The impact of mulberry leaf extract at three different levels on reducing the glycemic index of white bread.

In this study, the influences of mulberry leaf extract (MLE) addition on the physicochemical properties including the specific volume, texture and sensory features of white bread (WB) were evaluated by the sensory analysis technology. A double-blind, randomised, repeat-measure design was used to study the impact of MLE addition on the postprandial blood glucose response as well as the satiety index of WB. Results showed that the addition of MLE showed no significant effects on the physicochemical properties of WB except for the slight changes of color and bitterness. The addition of MLE significantly reduced the total blood glucose rise after ingestion of WB over 120 minutes, and reduced the GI value of WB in a dose-effect relationship. When the concentration of MLE reached 1.5 g per 100 g available carbohydrate, the GI value of WB could be reduced from 77 to 43. This study provides important information in terms of the appropriateness of MLE when added to more complex real food, the dose-dependent relationship could supply a reference for the application of MLE.

[Bushen Anshen acupuncture for perimenopausal insomnia of kidney-yin deficiency: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of Bushen Anshen acupuncture (acupuncture for tonifying kidney and calming spirit ) in treating perimenopausal insomnia (PMI) of kidney-yin deficiency. METHODS: A total of 72 patients with PMI of kidney-yin deficiency were randomized into an observation group (36 cases, 1 case dropped off) and a control group (36 cases, 1 case dropped off). Acupuncture was applied at Baihui (GV 20) and bilateral Shenshu (BL 23), Taixi (KI 3), Anmian (Extra) in the observation group, while sham acupuncture of shallow needling at non-acupoints was applied in the control group. The treatment was required once every other day, 3 times a week for 10 times in the two groups. Before and after treatment, Pittsburgh sleep quality index (PSQI) was used to evaluate the subjective sleep quality, and polysomnography (PSG) was used to monitor the objective sleep quality in the two groups. RESULTS: After treatment, the scores of sleep quality, sleep latency, sleep duration, sleep efficiency, hypnotic, daytime dysfunction and total score of PSQI were decreased compared with those before treatment in the observation group (P<0.01), the scores of sleep duration, sleep efficiency and total score of PSQI were decreased compared with those before treatment in the control group (P<0.05); the scores of sleep quality, sleep latency, sleep efficiency, hypnotic and total score of PSQI in the observation group were lower than those in the control group (P<0.05). After treatment, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index was reduced (P<0.01) when PSG indexes were monitored, and the percentage of non-rapid eye movement sleep period 1 (N1%) was decreased while the percentage of non-rapid eye movement sleep period 3 (N3%) was increased (P<0.05) compared with those before treatment in the observation group; there was no statistical difference in the PSG indexes compared with those before treatment in the control group (P>0.05). After treatment, compared with the control group, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index and N1% were decreased in the observation group (P<0.01). CONCLUSION: Bushen Anshen acupuncture can effectively improve the subjective and objective sleep quality in PMI patients of kidney-yin deficiency.

