A systematic approach for authentication of medicinal Patrinia species using an integration of morphological, chemical and molecular methods.

Four common Patrinia species, including P. heterophylla, P. monandra, P. scabiosifolia and P. villosa, have been documented as herbal medicines with various clinical applications, such as anti-cancer, anti-diarrhea and sedative. However, the authentication of medicinal Patrinia species poses a problem, particularly with the processed herbal materials. This study aimed to systematically authenticate the four medicinal Patrinia species in the market using morphological and chemical characterization, as well as DNA markers. We found the species identity authenticated by traditional morphologies were in good agreement with both chemical and molecular results. The four species showed species-specific patterns in chromatographic profiles with distinct chemical markers. We also revealed the power of complete chloroplast genomes in species authentication. The sequences of targeted loci, namely atpB, petA, rpl2-rpl23 and psaI-ycf4, contained informative nucleotides for the species differentiation. Our results also facilitate authentication of medicinal Patrinia species using new DNA barcoding markers. To the best of our knowledge, this is the first report on the application of morphology, chemical fingerprinting, complete chloroplast genomes and species-specific Insertion-Deletions (InDels) in differentiating Patrinia species. This study reported on the power of a systematic, multidisciplinary approach in authenticating medicinal Patrinia species.

Clinical Value of Heart Qi in the Treatment of Chronic Heart Failure With Depression.

Context: Chronic heart failure (CHF) is a form of persistent heart failure. If a patient develops depression, it can worsen the severity of heart failure and can lead to adverse outcomes. No researchers have studied the effects of tonic heart qi soup for patients with CHF and depression. Objective: The study intended to evaluate the clinical efficacy of tonic heart qi soup in the treatment of chronic heart failure (CHF) for patients with comorbid depression. Design: The research team performed a prospective randomized controlled trial. Setting: The study took place in the Department of Chinese Medicine at Cangzhou Central Hospital in Cangzhou, Hebei Province, China. Participants: Participants were 120 patients with CHF at the hospital as inpatients or outpatients between January 2016 and January 2019. Intervention: The research team divided participants into two groups, with 60 patients each: (1) an intervention group, which received conventional Western medical treatment combined with treatment with a commercial tonic heart qi soup and (2) a control group, which received conventional Western medical treatment only. Outcome Measures: The research team measured: (1) treatment efficacy, (2) cardiac function, (3) adverse reactions, (4) B-type natriuretic peptide (BNP) and Ghrelin, and (5) depression. Results: In the intervention group, 55 participants showed significant improvement in the degree of heart failure, for a total effectiveness rate of 91.67%, which was significantly higher than that of the control group (P = .000). The intervention group had 10 participants in class II, 18 in class III, and 22 in class IV. Among them, 28 participants improved, indicating significantly better outcomes than those of the control group. The intervention group's BNP levels, at 1031.58 ± 118.83 pg/ml, and ghrelin levels, at 481.46 ± 57.53%, were significantly lower than those of the control group. No liver- or renal-function damage, insomnia, or significant adverse reactions occurred for either group. The intervention group's total incidence rate for adverse reactions, at 1.67%, was significantly lower than that of the control group, at 11.67% (P = .000) and also had a higher total effective rate in reducing depression, at 86.67%, compared to that of the control group, at 43.33%. Conclusions: Heart Qi Tonic Tang, as an adjunctive therapy, significantly improved outcomes for CHF patients with depression. It effectively reduced heart failure symptoms, with minimal adverse reactions and increased patient comfort and compliance.

Identification of the Metabolites of Both Formononetin in Rat Hepatic S9 and Ononin in Rat Urine Samples and Preliminary Network Pharmacology Evaluation of Their Main Metabolites.

