A biodegradable semiconducting polymer phototherapeutic agent for safe cancer phototherapy.

Combined photodynamic therapy (PDT) and photothermal therapy (PTT) not only effectively reduce the hypoxic resistance to PDT, but also overcome the heat shock effect to PTT. However, the residual phototherapeutic agents still produce reactive oxygen species (ROS) to damage normal tissue under sunlight after treatment, which induces undesirable side effects to limit their biomedical application. Herein, a facile strategy is proposed to construct a biodegradable semiconducting polymer p-DTT, which is constructed by thieno[3,2-b]thiophene modified diketopyrrolopyrrole and (E)-1,2-bis(5-(trimethylstannyl)thiophen-2-yl)ethene moieties, to avoid the post-treatment side effects of phototherapy. Additionally, p-DTT exhibits strong photoacoustic (PA) for imaging, as well as good ROS production capacity and high photothermal conversion efficiency for synergistic PDT and PTT, which has been confirmed by both in vitro and in vivo results. After phototherapy, p-DTT could be gradually oxidized and degraded by endogenous ClO-, and subsequently lose ROS production and photothermal conversion capacities, which can guarantee the post-treatment safety, and address above key limitation of traditional phototherapy.

Vitamin D and hyperemesis gravidarum: A mendelian randomization study.

BACKGROUND: The causality between vitamin D and hyperemesis gravidarum remains unknown. Our aim was to investigate the causal effect of vitamin D on hyperemesis gravidarum using the two-sample Mendelian randomization method. METHODS: Independent single nucleotide polymorphisms significantly associated with serum 25-hydroxyvitamin D levels served as instrumental variables. The corresponding effect estimates for hyperemesis gravidarum were obtained from the Finngen Biobank. For Mendelian randomization analysis, inverse variance weighting was used as the primary method. We also used weighted median, MR-Egger regression, simple mode, and weighted mode as complementary methods to inverse variance weighting. The MR-Egger intercept test, Cochran's Q test, and "leave-one-out" sensitivity analysis were performed to assess the horizontal pleiotropy, heterogeneity, and stability of the causal association between 25-hydroxyvitamin D levels and hyperemesis gravidarum. RESULTS: We found that an increase in 25-hydroxyvitamin D level was associated with a lower risk of hyperemesis gravidarum [odds ratio (OR): 0.568, 95 % CI: 0.403-0.800, p = 0.001]. The result demonstrates the causal relationship between 25-hydroxyvitamin D level and the risk of hyperemesis gravidarum in the European population. CONCLUSIONS: The large Mendelian randomization analysis suggests that vitamin D may be causally associated with risk of hyperemesis gravidarum.

Geniposide ameliorates atherosclerosis by regulating macrophage polarization via perivascular adipocyte-derived CXCL14.

ETHNOPHARMACOLOGICAL RELEVANCE: Gardenia jasminoides Ellis is a traditional Chinese medicine that has been used for treatment of various diseases, including atherosclerosis by clearing heat and detoxication. Geniposide is considered as the effective compounds responsible for the therapeutic efficacy of Gardenia jasminoides Ellis against atherosclerosis. AIM OF THE STUDY: To investigate the effect of geniposide on atherosclerosis burden and plaque macrophage polarization, with focus on its potential impact on CXCL14 expression by perivascular adipose tissue (PVAT). MATERIALS AND METHODS: ApoE-/- mice fed a western diet (WD) were used to model atherosclerosis. In vitro cultures of mouse 3T3-L1 preadipocytes and RAW264.7 macrophages were used for molecular assays. RESULTS: The results revealed that geniposide treatment reduced atherosclerotic lesions in ApoE-/- mice, and this effect was correlated with increased M2 and decreased M1 polarization of plaque macrophages. Of note, geniposide increased the expression of CXCL14 in PVAT, and both the anti-atherosclerotic effect of geniposide, as well as its regulatory influence on macrophage polarization, were abrogated upon in vivo CXCL14 knockdown. In line with these findings, exposure to conditioned medium from geniposide-treated 3T3-L1 adipocytes (or to recombinant CXCL14 protein) enhanced M2 polarization in interleukin-4 (IL-4) treated RAW264.7 macrophages, and this effect was negated after CXCL14 silencing in 3T3-L1 cells. CONCLUSION: In summary, our findings suggest that geniposide protects ApoE-/- mice against WD-induced atherosclerosis by inducing M2 polarization of plaque macrophages via enhanced expression of CXCL14 in PVAT. These data provide novel insights into PVAT paracrine function in atherosclerosis and reaffirm geniposide as a therapeutic drug candidate for atherosclerosis treatment.

