Effects of mindfulness-based interventions on cardiovascular risk factors: An umbrella review of systematic reviews and meta-analyses.

OBJECTIVE: Reviews have shown that mindfulness-based interventions (MBIs) were effective in improving cardiovascular risk factors (CVRFs), but the results were contradictory. This umbrella review aimed to summarize and grade the existing reviews on CVRFs associated with MBIs. METHODS: The protocol of this umbrella review had been registered in PROSPERO (CRD42022356812). PubMed, Web of science, Embase, The Cochrane Library, Scopus, Medline, PsycINFO and CINAHL were searched from database inception to 20 July 2022. The quality of evidence was assessed through GRADE. RESULTS: Twenty-seven reviews with 14,923 participants were included. Overall, 45% of reviews had low heterogeneity (I2 < 25%). For the quality of evidence, 31% were rated very low, 42% were rated low, 17% were rated moderate and 10% were rated high. MBIs significantly improved systolic blood pressure [SMD -5.53 mmHg (95% CI -7.81, -3.25)], diastolic blood pressure [SMD -2.13 mmHg (95% CI -2.97, -1.30)], smoking [Cohen's d 0.42 (95% CI 0.20, 0.64)], glycosylated hemoglobin [MD 0.01 (95% CI -0.43, -0.07)], binge eating behavior [SMD -6.49 (95% CI -10.80, -2.18)], depression [SMD -0.72 (95% CI -1.23, -0.21)] and stress [SMD -0.67 (95% CI -1.00, -0.34)]. CONCLUSIONS: In conclusion, this umbrella review provided evidence for the role of MBIs in the improvement of CVRFs.

The effect of mindfulness-based interventions on mental health outcomes and wellbeing of informal caregivers of people with mental illness: A systematic review and meta-analysis.

The increasing prevalence of mental illness has resulted in a growing burden on informal caregivers. Mindfulness-based interventions, as a form of psychotherapy, have shown efficacy in alleviating psychological stress and enhancing emotional and physical well-being. However, the utilisation of mindfulness-based interventions for informal caregivers of individuals with mental illness remains limited. The aim of the meta-analysis is to evaluate the impact of mindfulness-based interventions on the mental health and well-being among informal caregivers of people with mental illness. A comprehensive literature search was conducted across seven electronic databases (PubMed, Scopus, Web of Science, Cochrane Library, Embase, APA PsycINFO and CINAHL Ultimate) from the inception of these databases until 20 July 2023. Two authors independently screened the studies and extracted the relevant data. The meta-analysis was performed by using Stata 12.0 software, and the effect sizes were calculated utilising standardised mean difference (SMD) along with their corresponding 95% confidence intervals (CI). The meta-analysis included 13 studies with 1007 participants, and the results demonstrated that mindfulness-based interventions were efficacious in reducing stress (SMD = -0.80, 95% CI [-1.33, -0.28], p = 0.003), depression (SMD = -0.43, 95% CI [-0.62, -0.24], p < 0.001) and caregiver burden (SMD = -0.21, 95% CI [-0.40, -0.01], p = 0.038), and enhancing the mindfulness level (SMD = 0.37, 95% CI [0.09, 0.65], P = 0.010) and quality of life (SMD = 0.22, 95% CI [0.04, 0.39], p = 0.015) among informal caregivers of people with mental illness, but not on anxiety reduction (SMD = -0.19, 95% CI [-0.49, 0.10], p = 0.198). Furthermore, future research should aim to employ more rigorous methodologies to confirm the effectiveness.

