis (RA) have not been demonstrated. AIM OF THE STUDY: To investigate the anti-arthritic effects and molecular mechanisms of Viscum coloratum (Kom.) Nakai on collagen-induced arthritic mice through network pharmacology technology and experimental validation. MATERIALS AND METHODS: First, the main ingredients of the extract of Viscum coloratum (Kom.) Nakai (EVC) were identified through chemical composition characterization using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS). Then, the collagen-induced arthritis (CIA) model was established in DBA/1 J mice and the ameliorative effects of EVC on the progression of CIA mice were evaluated by oral treatment with different doses of the EVC for 28 days. After that, cytokine antibody microarray assay was used to detect the levels of multiple inflammation-related cytokines and chemokines in each group, and performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analysis. Subsequently, the potential target for the effective chemical components of EVC in treating RA was identified using various databases. Additionally, a drug-disease target protein-protein interaction network (PPI) was conducted using Cytoscape for visualization and clustering, while GO and KEGG enrichment analyses were performed with the Metascape database. Finally, identified phenotypes and targets by network pharmacology analysis were experimentally validated in vivo. RESULTS: Treatment with EVC significantly suppressed the severity of CIA with a dramatic reduction of paw swelling, arthritis index, levels of IgGs (IgG, IgG1, IgG2a, and IgG2b), multi-inflammation-related cytokines and chemokines on the progression of CIA. Histopathological examinations showed EVC could markedly inhibit inflammatory cell infiltration, tartrate-resistant acid phosphatase (TRAP) activity of osteoclast, and bone destruction. Furthermore, GO and KEGG enrichment analyses revealed that EVC could ameliorate RA by inhibiting osteoclast differentiation and regulating multiple signaling pathways including Osteoclast differentiation, IL-17, and TNF. PPI network analysis demonstrated that AKT1, MMP9, MAPK3, and other genes were highly related to EVC in treating RA. Finally, we proved that EVC could inhibit the expression of NFTAc1, MMP9, Cathepsin K, and AKT which were closely related to osteoclast activity. CONCLUSIONS: EVC could treat RA through multiple components, multiple targets, and multiple pathways. The present study demonstrated the therapeutic efficacy of EVC and its molecular mechanisms in treating RA, indicating that it would be a potent candidate as a novel botanical drug for further investigation.

Chinmedomics: a potent tool for the evaluation of traditional Chinese medicine efficacy and identification of its active components.

As an important part of medical science, Traditional Chinese Medicine (TCM) attracts much public attention due to its multi-target and multi-pathway characteristics in treating diseases. However, the limitations of traditional research methods pose a dilemma for the evaluation of clinical efficacy, the discovery of active ingredients and the elucidation of the mechanism of action. Therefore, innovative approaches that are in line with the characteristics of TCM theory and clinical practice are urgently needed. Chinmendomics, a newly emerging strategy for evaluating the efficacy of TCM, is proposed. This strategy combines systems biology, serum pharmacochemistry of TCM and bioinformatics to evaluate the efficacy of TCM with a holistic view by accurately identifying syndrome biomarkers and monitoring their complex metabolic processes intervened by TCM, and finding the agents associated with the metabolic course of pharmacodynamic biomarkers by constructing a bioinformatics-based correlation network model to further reveal the interaction between agents and pharmacodynamic targets. In this article, we review the recent progress of Chinmedomics to promote its application in the modernisation and internationalisation of TCM.

Evaluation of the key ingredient from the main production areas of Phellodendri Amurensis Cortex using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry and ultra-high-performance liquid chromatography coupled to triple-quadrupole mass spectrometry.