Zhilong Huoxue Tongyu Capsule attenuates hemorrhagic transformation through the let-7f/TLR4 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hemorrhagic transformation after acute ischemic stroke is a life-threatening disease that currently has no effective chemotherapy. Zhilong Huoxue Tongyu Capsule (ZL) is an empirical prescription of traditional Chinese medicine that is used to prevent and treat cardiovascular and cerebrovascular diseases in China. However, only a few studies have addressed the mechanisms of ZL in treating hemorrhagic transformation. AIM OF THE STUDY: To evaluate the anti-inflammatory effects of ZL on hemorrhagic transformation model rats and lipopolysaccharide (LPS)-induced RAW264.7 macrophages and to explore the underlying molecular mechanisms. MATERIALS AND METHODS: Murine RAW264.7 cells were treated with ZL and LPS (1 µg/mL), and cell viability was detected by cell counting kit-8 assay. RT-qPCR was used to detect the expression of inflammatory chemokines, microRNA let-7a/e/i/f, toll like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa-B (NF-κB) p65. The protein expression levels of TLR4, MyD88, NF-κB p65, and apoptosis related molecules were determined by Western blotting. The apoptosis rate of RAW264.7 macrophages was detected by Annexin V-FITC/PI double staining. A hemorrhagic transformation model in rats was established by intraperitoneal injection of high glucose solution combined with thread embolization. Then, the model rats were observed behaviourally, pathologically, and molecularly. The gene expression of TLR4, MyD88, and NF-κB p65 was measured by RT-qPCR and used to evaluate the protective effect of ZL against hemorrhagic transformation in rats. RESULTS: ZL (5, 20, 40 µg/mL) was beneficial in cell proliferation. LPS (1 µg/mL) stimulated the production of inflammatory chemokines and inhibited the production of let-7a/e/i/f, with let-7f being influenced most strongly. Moreover, overexpression of let-7f decreased the gene and protein levels of TLR4, MyD88, and NF-κB p65, downregulated TLR4, and inhibited its transcriptional activity. ZL (5, 20, and 40 µg·mL-1) inhibited the production of TLR4, MyD88, and NF-κB p65 and promoted the production of let-7f in a concentration-dependent manner. Furthermore, the blockade of TLR4 antagonized the promoting effects of TLR4 pathway activation in cell inflammation and apoptosis by downregulating let-7f. Critically, it was confirmed in vivo and in vitro that ZL upregulated the expression of let-7f and inhibited the gene expression of TLR4, MyD88, and NF-κB p65 to reduce inflammatory cell infiltration, which determined the occurrence of hemorrhagic transformation. CONCLUSIONS: ZL can reduce inflammatory response by upregulating let-7f and subsequently inhibiting the TLR4 signaling pathway, thereby decreasing the occurrence of hemorrhagic transformation.

Efficacy of acupuncture in patients with mild Alzheimer's disease and its impact on gut microbiota: Study protocol for a randomized sham-controlled trial.

Introduction: Acupuncture is used as an adjuvant therapy for Alzheimer's disease (AD), but available evidence for efficacy is limited so far. Growing studies suggest that resident gut microbiota contributes to the development and progression of AD. Meanwhile, acupuncture is reported to treat gastrointestinal and neurodegenerative disorders via the gut-brain axis. Therefore, our aim is to confirm the adjunctive therapeutic effects of acupuncture for AD, and explore the relationship between clinical efficacy and shifts of gut microbiota. Methods and analysis: This is a randomized, participant-masked, sham-controlled trial. One hundred and sixty participants with mild AD will be randomly assigned (1:1) to either active acupuncture or non-penetrating sham acupuncture (three times weekly for 14 weeks) added to donepezil treatment (5 mg per day for 28 weeks). The primary efficacy outcome is the change from baseline to week 28 in the Alzheimer's disease Assessment Scale (ADAS-cog12). Secondary efficacy outcomes include other assessments of the Mini-Mental State Examination (MMSE), the Alzheimer's disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and Neuropsychiatric Inventory (NPI). Gut microbiota will be measured using 16S rRNA tag sequencing. Discussion: This rigorous trial will provide high-quality evidence on the efficacy of acupuncture as adjunctive treatment for mild AD, and identify the possible mechanisms of acupuncture from gut microbiota. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT05078944], ClinicalTrials.gov [NCT05078944]. Registered 15 October 2021.

Effects of electroacupuncture on dry eye: A pilot randomized controlled trial.

