Polydopamine-containing nano-systems for cancer multi-mode diagnoses and therapies: A review.

Polydopamine (PDA) has fascinating properties such as inherent biocompatibility, simple preparation, strong near-infrared absorption, high photothermal conversion efficiency, and strong metal ion chelation, which have catalyzed extensive research in PDA-containing multifunctional nano-systems particularly for biomedical applications. Thus, it is imperative to overview synthetic strategies of various PDA-containing nanoparticles (NPs) for state-of-the-art cancer multi-mode diagnoses and therapies applications, and offer a timely and comprehensive summary. In this review, we will focus on the synthetic approaches of PDA NPs, and summarize the construction strategies of PDA-containing NPs with different structure forms. Additionally, the application of PDA-containing NPs in bioimaging such as photoacoustic imaging, fluorescence imaging, magnetic resonance imaging and other imaging modalities will be reviewed. We will especially offer an overview of their therapeutic applications in tumor chemotherapy, photothermal therapy, photodynamic therapy, photocatalytic therapy, sonodynamic therapy, radionuclide therapy, gene therapy, immunotherapy and combination therapy. At the end, the current trends, limitations and future prospects of PDA-containing nano-systems will be discussed. This review aims to provide guidelines for new scientists in the field of how to design PDA-containing NPs and what has been achieved in this area, while offering comprehensive insights into the potential of PDA-containing nano-systems used in cancer diagnosis and treatment.

Research progress on chemical constituents and pharmacological effects of Kaixin Powder and predictive analysis of its Q-markers / 中国中药杂志

Kaixin Powder is a classic prescription for invigorating Qi, nourishing the mind, and calming the mind. It has pharmacological effects of improving learning and memory ability, resisting oxidation, delaying aging, and promoting the differentiation and regeneration of nerve cells. It is mainly used in the modern clinical treatment of amnesia, depression, dementia, and other diseases. The present paper reviewed the research progress on the chemical composition and pharmacological action of Kaixin Powder, predicted and analyzed its quality markers(Q-markers) according to the concept of Chinese medicine Q-markers, including transmission and traceability, specificity, effectiveness, measurability, and compound compatibility environment. The results suggested that sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3',6-disinapoylsucrose, tenuifoliside A, ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, pachymic acid, β-asarone, and α-asarone could be used as Q-markers of Kaixin Powder. This study is expected to provide a scientific basis for establishing the quality control system and the whole process quality traceability system of Kaixin Powder compound preparations.

Application of Internet-based hospital-institution linkage care management model in elderly care for elderly people with dementia / 中国实用护理杂志

Objective:To explore the application effect of Internet-based hospital-institution linkage care management model in elderly care for the elderly of dementia.Methods:The research was a quasi-experiment study. A total of 80 elderly people of dementia from three combined medical and nursing institutions, Beijing Fangshan District Mental Health Care Hospital, Beijing Jinhai Hospital of Traditional Chinese Medicine, and Beijing Yiciyuan Nursing Care Center, were selected as the research objects by convenient sampling. The elderly people of dementia enrolled from May to August 2021 served as the control group, and elderly people of dementia enrolled from September to December 2021 served as the experimental group, with 40 cases in each group. Conventional management methods were taken in the control group, while Internet-based hospital-institution linkage care management model was taken in the experimental group. Before the intervention, at 3 months of intervention, the Mini-Mental State Examination (MMSE), Barthel index (BI) and Cohen Mansfield agitation behavior inventory (CMAI) were used to evaluate the cognitive function, activities of daily living and agitation behavior of two groups.Results:A total of 78 cases were included, including 39 cases in the experimental group and 39 cases in the control group, respectively. Before intervention, there was no significant difference in scores of MMSE, BI, and CMAI in the two groups of elderly people with dementia ( P>0.05). After 3 months of intervention, the score of MMSE in the experimental group was (17.36±5.67) points, which was higher than (15.05 ± 2.70) points of the control group, and the difference was statistically significant ( t=2.13, P<0.05). The score of CMAI in the experimental group was (34.18 ± 4.37) points, which was lower than (37.13 ± 5.06) points of the control group, and the difference was statistically significant ( t=2.76, P<0.05). There was no significant difference in BI scores ( t=0.13, P>0.05). Conclusions:The Internet-based hospital-institution linkage care management model improves the cognitive function and agitated behavior of the elderly with dementia in medical-nursing institutions.

Gelatinase Responsive Nanogel for Antibacterial Phototherapy and Wound Healing.

The unique bactericidal mechanism of metal nanoparticles (MNPs) is considered to be an effective strategy to deal with antibiotic resistance, but the oxidative stress damage caused by excessive accumulation of MNPs to normal cells cannot be ignored. Achieving on-demand release of nano-drugs in specific infection environments is highly attractive. Herein, we constructed a "core-shell" nanogel (G@CuS) based on a copper sulfide (CuS) antimicrobial agent and gelatin for targeted drug release and bacterial clearance in a gelatinase infected microenvironment. G@CuS produced heat and reactive oxygen species (ROS) under the irradiation of a laser, which together with the released Cu2+ cause irreversible and efficient physical damage to the bacteria. Moreover, the encapsulation of gelatin not only limits the biotoxicity of CuS nanodots (NDs), but also effectively promotes the proliferation of mammalian cells. Under the synergy of multiple mechanisms, G@CuS eradicated the colonized bacteria in the wound of mice infected with Staphylococcus aureus (S. aureus) and accelerated wound healing. The proposed application strategy of nanogel is expected to provide a new idea for clinical transformation.