Phellodendri Amurensis Cortex (PAC) is a medicinal herb that has been generally used to treat diarrhea and jaundice. In order to comprehensively evaluate the PAC in the main production areas quality, a qualitative and quantitative method with highly effective, sensitive, and reliable was developed. The chemical compositions of PAC were analyzed, and fingerprints were established by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS). Then, the determination of berberine, canthin-6-one, dictamnine, γ-fagarine, and magnoflorine from PAC samples was simultaneously performed using UPLC-QQQ-MS. Furthermore, the chemical components of PAC from different regions were compared and analyzed by combining hierarchical cluster analysis, principal component analysis, and orthogonal partial least squares discriminant analysis. A total of 58 compounds were identified, including 36 alkaloids, four phenylpropanoids, seven terpenoids, four flavonoids and their glycosides, an organic acid compound, and six other components. The fingerprint results show that samples have good similarity. Meanwhile, the content of the five ingredients in different habitats is quite different. By multivariate statistical analysis, 18 batches of PAC could be divided into three categories, and 20 components were identified as differential markers of various origins. A comprehensive method of PAC quality evaluation and chemical composition difference analysis was established, which provided the scientific basis for quality evaluation and further pharmacological mechanism research.

Five new sesquiterpenoids isolated from Dictamnus dasycarpus Turcz.

Five new sesquiterpenoids, dictamtrinorguaianols E and F (1-2), and dictameudesmnosides F, G, and H (3-5), along with seven known sesquiterpenoids (6-12) were isolated from Dictamnus dasycarpus Turcz. The structures of all new compounds were characterized by spectroscopic methods, including UV, IR, HR-ESI-MS, and 1D and 2D NMR. The In-vitro anti-proliferative activities of all the compounds against two human cancer cell lines (SW982 and A549) were evaluated by CCK-8 assay. Compounds 1 and 4 showed medium anti-proliferative activity against SW982 cells, with IC50 values of 3.49 ± 0.10 and 6.42 ± 1.23 µM, respectively. Additionally, compounds 2, 7, and 8 exhibited medium anti-proliferative activity against A549 cells, with IC50 values ranging from 0.80 ± 0.05 to 6.60 ± 0.46 µM.

Chemical profiling of Simiao pill and quantification of main effective constituents in it by ultra-high-performance liquid chromatography coupled with Q Exactive Orbitrap and triple quadrupole mass spectrometry.

Simiao pill is one of the most commonly used prescriptions in traditional Chinese medicine for the treatment of hyperuricemia and gout. However, methods based on more accurate and comprehensive qualitative and quantitative analyses of the active ingredients are not yet perfect due to limited methodology. This not only hinders the elucidation of the pharmacological mechanism of Simiao pill, but also its comprehensive clinical development and utilization. In this study, we employed ultra-high-performance liquid chromatography-Q Exactive Orbitrap-mass spectrometry technology to perform rapid analysis and identification of the chemical constituents in Simiao pill. A total of 101 chemical components were identified, including 26 alkaloids, 15 terpenoids, 11 flavonoids, eight steroids, six fatty acids, five limonoids, four saponins, five phenylpropanoids, and 21 other compounds. In addition, we established a new method by high-throughput ultra-high-performance liquid chromatography-Q Exactive Orbitrap-mass spectrometry combined with ultra-high-performance liquid chromatography-triple quadrupole-tandem mass spectrometry technology for quantification of 14 main active ingredients, such as adenosine (1), phellodendrine (2), mangnoflorine (3), ß-ecdysterone (4), 25R-inokosterone (5), 25S-inokosterone (6), jatrorrhizine (7), palmatine (8), chikusetsu saponin IVa (9), limonin (10), atractylenolide III (11), atractylenolide I (12), obacunone (13), and atractylenolide II (14) in Simiao pill. This work laid a foundation for further analysis and quality control of effective components in Simiao pill.

TCM and related active compounds in the treatment of gout: the regulation of signaling pathway and urate transporter.

Gout represents a metabolic ailment resulting from the accumulation of monosodium urate crystals within joints, causing both inflammation and, harm to tissues. The primary contributor to gout's emergence is an elevated presence of serum urate, which is under the regulation of kidney and, gut urate transporters. Mitigating this risk factor is crucial for averting gout's onset. Several treatments rooted in TCM and related active compounds have demonstrated efficacy in managing gout, skillfully regulating serum uric acid (UA) levels and curbing inflammation's progression. This analysis compiles key foundational research concerning the molecular signaling pathways and UA transporters linked to gout, under the regulation of TCM. The focus includes individual botanical drug, active compounds, and TCM formulations, which have been consolidated and examined in this overview. The primary keywords chosen were "gout, hyperuricemia, gouty arthritis, traditional Chinese medicine, Chinese botanical drug, medicinal botanical drug, and natural plant". Various relevant literature published within the last 5 years were gathered from electronic databases, including PubMed, Web of Science, CNKI, and others. The findings revealed that TCM has the capacity to modulate various signaling pathways, including MAPK, NF-κB, PI3K/Akt, NLRP3 and JAK/STAT. Additionally, it impacts UA transporters like URAT1, GLUT9, ABCG2, as well as OATs and OCTs, thereby contributing to gout treatment. TCM helps maintain a balanced inflammatory interaction and facilitates UA excretion. This study enhances our understanding of TCM's anti-gout mechanisms and introduces novel perspectives for establishing the clinical significance and future prospects of TCM-based gout treatment.