PURPOSE: The purpose of the study was to assess the efficacy of electroacupuncture on dry eye (DE). METHODS: Eighty-four DE patients were randomly assigned to receive electroacupuncture (EAG) three times a week or 0.1% sodium hyaluronate artificial tears (ATG) four times per day for 4 weeks. The primary outcomes were non-invasive tear film breakup time (NIBUT) and tear meniscus height (TMH). The secondary outcomes included the ocular surface disease index (OSDI), Schirmer I test (SIT), corneal sodium fluorescein staining (CFS) score, corneal topography descriptors surface asymmetry index (SAI) and surface regularity index (SRI), corneal sensitivity, 36-item Short-form Health Survey (SF-36) score and Hospital Anxiety and Depression Scale (HADS) score. All outcomes were assessed at Week 0 (baseline), Week 4 (after-treatment) and Week 8 (follow-up). RESULTS: Between-group comparisons showed significant differences in the changes in NIBUT (Week 4, p = 0.003; Week 8, p = 0.008), TMH (Week 4, p = 0.014; Week 8, p = 0.009), OSDI (Week 4, p = 0.029; Week 8, p = 0.022), CFS score (Week 8, p = 0.036) and SF-36 role-physical score (Week 4, p = 0.010), favouring EAG. Mean changes in SIT, SAI, SRI, corneal sensitivity and HADS scores were statistically equal between the two groups (all p > 0.05). Treatment with electroacupuncture was well-tolerated and showed minimal adverse events. CONCLUSIONS: Compared with artificial tears, electroacupuncture shows superior efficacy in improving tear film stability and symptoms of DE.

Recent advances in small molecule dye-based nanotheranostics for NIR-II photoacoustic imaging-guided cancer therapy.

Photoacoustic (PA) imaging in the second near-infrared (NIR-II) window has gained more and more attention in recent years and showed great potential in the field of bioimaging. Until now, numerous materials have been developed as contrast agents for NIR-II PA imaging. Among them, small molecule dyes hold unique advantages such as definite structures and capability of fast clearance from body. By virtue of these advantages, small molecule dyes-constructed nanoparticles have relatively small size and show promise in the clinical translation. Thus, in this minireview, we summarize recent advances in small molecule dyes-based nanotheranostics for NIR-II PA imaging and cancer therapy. Studies about NIR-II PA imaging-guided phototherapy are first introduced. Then, NIR-II PA imaging-guided phototherapy-based combination therapeutic systems are reviewed. Finally, the conclusion and perspectives of this field are summarized and discussed.

An AIPH-decorated semiconducting nanoagonist for NIR-II light-triggered photothermic/thermodynamic combinational therapy.

A multifunctional semiconducting nanoagonist with high photothermic conversion efficiency (86.2%) and alkyl radical generation ability was developed. The nanoagonist demonstrated excellent anticancer performance through NIR-II light-triggered photothermic/thermodynamic combinational therapy both in vitro and in vivo.

Xiaoyao-Qingluoyin Cure Adjuvant-Induced Arthritis by Easing LPS Response-Related Pathway-Mediated Immune Abnormality.

Qingluoyin (QLY) is a representative herbal formula prescribed for hot symptom-related rheumatoid arthritis treatment. Among its derivatives, Xiaoyao-Qingluoyin (XYQLY) attracts increasing attention due to the notable clinical efficacy. In this study, we compared its effects with QLY on adjuvant-induced arthritis (AIA) in rats and partially elucidated the antirheumatic mechanism using a network pharmacology-based strategy. After continuous oral treatments, clinical outcomes were systematically evaluated by radiographic, histological, immunohistochemical, and serological analyses. Possibly altered pathways were predicted based on reported interactions between the related chemicals and proteins/genes. The obtained conclusion was further validated by experiments in vitro. QLY and XYQLY eased polyarthritis in AIA rats after repeated doses, which reflected in reduced inflammation and bone degradation and downregulated p-p65, MMP3, and TLR4 expressions in joints. Meanwhile, they restored oxidative stress (MDA, SOD, GSH, T-AOC, and NO) and inflammatory indicators (TNF-α and CO) in serum. Synovium-based immunoblotting assay revealed that QLY and XYQLY were similarly effective in downregulating MMP3 and COX-2, but XYQLY treatment exhibited notable merit in suppressing p-p65 expression. Network pharmacology analysis hinted that XYQLY should exert greater impacts on LPS signaling and the downstream. Based on results from LC-MS analysis, we treated AIA rat-derived peripheral blood mononuclear cells with either QLY or XYQLY-based chemical combinations and confirmed that XYQLY had the better potential in inhibiting TLR4/NF-κB-controlled IL-6 production. Consequently, it led to a more profound decrease in Th17 cells counts. Overall evidence demonstrated that XYQLY was especially effective in regulating innate immunity and, therefore, improved immune environment in AIA rats as a whole.