Astragalus membranaceus is a traditional Chinese medicine derived from the roots of Astragalus membranaceus (Fisch.) Bge., which has the same medicinal and edible uses in China. It is also widely used in daily food, and its pharmacological effects mainly include antioxidant effects, vascular softening effects, etc. Currently, it is increasingly widely used in the prevention of hypertension, cerebral ischemia, and stroke in China. Formononetin and its glucopyranoside (ononin) are both important components of Astragalus membranaceuss and may play important roles in the treatment of cardiovascular diseases (CVDs). This study conducted metabolic studies using formononectin and its glucopyranoside (ononin), including a combination of the in vitro metabolism of Formonetin using rat liver S9 and the in vivo metabolism of ononin administered orally to rats. Five metabolites (Sm2, 7, 9, 10, and 12) were obtained from the solution incubated with formononetin and rat hepatic S9 fraction using chromatographic methods. The structures of the five metabolites were elucidated as (Sm2)6,7,4'-trihydroxy-isoflavonoid; (Sm7)7,4'-dihydroxy-isoflavonoid; (Sm9)7,8,4'-trihydroxy-isoflavonoid; (Sm10)7,8,-dihydroxy-4'-methoxy-isoflavonoid; and (Sm12)6,7-dihydroxy-4'-methoxy- isoflavonoid on the basis of UV, NMR, and MS data. Totally, 14 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSn analysis, from which the formononetin was incubated with rat hepatic S9 fraction, and the main metabolic pathways were hydroxylation, demethylation, and glycosylation. Then, 21 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSn analysis from the urine samples from SD rats to which ononin was orally administered, and the main metabolic pathways were glucuronidation, hydroxylation, demethylation, and sulfonation. The main difference between the in vitro metabolism of formononetin and the in vivo metabolism of ononin is that ononin undergoes deglycemic transformation into Formonetin in the rat intestine, while Formonetin is absorbed into the bloodstream for metabolism, and the metabolic products also produce combined metabolites during in vivo metabolism. The six metabolites obtained from the aforementioned separation indicate the primary forms of formononetin metabolism, and due to their higher contents of similar isoflavone metabolites, they are considered the main active compounds that are responsible for pharmacological effects. To investigate the metabolites of the active ingredients of formononetin in the rat liver S9 system, network pharmacology was used to evaluate the cardiovascular disease (CVD) activities of the six primary metabolites that were structurally identified. Additionally, the macromolecular docking results of six main components and two core targets (HSP90AA1 and SRC) related to CVD showed that formononetin and its main metabolites, Sm10 and Sm12, may have roles in CVD treatment due to their strong binding activities with the HSP90AA1 receptor, while the Sm7 metabolite may have a role in CVD treatment due to its strong binding activity with the SRC receptor.

Inhibition of Acetylcholine Expression in the Tumor Microenvironment by Mustard Oil: A Potential Strategy to Retard Colon Cancer Progression.

Objective: This study aims to investigate the potential of mustard oil-induced reduction in acetylcholine expression as a means to delay the progression of colon cancer within the internal environment. Methods: The study design in this research involved both in vitro cellular experiments and in vivo animal experiments to employ mustard oil to modulate acetylcholine expression levels and evaluate its impact on colon cancer. Cellular experiments involved the introduction of six concentrations of acetylcholine (10-2, 10-3, 10-4, 10-5, 10-6, and 10-7 mol/L) into colon cancer cell cultures to monitor cell proliferation. Animal experiments encompassed the subcutaneous CT26 colon cancer cells implantation into 28 Balb/c mice, divided into experimental and control groups. After tumor establishment, both groups were fed standard diets for two weeks. Serum acetylcholine concentrations were measured from eye blood samples. Additionally, Balb/c mice were inoculated with CT26-derived colon cancer cells and further categorized into experimental and control groups. A total of 14 mice comprised each group, with experimental mice fed mustard oil and control mice fed soybean oil. Post two weeks, serum acetylcholine expression in both groups was assessed. After sacrifice, subcutaneous tumors were excised, and tumor dimensions were measured using a Vernier scale. Results: Acetylcholine concentration augmentation in the culture medium corresponded to gradual cell proliferation escalation, peaking at 10-5 mol/L, exhibiting statistical significance. Comparative analysis revealed significantly elevated relative acetylcholine expression levels in Balb/c mice with tumor-bearing colon cancers compared to normal Balb/c mice. Experimental group mice exhibited substantially lower serum acetylcholine concentrations than control group mice. Mustard oil administration effectively curtailed acetylcholine expression in normal Balb/c mice, consequently retarding tumor growth. These findings underscore mustard oil's potential to diminish serum acetylcholine expression, thereby delaying colon cancer progression. Conclusions: This study suggests that mustard oil's modulation of acetylcholine expression within the internal environment holds the potential for impeding colon cancer growth.

Impacts of sulfur fumigation on the chemistry and immunomodulatory activity of polysaccharides in ginseng.

Ginseng is widely regarded as a panacea in Oriental medicine mainly due to its immunomodulatory activity. We previously found that sulfur fumigation, a commonly used pesticidal and anti-bacterial processing practice, weakened the immunomodulatory activity of ginseng. However, if and how sulfur fumigation affects the polysaccharides in ginseng, the crucial components contributing to the immunomodulatory function, remain unknown. Here we report that polysaccharides extracted from sulfur-fumigated ginseng (SGP) presented different chemical properties with polysaccharides extracted with non-fumigated ginseng (NGP), particularly increased water extraction yield and decreased branching degree. SGP had weaker immunomodulatory activity than NGP in immunocompromised mice, as evidenced by less improved immunophenotypes involving body weight, immune organ indexes, white blood cells, lymphocyte cell populations and inflammation. The different immunomodulatory activities were accompanied by changes in the interaction between the polysaccharides and gut microbiota, in which SGP stimulated the growth of different bacteria but produced less SCFAs as compared to NGP. Fecal microbiota transplantation experiment suggested that gut microbiota played a central role in causing the weakened immunomodulatory activity in vivo. This study provides definite evidence that sulfur fumigation affects the chemistry and bioactivity of ginseng polysaccharides, thereby contributing to understanding how sulfur fumigation weakens the immunomodulatory activity of ginseng.