Mechanism of electroacupuncture at acupoints of the lung meridian through PKA/PKC regulation of TRPV1 in chronic cough after lung surgery in guinea pigs.

Background: Acupuncture has achieved good results in the treatment of cough, asthma, chronic obstructive pulmonary disease (COPD) and other lung diseases, but the mechanism associated with acupuncture in the treatment of chronic cough induced by lung surgery is unknown. We investigated whether acupuncture therapy could improve the symptoms of chronic cough after lung surgery through cyclic-AMp dependent protein kinase A (PKA)/cyclic-AMp dependent protein kinase C (PKC) regulation of the transient receptor potential vanilloid-1 (TRPV1) signaling pathway. Methods: The guinea pigs were divided into 5 groups: the Sham operation Group (Sham), the Model Group (Model), the Electroacupuncture + Model Group (EA + M), the H89 + Model Group (H89 + M) and the Go6983 + Model Group (Go6983 + M). The effect of treatment was determined by measuring cough symptoms (number of coughs/cough incubation period) as the outcome criterion. The levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and blood were determined by enzyme-linked immunosorbent assays (ELISA). Lung tissue was stained with hematoxylin and eosin (H&E). The expression of p-PKA, p-PKC and p-TRPV1 proteins was measured by Western blotting. The mRNA levels of TRPV1, Substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin-1R (NK1R) were measured by real-time polymerase chain reaction (RT-PCR). Results: Acupuncture significantly reduced the cough frequency and prolonged the cough latency of chronic cough in guinea pigs after lung surgery. In addition, acupuncture reduced the damage to lung tissue. The levels of inflammatory cytokines decreased in all treatment groups, the expression levels of p-PKA, p-PKC and p-TRPV1 were significantly inhibited and the mRNA levels of TRPV1, SP, CGRP and NK1R decreased significantly after acupuncture treatment. Conclusions: Acupuncture therapy ameliorated chronic cough in guinea pigs after lung surgery by regulating the TRPV1 signaling pathway via PKA/PKC. Our results showed that acupuncture may be an effective treatment of chronic cough after lung surgery, and also clarified the potential mechanism, which provides a theoretical basis for the clinical treatment of patients with chronic cough after lung surgery.

Albumin-based near-infrared phototheranostics for frequency upconversion luminescence/photoacoustic dual-modal imaging-guided photothermal therapy.

Engineering versatile phototheranostics for multimodal diagnostic imaging and effective therapy has great potential in cancer treatment. However, developing an inherently versatile molecule is a huge challenge. In this work, a near-infrared organic dye (NRh) was synthesized and further bound with bovine serum albumin (BSA) to construct facile "one-for-all" phototheranostics (NRh-BSA NPs), which exhibited enhanced frequency upconversion luminescence (FUCL, λex/em = 850/825 nm) and excellent photoacoustic (PA) and photothermal properties (λ'ex = 808 nm). Additionally, the BSA-modified phototheranostics NRh-BSA NPs showed specific accumulation in the tumor region through passive targeting. Based on the FUCL/PA dual modal imaging-guidance, the NRh-BSA NPs not only can guarantee the accuracy of imaging of the U87MG tumor sites, but also can improve the therapeutic effect on ablating tumors without recurrence by photothermal therapy (PTT). Collectively, our work proposed a novel strategy to construct versatile phototheranostics with the unique FUCL/PA imaging-guided technique for accurate cancer theranostics.