A review of hemostatic chemical components and their mechanisms in traditional Chinese medicine and ethnic medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine and ethnic medicine together play an important value in the modern medicine system that is different from that of chemical drugs. Chinese medicine and ethnic medicine with hemostatic effect have unique advantages and development potential in the prevention and treatment of clinical hemorrhagic diseases, reflecting multi-component, multi-target and multi-pathway effects. AIM OF THE STUDY: In this paper, the active ingredients related to the hemostatic effect of traditional Chinese medicine and ethnic medicine are taken as the starting point, and the traditional Chinese medicine and ethnic medicine with traditional hemostatic purposes are reviewed, and the existing research progress on the active ingredients and their mechanism of action of these drugs is systematically expounded, aiming to provide theoretical reference for the development of traditional hemostatic drugs, the discovery of hemostatic active ingredients and the research of new hemostatic methods. MATERIALS AND METHODS: Hemostatic chinese medicine and ethnic medicine were collected and summarized from the classic books of Materia Medica, public literature database and doctoral or master's thesis repositories. At the same time, we discussed the classification of various types of hemostatic active ingredients of traditional Chinese medicine and ethnic medicine according to the different mechanisms of hemostasis. RESULTS: A total of 436 traditional Chinese medicine and ethnic medicine with hemostatic effects have been collected, and their hemostatic active ingredients include alkaloids, quinones, flavonoids, phenylpropanoids, organic acids, amino acids, terpenoids, steroids, phenols, tannins, esters, polysaccharides and herbal extracts, etc. These active ingredients accelerate the formation of hemostasis by improving endogenous and exogenous hemostatic pathways mainly through enhancing vascular wall contraction, increasing platelet aggregation, promoting coagulation system activation and inhibiting fibrinolysis. CONCLUSIONS: This article reviews the previous data on various aspects of the hemostatic effect of traditional Chinese medicine and ethnomedicine. Many traditional hemostatic drugs have been discovered and many active ingredients and mechanisms have been reported. However, although there are a large number of drugs with traditional hemostatic effects, there are still few developed and applied. At the same time, the hemostatic components of many drugs still remain in the study of the activity of their total extracts, and the potential link between some drug components achieving hemostatic effects through different mechanisms remains to be elucidated.

The effect of tomato and lycopene on clinical characteristics and molecular markers of UV-induced skin deterioration: A systematic review and meta-analysis of intervention trials.

Lycopene as a natural antioxidant that have been studied for ultraviolet radiation (UVR) photo protection and is one of the most effective carotenoids to scavenge reactive oxygen species (ROS). This review aims to summarize the protective effect of tomato and lycopene on skin photo damage and skin photoaging in healthy subjects by reviewing the existing population intervention experiments. A total of five electronic databases including PubMed, Scopus, EBSCO, Web of Science and Cochrane Library were searched from inceptions to January 2021 without any restriction. Out of 19336 publications identified, 21 fulfilled the inclusion criteria and were meta-analysis. Overall, interventions supplementing tomato and lycopene were associated with significant reductions in Δa*, MMP-1, ICAM-1 and skin pigmentation; while tomato and lycopene supplementation were associated with significant increase in MED, skin thickness and skin density. Based on the results of this systematic review and meta-analysis, supplementation with tomato and lycopene could reduce skin erythema formation and improve the appearance and pigmentation of the skin, thereby preventing light-induced skin photodamage and skin photoaging. Lycopene-rich products could be used as endogenous sun protection and may be a potential nutraceutical for sun protection.

Characterization and molecular evolution analysis of Periploca forrestii inferred from its complete chloroplast genome sequence.

Periploca forrestii, a medicinal plant of the family Apocynaceae, is known as an effective and widely used clinical prescription for the treatment of rheumatoid diseases. In this study, we de novo sequenced and assembled the completement chloroplast (cp) genome of P. forrestii based on combined Oxford Nanopore PromethION and Illumina data. The cp genome was 153 724 bp in length and had four subregions. Moreover, an 84 433 bp large single-copy and a 17 731 bp small single-copy were separated by 25 780 bp inverted repeats (IRs). The cp genome included 132 genes with 18 duplicates in the IRs. A total of 45 repeat structures and 183 simple sequence repeats were detected. Codon usage showed a bias toward A/T-ending codons. A comparative study of Apocynaceae revealed that an IR expansion occurred on P. forrestii. The Ka/Ks values of eight species of Apocynaceae suggested that positive selection was exerted on the psaI and ycf2 genes, which might reflect specific adaptions to the P. forrestii particular growth environment. Phylogenetic analysis indicated that Periplocoideae was a sister to Asclepiadoideae, forming a monophyletic group in the family Apocynaceae. This study provided an important P. forrestii genomic resource for future evolutionary studies and the phylogenetic reconstruction of the family Apocynaceae.

Plant polysaccharides as novel biomaterials for microcapsule construction and therapeutics delivery.