Study on the mechanism of Fufang E'jiao Jiang on precancerous lesions of gastric cancer based on network pharmacology and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang E'jiao Jiang (FEJ) is a prominent traditional Chinese medicine prescription, which consists of Asini Corii Colla (Donkey-hide gelatin prepared by stewing and concentrating from the hide of Equus asinus Linnaeus., ACC), Codonopsis Radix (the dried roots of Codonopsis pilosula (Franch.) Nannf., CR), Ginseng Radix et Rhizoma Rubra (the steamed and dried root of Panax ginseng C.A. Mey., GRR), Crataegi Fructus (the mature fruits of Crataegus pinnatifida Bunge., CF), and Rehmanniae Radix Praeparata (the steamed and sun dried tuber of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey., RRP). It is a popularly used prescription for "nourishing Qi and nourishing blood". AIM OF THE STUDY: To explore the potential mechanism of FEJ on precancerous lesion of gastric cancer in rats by combining network pharmacology and metabolomics. METHODS: Traditional Chinese Medicine Systems Pharmacology and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine were used to identify the ingredients and potential targets of FEJ. GeneCards database was used to define PLGC-associated targets. We built a herb-component-disease-target network and analyzed the protein-protein interaction network. Underlying mechanisms were identified using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. In addition, 40% ethanol, N-methyl-N'-nitro-N-nitroguanidine and irregular eating were used to establish PLGC rats model. We also evaluated the efficacy of FEJ on MNNG-induced PLGC rats by body weight, histopathology, blood routine and cytokine levels, while the predicted pathway was determined by the Western blot. Ultra-performance liquid chromatography-tandem mass spectrometry-based serum non-targeted metabolomics was used to select potential biomarkers and relevant pathways for FEJ in the treatment of PLGC. RESULTS: Network pharmacology showed that FEJ exhibited anti-PLGC effects through regulating ALB, TNF, VEGFA, TP53, AKT1 and other targets, and the potential pathways mainly involved cancer-related, TNF, PI3K-AKT, HIF-1, and other signaling pathways. Animal experiments illustrated that FEJ could suppress inflammation, regulate gastrointestinal hormones, and inhibit the expression of PI3K/AKT/HIF-1α pathway-related proteins. Based on serum non-targeted metabolomics analysis, 12 differential metabolites responding to FEJ treatment were identified, and metabolic pathway analysis showed that the role of FEJ was concentrated in 6 metabolic pathways. CONCLUSION: Based on network pharmacology, animal experiments and metabolomics, we found that FEJ might ameliorate gastric mucosal injury in PLGC rats by regulating gastrointestinal hormones and inhibiting inflammation, and its mechanism of action is related to the inhibition of excessive activation of PI3K/AKT/HIF-1α signaling pathway and regulation of disorders of body energy metabolism. This comprehensive strategy also provided a reasonable way for unveiling the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in Traditional Chinese Medicine.

Expert consensus on multi-disciplinary treatment, whole-course pulmonary rehabilitation management in patients with lung cancer and chronic obstructive lung disease.