Quality marker discovery of Danggui Jianzhong decoction for treating primary dysmenorrhoea based on chinmedomics strategy.

BACKGROUND: Danggui Jianzhong Decoction (DGJZD) has been proven as an effective classical prescription for clinically treating primary dysmenorrhoea (PD). However, the industrialisation development and drug innovation of DGJZD remain limited due to its undefined effective constituents and quality markers (Q-markers). PURPOSE: Elucidating the Q-markers of DGJZD, which is related to clinical efficacy. METHODS: In accordance with chinmedomics strategy, we evaluated the therapeutic efficacy of DGJZD on the basis of the metabolomic profile and biomarker of a PD rat model to further identify the constituents of DGJZD in vivo that originated from the formula under the acting condition of DGJZD. The potential effective constituents and Q-markers were identified by mining the dynamic relation between the constituents in vivo and the biomarkers. RESULTS: Subsequently, 29 serum metabolites were characterized as biomarkers for PD, and DGJZD adjusted the levels of the primary biomarkers involved in arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism as well as the synthesis of steroid hormones. Under the active condition of DGJZD, 20 prototype ingredients and 4 metabolites of DGJZD were found in vivo, five of which were mostly related with the efficacy of PD, namely, ferulic acid, zizyphusin, cinnamic acid, protocatechuic acid-3-glucoside, and azelaic acid. They were the potential pharmacodynamic constituents for treating PD, and they could be regarded as the Q-markers of DGJZD. CONCLUSION: Taken together, the Q-markers of DGJZD identified in this research are credible and assist in solving problems related to quality control and drug innovation, accelerating industrialisation development. Besides, the efficacy, mechanism and active ingredients of DGJZD for the treatment of PD were innovatively elucidated for the first time on the basis of the chinmedomics strategy for uncovering the Q-markers of drugs from the system perspective.

[Analysis and evaluation on Paeoniae Radix Alba from different cultivars by UPLC-Q-TOF-MS and HPLC].

In this study, an established ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method was combined with multivariate statistical analysis to investigate the commonality and difference of main chemical components in the medicinal parts of Paeonia lactiflora from different cultivars; in addition, a high performance liquid chromatography(HPLC) method was established to simultaneously determine the content of eight active components in Paeoniae Radix Alba. Non-targeted analysis was carried out by UPLC-Q-TOF-MS on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 µm) column with a gradient elution of 0.1% aqueous formic acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 0.2 mL·min~(-1). The column temperature was 30 ℃, and an electrospray ionization source was used to acquire mass spectrometry data in positive and negative ion modes. According to the accurate molecular weight and fragment ion information provided by multi-stage mass spectrometry and by comparison with reference substances and literature reports, thirty-six identical components were identified in Paeoniae Radix Alba from different cultivars with positive and negative ion modes. In the negative ion mode, two groups of samples were well separated; specifically, seventeen components with significant differences in content were screened and identified, and one component unique in "Bobaishao" was obtained. Quantitative analysis was conducted by high-performance liquid chromatography(HPLC) on an Agilent HC-C_(18)(4.6 mm×250 mm, 5 µm) column with a gradient elution of 0.1% aqueous phosphoric acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 1.0 mL·min~(-1). The column temperature was 30 ℃ and the detection wavelength was at 230 nm. An HPLC method was developed for the simultaneous determination of eight active components(gallic acid, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, galloylpaeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, benzoyl-paeoniflorin) in Paeoniae Radix Albaa from different cultivars. Satisfactory linearity was achieved within the investigated linear ranges and with fine coefficients(r>0.999 0), and the methodological investigation showed that the method had good precision, repeatability and stability. The mean recoveries were 90.61% to 101.7% with RSD of 0.12% to 3.6%(n=6). UPLC-Q-OF-MS provided a rapid and efficient qualitative analytical method for the identification of the chemical components in Paeoniae Radix Alba, and the developed HPLC method was simple, rapid and accurate, which could provide a scientific basis for the evaluation of the germplasm resources and herbal quality of Paeoniae Radix Alba from different cultivars.

Systematic Literature Review of the Nutrient Status, Intake, and Diet Quality of Chinese Children across Different Age Groups.