Effects of traditional Chinese exercises on the rehabilitation of patients with chronic heart failure: A meta-analysis.

Background: With the development of rehabilitation medicine, exercise therapy has gradually become one of the methods to prevent and treat cardiovascular diseases. It is widely used in clinic because it can further reduce the mortality rate, improve clinical symptoms, restore the activity ability of the body, improve the quality of life of patients and reduce the hospitalization rate. Traditional Chinese exercises have developed rapidly in recent years, which mainly include Baduanjin, Tai Ji, etc. However, meta-analyses of all types of exercises are not well characterized. Objectives: To evaluate the effect of traditional Chinese exercises (TCEs) on the rehabilitation of patients with chronic heart failure (CHF) using a meta-analysis. Methods: A systematic search of randomized controlled trials (RCTs) on TCEs for patients with CHF in 13 databases (PubMed, China National Knowledge Infrastructure, etc.). Meta-analysis was performed using Review Manager software (version 5.3) after two investigators independently screened the studies, assessed the quality of the studies, and extracted the data. Results: Meta-analysis of 21 randomized controlled trials which involved 1,665 patients with chronic heart failure showed that practicing TCEs was effective in improving patients' physiological outcomes such as VO2max [MD = 2.14, 95% CI (1.02, 3.26), P < 0.001], AT [MD = 1.61, 95% CI (1.06, 2.16), P < 0.001], and left ventricular ejection fraction [MD = 2.60, 95% CI (1.17, 4.02), P < 0.001]. Non-physiological outcomes benefited from the application of TCEs: 6-min walking distance [MD = 38.55, 95% CI (36.67, 40.42), P < 0.001], quality of life [MD = 5.52, 95% CI (3.17, 7.88), P < 0.001], and single-item TCM symptom scores in CHF patients: tiredness and fatigue [MD = 0.78, 95% CI (0.03, 1.53), P = 0.04], shortness of breath [MD = 0.44,95% CI (0.26, 0.62), P < 0.0001], facial puffiness and limb swelling [MD = 0.44,95% CI (0.12, 0.76), P = 0.007], palpitations [MD = 0.68,95% CI (0.14, 1.21), P = 0.01] were improved. Conclusions: TCEs improved several recovery indicators, heart failure-related clinical symptoms, quality of life, and physiological indicators in patients with CHF. It is worthwhile to expand the participants for practical application in clinical practice, but the existing evidence is insufficient and the heterogeneity of outcome is large. Therefore, more high-quality clinical trials are needed to support these results. Systematic review registration: PROSPERO, identifier [CRD42022383246].

Evaluation of the Role of Soybean Lecithin, Egg Yolk Lecithin, and Krill Oil in Promoting Ovarian Development in the Female Redclaw Crayfish Cherax quadricarinatus.

The optimal supplementation of lipid nutrients in the diet showed crucial physiological functions in gonadal development and maturation in adult female aquatic animals. Four isonitrogenous and isolipidic diets with no extra lecithin supplementation (control), 2% soybean lecithin (SL), egg yolk lecithin (EL), or krill oil (KO) supplementation were formulated for Cherax quadricarinatus (72.32 ± 3.58 g). Ovary development and physiological characteristics of crayfish were evaluated after a 10-week feeding trial. The results indicated that SL, EL, or KO supplementation all significantly increased the gonadosomatic index, especially in the KO group. Crayfish fed the diet with SL showed the highest hepatosomatic index compared with those fed the other experimental diets. KO was more efficient than SL and EL in promoting triacylglycerol and cholesterol deposition in the ovary and hepatopancreas but also showed the lowest concentration of low-density lipoprotein cholesterol in the serum. KO significantly increased yolk granule deposition and accelerated oocyte maturation than other experimental groups. Furthermore, dietary phospholipids significantly enhanced the gonad-stimulating hormone concentration in the ovary and reduced the secretion of gonad-inhibiting hormones in the eyestalk. KO supplementation also significantly improved organic antioxidant capacity. From the ovarian lipidomics results, phosphatidylcholine and phosphatidylethanolamine are two main glycerophospholipids that respond to different dietary phospholipids. Polyunsaturated fatty acids (especially C18:2n-6, C18:3n-3, C20:4n-6, C20:5n-3, and C22:6n-3) were pivotal participants during ovarian development of crayfish regardless of lipid type. Combined with the ovarian transcriptome, the best positive function of KO was due to activated steroid hormone biosynthesis, sphingolipid signaling, retinol metabolism, lipolysis, starch and sucrose metabolism, vitamin digestion and absorption, and pancreatic secretion. As a consequence, dietary supplementation with SL, EL, or KO all improved the ovarian development quality of C. quadricarinatus, especially KO, which was the optimum choice for promoting ovary development in adult female C. quadricarinatus.