Natural polysaccharides derived from medicinal plants, that are Dendrobium (DPS), Lycium barbarum (LBP), Ginseng (GPS), and Poria Cocos (PCP) were firstly combined with sodium alginate (SA) to construct microcapsules and improved the morphology, encapsulation efficiency, Biocompatibility and protective capability in drug loading. Diverse typical therapeutics, including VO2@ZIF67 nanoparticles, small molecule drugs salvianolic acid B (SaB)/ginsenoside (Rg1), probiotic Bacillus bifidus, and biomacromolecules SDF-1 were wrapped into 1.5 % GPS-0.5 % SA model microcapsules, respectively. Better mobility and formability were significantly observed, and showed 75 % survival rate of probiotics in simulated gastric juice and around 99 % encapsulation efficiency which is higher than single 2 % SA microcapsules. The microcapsules also obtained a delayed release and a higher cell index for SDF-1, which indicated better stability, biocompatibility and protective effect than single 2 % SA microcapsules. This study provides a strategy in developing plant derived polysaccharides as novel materials for the construction and improvement of traditional microcapsules.

Antirheumatoid Arthritic Effects of Sabia parviflora Wall. Leaf Extracts via the NF-κB Pathway and Transient Receptor Potential Protein Family.

As an important traditional medicine of Buyi and Miao ethnic groups in Guizhou, Sabia parviflora Wall. provides antiviral properties against hepatitis, eliminates wind and dampness, and exhibits anti-inflammatory and pain relief properties. It has also been shown to treat rheumatoid arthritis (RA) and other diseases. However, the pharmacodynamic mechanism of S. parviflora Wall. for RA has not been reported. In this study, we identified the effective compounds of S. parviflora Wall. leaves against RA and discussed the mechanism against complete Freund's adjuvant-induced arthritis (AIA) based on inflammatory proteins and transient receptor potential (TRP) proteins. S. parviflora Wall. leaf extracts (0.64 g/kg, 0.32 g/kg, and 0.16 g/kg, once daily) were given orally for 21 days. On the 15th day of complete Freund's adjuvant-induced RA, the effects of this medicine on RA rats were investigated. S. parviflora Wall. extracts increased body weight, decreased foot swelling, and reduced thymus and spleen indices in model rats. Most of pannus in the synovial tissue of RA rats disappeared upon treatment, and the local inflammatory cells were greatly reduced when given the fraction of n-butanol (0.64 g/kg/d, 0.32 g/kg/d, and 0.16 g/kg/d) of 70% alcohol-soluble fraction of S. parviflora Wall. leaves. In addition, the release of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-15 (IL-15), and vascular endothelial growth factor (VEGF) in the RA rat serum was inhibited. The active compounds inhibited the expression of TNF-α, IL-1ß, IL-6, IL-10, IL-15 and nuclear factor kappa-Bp65 (NF-κBp65) inflammatory protein and TRP protein transient receptor potential melastatin-5 (TRPM-5) and transient receptor potential channel-6 (TRPC-6), to reduce the expression of VEGF in synovial tissue of RA rats and relieve redness and edema. High-performance liquid chromatography identified six flavonoids and three triterpenoid saponins as active compounds. These findings suggest S. parviflora Wall. leaves may play a role in RA treatment by inhibiting the release of inflammatory factors as well as participating in the inflammatory protein expression in the NF-κB pathway and TRP protein family.

Soil Microbial Communities Affect the Growth and Secondary Metabolite Accumulation in Bletilla striata (Thunb.) Rchb. f.

Bletilla striata (Thunb.) Rchb.f. is a perennial herb belonging to the Orchidaceae family. Its tubers are used in traditional Chinese medicine to treat gastric ulcers, inflammation, silicosis tuberculosis, and pneumogastric hemorrhage. It has been reported that different soil types can affect the growth of B. striata and the accumulation of secondary metabolites in its tubers, but the biological mechanisms underlying these effects remain unclear. In this study, we compared agronomic traits and the accumulation of secondary metabolites (extractum, polysaccharide, total phenol, militarine) in B. striata grown in sandy loam or sandy clay soil. In addition, we compared physicochemical properties and microbial communities between the two soil types. In pot experiments, we tested how irradiating soil or transplanting microbiota from clay or loam into soil affected B. striata growth and accumulation of secondary metabolites. The results showed that sandy loam and sandy clay soils differed significantly in their physicochemical properties as well as in the structure and composition of their microbial communities. Sandy loam soil had higher pH, SOM, SOC, T-Ca, T-N, T-Mg, T-Mn, T-Zn, A-Ca, A-Mn, and A-Cu than sandy clay soil, but significantly lower T-P, T-K, T-Fe, and A-P content. Sandy loam soil showed 7.32% less bacterial diversity based on the Shannon index, 19.59% less based on the Ace index, and 24.55% less based on the Chao index. The first two components of the PCoA explained 74.43% of the variation in the bacterial community (PC1 = 64.92%, PC2 = 9.51%). Similarly, the first two components of the PCoA explained 58.48% of the variation in the fungal community (PC1 = 43.67%, PC2 = 14.81%). The microbiome associated with sandy clay soil can promote the accumulation of militarine in B. striata tubers, but it inhibits the growth of B. striata. The accumulation of secondary metabolites such as militarine in B. striata was significantly higher in sandy clay than in sandy loam soil. Conversely, B. striata grew better in sandy loam soil. The microbiome associated with sandy loam soil can promote the growth of B. striata, but it reduces the accumulation of militarine in B. striata tubers. Pot experiment results further confirmed that the accumulation of secondary metabolites such as militarine was higher in soil transplanted with loam microbiota than in soil transplanted with clay microbiota. These results may help guide efforts to improve B. striata yield and its accumulation of specific secondary metabolites.