There is a lack of comprehensive reports on nutrient deficiencies and dietary intake among various age groups of children in China. The objective of this review is to provide an overview of the nutrient status, intake, and diet adequacy of Chinese children (0-18 years old). PubMed and Scopus were searched for literature published between January 2010 and July 2022. A systematic review approach with a quality assessment was performed to analyze 2986 identified articles in English and Chinese. Eighty-three articles were included in the analysis. In younger children, anemia and iron and Vitamin A deficiencies remain severe public health problems, despite high Vitamin A and adequate iron intake. In older children, a high prevalence of selenium; Vitamin A and D deficiencies; and inadequate intakes of Vitamins A, D, B, C, selenium, and calcium were reported. Intakes of dairy, soybeans, fruits, and vegetables were below recommended levels. High intakes of iodine, total and saturated fat, and sodium and low dietary diversity scores were also reported. As nutritional concerns vary with age and region, future nutrition interventions should be tailored accordingly.

Chromosome-level genome assembly and functional characterization of terpene synthases provide insights into the volatile terpenoid biosynthesis of Wurfbainia villosa.

Wurfbainia villosa is a well-known medicinal and edible plant that is widely cultivated in the Lingnan region of China. Its dried fruits (called Fructus Amomi) are broadly used in traditional Chinese medicine for curing gastrointestinal diseases and are rich in volatile terpenoids. Here, we report a high-quality chromosome-level genome assembly of W. villosa with a total size of approximately 2.80 Gb, 42 588 protein-coding genes, and a very high percentage of repetitive sequences (87.23%). Genome analysis showed that W. villosa likely experienced a recent whole-genome duplication event prior to the W. villosa-Zingiber officinale divergence (approximately 11 million years ago), and a recent burst of long terminal repeat insertions afterward. The W. villosa genome enabled the identification of 17 genes involved in the terpenoid skeleton biosynthesis pathway and 66 terpene synthase (TPS) genes. We found that tandem duplication events have an important contribution to the expansion of WvTPSs, which likely drove the production of volatile terpenoids. In addition, functional characterization of 18 WvTPSs, focusing on the TPS-a and TPS-b subfamilies, showed that most of these WvTPSs are multi-product TPS and are predominantly expressed in seeds. The present study provides insights into the genome evolution and the molecular basis of the volatile terpenoids diversity in W. villosa. The genome sequence also represents valuable resources for the functional gene research and molecular breeding of W. villosa.

Overcoming Basal Autophagy, Kangai Injection Enhances Cisplatin Cytotoxicity by Regulating FOXO3a-Dependent Autophagic Cell Death and Apoptosis in Human Lung Adenocarcinoma A549/DDP Cells.

Cisplatin resistance is one of the major obstacles in the treatment of nonsmall cell lung cancer (NSCLC). Kangai injection (KAI), a Chinese herbal medicine, has been used in tumors as adjuvant treatment, but its exact antitumor mechanism is still unclear. In this study, we first demonstrated that cisplatin-resistant A549/DDP cells showed a higher level of basal autophagy in response to cisplatin treatment with increasing autophagic protein expression levels of Beclin 1, p62, and LC3 compared to cisplatin-sensitive A549/DDP cells; then, we assessed the antitumor effect of KAI in cisplatin-resistant lung adenocarcinoma A549/DDP cells. Our results showed that KAI exhibited direct cytotoxic and chemosensitizing effects in A549/DDP cells. Combining KAI with cisplatin promoted A549/DDP cell apoptosis, which was confirmed by cell cycle arrest, condensed nuclear chromatin, annexin V fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining, and apoptosis-related protein expression. In addition, combining KAI with cisplatin induced autophagic cell death in A549/DDP cells with a high level of basal autophagy, as indicated by an increase in LC3 spot count, an accumulation of Beclin 1 and LC3 II, and reduced p62 protein expression. We also found that the apoptosis and autophagic cell death induced by cotreatment of KAI and cisplatin in A549/DDP cells were FOXO3a-dependent as indicated by decreased p-FOXO3a expression and increased FOXO3a nuclear localization, respectively. Furthermore, the FOXO3a gene knockdown assay further confirmed that KAI enhanced cisplatin cytotoxicity in A549/DDP cells with a high level of basal autophagy by inducing apoptosis and autophagic cell death in a FOXO3a-dependent manner. These findings suggest that the combination of KAI and cisplatin might support the potential clinical treatment as a novel strategy to overcome cisplatin resistance.