Genome-wide identification of GSK gene family in Senna tora L. and expression analyses / 药学学报

Glycogen synthase kinase 3/SHAGGY-like kinase (GSK3) proteins play important roles in regulating plant growth, development, and stress response. In order to reveal the characteristics of GSK family members in the medicinal plant Senna tora L., in this study, we conducted the identification and expression analyses of GSKs in S. tora based on its whole genome data, combined with bioinformatics and gene expression research methods. The results showed that a total of nine S. tora GSK genes were identified, all of which contained the GSK characteristic kinase domains. All members were distributed on six chromosomes, the encoding amino acid length ranged from 465 to 943 aa, the protein molecular weight was from 33.57 to 88.83 kDa, and the average isoelectric point was 8.2. The StoSKs were divided into four evolutionary branches, and the StoSKs in the same evolutionary branch shared the same exon/intron structure and conserved motifs. The expansion of the StoSKs gene family was mainly due to segment duplication events, and there were 17, 11, 8 and 7 pairs of collinear genes with Glycine max, Medicago truncatula, Arabidopsis thaliana and Oryza sativa, respectively. The promoter regions of StoSKs mostly contained responses elements related to stress stimulation, growth and development, and hormone induction. Transcriptome data analysis showed that StoSKs were expressed in different tissues, with the highest expression level in roots. Quantitative real-time PCR (qRT-PCR) analysis indicated that StoSKs in different evolutionary branches displayed a synergistic expression pattern response to light, and most of StoSKs could rapidly respond to NaCl stress with significantly up-regulated expression. All the results provide a basis for further analysis of the biological functions of the GSKs gene family in S. tora.

[Tea Polyphenols Regulate Renin-angiotensin-aldosterone System and Transforming Growth Factor-ß1/Smads Signaling Pathway in Heart Failure Rats].

Objective To investigate the effects of tea polyphenols on the renin-angiotensin-aldosterone system and the transforming growth factor-ß1(TGF-ß1)/Smads signaling pathway in heart failure rats.Methods SD rats were randomly assigned into a sham group,a model group,a captopril group(PC group),and a tea polyphenol group(TP group).The left anterior descending coronary artery was ligated with silk thread to establish the rat model of heart failure after myocardial infarction in the model group,PC group,and TP group,while it was not ligated in the sham group.Echocardiography was used to detect cardiac function.HE staining and Masson staining were conducted for the observation of myocardial pathological changes and myocardial fibrosis,respectively.Immunohistochemistry was employed to detect the expression of collagen Ⅰ and collagen Ⅲ.ELISA kits were used to measure the levels of angiotensin Ⅱ(AngⅡ),aldosterone(ALD),plasma renin activity(PRA),interleukin-1ß(IL-1ß),IL-6,and tumor necrosis factor-α(TNF-α).Western blotting was employed to determine the protein levels of TGF-ß1,phosphorylated Smad2(p-Smad2),Smad2,p-Smad3,and Smad3.Results Compared with the sham group,the model group showed disordered myocardial cells with obvious inflammatory cell infiltration,increased degree of myocardial fibrosis(t=9.748,P=0.001),elevated levels of collagen Ⅰ(t=11.754,P=0.001) and collagen Ⅲ(t=10.573,P=0.001),decreased ejection fraction(EF)(t=13.174,P=0.002) and left ventricular short axis shortening rate(LVFS)(t=11.853,P=0.001),and up-regulated expression of AngⅡ(t=4.246,P=0.001),ALD(t=5.385,P=0.004),PRA(t=4.386,P=0.004),IL-1ß(t=4.393,P=0.001),IL-6(t=6.375,P=0.002),and TNF-α(t=4.753,P=0.002),and up-regulated protein levels of TGF-ß1(t=6.365,P=0.001),p-Smad2/Smad2(t=13.755,P=0.001),and p-Smad3/Smad3(t=11.657,P=0.002).Compared with the model group,PC and TP alleviated the myocardial pathological changes,decreased the left ventricular end-diastolic diameter(LVEDd)(t=6.367,P=0.003 and t=5.264,P=0.003),left ventricular end-systolic diameter(LVEDs)(t=5.253,P=0.002 and t=5.974,P=0.001),heart mass index(HMI)(t=5.012,P=0.007 and t=4.953,P=0.005),left ventricular mass index(LVMI)(t=5.531,P=0.003 and t=5.483,P=0.004),and the degree of myocardial fibrosis(t=6.734,P=0.001 and t=5.362,P=0.001).Furthermore,they lowered the levels of collagen Ⅰ (t=5.373,P=0.001 and t=4.364,P=0.001) and collagen Ⅲ(t=6.764,P=0.001 and t=4.579,P=0.001),increased EF(t=11.264,P=0.002 and t=10.356,P=0.001) and LVFS(t=8.246,P=0.002 and t=7.824,P=0.001),and down-regulated the expression of AngⅡ(t=3.126,P=0.001 and t=2.853,P=0.001),ALD(t=3.854,P=0.004 and t=3.164,P=0.004),PRA(t=3.126,P=0.004 and t=3.063,P=0.004),IL-1ß(t=2.964,P=0.001 and t=2.765,P=0.001),IL-6(t=4.865,P=0.002 and t=4.275,P=0.002),and TNF-α(t=3.146,P=0.002 and t=2.973,P=0.002).In addition,they down-regulated the protein levels of TGF-ß1(t=4.657,P=0.001 and t=4.176,P=0.001),p-Smad2/Smad2(t=9.687,P=0.001 and t=6.753,P=0.001) and p-Smad3/Smad3(t=6.477,P=0.002 and t=4.754,P=0.002).Conclusion Tea polyphenols protect rats from heart failure by inhibiting the activation of renin-angiotensin-aldosterone system and TGF-ß1/Smads pathway.