Comorbidity of lung cancer and chronic obstructive pulmonary disease (COPD) is very common. Surgical operation is the initial treatment of lung cancer. But surgery operation will aggravate the symptoms of COPD, such as shortness of breath, chest tightness. On the other side, the COPD also increase the perioperative complications. Besides, the COPD may also influence the anti-cancer treatment and long-term survival of lung cancer patients. At present, there are guidelines for pulmonary rehabilitation (PR) of COPD or lung cancer respectively, but there is no reference expert consensus on the PR of patients with lung cancer who are comorbidity of COPD. Primary care has to satisfy the patient's complex needs holistically, and single-disease guidelines are unsuitable. In view of this, we organized experts from respiratory department, thoracic surgery department, oncology department, nursing department, etc., to write the expert consensus. We discussed the contents of the expert consensus through literature review, expert correspondence, expert meeting and discussion. This expert consensus contain five parts: introduction, respiratory assessment, timing of PR, PR strategies, perioperative PR management strategies in lung cancer patients with COPD. This expert consensus focuses on patients with COPD comorbid lung cancer and undergoing surgery operation, highlighting the concept of whole process management. For clinical medical staff, this expert consensus will promote the practice of PR in and out the hospital for this specific patient; for patients, this expert consensus is helpful to better understand PR and improve the enthusiasm of participating in PR in the whole process.

Aqueous Extract of Guava (Psidium guajava L.) Leaf Ameliorates Hyperglycemia by Promoting Hepatic Glycogen Synthesis and Modulating Gut Microbiota.

Type 2 diabetes mellitus (T2DM) is a major global health concern. Psidium guajava L. (guava) is widely used for food as well as a folk medicine. Previous studies have shown its anti-diabetic and anti-inflammatory properties. However, the underlying mechanisms remains to be elusive. In this study, we assessed the potential therapeutic effects of aqueous extract of guava leaves (GvAEx) on T2DM and explored their potential mechanisms in vivo and in vitro. GvAEx was gavage administered for 12 weeks in diabetic db/db mice. Our results have demonstrated that GvAEx significantly lowered fasting plasma glucose levels (p < 0.01) and improved glucose tolerance and insulin sensitivity (p < 0.01, p < 0.05, respectively). Additionally, GvAEx increased hepatic glycogen accumulation, glucose uptake and decreased the mRNA expression levels of gluconeogenic genes. Furthermore, GvAEx-treatment caused higher glucose transporter 2 (GLUT2) expression in the membrane in hepatocytes. Notably, for the first time, we have elaborated the possible mechanism of the hypoglycemic effect of GvAEx from the perspective of intestinal microbiota. GvAEx has significantly changed the composition of microbiota and increased short chain fatty acid (SCFA) -producing Lachnospiraceae family and Akkermansia genus in the gut. Taken together, GvAEx could alleviate hyperglycemia and insulin resistance of T2DM by regulating glucose metabolism in the liver and restoring the gut microbiota. Thus, GvAEx has the potential for drug development against T2DM.

[Influence of processing factors on honey-fried Codonopsis Radix].

The present study investigated the influence of heating and honey addition on the appearance, chemical component content, and pharmacological activity of Codonopsis Radix decoction pieces in the honey-frying process, and explored the processing mechanism of honey-fried Codonopsis Radix. The color, sweetness, and content of macromolecular components(e.g., oligosaccharides and polysaccharides) and small molecular components(e.g., lobetyolin and atractylenolide Ⅲ) of raw Codonopsis Radix, fried Codonopsis Radix, honey-mixed Codonopsis Radix, and honey-fried Codonopsis Radix were determined, and the antioxidant activities in vitro of their water extract, polysaccharide extract, and oligosaccharide extract were compared. The results showed that in terms of color and sweetness, compared with the raw Codonopsis Radix, the fried Codonopsis Radix slightly changed, the honey-mixed Codonopsis Radix changed significantly, and the honey-fried Codonopsis Radix changed with high significance. In terms of the content of lobetyolin, atractylenolide Ⅲ, and polysaccharides, the samples were ranked as raw Codonopsis Radix > fried Codonopsis Radix > honey-mixed Codonopsis Radix > honey-fried Codonopsis Radix, which indicated that heating and honey addition could reduce the content of these three components. In terms of the content of oligosaccharides, the samples were ranked as honey-fried Codonopsis Radix ≈ honey-mixed Codonopsis Radix > fried Codonopsis Radix ≈ raw Codonopsis Radix, indicating that honey addition could increase the content of oligosaccharides. In terms of antioxidant activity in vitro, ABTS radical scavenging ability of water extract, polysaccharides, and oligosaccharides of honey-fried Codonopsis Radix was most potent, while the change of antioxidant activity in vitro of each extract in the other three processed products was different. In short, both heating and honey addition can affect the appearance, chemical component content, and antioxidant activity in vitro of Codonopsis Radix decoction pieces, but the effect of the combination of the two factors is the best. The comprehensive analysis of the effects of heating and honey addition on Codonopsis Radix decoction pieces indicates that honey addition followed by heating at high temperature is the necessary condition for honey-fried Codonopsis Radix to enhance its activity.