[Electroacupuncture improves long-term survival of myocardial infarction mice by promoting myocardial angiogenesis and inhibiting ventricular remodeling].

OBJECTIVE: To investigate the mechanism of electroacupuncture (EA) in improving the long-term survival rate of mice after myocardial infarction by promoting angiogenesis and inhibiting ventricular remodeling. METHODS: A total of 102 male C57BL/6 mice were randomly divided into sham operation, model and EA groups (n=34 /group). The myocardial infarction model was established by permanent ligation of the anterior descending branch of the left coronary artery. Beginning from the 3rd day after ligation, EA (2 Hz/20 Hz) was applied to bilateral "Neiguan" (PC6) and "Ximen" (PC4) for 30 min, once a day for 28 days. The survival rate in 140 d was recorded and the left ventricular ejection fraction (EF) calculated by using echocardiography after the treatment. The left cardiac ventricular tissue was cut into sections to be stained with Masson's trichrome, wheat germ agglutinin (WGA) or α-smooth muscle actin (α-SMA) immunohistochemistry method, followed by measuring the collagen area in the marginal region of myocardial infarction and calculating the collagen volume fraction (for assessing the severity of myocardial fibrosis), measuring the sectional area of cardiomyocytes (for assessing the degree of myocardial hypertrophy), and ob-serving the newborn blood vessels and calculating the ratio of neovascularization area (for assessing the state of angiogenesis). The expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α protein in the boundary area of myocardial infarction were detected by Western blot. RESULTS: After modeling, the survival rate, EF, and the thickness of the left cardiac ventricle were significantly decreased (P<0.01), whereas the percentage of collagen deposition area, sectional area of cardiomyocyte, percentage of angiogenesis area, and the expression levels of VEGF and HIF-1α proteins were significantly increased (P<0.01) in the model group relevant to the sham operation group. Compared with the model group, the survival rate, EF, the thickness of the left cardiac ventricle, the percentage of angiogenesis area, and the expression levels of VEGF and HIF-1α proteins were significantly increased (P<0.05, P<0.01), while the percentage of collagen deposition area and the sectional area of the cardiomyocyte were considerably decreased in the EA group (P<0.01, P<0.05). CONCLUSION: EA of PC6 and PC4 can significantly improve the cardiac function and long-term survival rate in mice with myocardial infarction, which may be related to its functions in up-regulating the expression of HIF-1α and VEGF to promote angiogenesis and in inhibiting ventricular remodeling.

Semiconducting Polymer Nanoparticles for Photoactivatable Cancer Immunotherapy and Imaging of Immunoactivation.

Immunotherapy that stimulates the body's own immune system to kill cancer cells has emerged as a promising cancer therapeutic method. However, some types of cancer exhibited a low response rate to immunotherapy, and the high risk of immune-related side effects has been aroused during immunotherapy, which greatly restrict its broad applications in cancer therapy. Phototherapy that uses external light to trigger the therapeutic process holds advantages including high selectivity and efficiency, and low side effects. Recently, it has been proven to be able to stimulate immune response in the tumor region by inducing immunogenic cell death (ICD), the process of which was termed photo-immunotherapy, dramatically improving therapeutic specificity over conventional immunotherapy in several aspects. Among numerous optical materials for photo-immunotherapy, semiconducting polymer nanoparticles (SPNs) have gained more and more attention owing to their excellent optical properties and good biocompatibility. In this review, we summarize recent developments of SPNs for immunotherapy and imaging of immunoactivation. Different therapeutic modalities triggered by SPNs including photo-immunotherapy and photo-immunometabolic therapy are first introduced. Then, applications of SPNs for real-time monitoring immunoactivation are discussed. Finally, the conclusion and future perspectives of this research field are given.