Functional nanovesicles displaying anti-PD-L1 antibodies for programmed photoimmunotherapy.

BACKGROUND: Photoimmunotherapy is one of the most promising strategies in tumor immunotherapies, but targeted delivery of photosensitizers and adjuvants to tumors remains a major challenge. Here, as a proof of concept, we describe bone marrow mesenchymal stem cell-derived nanovesicles (NVs) displaying anti-PD-L1 antibodies (aPD-L1) that were genetically engineered for targeted drug delivery. RESULTS: The high affinity and specificity between aPD-L1 and tumor cells allow aPD-L1 NVs to selectively deliver photosensitizers to cancer tissues and exert potent directed photothermal ablation. The tumor immune microenvironment was programmed via ablation, and the model antigen ovalbumin (OVA) was designed to fuse with aPD-L1. The corresponding membrane vesicles were then extracted as an antigen-antibody integrator (AAI). AAI can work as a nanovaccine with the immune adjuvant R837 encapsulated. This in turn can directly stimulate dendritic cells (DCs) to boast the body's immune response to residual lesions. CONCLUSIONS: aPD-L1 NV-based photoimmunotherapy significantly improves the efficacy of photothermal ablation and synergistically enhances subsequent immune activation. This study describes a promising strategy for developing ligand-targeted and personalized cancer photoimmunotherapy.

A super-stable homogeneous Lipiodol-hydrophilic chemodrug formulation for treatment of hepatocellular carcinoma.

Background: Though lipiodol formulations are major options in transcatheter arterial chemoembolization (TACE) of advanced unresectable hepatocellular carcinoma (HCC) in the clinic, their application is severely limited by insufficient physical stability between the hydrophobic lipiodol and hydrophilic drugs; thus, most chemotherapeutic drugs are quickly released into systemic circulation resulting in poor therapeutic outcomes and serious side effects. Methods: The typical hydrophilic drug doxorubicin hydrochloride (DOX) was prepared as a pure nanomedicine and then stably and homogeneously dispersed in lipiodol (SHIFT&DOX) via slightly ultrasonic dispersion. The drug release profiles of SHIFT&DOX were defined in a decellularized liver model. In vivo therapeutic studies were performed in rat-bearing N1S1 orthotopic HCC models and rabbit-bearing VX2 orthotopic HCC models. Results: SHIFT&DOX features an ultrahigh homogeneous dispersibility over 21 days, which far surpassed typical Lipiodol-DOX formulations in clinical practice (less than 0.5 h). SHIFT&DOX also has excellent sustained drug release behavior to improve the local drug concentration dependence and increase the time dependence, leading to remarkable embolic and chemotherapeutic efficacy, and eminent safety in all of the orthotopic HCC models. Conclusions: The carrier-free hydrophilic drug nanoparticle technology-based lipiodol formulation provides a promising approach to solve the problem of drug dispersion in TACE with the potential for a translational pipeline.

Identification, tissue distribution, and anorexigenic effect of amylin in Siberian sturgeon (Acipenser baeri).