The complete chloroplast genome of Bletilla ochracea Schltr., a medicinal plant with yellow flowers.

Bletilla ochracea Schltr. (Orchidaceae) is a traditional medicinal plant widely distributed in the south-central part of China. The complete chloroplast genome of B. ochracea was sequenced using the Illumina HiSeq X Ten platform. The chloroplast genome was 160,018 bp in length, which contained two short inverted repeat (IRa and IRb) regions of 26,295 bp and was separated by a large single copy (LSC) region of 88,270 bp and a small single copy (SSC) region of 19,158 bp. The GC content of the whole chloroplast genome was 37.2%. The chloroplast DNA of B. ochracea consisted of 114 distinct genes, including 80 protein-coding genes, 4 ribosomal RNA genes, and 30 transfer RNA genes. The phylogenetic tree showed that B. ochracea was sister to B. formosana. Meanwhile, the monophyletic clade formed by all species of genus Bletilla was closely related to genus Thunia.

[Research progress on role of Chinese medicinal materials and their topical preparations in wound healing by regulating cytokines and growth factors].

Delayed-or non-healing wounds caused by trauma, surgical procedures, acute diseases, or chronic diseases, and proli-ferating scar have a serious impact on patients' quality of life and increase the economic and psychological burden on their families. Therefore, how to accelerate wound healing and obtain satisfactory aesthetic results is of great concern to researchers and is an urgent clinical problem to be solved. In recent years, the mechanisms of Chinese medicinal materials in accelerating wound healing and inhi-biting scar formation by regulating cytokines have been clarified, which provides a scientific basis for revealing the efficacy of Chinese medicinal materials against clinical trauma. This review focuses on the therapeutic effects of active ingredients, extracts, and topical preparations of Chinese medicinal materials through regulating cytokines in the inflammation, proliferation, and remodeling phases of wound healing. It is expected to provide evidence for the application of Chinese medicinal materials in wound therapy.

[Preparation of triptolide-loaded dissolving microneedles and its transdermal penetration].

Triptolide(TP), the main active and toxic component of Tripterygium wilfordii, has the limitations of low bioavailability, poor absorption, low concentration in plasma, and small lethal dose. Microneedle(MN), the hybrid of hypodermic needle and transdermal patch, is a physical penetration-enhancing system. Dissolving microneedles(DMNs) can be tailored to specific needs of degradation rate. In this study, the TP-loaded DMNs(DMNs-TP) were prepared with the two-step centrifugation method. The optimal ratio of PVA to PVP K30, water content in matrix solution, demoulding method, and plasticizer for preparing DMNs were investigated with the indexes of formability and mechanical strength. The drug loading capacity was determined by HPLC and morphological characteristics were observed under an optical microscope. The mechanical properties were investigated by H&E staining and Franz diffusion cell was used to detect the in vitro skin permeation characteristics. Through the experiment, we confirmed that the optimal backing material should be PVA and PVP K30(3∶1) and the optimal ratio of matrix material to water should be 3∶4. The prepared DMNs-TP were pyramidal with smooth surface and length of approximately 550 µm. Each patch(2.75 cm~2) had the drug loading capacity of(153.41±2.29) µg, and TP was located in the upper part of the needle. The results of in vitro skin permeation assay demonstrated that the cumulative penetration of TP in DMNs-TP reached 80% in 24 h, while little TP solution penetrated the skin, which proved that DMNs promoted the transdermal delivery of TP.