Adjuvant Application of Shenmai Injection for Sepsis: A Systematic Review and Meta-Analysis.

Objective: To compare the efficacy and safety of Shenmai injection plus regular treatment versus regular treatment alone in the treatment of sepsis. Methods: Review Manager 5.3 was used. Databases including PubMed, Cochrane Library, Wan-FANG, VIP, CNKI, and CBM were searched for the relative control and randomized studies till June 2022. Primary outcomes were 28-day mortality; case fatality rate; APACHE II score; and levels of procalcitonin, tumor necrosis factor-α, interleukin-6, and C-reaction protein. Secondary outcomes were measurements related to inflammatory reactions, coagulation function, immune function, and organ function. Results: In total 21 studies with 1469 patients were included. Shenmai injection plus regular treatment of sepsis significantly decreased 28-day mortality rate (odds ratio: 0.36 (0.20, 0.63); p=0.0004) and case fatality rate (odds ratio: 0.32 (0.19, 0.54), p < 0.0001) and significantly further reduced APACHE II score (standard mean deviation: -1.14 (-1.30, 0.99); p < 0.00001). Procalcitonin reduction was similar in the two groups (standard mean deviation: -0.59 (-1.64, 0.46); p=0.27). Tumor necrosis factor-α (standard mean deviation: -1.96 (-2.79, -1.13); p < 0.00001), interleukin-6 (standard mean deviation: -1.52 (-2.13, -0.91); p < 0.00001), and C-reaction protein (standard mean deviation: -2.37 (-4.26, -0.49); p=0.01) levels were significantly further decreased in the Shenmai injection group. Most of the measurements related to inflammatory reaction, coagulation function, immune function, and organ function were significantly regulated in the Shenmai injection group. Furthermore, there was no adverse event, and two study groups had similar adverse event rates. Conclusion: Shenmai injection as adjuvant therapy shall be effective and safe in the treatment of sepsis. However, further investigation is still warranted especially regarding safety. Adjuvant application of Shenmai injection in sepsis is worth further investigation.

Regulatory effect of gut microbes on blood pressure.

Hypertension is an important global public health issue because of its high morbidity as well as the increased risk of other diseases. Recent studies have indicated that the development of hypertension is related to the dysbiosis of the gut microbiota in both animals and humans. In this review, we outline the interaction between gut microbiota and hypertension, including gut microbial changes in hypertension, the effect of microbial dysbiosis on blood pressure (BP), indicators of gut microbial dysbiosis in hypertension, and the microbial genera that affect BP at the taxonomic level. For example, increases in Lactobacillus, Roseburia, Coprococcus, Akkermansia, and Bifidobacterium are associated with reduced BP, while increases in Streptococcus, Blautia, and Prevotella are associated with elevated BP. Furthermore, we describe the potential mechanisms involved in the regulation between gut microbiota and hypertension. Finally, we summarize the commonly used treatments of hypertension that are based on gut microbes, including fecal microbiota transfer, probiotics and prebiotics, antibiotics, and dietary supplements. This review aims to find novel potential genera for improving hypertension and give a direction for future studies on gut microbiota in hypertension.

Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic Retinopathy.