Characterization of chemical composition variations in raw and processed Codonopsis Radix by integrating metabolomics and glycomics based on multiple chromatography-mass spectrometry technology.

Codonopsis Radix, a popular food homology medicine, is widely used in clinical traditional Chinese medicine and food supplement, raw products and three types of processed products are the main forms of decoction pieces in China. However, there is no scientific basis for comprehensive chemical characterization of raw and three types of processed products. Herein, we investigated qualitatively and quantificationally secondary and primary metabolites in raw Codonopsis Radix and three types of processed products by metabolomics and glycomics employing multiple chromatography-mass spectrometry technology combined with chemometric analysis further to look for differential compounds and propose the processing-induced chemical mechanisms. The results indicated that Codonopsis Radix became dark-colored and the smell of burnt incense odor was observed after processing. The principal component analysis demonstrated that secondary metabolome and glycome were significantly altered between raw and processed products, and 36 differential secondary metabolites and 11 differential primary metabolites were finally screened through orthogonal partial least-squares-discriminant analysis. The main types of compounds are alkaloids, terpenoids, glycosides, amino acids, monosaccharides, oligosaccharides, and furfural derivatives. Meanwhile, Chemical mechanisms could be involved, including oxidation, glycosidic hydrolysis, esterification, dehydration, and Maillard reaction. This work supplies a chemical basis for the application of various types of Codonopsis Radix decoction pieces.

Unique BiFeO3/g-C3N4 mushroom heterojunction with photocatalytic antibacterial and wound therapeutic activity.

Bacterial infections have become a major problem threatening public health, and it is of great significance to treat wound infections in biological systems caused by bacteria. However, traditionally used bacteriostatic agents usually cause additional pollution. Herein a mushroom-shaped clean and Green BiFeO3/g-C3N4 composite is employed for the first time for photocatalytic antibacterial activity and for the further promotion of wound healing. The ratio between BiFeO3 and g-C3N4 was delicately regulated to control the generated amount of ˙OH and ˙O2- by catalyzing the decomposition of hydrogen peroxide (H2O2) under illumination. Results show that 10%BFO/CN demonstrates the best performance for ˙OH and ˙O2- production, resulting in the highest antibacterial ability against E. coli and S. aureus. In addition, the catalytic mechanism of BiFeO3/g-C3N4 towards antibacterial activity is disclosed by a combination of ESR monitoring and analysis of the Mott-Schottky diagram. Furthermore, in vivo experiments prove that 10%BFO/CN can effectively promote anti-infection and wound healing in nude mice. This work sheds deep scientific insight on the synergistic effect of photocatalysis and photo-Fenton degradation as well as their application in antibacterial and wound therapeutic activity.

Two new aromatic derivatives from Codonopsis pilosula and their α-glucosidase inhibitory activities.