Amylin is a 37-amino acid polypeptide that has been found to be involved in feeding regulation in some mammals, birds, and goldfish. We cloned amylin of Siberian sturgeon and detected its distribution pattern in 15 tissues. The expression levels in the periprandial period (pre-and post-feeding), the changes in the food intake, and the expression levels of related appetite factors after the intraperitoneal injection of amylin were detected. The expression of amylin was found to be the highest in the hypothalamus. Compared with 1 h pre-feeding, the expression levels of amylin in the hypothalamus and duodenum were increased significantly 1 h post-feeding. Compared with the control group (saline), intraperitoneal injection of 50 ng/g, 100 ng/g, and 200 ng/g of amylin significantly inhibited food intake at 1 h post injection, but not at 3 h and 6 h. The injection of 50 ng/g, 100 ng/g, and 200 ng/g amylin significantly inhibited the cumulative feed. After 1 h of 50 ng/g amylin injection, the levels of MC4R and somatostatin in the hypothalamus increased significantly, while the levels of amylin and NPY decreased significantly. The levels of CCK in the valvular intestine were increased significantly. Insulin in the duodenum was also increased significantly, but there was no significant change in ghrelin in the duodenum. These results show that amylin inhibits feeding in Siberian sturgeon by down-regulating the appetite-stimulating factor NPY and up-regulating the appetite-suppressing factors somatostatin, MC4R, CCK, and insulin. This study provides a theoretical basis for studying the feeding function and action mechanisms of amylin in Siberian sturgeon.

Dual Tumor Microenvironment Remodeling by Glucose-Contained Radical Copolymer for MRI-Guided Photoimmunotherapy.

Aberrant glucose metabolism and immune evasion are recognized as two hallmarks of cancer, which contribute to poor treatment efficiency and tumor progression. Herein, a novel material system consisting of a glucose and TEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyl) at the distal ends of PEO-b-PLLA block copolymer (glucose-PEO-b-PLLA-TEMPO), is designed to encapsulate clinical therapeutics CUDC101 and photosensitizer IR780. The specific core-shell rod structure formed by the designed copolymer renders TEMPO radicals excellent stability against reduction-induced magnetic resonance imaging (MRI) silence. Tumor-targeting moiety endowed by glucose provides the radical copolymer outstanding multimodal imaging capabilities, including MRI, photoacoustic imaging, and fluorescence imaging. Efficient delivery of CUDC101 and IR780 is achieved to synergize the antitumor immune activation through IR780-mediated photodynamic therapy (PDT) and CUDC101-triggered CD47 inhibition, showing M1 phenotype polarization of tumor-associated macrophages (TAMs). More intriguingly, this study demonstrates PDT-stimulated p53 can also re-educate TAMs, providing a combined strategy of using dual tumor microenvironment remodeling to achieve the synergistic effect in the transition from cold immunosuppressive to hot immunoresponsive tumor microenvironment.

A pure nanoICG-based homogeneous lipiodol formulation: toward precise surgical navigation of primary liver cancer after long-term transcatheter arterial embolization.

PURPOSE: To surmount the critical issues of indocyanine green (ICG), and thus achieving a precise surgical navigation of primary liver cancer after long-term transcatheter arterial embolization. METHODS: In this study, a facile and green pure-nanomedicine formulation technology is developed to construct carrier-free indocyanine green nanoparticles (nanoICG), and which subsequently dispersed into lipiodol via a super-stable homogeneous lipiodol formulation technology (SHIFT nanoICG) for transcatheter arterial embolization combined near-infrared fluorescence-guided precise hepatectomy. RESULTS: SHIFT nanoICG integrates excellent anti-photobleaching capacity, great optical imaging property, and specific tumoral deposition to recognize tumor regions, featuring entire-process enduring fluorescent-guided precise hepatectomy, especially in resection of the indiscoverable satellite lesions (0.6 mm × 0.4 mm) in rabbit bearing VX2 orthotopic hepatocellular carcinoma models. CONCLUSION: Such a simple and effective strategy provides a promising avenue to address the clinical issue of clinical hepatectomy and has excellent potential for a translational pipeline.

Enhanced drug retention by anthracene crosslinked nanocomposites for bimodal imaging-guided phototherapy.