Endogenous ω-3 fatty acids in Fat-1 mice attenuated depression-like behaviors, spatial memory impairment and relevant changes induced by olfactory bulbectomy.

OBJECTIVES: Olfactory bulbectomy (OB) induced behaviors, hypercortisolism, inflammation and neurotrophin dysfunctions are similar to those observed in depressed patients. Omega (n)-3 polyunsaturated fatty acids (PUFAs) can effectively treat depression via anti-inflammatory and neuroprotective effects. However, n-3 PUFA purities, caloric contents, and ratios in different diets often cause contradictive results. This study used Fat-1 mice, which can convert n-6 to n-3 PUFAs in the brain, to study the effect of n-3 PUFAs on OB-induced behaviors and related changes. METHODS: Fat-1 and wild-type littermates were fed safflower oil for 3 months. Behaviors were tested on day 21 after surgery. Monoamine neurotransmitters were measured by HPLC. Macrophage activity was measured by MTT assay. Astrocyte phenotypes A1 S100ß, A2 BDNF and cholesterol level were measured by ELISA and total cholesterol assay kits respectively. PUFA profile and membrane fluidity were detected by GC and DPH fluorescence probe respectively. RESULTS: OB significantly induced animal hyperactivity and spatial memory impairment, while decreased sucrose consumption and social contact with decreased 5-HT turnover, increased the macrophage activity and S100ß/BDNF ratio. Meanwhile, n-3/n-6 PUFAs ratio and total cholesterol level were reduced in OB mice. Whereas, OB-induced behavioral changes were attenuated, which were associated with increasing 5-HT turnover, decrease macrophage activity, restored S100ß/BDNF and n-3/n-6 PUFAs ratios, and total cholesterol concentrations in Fat-1 mice. CONCLUSION: The present study for the first time demonstrated that endogenous n-3 PUFAs attenuated OB-induced depression-like behaviors and spatial memory impairment through modulating serotonergic and immune function, balancing the astrocyte A1/A2 phenotypes, and normalizing PUFAs profile and membrane function.

Chinese pediatric Tuina on children with acute diarrhea: a randomized sham-controlled trial.

BACKGROUND: Pediatric Tuina has been widely used in children with acute diarrhea in China. However, due to the lack of high-quality clinical evidence, the benefit of Tuina as a therapy is not clear. We aimed to assess the effect of pediatric Tuina compared with sham Tuina as an add-on therapy in addition to usual care for 0-6-year-old children with acute diarrhea. METHODS: Eighty-six participants aged 0-6 years with acute diarrhea were randomized to receive pediatric Tuina plus usual care (n = 43) or sham Tuina plus usual care (n = 43). The primary outcomes were days of diarrhea from baseline and times of diarrhea on day 3. Secondary outcomes included a global change rating (GCR) and the number of days when the stool characteristics returned to normal. Adverse events were assessed. RESULTS: Pediatric Tuina was associated with a reduction in times of diarrhea on day 3 compared with sham Tuina in both ITT (crude RR, 0.73 [95% CI, 0.59-0.91]) and PP analyses (crude RR, 0.66 [95% CI, 0.53-0.83]). However, the results were not significant when we adjusted for social demographic and clinical characteristics. No significant difference was found between groups in days of diarrhea, global change rating, or number of days when the stool characteristics returned to normal. CONCLUSIONS: In children aged 0-6 years with acute diarrhea, pediatric Tuina showed significant effects in terms of reducing times of diarrhea compared with sham Tuina. Studies with larger sample sizes and adjusted trial designs are warranted to further evaluate the effect of pediatric Tuina therapy. TRIAL REGISTRATION: Clinicaltrials.gov, Identifier: NCT03005821 , Data of registration: 2016-12-29.

Comparative Evaluation of the Transdermal Permeation Effectiveness of Fu's Cupping Therapy on Eight Different Types of Model Drugs.