Semiconducting polymer nanoparticles for NIR-II fluorescence imaging-guided photothermal/thermodynamic combination therapy.

Photothermal therapy is a promising phototherapeutic modality that has been widely studied in cancer therapy. However, because of the influence of heat shock protein (HSP), the therapeutic efficacy of photothermal therapy (PTT) is significantly suppressed. To improve the therapeutic efficacy, different tumor-specific therapeutic modalities have been chosen to combine with PTT. However, most of them rely on endogenous stimuli to trigger combination therapy, which may suffer from the issue of incomplete activation. Herein, we develop a PTT/thermodynamic combination therapeutic nanosystem whose therapeutic process is controlled by an external stimulus, near-infrared (NIR) light. The nanosystem (ADPPTN) is composed of a second NIR (NIR-II) fluorescent semiconducting polymer (SP) (DPPT) as the core, and a carboxyl group-decorated amphiphilic copolymer (PSMA-PEG) as the shell with an azo-containing compound (AIPH) loaded via electrostatic interaction. Under 808 nm laser irradiation, DPPT can generate heat to conduct PTT, while the elevated temperature may further trigger the release of AIPH radicals, conducting thermodynamic therapy (TDT). In addition, the NIR-II fluorescence signal emitted from DPPT can light the tumor. Compared with the nanoparticles without AIPH (DPPTN), ADPPTN has better anticancer efficacy under laser irradiation both in vitro and in vivo. Thus, our study provides an NIR-II fluorescence imaging-guided PTT/TDT combination therapeutic nanosystem for efficient cancer theranostics.

Potato tillage method is associated with soil microbial communities, soil chemical properties, and potato yield.

Intensive potato continuous cropping (IPCC) results in low potato yields compared with non-intensive potato continuous cropping (PCC) and potato-maize rotation (PMRC). However, it is still unclear whether the degree of potato continuous cropping obstacle is related to the soil environment formed by the previous crop. To investigate the effect of planting potatoes and planting maize after harvesting the spring potatoes on soil chemical properties and soil microbial community structure, an experiment was carried out in the same origin soil environment over a period of seven years: (a) PCC, i.e., spring planting; (b) IPCC, i.e., autumn and spring planting (IPCC); (c) PMRC, i.e., spring potatoes and summer maize (PMRC), and (d) fallow (CK). We confirmed that the potato yield under PMRC was significantly higher than that under PCC and IPCC. Under IPCC, soil total phosphorus content was significantly higher than other treatments, whereas ammonium nitrogen content was the lowest. Compared with PCC and IPCC, PMRC had a higher ammonium nitrogen content and lower total phosphorus content. The significantly different fungal taxa in IPCC (Glomerellales, Plectosphaerella, Thelebolales) may threaten the health of the plant and positive correlated with soil total phosphorus, while other microbial taxa in PMRC (Bacillales, Polythrincium, Helotiales) can mainly promotes plant nitrogen uptake and protects plants against diseases. The PMRC-promoting taxa were positively correlated with the ammonium nitrogen content and negative correlated with soil total phosphorus content. In summary, the cropping systems might have affected potato yields by changed soil microorganism community structures - especially fungal community structures - and by the chemical properties of the soils that also depends on microbes.

[Spectrum and indications of acupuncture and moxibustion therapy based on bibliometric analysis].