Efficient drug delivery, multifunctional combined therapy and real-time diagnosis are the main hallmarks in the exploitation of precision nanomedicine. Herein, an anthracene-functionalized micelle containing a magnetic resonance imaging (MRI) contrast agent, upconversion nanoparticles (UCNPs) and the photosensitizer IR780 is designed to achieve sustained drug release and enhanced photothermal and photodynamic therapy. The polymer-coated hybrid micelle was achieved by crosslinking anthracene-dimer with UV light (λ > 300 nm), which is converted from near-infrared (NIR) irradiation upon UCNPs. Besides, the water-insoluble photosensitizer IR780 is introduced into the system to achieve efficient drug delivery and photothermal and photodynamic synergistic therapy. As a consequence of NIR-induced anthracene-dimer formation, the cross-linked nanocomposite shows sustained drug release, and the enhanced retention effect of IR780 could increase the photothermal conversion efficiency. Importantly, the incorporation of 2,2,6,6-tetramethyl-piperidineoxyl (TEMPO) as a nitroxide MRI contrast agent presents the potential for real-time diagnosis via nanotheranostics, and the fluorescence imaging of IR780 is applied to monitor drug distribution and metabolism. This strategy of sustained drug delivery by anthracene-dimer formation through the better penetration depth of NIR-II fluorescence provides an executable platform to achieve enhanced phototherapy in biomedical applications.

Effects of dehydroepiandrosterone (DHEA) supplementation on cortisol, leptin, adiponectin, and liver enzyme levels: A systematic review and meta-analysis of randomised clinical trials.

BACKGROUND AND AIMS: Dehydroepiandrosterone (DHEA) supplementation has been investigated in patients with altered cortisol levels and is proposed to ameliorate the metabolic profile related to adipose tissue. However, further research is warranted and evidence is no compelling for liver safety. Hence, we aimed to meta-analyse the effects of DHEA supplementation on circulating levels of cortisol, liver enzymes, and adipokines. METHODS: We searched literature published in PubMed, Web of Science, Embase and Scopus, until December 2020. We obtained overall results using the generic inverse of variance method with a random-effects model. RESULTS: Through 10 arms, serum cortisol levels decreased significantly after DHEA supplementation [weighted mean difference (WMD): -53.581 nmol/L, 95% confidence interval (CI): -88.2, -18.9, P = .002], without significant heterogeneity (I2  = 36%, P = .117). In contrast, any significance was noted for adiponectin (WMD: -0.045 µg/mL, 95% CI: -0.56, 0.47; P = .865), leptin (WMD: -2.55 µg/mL, 95% CI: -6.2, 1.06; P = .166), aspartate transaminase (AST) (WMD: -3.7 U/L, 95% CI: -10.35, 2.95; P = .276), and alanine aminotransferase (ALT) (WMD: -1.7 U/L, 95% CI: -3.45, 0.06; P = .058). CONCLUSION: DHEA supplementation decreased circulating cortisol but did not alter adiponectin, leptin, AST, and ALT levels. Hence, DHEA supplementation could be considered as an adjunct in the management of hypercortisolaemia and is safe for the liver.

Ginseng ameliorates exercise-induced fatigue potentially by regulating the gut microbiota.

The therapeutic effects of water extract of ginseng (WEG) on exercise-induced fatigue (EF) have been reported in several previous studies, but the molecular mechanisms involved remain unexplored. In this study, the anti-EF effects of WEG were studied, and the potential mechanisms were discussed. We characterized the chemical components of WEG by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) and high performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD), and then examined the anti-EF effects of WEG on a rat model of weight-loaded swimming with a focus on endogenous metabolism and gut microbiota. WEG contains abundant (90.15%, w/w) saccharides and ginsenosides with structurally diverse glycosyls. WEG taken orally showed strong anti-EF effects by ameliorating energy metabolism abnormality, oxidative stress, lipid peroxidation, inflammatory response, disorders in the metabolism of bile acid, amino acid, fatty acid and lipid, as well as the gut microbiota dysbiosis. Given that gut microbiota is significantly associated with energy expenditure, systemic inflammation and host metabolism, these findings suggest a potential central role of the gut microbiota in mediating the anti-EF effect of WEG. That is, the saccharides and ginsenosides in WEG serve as energy substrates for specific intestinal bacteria, thereby beneficially regulating the gut microbiota, and the reshaped gut microbial ecosystem then triggers several molecular and cellular signaling pathways (e.g. butyrate or TGR5 signals) to achieve the therapeutic effects on EF. The outcomes highlighted here enable deeper insight into how WEG overcomes EF.

Modulation of the 5-HT3A receptor current by desacylbaldrinal.

The serotonin (5-hydroxytryptamine) type 3 receptor is an important target in the control of digestive dysfunction such as anorexia and bulimia, and 5-HT3 receptor antagonists are effective against eating disorder and the early-phase chemotherapy and radiotherapy evoked vomiting. Our previous research of Valeriana jatamansi revealed the presence of iridoids, which showed potent antitumor activities. Here, we explored the effects of 10π aromatic iridoid desacylbaldrinal isolated from V. jatamansi on the 5-HT3 receptor current. We performed whole cell recordings of 5-HT3A receptor currents in the presence of the compound. The result indicated that desacylbaldrinal inhibited the 5-HT-mediated 5-HT3A receptor current.