The ethanol extract of the roots of Codonopsis pilosula was subjected to chromatographic fractionation, which result in the isolation and characterization of two new aromatic derivatives 2,3-dihydroxypropyl 2,4-dihydroxy-3,6-dimethylbenzoate (1) and 2-oxopropyl 3-hydroxy-4-methoxybenzoate (2), along with three known compounds pilosulinene A (3), pollenfuran B (4) and (+)-pinoresinol (5). Their structures were demonstrated by HRESIMS and spectroscopic methods including NMR and IR. It is worth noting that compound 4 was isolated for the first time from the genus Codonopsis. The potential hypoglycemic properties of compounds 2-5 were evaluated by measuring their α-glucosidase inhibitory effects. As a result, compounds 2 and 3 showed weak α-glucosidase inhibitory activities with IC50 values of 154.8 ± 11.0 µM and 24.0 ± 2.2 µM, respectively.[Formula: see text].

Effect of Vitamin B2 supplementation on migraine prophylaxis: a systematic review and meta-analysis.

OBJECTIVE: Migraine is a common disease worldwide and migraine prevention is primarily currently based on pharmaceuticals. The mechanism of Vitamin B2 may positively contribute to migraine. This systematic review and meta-analysis aimed to evaluate the impact of Vitamin B2 supplementation on the days, duration, frequency, and pain score of the migraine attack. METHODS: : The PRISMA guideline was used for the studying process. Five electronic databases, PubMed, Embase, Cochrane, CINAHL, and CEPS were searched from 1990 to March 2019. The search terms were Vitamin B2, migraine, and prophylactic. A meta-analysis was performed using Comprehensive Meta-Analysis (CMA) version. RESULTS: : Nine articles were included in systemic review and finally meta-analysis. Eight randomized controlled trials and one controlled clinical trial with 673 subjects were analyzed using meta-analysis. Vitamin B2 supplementation significantly decreased migraine days (p = .005, I2 = 89%), duration (p = .003, I2 = 0), frequency (p = .001, I2 = 65%), and pain score (p = .015, I2 = 84%). CONCLUSIONS: A pooled analysis of available randomized controlled clinical trials demonstrated that Vitamin B2 400 mg/day for three months supplementation had significant effect on days, duration, frequency, and pain score of migraine attacks.

Blood cell characterization and transcriptome analysis reveal distinct immune response and host resistance of different ploidy cyprinid fish following Aeromonas hydrophila infection.

Aeromonas hydrophila can pose a great threat to survival of freshwater fish. In this study, A. hydrophila infection could decrease blood cell numbers, promote blood cell damage as well as alter the levels of alkaline phosphatase (ALP), lysozyme (LZM), aspartate aminotransferase (AST), total antioxidant capacity (T-AOC), total superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in immune-related tissues of red crucian carp (RCC, 2 N = 100) and triploid cyprinid fish (3 N fish, 3 N = 150). In addition, the significant alternation of antioxidant status was observed in PBMCs isolated from RCC and 3 N following LPS stimulation. The core differential expression genes (DEGs) involved in apoptosis, immunity, inflammation and cellular signals were co-expressed differentially in RCC and 3 N following A. hydrophila challenge. NOD-like receptor (NLR) signals appeared to play a critical role in A. hydrophila-infected fish. DEGs of NLR signals in RCCah vs RCCctl were enriched in caspase-1-dependent Interleukin-1ß (IL-1ß) secretion, interferon (IFN) signals as well as cytokine activation, while DEGs of NLR signals in 3Nah vs 3Nctl were enriched in caspase-1-dependent IL-1ß secretion and antibacterial autophagy. These results highlighted the differential signal regulation of different ploidy cyprinid fish to cope with bacterial infection.

Tribulus terrestris L. protects glomerular endothelial cells via the miR155-H2AC6 interaction network in hypertensive renal injury.