Keluoxin (KLX) is an active agent in the treatment of diabetic retinopathy (DR). However, its mechanism, targets, and effective constituents against DR are still unclear, which seriously restricts its clinical application. Chinmedomics has the promise of explaining the pharmacological effects of herbal medicines and investigating the effective mechanisms. The research results from electroretinography and electron microscope showed that KLX could reduce retinal dysfunction and pathological changes by the DR mouse model. Based on effectiveness, we discovered 64 blood biomarkers of DR by nontargeted metabolomics analysis, 51 of which returned to average levels after KLX treatment including leukotriene D4 and A4, l-tryptophan, 6-hydroxymelatonin, l-phenylalanine, l-tyrosine, and gamma-linolenic acid (GLA). The metabolic pathways involved were phenylalanine metabolism, steroid hormone biosynthesis, sphingolipid metabolism, etc. Adenosine monophosphate-activated protein kinase (AMPK), extracellular signal-regulated protein kinase1/2 (ERK1/2), phosphatidylinositol-3-kinase (PI3K), and protein 70 S6 kinase (p70 S6K) might be potential targets of KLX against DR. This was related to the mammalian target of rapamycin (mTOR) signaling and AMPK signaling pathways. We applied the chinmedomics strategy, integrating serum pharm-chemistry of traditional Chinese medicine (TCM) with metabolomics, to discover astragaloside IV (AS-IV), emodin, rhein, chrysophanol, and other compounds, which were the core effective constituents of KLX when against DR. Our study was the first to apply the chinmedomics strategy to discover the effective constituents of KLX in the treatment of DR, which fills the gap of unclear effective constituents of KLX. In the next step, the research of effective constituents can be used to optimize prescription preparation, improve the quality standard, and develop an innovative drug.

Au@MnSe2 Core-Shell Nanoagent Enabling Immediate Generation of Hydroxyl Radicals and Simultaneous Glutathione Deletion Free of Pre-Reaction for Chemodynamic-Photothermo-Photocatalytic Therapy with Significant Immune Response.

As a typical tumor microenvironment-responsive therapy, chemodynamic therapy (CDT), producing hydroxyl radicals (• OH) to eliminate tumor cells, has demonstrated great promise. Nevertheless, there are still major challenges: • OH generated from endogenous H2 O2 is usually insufficient; the CDT effect is strongly dependent on the pre-reaction with glutathione. Addressing the challenges, Au@MnSe2 core-shell nanoagent for synergetic chemodynamic-photothermo-photocatalytic therapy combined with tetramodal imaging, including magnetic resonance imaging, computed tomography, photoacoustic, and infrared thermal imaging is reported. Distinct from the reported glutathione-depleting agents, Mn2+ in MnSe2 allows immediate generation of • OH, independent of pre-reaction. Meanwhile, Mn3+ consumes glutathione by its conversion to Mn2+ . The Au-MnSe2 combination promotes photothermal conversion and photocatalytic reaction, resulting in largely enhanced • OH generation from endogenous H2 O2 and significant hyperthermia. Meanwhile, immune response is effectively activated: the intratumoral expression of programmed cell death-1 and proinflammatory cytokines increase to 4-7 folds; the cytotoxic and helper T lymphocytes cells in the tumor area increase to more than 2.5-folds; an evident, temporary systemic immunostimulatory effect is demonstrated. High tumor inhibition rate (≈97.3%) and greatly prolonged survival are obtained. This highly-integrated design coordinating three different therapies with four different imaging modals provide new possibilities for high-performance theranostic nanoagents.

The association between essential trace element mixture and cognitive function in Chinese community-dwelling older adults.

BACKGROUND: The evidence about the effect of essential trace element (ETE) mixture on cognitive function amongst older adults is limited. This study aims to evaluate the associations of single ETEs and ETE mixture with cognitive function using a representative sample of community-dwelling older adults in China. METHODS: A total of 3814 older adults were included in the study. Urinary concentrations of selenium (Se), vanadium (V), cobalt (Co), strontium (Sr), and molybdenum (Mo) were detected by inductively coupled plasma mass spectrometry. Cognitive function in older adults was assessed using the Chinese version of the Mini-Mental State Examination (MMSE). Linear regression and Bayesian kernel machine regression (BKMR) were performed to explore the associations of single ETEs and ETE mixture with cognitive function, respectively. RESULTS: Linear regression showed that urinary levels of Se and V were positively associated with MMSE scores in the adjusted single-element models. BKMR also showed marginally positive associations of Se and V with MMSE scores. Moreover, higher urinary levels of ETE mixture were significantly associated with increased MMSE scores in a dose-response pattern, and Se was the most important contributor within the mixture. Both Se and V demonstrated positive additive effects on the associations of other ETEs with MMSE scores, whereas Co had a negative additive effect. CONCLUSIONS: V and Se are positively associated with cognitive function, individually and as a mixture. ETE mixture exhibits a linear dose-response association with improved cognitive function, with Se being the most important component within the mixture. Mixture analyses rather than single ETE analyses may provide a real-world perspective on the relationship between ETE mixture and cognitive function. Further cohort studies are needed to clarify the association of multiple ETEs with cognitive function.