Tu-San-Qi (Gynura japonica): the culprit behind pyrrolizidine alkaloid-induced liver injury in China.

Herbs and dietary supplement-induced liver injury (HILI) is the leading cause of drug-induced liver injury in China. Among different hepatotoxic herbs, the pyrrolizidine alkaloid (PA)-producing herb Gynura japonica contributes significantly to HILI by inducing hepatic sinusoidal obstruction syndrome (HSOS), a liver disorder characterized by hepatomegaly, hyperbilirubinemia, and ascites. In China, G. japonica has been used as one of the plant species for Tu-San-Qi and is often misused with non-PA-producing Tu-San-Qi (Sedum aizoon) or even San-Qi (Panax notoginseng) for self-medication. It has been reported that over 50% of HSOS cases are caused by the intake of PA-producing G. japonica. In this review, we provide comprehensive information to distinguish these Tu-San-Qi-related herbal plant species in terms of plant/medicinal part morphologies, medicinal indications, and chemical profiles. Approximately 2156 Tu-San-Qi-associated HSOS cases reported in China from 1980 to 2019 are systematically reviewed in terms of their clinical manifestation, diagnostic workups, therapeutic interventions, and outcomes. In addition, based on the application of our developed mechanism-based biomarker of PA exposure, our clinical findings on the definitive diagnosis of 58 PA-producing Tu-San-Qi-induced HSOS patients are also elaborated. Therefore, this review article provides the first comprehensive report on 2214 PA-producing Tu-San-Qi (G. japonica)-induced HSOS cases in China, and the information presented will improve public awareness of the significant incidence of PA-producing Tu-San-Qi (G. japonica)-induced HSOS and facilitate future prevention and better clinical management of this severe HILI.

Analysis of Chemical Composition in Essential Oil of Zanthoxyli Pericarpium from Different Producing Areas and Investigation of Antifungal Effect of Zanthoxyli Pericarpium Essential Oil Solid Preparation / 中国实验方剂学杂志

Objective:To extract essential oil of Zanthoxyli Pericarpium， to prepare Zanthoxyli Pericarpium essential oil solid preparation and investigate its anti-fungal effect， in order to provide safe， green and efficient fungicide for the storage of Chinese herbal medicine and food. Method:The essential oil of Zanthoxyli Pericarpium was extracted by steam distillation method， gas chromatography-mass spectrometry （GC-MS） was adopted to analyze the chemical compositions and their relative contents in essential oil of Zanthoxyli Pericarpium from different producing areas， Agilent HP-5 capillary column was used for separation at programmed temperature （the initial temperature was 60 ℃， kept for 2 min， then increased to 280 ℃ by 10 ℃·min^-1， kept for 5 min）， the scanning range was <italic>m</italic>/<italic>z</italic> 35-590. Zanthoxyli Pericarpium essential oil solid preparation was prepared by nanomolecular sieve adsorption method， and its inhibitory effect on <italic>Aspergillus flavus</italic> and its conidia was investigated. Ultra-high performance liquid chromatography-fluorescence detector （UPLC-FLD） was used to analyze the inhibitory effect of Zanthoxyli Pericarpium essential oil solid preparation on aflatoxin under the conditions of excitation wavelength of 360 nm and emission wavelength of 440 nm. Result:The average extraction rate of essential oil in Zanthoxyli Pericarpium from four producing areas was 5.2%. （+）-Limonene， linalool and linalyl acetate were the main components of Zanthoxyli Pericarpium<italic> </italic>essential oil<italic> </italic>from different producing areas. When the volume fraction of essential oil in the solid preparation was 0.1%， the inhibition rate of the solid preparation on the conidia of <italic>A</italic>. <italic>flavus</italic> was （16.41±8.89）%. When the volume fraction of essential oil in the solid preparation was 0.2%， the inhibition rate for the growth of <italic>A</italic>. <italic>flavus</italic> was （8.11±2.70）%. When the volume fraction of essential oil in the solid preparation was 0.5%， the inhibition rate for the growth of <italic>A</italic>. <italic>flavus </italic>was （21.62±5.41）%， the inhibition rate for <italic>A</italic>. <italic>flavus</italic> conidia was （45.43±5.67）%， and the inhibition effect for the aflatoxin could reach （90.47±12.77）%. Conclusion:There are some differences in the chemical composition of essential oil of Zanthoxyli Pericarpium from different producing areas. Zanthoxyli Pericarpium<italic> </italic>essential oil has a certain inhibitory effect on the formation of <italic>A. flavus</italic> conidia and the production of aflatoxin B₁. It shows that Zanthoxyli Pericarpium essential oil can be developed into bacteriostatic preparation and used in the storage of Chinese medicinal materials and food.