BACKGROUND: Hypertensive renal injury is one of the most lethal complications of hypertension. At present, renin-angiotensin-aldosterone system (RAAS) blockers are considered the best drugs for the treatment of renal injury in hypertension because of their nephroprotective effect of reducing proteinuria, but there are no specific drugs for this purpose, however, clinical trials proved that Chinese medicine has a protective effect on target organs in the treatment of hypertension. Tribulus terrestris L. (TrT), a traditional Chinese medicine (TCM), has potential applications due to its reno-protective and immunomodulatory effects. METHODS: We investigated the underlying reno-protective mechanism of TrT on Angiotensin II (AngII)-induced hypertensive renal injury in glomerular endothelial cells by integrating the differential expression profiles of micro RNA (miRNA) and messenger RNA (mRNA) to construct a miRNA-mRNA interaction network associated with hypertensive kidney injury, followed by quantitative real-time polymerase chain reaction (qRT-PCR) for validation. RESULTS: Seventy-six differentially expressed mRNAs (DEmRNAs) and 1 differentially expressed miRNAs (DEmiRNAs) were identified in the control group and the AngII-induced hypertensive renal injury group, respectively. 110 DEmRNAs and 27 DEmiRNAs were identified in the TrT treatment group and the AngII-induced group, respectively. The core component of the miRNA-mRNA network was miR-155-5p. Our study showed that miR-155-5p expression levels were more decreased in the AngII-induced hypertensive renal injury group than the control group. TrT treatment also significantly upregulated miR-155-5p. Additionally, we found that miR-155-5p expression levels were negatively correlated with H2A clustered histone 6 (H2AC6). CONCLUSIONS: The results of this study indicate that TrT has a reno-protective effect on AngII-induced hypertensive renal injury by miR-155-5p, which negatively regulates the expression of H2AC6. Our findings offer a new therapeutic strategy and have identified an effective candidate target for the treatment of hypertensive renal injury in clinical settings.

Activation of Neuronal Voltage-Gated Potassium Kv7/KCNQ/M-Current by a Novel Channel Opener SCR2682 for Alleviation of Chronic Pain.

Treatment of chronic pain remains an unmet medical need. The neuronal voltage-gated potassium Kv7/KCNQ/M channel has been implicated as a therapeutic target for chronic pain. However, whether pharmacological activation of the Kv7 channel can alleviate pain remains elusive. In this study, we show that selective activation of native M-currents by a novel channel opener SCR2682 reduces repetitive firings of dorsal root ganglia (DRG) sensory neurons. Intraperitoneal administration of SCR2682 relieves mechanical allodynia and thermal hyperalgesia in rat models of pain induced by complete Freund's adjuvant (CFA) or spared nerve injury (SNI) in a dose-dependent manner without affecting locomotor activity. The antinociceptive efficacy of SCR2682 can be reversed by the channel-specific blocker XE991. Furthermore, SCR2682 increases Kv7.2/KCNQ2 mRNA and protein expression in DRG neurons from rats in the SNI model of neuropathic pain. Taken together, pharmacological activation of neuronal Kv7 channels by opener SCR2682 can alleviate pain in rats, thus possessing therapeutic potential for chronic pain or hyperexcitability-related neurologic disorders. SIGNIFICANCE STATEMENT: A novel voltage-gated potassium Kv7 channel opener SCR2682 inhibits action potential firings in dorsal root ganglia sensory neurons and exhibits efficacy in antinociception, thus possessing a developmental potential for treatment of chronic pain or epilepsy.

Network pharmacology unveils spleen-fortifying effect of Codonopsis Radix on different gastric diseases based on theory of "same treatment for different diseases" in traditional Chinese medicine.