BACKGROUND: Overcoming the skin barrier to achieve the transdermal penetration of drugs across the Stratum Corneum (SC) remains a significant challenge. Our previous study showed that Fu's Cupping Therapy (FCT) contributes to the transdermal enhancement and percutaneous absorption rate of representative drugs and improves their clinical effects. This work evaluated the transdermal enhancement effect of FCT on drugs with different Molecular Weights (MW). METHODS: We investigated the enhancements in the transdermal penetration of eight types of model drugs through the skin of BALB/c-nu mice and Sprague Dawley rats using Franz diffusion devices. In addition, 3% azone, 5% azone, 3% peppermint oil, and 5% peppermint oil were used as penetration enhancers to study the transdermal behaviour of these drugs. RESULTS: Our results showed that the BALB/c-nu mouse skin was the best transdermal media, and the optimal time for FCT was 10 min. Compared with other penetration enhancers, FCT exerted a significantly improved effect on enhancing the percutaneous penetration of the selected log(P)- model drugs in addition to the two large MW drugs (ginsenoside Rg1 and notoginsenoside R1). Statistical analysis revealed that the relationship between the log(P) of various model drugs and the permeability coefficient [log(Pcm)] of the FCT group was log(Pcm)=0.080(log(P))2-0.136 (log(P))-0.282. CONCLUSION: FCT may be used as a novel method for enhancing physical penetration and thus effectively promoting the transdermal absorption of drugs and might lay a foundation for future research on drug transdermal technology.

Chemical Composition and Anti-Alzheimer's Disease-Related Activities of a Functional Oil from the Edible Seaweed Hizikia fusiforme.

Cholinergic disorder, oxidative stress, and neuroinflammation play important roles in the pathology of Alzheimer's disease. To explore the healthy potential of the edible seaweed Hizikia fusiforme on this aspect, a functional oil (HFFO) was extracted from this alga and investigated on its constituents by gas chromatography-mass spectrometry (GC/MS) in this study. Its anti-Alzheimer's related bioactivities including acetylcholinesterase (AChE) inhibition, antioxidation, and anti-neuroinflammation were evaluated, traced, and simulated by in vitro and in silico methods. GC/MS analysis indicated that HFFO mainly contained arachidonic acid (ARA), 11,14,17-eicosatrienoic acid (ETrA), palmitic acid, phytol, etc. HFFO showed moderate AChE inhibition and antioxidant activity. Bioactivity tracing using commercial standards verified that AChE inhibition of HFFO mainly originated from ARA and ETrA, whereas antioxidant activity mainly from ARA. Lineweaver-Burk plots showed that both ARA and ETrA are noncompetitive AChE inhibitors. A molecular docking study demonstrated low CDOCKER interaction energy of -26.33 kcal/mol for ARA and -43.70 kcal/mol for ETrA when interacting with AChE and multiple interactions in the ARA (or ETrA)-AChE complex. In the anti-neuroinflammatory evaluation, HFFO showed no toxicity toward BV-2 cells at 20 µg/mL and effectively inhibited the production of nitroxide and reduced the level of reactive oxygen species in lipopolysaccharide-induced BV-2 cells. The results indicated that HFFO could be used in functional foods for its anti-Alzheimer's disease-related activities.

EPA is More Effective than DHA to Improve Depression-Like Behavior, Glia Cell Dysfunction and Hippcampal Apoptosis Signaling in a Chronic Stress-Induced Rat Model of Depression.

Clinical evidence indicated that eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) in depression treatment. However, possible mechanisms remain unclear. Here, a chronic unpredictable mild stress (CUMS)-induced model of depression was used to compare EPA and DHA anti-depressant effects. After EPA or DHA feeding, depression-like behavior, brain n-3/n-6 PUFAs profile, serum corticosterone and cholesterol concentration, hippocampal neurotransmitters, microglial and astrocyte related function, as well as neuronal apoptosis and survival signaling pathways were studied. EPA was more effective than DHA to ameliorate CUMS-induced body weight loss, and depression-like behaviors, such as increasing sucrose preference, shortening immobility time and increasing locomotor activity. CUMS-induced corticosterone elevation was reversed by bother fatty acids, while increased cholesterol was only reduced by EPA supplement. Lower hippocampal noradrenaline and 5-hydroxytryptamine concentrations in CUMS rats were also reversed by both EPA and DHA supplement. However, even though CUMS-induced microglial activation and associated increased IL-1ß were inhibited by both EPA and DHA supplement, increased IL-6 and TNF-α levels were only reduced by EPA. Compared to DHA, EPA could improve CUMS-induced suppressive astrocyte biomarkers and associated BDNF-TrkB signaling. Moreover, EPA was more effective than DHA to attenuate CUMS-induced higher hippocampal NGF, GDNF, NF-κB, p38, p75, and bax expressions, but reversed bcl-2 reduction. This study for the first time revealed the mechanisms by which EPA was more powerful than DHA in anti-inflammation, normalizing astrocyte and neurotrophin function and regulating NF-κB, p38 and apoptosis signaling. These findings reveal the different mechanisms of EPA and DHA in clinical depression treatment.