OBJECTIVE: To analyze the literature of acupuncture and moxibustion for diseases in the recent 5 years, and discuss the spectrum and indications of acupuncture and moxibustion. METHODS: The literature on acupuncture and moxibustion for diseases in CNKI, Wanfang and VIP databases from January 1, 2015 to December 31, 2019 was searched, summarized and analyzed, and the disease spectrum was summarized. At the same time, the literature from 2015 to 2019 (group A), 1978 to 2005 (group B), and 1949 to 2005 (group C) was compared, and the indications of acupuncture and moxibustion therapy were summarized. RESULTS: There were 32 011 articles on acupuncture and moxibustion for diseases in the recent 5 years, including 377 kinds of indications. These indications can be mostly classified as neurology (9384), orthopedics and traumatology (7765), gastroenterology (3529) and obstetrics and gynecology (2283). The types of diseases were mostly gastroenterology (52 types), neurology (47 types), ophthalmology and otorhinolaryngology (47 types), and obstetrics and gynecology (42 types). The first-class indications of acupuncture and moxibustion therapy in the recent 5 years were hemiplegia, lumbar disc herniation, cervical spondylosis, knee osteoarthritis, insomnia, constipation and cerebrovascular diseases; the second-class were facial neuritis, shoulder pain and headache; the third-class were dysphagia, dysmenorrhea and depression; the forth-class were asthma, urinary retention, cerebral palsy, hypertension, dementia, side effects of radiotherapy and chemotherapy, infertility, allergic rhinitis, vertigo, shoulder-hand syndrome, diabetic neuropathy, herpes zoster, pain, hiccup, diarrhea, lumbar sprain and sciatica. CONCLUSION: Although the disease spectrum and indications of acupuncture and moxibustion therapy have changed to some extent in the recent 5 years, neurology and orthopedics and traumatology are still predominant, and the observation objects tend to transition from symptoms to diseases.

Effects of Electroacupuncture on Sleep via the Dopamine System of the HPA Axis in Rats after Cage Change.

BACKGROUND: Insomnia is often related to stressful events. The hypothalamus-pituitary-adrenal (HPA) axis is related to stress, and dopamine (DA) and DA receptors are involved in the regulation of HPA axis. Electroacupuncture (EA) can improve sleep in individuals with insomnia, but the mechanism is unclear. We demonstrated that EA can improve sleep in rats after cage change through DA and the DA receptors in the HPA axis. METHODS: A rat model of insomnia was established by cage change to a dirty cage. The rats in treatment groups were intervened by EA and D1R (or D2R) antagonists. Electroencephalography (EEG) and electromyogram (EMG) were recorded to compare the changes in sleep. The DA, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol (CORT) levels in the plasma and hypothalamus were measured by ELISAs, and the D1R and D2R levels were measured by RT-PCR and immunohistochemistry. RESULTS: The dirty group showed a significant increase in the amount of wakefulness and decrease in the amount of NREM sleep, with decreased numbers of long NREM sleep bouts and REM sleep bouts and increased mean duration of wakefulness during the light period. EA and D1R (or D2R) antagonists intervention could improve sleep disturbance by decreasing wakefulness in the light period after cage change, EA and D1R (or D2R) antagonists could increase the hypothalamus DA, CRH, ACTH, CORT level, and the D1R and D2R mRNA levels in the HPA axis, and the effect of EA plus D1R (or D2R) antagonist was not superior to that of EA or D1R (or D2R) antagonists alone. CONCLUSIONS: EA can improve the sleep of rats after cage change, and the mechanism may be related to the regulation of DA and D1R or D2R in the HPA axis.

[Effect on 6-23 months infants by Yingyangbao intervention in impoverished regions of Henan Province].

OBJECTIVE: To observe the effect of 6-23 months infants by Yingyangbao(YYB) intervention in impoverished areas of Henan Province. METHODS: A multi-stage random sampling method was used to select infants aged 6-23 months from 51 project counties in Henan Province from September to November 2019. Physical anthropometric measurement and hemoglobin detection were performed, and face-to-face questionnaires surveyed with caregivers of the children. Children in 12 regions covered by YYB were defined as intervention group, and controls were selected from the baseline survey of children in 39 regions not covered by YYB according to the 1∶1 matching principle. The analysis between YYB and control groups were analyzed by χ~2 or t test. χ~2 test for trend to compare trend of children health status. RESULTS: A total of 7738 subjects were selected in the study, including 3869 in the intervention group and 3869 in the control group. The average length, weight and hemoglobin level of YYB group were 1. 1 cm, 0. 67 kg and 3. 8 g/L, respectively, which were higher than that of the control group. The anemia rate, underweight rate, stunting rate and wasting rate in intervention group were 13.1%, 1.7%, 2.1% and 1.9%, respectively, significantly lower than control group. Compared with the control group, the two-week prevalence of fever and diarrhea in the intervention group decreased by 5. 6% and 7. 2%, respectively. In addition, nutrition knowledge score of the parents, minimum dietary diversity rate, minimum meal frequency rate and minimum acceptable diet rate of intervention group were 62. 4%, 71. 1%, 73. 7% and 55. 8%, respectively, significantly better than that of control group. From 2015 to 2019, the anemia rate, underweight rate, stunting rate of children in regions covered by YYB showed a downward trend. CONCLUSION: YYB can effectively improve the nutrition, physical development and health status of 6-24 months infants. Through the implementation of the project, the knowledge and skills of scientific feeding in impoverished regions were significantly improved.