Objective: "Same treatment for different diseases" is a unique treatment strategy under the guidance of traditional Chinese medicine (TCM) theory. Codonopsis Radix (Codonopsis pilosula, Dangshen in Chinese) with spleen-fortifying effect was employed to understand the strategy of "Same treatment for different diseases", based on its common mechanism in the treatment of gastric diseases including gastric ulcer, gastritis and gastric cancer via network pharmacology research. Methods: Network pharmacology research methods were used to analyze the interaction network and potential mechanisms of Dangshen in treating gastric ulcer, gastritis and gastric cancer. The active components and their target proteins of Dangshen were integrated from TCMSP, BATMAN-TCM databases. The targets of gastric ulcer, gastritis and gastric cancer were collected through GeneCards, PubMed, TDD and DisGeNET Database. Through screening, the key components and the key targets of Dangshen in treating gastric ulcer, gastritis and gastric cancer were obtained. After KEGG pathway analysis and GO analysis, the important pathways and biological processes were analyzed. Results: Through data and literature mining, the common and specific pharmaceutical effects and mechanism of Dangshen were summarized in these three gastric lesions. It was shown that Dangshen mainly acted on gastric ulcer, gastritis and gastric cancer through the overall regulation of the PI3K-AKT signaling pathway. With the development of the disease, it will gradually increase the control of inflammation through TNF, NF-κB and other inflammation-related signaling pathways to reduce inflammatory damage. For tumorigenesis, it pays more attention to inhibiting the ErbB signaling pathways to reduce the proliferation and migration of tumor cells. In addition, Dangshen's regulation of HIF-1 signaling pathway may also be beneficial for the treatment of gastric ulcer, gastritis and gastric cancer. Conclusion: Dangshen achieves spleen-fortifying effect on gastric diseases including gastric ulcer, gastritis and gastric cancer through multiple targets in multiple pathways, especially PI3K-AKT pathway and HIF-1 pathway. It could provide a scientific basis for understanding the strategy of "Same treatment for different diseases" in traditional Chinese medicine.

Nanomedicine of Plant Origin for the Treatment of Metabolic Disorders.

Metabolic disorders are major clinical challenges of health that are progressing globally. A concurrence of metabolic disorders such as obesity, insulin resistance, atherogenic dyslipidemia, and systematic hypertension leads to metabolic syndrome. Over the past years, the metabolic syndrome leads to a five- and two-fold rise in diabetes mellitus type II and cardiovascular diseases. Natural products specifically plant extracts have insulin-sensitizing, anti-inflammatory, and antioxidant properties and are also considered as an alternative option due to few adverse effects. Nanotechnology is one of the promising strategies, which improves the effectiveness of treatment and limits side effects. This review mainly focuses on plant extract-based nanosystems in the management of the metabolic syndrome. Numerous nano-drug delivery systems, i.e., liposomes, hydrogel nanocomposites, nanoemulsions, micelles, solid lipid, and core-shell nanoparticles, have been designed using plant extracts. It has been found that most of the nano-formulations successfully reduced oxidative stress, insulin resistance, chronic inflammation, and lipid profile in in vitro and in vivo studies as plant extracts interfere with the pathways of metabolic syndrome. Thus, these novel plant-based nanosystems could act as a promising candidate for clinical applications.

Protective effects of natural compounds against oxidative stress in ischemic diseases and cancers via activating the Nrf2 signaling pathway: A mini review.

Oxidative stress, an imbalance between reactive oxygen species and antioxidants, has been seen in the pathological states of many disorders such as ischemic diseases and cancers. Many natural compounds (NCs) have long been recognized to ameliorate oxidative stress due to their inherent antioxidant activities. The modulation of oxidative stress by NCs via activating the Nrf2 signaling pathway is summarized in the review. Three NCs, ursolic acid, betulinic acid, and curcumin, and the mechanisms of their cytoprotective effects are investigated in myocardial ischemia, cerebral ischemia, skin cancer, and prostate cancer. To promote the therapeutic performance of NCs with poor water solubility, the formulation approach, such as the nano drug delivery system, is elaborated as well in this review.

Application of N-methyl-D-aspartate receptor nanopore in screening ligand molecules.