Antibiofouling Ultrathin Poly(amidoxime) Membrane for Enhanced U(VI) Recovery from Wastewater and Seawater.

Although eco-friendly amidoxime-based adsorbents own an excellent uranium (U)-adsorption capacity, their U-adsorption efficiency is commonly reduced and even damaged by the biological adhesion from bacteria/microorganisms in an aqueous environment. Herein, we present an antibiofouling ultrathin poly(amidoxime) membrane (AUPM) with highly enhanced U-adsorption performance, through dispersing the quaternized chitosan (Q-CS) and poly(amidoxime) in a cross-linked sulfonated cellulose nanocrystals (S-CNC) network. The cross-linked S-CNC not only can elevate the hydrophilicity to improve the U-adsorption efficiency of AUPM but also can enhance the mechanical strength to form a self-supporting ultrathin membrane (17.21 MPa, 10 µm thickness). More importantly, this AUPM owns a good antibiofouling property, owing to the broad-spectrum antibacterial quaternary ammonium groups of the Q-CS. As a result, within the 1.00 L of low-concentration (100 ppb) U-added pure water (pH ≈ 5) and seawater (pH ≈ 8) for 48 h, 30 mg of AUPM can recover 93.7% U and 91.4% U, respectively. Furthermore, compared with the U-absorption capacity of a blank membrane without the Q-CS, that of AUPM can significantly increase 37.4% reaching from 6.39 to 8.78 mg/g after being in natural seawater for only 25 d. Additionally, this AUPM can still maintain almost constant tensile strength during 10 cycles of adsorption-desorption, which indicates the relatively long-term usability of AUPM. This AUPM will be a promising candidate for highly efficient and large-scale U-recovery from both U-containing waste freshwater/seawater and natural seawater, which will be greatly helpful to deal with the U-pollution and enrich U for the consumption of nuclear power. More importantly, the work will provide a new convenient but universal strategy to fabricate new highly enhanced low-cost U-adsorbents, through the introduction of both an antibacterial property and a high mechanical performance, which will be a good reference for the design of new highly efficient U-adsorbents.

Transformation from acute promyelocytic leukemia to acute myeloid leukemia with a CEBPA double mutation: A case report and review of the literature.

INTRODUCTION: The transformation of acute promyelocytic leukemia (APL) to acute mononuclear leukemia during treatment is a rare clinical phenomenon, and no CCAAT/enhancer-binding protein alpha (CEBPA) double mutations have been reported. PATIENT CONCERNS: A 42-year-old male was hospitalized for ecchymosis of the left lower limb for more than 1 month, gingival bleeding, and fatigue for 10 days, with aggravation of symptoms for 2 days. DIAGNOSIS: A diagnosis of APL was based on bone marrow (BM) morphology, immunophenotyping, fusion gene analysis, and fluorescence in situ hybridization. At a 1-year follow-up of maintenance treatment, he developed thrombocytopenia and was diagnosed with acute myeloid leukemia (AML) with a CEBPA double mutation by BM morphology, immunotyping, chromosomal analysis, polymerase chain reaction, and next generation sequencing. INTERVENTIONS: Complete remission of APL was achieved after all-trans retinoic acid and arsenic trioxide double induction therapy, followed by 2 cycles of mitoxantrone and cytarabine, and 1 cycle of idarubicin and cytarabine. Thereafter, sequential maintenance therapy of arsenic trioxide + all-trans retinoic acid + methotrexate was started. In the fourth cycle of maintenance therapy, APL was transformed into AML with a CEBPA double mutation. After 1 cycle of idarubicin and cytarabine, the patient achieved complete remission and received 3 cycles of idarubicin and cytarabine and three cycles of high-dose cytarabine as consolidation therapy. OUTCOMES: At present, the patient is in continuous remission with minimal residual disease negative for both of APL and AML. CONCLUSION: AML with a CEBPA double mutation after APL treatment is very rare, thus the prognosis of this event will require further observation.