Rational design of high performance nanotheranostics for NIR-II fluorescence/magnetic resonance imaging guided enhanced phototherapy.

Nanotheranostics, which can provide great insight into cancer therapy, has been deemed as a promising technology to settle the unmet medical needs. The rational design of high performance nanotheranostics with multiple complementary imaging features and satisfactory therapeutic efficacy is particularly valuable. Herein, versatile nanotheranostic agents DPPB-Gd-I NPs were fabricated by using gadolinium-diethylenetriaminepentaacetic acid chelates and an iodine-decorated copolymer as encapsulation matrixes to encapsulate a polymer DPPB through one-step nanoprecipitation. We have demonstrated that such nanoagents are able to efficiently damage tumors under single dose injection and NIR laser illumination conditions due to the enhanced photodynamic therapy and enhanced photothermal therapy (the tumor inhibition rate was as high as 94.5%). Moreover, these nanoagents can be utilized as dual-modal NIR-II fluorescence/magnetic resonance imaging probes for tumor diagnosis with high sensitivity, deep tissue penetration, and excellent spatial resolution. Overall, this work offers a powerful tactic to fabricate high performance nanotheranostics for clinical application.

Computational Investigation of Protein Photoinactivation by Molecular Hyperthermia.

To precisely control protein activity in a living system is a challenging yet long-pursued objective in biomedical sciences. Recently, we have developed a new approach named molecular hyperthermia (MH) to photoinactivate protein activity of interest without genetic modification. MH utilizes nanosecond laser pulse to create nanoscale heating around plasmonic nanoparticles to inactivate adjacent protein in live cells. Here we use a numerical model to study important parameters and conditions for MH to efficiently inactivate proteins in nanoscale. To quantify the protein inactivation process, the impact zone is defined as the range where proteins are inactivated by the nanoparticle localized heating. Factors that reduce the MH impact zone include the laser pulse duration, temperature-dependent thermal conductivity (versus constant properties), and nonspherical nanoparticle geometry. In contrast, the impact zone is insensitive to temperature-dependent material density and specific heat, as well as thermal interface resistance based on reported data in the literature. The low thermal conductivity of cytoplasm increases the impact zone. Different proteins with various Arrhenius kinetic parameters have significantly different impact zones. This study provides guidelines to design the protein inactivation process by MH.