Seahorse treatment improves depression-like behavior in mice exposed to CUMS through reducing inflammation/oxidants and restoring neurotransmitter and neurotrophin function.

ETHNOPHARMACOLOGICAL RELEVANCE: Seahorses (Hippocampus erectus), belonging to syngnathidae of syngnathiformes, are a traditional Chinese medicine for increasing and balancing vital energy within the body and brain, as well as calming mood and improving sleep. AIM OF THE STUDY: Based on the hypothesis of monoamine neurotransmitter deficiency, current antidepressant treatments, with many side effects, are ineffective. Thus, novel hypotheses, inflammation, oxidative stress and neurotrophin dysfunction were proposed. Since seahorses can modulate immune function, reduce oxidants and nourish brain function, it may effectively treat depression. Therefore, this study aimed to detect the predominant chemical characterization of seahorses and investigate the mechanism by which seahorses exert antidepressant effects by using a chronic unpredictable mild stress (CUMS)-induced model of depression. METHODS: Control and CUMS-exposed mice were fed normal or seahorse diet (0.018 g seahorses power) for 8-weeks. After behavioral tests, serum corticosterone, hippocampal expression of CD11b, glial fibrillary acidic protein (GFAP), and brain derived neurotrophic factor (BDNF), and the concentration of interleukin (IL)-1ß and monoamine neurotransmitters were measured, while amygdala IL-1ß and IL-10, anti-oxidative and oxidative enzyme were also studied. Then main phytoconstituents of seahorses was analyzed using liquid chromatography-mass spectrometry (LC-MS) methods. RESULTS: Compared to controls, sucrose preference, exploration in open field, social interaction, entry numbers into and times spent on the open arms of elevated plus maze were significantly decreased, while immobility times in forced-swimming was increased in CUMS mice. These changes were associated with significantly reduced levels of serotonin, noradrenaline and dopamine, also expressions of GFAP and BDNF. Moreover, CUMS elevated IL-1ß concentrations and reactive oxygen species (ROS), while decreased IL-10 concentration and anti-oxidative super oxide dismutase and glutathione peroxidase. Seahorse diet significantly reversed anxiety- and depression-like behaviors, which were correlated with reducing IL-1ß and ROS, but increasing neurotransmitter concentrations and BDNF expression. Several compounds were found in seahorses, including docosahexaenoic acid, eicosapentaenoic acid, bis(2-ethylheptyl) phthalate, chrysophanol, and hypoxanthine. CONCLUSION: Seahorses could attenuate the CUMS-induced anxiety- and depression-like behaviors by reducing oxidative stress and inflammation, and normalizing neurotransmitter and neurotrophin function, which are possibly due to the activities of one or more or mixture of these identified compounds.

Chinese pediatric Tuina on children with acute diarrhea: study protocol for a randomized sham-controlled trial.

BACKGROUND: Acute pediatric diarrhea is one of the most common causes of morbidity and mortality worldwide and seriously affects the health of children. Previous studies have shown that pediatric Tuina, a traditional Chinese medicine therapy, has potential therapeutic benefits for acute pediatric diarrhea. However, the evidence for its effectiveness is insufficient due to the lack of high-quality clinical studies. Our aim is to evaluate the efficacy of Chinese pediatric Tuina for children aged 0-6 years with acute diarrhea. METHODS/DESIGN: This study is a randomized, double-blind, sham-controlled trial. We will include 122 children with acute diarrhea from Dongguan Kanghua Hospital in Guangdong province, China. The patients will be allocated into either the pediatric Tuina group or the sham Tuina group in a 1:1 ratio. The treatment will last for 3 days followed by an 11-day follow-up period. Both groups will receive usual care. In addition, the experimental group will receive 15-25 min of Chinese pediatric Tuina, while the control group will receive 15-25 min of sham pediatric Tuina. Both groups will receive treatments once per day, for 3 consecutive days. Primary outcome measures are diarrhea days from baseline and diarrhea times on the third day. Secondary outcome measures are the global change rating and period of days when the stool character changes to normal. Safety assessments will be monitored during each visit. DISCUSSION: This clinical trial is designed to evaluate the efficacy of pediatric Tuina for children with acute diarrhea. We expect results to provide solid evidence and support for pediatric Tuina as an appropriate treatment for children with acute diarrhea. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03005821. Registered on 29 December 2016.