N-methyl-D-aspartate receptors (NMDARs) are crucial for excitatory synaptic transmission in the central nervous system. To study NMDARs more accurately and conveniently, we developed a stable NMDAR nanopore in a planar lipid bilayer. Pharmacological properties were validated using the allosteric modulator Ro 25-6981 and antagonist D-2-amino-5-phosphonopentanoic acid (D-APV). The cyanotoxin ß-N-methylamino-L-alanine (BMAA) found in fresh water systems is suspected to be associated with the development of neurodegenerative diseases. Therefore, BMAA and its two isomers L-2, 4-Diaminobutyric acid dihydrochloride (DAB) and N-(2-aminoethyl) glycine (AEG) and an endogenous excitotoxin, quinolinic acid (QA), were studied using the NMDAR nanopores to assess their effects on NMDAR modulation. We demonstrated that the NMDAR nanopore could reliably detect its ligand molecules at the single-channel level. The study also demonstrated the practicability of NMDAR nanopores, and results were validated using two-electrode voltage-clamp (TEVC) recording. Compared with TEVC recording, the NMDAR nanopores conducted ion channel gating at the single-channel level without being affected by other proteins on the cell membrane. The highly sensitive and accurate NMDAR nanopore technique thus has a unique advantage in screening NMDAR ligand molecules that could be associated with neurodegenerative disease.

Symptom Distribution Regularity of Insomnia: Network and Spectral Clustering Analysis.

BACKGROUND: Recent research in machine-learning techniques has led to significant progress in various research fields. In particular, knowledge discovery using this method has become a hot topic in traditional Chinese medicine. As the key clinical manifestations of patients, symptoms play a significant role in clinical diagnosis and treatment, which evidently have their underlying traditional Chinese medicine mechanisms. OBJECTIVE: We aimed to explore the core symptoms and potential regularity of symptoms for diagnosing insomnia to reveal the key symptoms, hidden relationships underlying the symptoms, and their corresponding syndromes. METHODS: An insomnia dataset with 807 samples was extracted from real-world electronic medical records. After cleaning and selecting the theme data referring to the syndromes and symptoms, the symptom network analysis model was constructed using complex network theory. We used four evaluation metrics of node centrality to discover the core symptom nodes from multiple aspects. To explore the hidden relationships among symptoms, we trained each symptom node in the network to obtain the symptom embedding representation using the Skip-Gram model and node embedding theory. After acquiring the symptom vocabulary in a digital vector format, we calculated the similarities between any two symptom embeddings, and clustered these symptom embeddings into five communities using the spectral clustering algorithm. RESULTS: The top five core symptoms of insomnia diagnosis, including difficulty falling asleep, easy to wake up at night, dysphoria and irascibility, forgetful, and spiritlessness and weakness, were identified using evaluation metrics of node centrality. The symptom embeddings with hidden relationships were constructed, which can be considered as the basic dataset for future insomnia research. The symptom network was divided into five communities, and these symptoms were accurately categorized into their corresponding syndromes. CONCLUSIONS: These results highlight that network and clustering analyses can objectively and effectively find the key symptoms and relationships among symptoms. Identification of the symptom distribution and symptom clusters of insomnia further provide valuable guidance for clinical diagnosis and treatment.

Immune-enhancement effects of oligosaccharides from Codonopsis pilosula on cyclophosphamide induced immunosuppression in mice.

As an important edible traditional Chinese medicine, Codonopsis pilosula has good immunomodulation effects. This study focuses on C. pilosula oligosaccharides (CPO), which are the sweetness components of C. pilosula. CPO were obtained through systematic separation and purification (the yield is 14.3%), and the effect of CPO on the immunological activities of immunocompromised mice induced by cyclophosphamide (CTX) was evaluated. The results showed that CPO could increase immune organ indices, phagocytic index and immunoglobulin contents, stimulate the proliferation of splenic lymphocytes (coordinating with ConA and LPS), enhance the earlap swelling of the DTH reaction, promote the production of NO and cytokines (IL-2 and IFN-γ) and upregulate the expression of the corresponding mRNA. In addition, CPO upregulated the protein expression of phosphorylated p38, phosphorylated ERK1/2 and phosphorylated JNK, which indicated that CPO might exert immunomodulatory effects through the MAPK signaling pathway. These findings indicated that CPO are important immunomodulatory components in C. pilosula and could be developed as immunomodulators in medicine or functional food areas.