[Effect of electroacupuncture pretreatment on differential expression profiles of myocardial long non-coding RNA and mRNA in mice with myocardial ischemia-reperfusion injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment at "Neiguan" (PC6) on expression profiles of myocardial long non-coding RNAs (LncRNAs) and mRNAs in myocardial ischemia-reperfusion injury (MIRI) mice, so as to explore its mechanisms underlying prevention of MIRI via regulating LncRNA expression. METHODS: C57BL/6 mice were randomly divided into sham, model, and EA groups (n=4 in each group). The MIRI model was established by occlusion of the anterior descending branch (ADB) of the left coronary artery for 30 min, followed by reperfusion for 24 h. In the sham group, the ADB was only threaded beneath the artery without ligation. EA was applied to bilateral PC6 for 30 min prior to ischemia induction. Surgery was performed within 30 min at the end of EA stimulation. The expression profiles of differentially expressed LncRNAs and mRNAs in the left ventricular myocardium were analyzed by using LncRNA microarray. RESULTS: There was a significant diffe-rence in the expression pattern of LncRNAs and mRNAs among the sham, model and EA groups. A total of 1 693 LncRNAs and 2 858 mRNAs between the model and sham groups, and 3 859 LncRNAs and 1 343 mRNAs between the EA and model groups were identified to be differentially expressed candidates. According to Venn intersection analysis, LncRNAs with opposite regulative orientations in the model and EA groups were screened and defined as EA-related LncRNAs. LncRNA-mRNA co-expression analysis and Gene Ontology enrichment analysis of the EA-related LncRNAs predicted their roles to regulating post-traumatic stress and repairing of myocardial cells. Meanwhile, the proteins' function encoded by EA-related mRNAs mainly involved post-traumatic stress and inflammatory regulation. CONCLUSION: EA pretreatment at PC6 acupoint can produce extensive regulation on myocardial LncRNAs and mRNAs in MIRI mice, suggesting an involvement of LncRNAs in EA pretreatment induced improvement of MIRI. These results may provide direction and molecular basis for subsequent in-depth studies to reveal the underlying mechanisms of EA pretreatment for MIRI.

Grafted semiconducting polymer amphiphiles for multimodal optical imaging and combination phototherapy.

Semiconducting polymer nanoparticles (SPNs) have gained growing attention in biomedical applications. However, the preparation of SPNs is usually limited to nanoprecipitation in the presence of amphiphilic copolymers, which encounters the issue of dissociation. As an alternative to SPNs, grafted semiconducting polymer amphiphiles (SPAs) composed of a semiconducting polymer (SP) backbone and hydrophilic side chains show increased physiological stability and improved optical properties. This review summarizes recent advances in SPAs for cancer imaging and combination phototherapy. The applications of SPAs in optical imaging including fluorescence, photoacoustic, multimodal and activatable imaging are first described, followed by the discussion of applications in imaging-guided phototherapy and combination therapy, light-triggered drug delivery and gene regulation. At last, the conclusion and future prospects in this field are discussed.

Gegen Qinlian decoction enhances immunity and protects intestinal barrier function in colorectal cancer patients via gut microbiota.

BACKGROUND: We previously showed, using the Traditional Chinese Medicine System Pharmacology Database, that Gegen Qinlian decoction (GQD) had a direct antitumor effect, and was combined with programmed cell death protein (PD)-1 inhibitors to treat microsatellite stable (MSS) tumor-bearing mice. However, the effect of GQD on patients with colorectal cancer (CRC) is not clear. AIM: To determine the therapeutic mechanism of GQD in improving immune function, reducing inflammation and protecting intestinal barrier function. METHODS: Seventy patients with CRC were included in this study: 37 in the control group and 33 in the treatment group. The proportions of CD4+ T, CD8+ T, natural killer (NK), NKT and T regulatory cells were measured by flow cytometry. Levels of the cytokines tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-6, IL-10 and serotonin (5-hydroxytryptamine; 5-HT) in serum were assessed by enzyme-linked immunosorbent assay (ELISA). The expression of zonula occludens (ZO)-1, occludin, nuclear factor (NF)-κB and TNF-α in tumor and normal tissues was measured by immunohistochemistry. The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis. RESULTS: There were no adverse events in the treatment group. The proportion of CD4+ T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups (P < 0.05). The level of TNF-α in the post-treatment group was significantly lower than that in the pre-treatment and control groups (P < 0.05). The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group (P < 0.05). The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group (P < 0.05). The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group (P = 0.010). Compared with the control group, expression of NF-κB and TNF-α in tumor tissues of the treatment group was significantly decreased (P < 0.05). Compared with the pre-treatment group, GQD decreased the relative abundance of Megamonas and Veillonella. In addition, GQD increased the relative abundance of Bacteroides, Akkermansia and Prevotella. CONCLUSION: GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.