Monitoring the Early Response of Fulvestrant Plus Tanshinone IIA Combination Therapy to Estrogen Receptor-Positive Breast Cancer by Longitudinal 18F-FES PET/CT.

Endocrine monotherapy of breast cancers is generally hampered by the primary/acquired resistance and adverse sides in clinical settings. Herein, advantaging the multitargeting antitumor effects and normal organ-protecting roles of Chinese herbal medicine, the aim of this study was to investigate the enhanced synergistic efficacy of fulvestrant plus Tan IIA combination therapy in ER-positive breast cancers and to monitor the early response by longitudinal 18F-FES PET/CT imaging. The experimental results showed FUL + Tan IIA combination therapy significantly inhibited tumor growth of ER-positive ZR-75-1 tumor xenografts and exhibited distinct antitumor effects at an earlier time point after treatment than did the monotherapy of FUL or Tan IIA. Moreover, 18F-FES PET/CT imaging competently monitored the early response of FUL + Tan IIA combination therapy. The quantitative 18F-FES %ID/gmax in vivo was further confirmed by and correlated well with ERα expression ex vivo. In conclusion, the synergic effect of FUL + Tan IIA combination therapy to ER-positive breast cancers was verified in the preclinical tumor models and the early treatment response could be monitored by 18F-FES PET/CT.

A novel RGDyC/PEG co-modified PAMAM dendrimer-loaded arsenic trioxide of glioma targeting delivery system.

BACKGROUND: The Traditional Chinese Medicine, arsenic trioxide (ATO, As2O3) could inhibit growth and induce apoptosis in a variety of solid tumor cells, but it is severely limited in the treatment of glioma due to its poor BBB penetration and nonspecifcity distribution in vivo. PURPOSE: The objective of this study was encapsulating ATO in the modified PAMAM den-drimers to solve the problem that the poor antitumor effect of ATO to glioma, which provide a novel angle for the study of glioma treatment. METHODS: The targeting drug carrier (RGDyC-mPEG-PAMAM) was synthesized based on Arg-Gly-Asp (RGDyC) and αvß3 integrin targeting ligand, and conjugated to PEGylated fifth generation polyamidoamine dendrimer (mPEG-PAMAM). It was characterized by nuclear magnetic resonance, fourier transform infrared spectra, Nano-particle size-zeta potential analyzer,etc. The in vitro release characteristics were studied by dialysis bag method. MTT assay was used to investigate the cytotoxicity of carriers and the antitumor effect of ATO formulation. In vitro blood-brain barrier (BBB) and C6 cell co-culture models were established to investigate the inhibitory effect of different ATO formulation after transporting across BBB. Pharmacokinetic and antitumor efficacy studies were investigated in an orthotopic murine model of C6 glioma. RESULTS: The prepared RGDyC-mPEG-PAMAM was characterized for spherical dendrites, comparable size (21.60±6.81 nm), and zeta potential (5.36±0.22 mV). In vitro release showed that more ATO was released from RGDyC-mPEG-PAMAM/ATO (79.5%) at pH 5.5 than that of pH 7.4, during 48 hours. The cytotoxicity of PEG-modified carriers was lower than that of the naked PAMAM on both human brain microvascular endothelial cells and C6 cells. In in vitro BBB model, modification of RGDyC heightened the cytotoxicity of ATO loaded on PAMAM, due to an increased uptake by C6 cells. The results of cell cycle and apoptosis analysis revealed that RGDyC-mPEG-PAMAM/ATO arrested the cell cycle in G2-M and exhibited threefold increase in percentage of apoptosis to that in the PEG-PAMAM/ATO group. Compared with ATO-sol group, both RGDyC-mPEG-PAMAM/ATO and mPEG-PAMAM/ATO groups prolonged the half-life time, increased area under the curve, and improved antitumor effect, significantly. While the tumor volume inhibitory of RGDyC-mPEG-PAMAM/ATO was 61.46±12.26%, it was approximately fourfold higher than the ATO-sol group, and twofold to the mPEG-PAMAM/ATO group. CONCLUSION: In this report, RGDyC-mPEG-PAMAM could enhance the antitumor of ATO to glioma, it provides a desirable strategy for targeted therapy of glioma.