Gamma-oryzanol alleviates intervertebral disc degeneration development by intercepting the IL-1ß/NLRP3 inflammasome positive cycle.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a highly prevalent musculoskeletal disorder characterized by a local inflammatory response associated with the IL-1ß/NLRP3 inflammasome positive feedback loop. Rice bran-derived gamma-oryzanol (Ory) as a sterol ferulate has attracted much attention due to its powerful anti-inflammatory, hypoglycemic and hypolipidemic health effects. As a clinical pharmaceutical for autonomic disorders, Ory's role in musculoskeletal degenerative disease remains unknown. PURPOSE: This study aims to validate the role of Ory in IVDD and explore the potential mechanism. STUDY DESIGN: Establishing the in vitro and in vivo IVDD models to detect the protective effect and molecular mechanism of Ory. METHOD: The anti-ECM degradation, antioxidant and anti-NLRP3 inflammasome activation effects of Ory on IL-1ß-stimulated nucleus pulposus (NP) cells were assessed by immunoblotting and immunofluorescence, etc. MRI, S-O staining and immunohistochemistry were performed to estimate the effects of Ory administration on acupuncture-mediated IVDD in rats at imaging and histological levels. RESULTS: Ory treatment inhibited IL-1ß-mediated ECM degradation, oxidative stress and NLRP3 inflammasome activation in NP cells. By interfering with NF-κB signaling and ROS overproduction, Ory interrupted IL-1ß/NLRP3-inflammasome positive cycle. In vivo experiments showed that Ory delayed acupuncture-mediated IVDD development. CONCLUSION: Our results support the potential application of Ory as a therapeutic compound for IVDD.

MAP30 protein from Momordica charantia is therapeutic and has synergic activity with cisplatin against ovarian cancer in vivo by altering metabolism and inducing ferroptosis.

Increasing evidence shows that Traditional Chinese Medicine (TCM) has an obvious appeal for cancer treatment, but there is still a lack of scientific investigation of its underlying molecular mechanisms. Bitter melon or bitter gourd (Momordica charantia) is an edible fruit that is commonly consumed, and it is used to cure different diseases in various ancient folk medical practices. We report that a bioactive protein, MAP30, isolated from bitter melon seeds exhibited potent anticancer and anti-chemoresistant effects on ovarian cancer cells. Functional studies revealed that MAP30 inhibited cancer cell migration, cell invasion, and cell proliferation in various ovarian cancer cells but not normal immortalized ovarian epithelial cells. When administered with cisplatin, MAP30 produced a synergistic effect on cisplatin-induced cell cytotoxicity in ovarian cancer cells. When low doses of cisplatin and MAP30 were co-injected intraperitoneally, a remarkable reduction of tumor dissemination and tumor growth was observed in an ovarian cancer ascites mouse model. Notably, blood tests confirmed that MAP30 did not cause any adverse effects on liver and kidney functions in the treated mice. MAP30 activated AMP-activated protein kinase (AMPK) signaling via CaMKKß and induced cell cycle arrest in the S-phase. MAP30 modulated cell metabolism of ovarian cancer cells via suppression of GLUT-1/-3-mediated glucose uptake, adipogenesis, and lipid droplet formation in tumor development and progression. MAP30 also induced an increase in intracellular Ca2+ ion concentration, which triggered ROS-mediated cancer cell death via apoptosis and ferroptosis. Collectively, these findings suggest that natural MAP30 is a non-toxic supplement that may enhance chemotherapeutic outcomes and benefit ovarian cancer patients with peritoneal metastases.

A hypothalamus-habenula circuit controls aversion.

Encoding and predicting aversive events are critical functions of circuits that support survival and emotional well-being. Maladaptive circuit changes in emotional valence processing can underlie the pathophysiology of affective disorders. The lateral habenula (LHb) has been linked to aversion and mood regulation through modulation of the dopamine and serotonin systems. We have defined the identity and function of glutamatergic (Vglut2) control of the LHb, comparing the role of inputs originating in the globus pallidus internal segment (GPi), and lateral hypothalamic area (LHA), respectively. We found that LHb-projecting LHA neurons, and not the proposed GABA/glutamate co-releasing GPi neurons, are responsible for encoding negative value. Monosynaptic rabies tracing of the presynaptic organization revealed a predominantly limbic input onto LHA Vglut2 neurons, while sensorimotor inputs were more prominent onto GABA/glutamate co-releasing GPi neurons. We further recorded the activity of LHA Vglut2 neurons, by imaging calcium dynamics in response to appetitive versus aversive events in conditioning paradigms. LHA Vglut2 neurons formed activity clusters representing distinct reward or aversion signals, including a population that responded to mild foot shocks and predicted aversive events. We found that the LHb-projecting LHA Vglut2 neurons encode negative valence and rapidly develop a prediction signal for negative events. These findings establish the glutamatergic LHA-LHb circuit as a critical node in value processing.

In situ aqueous synthesis of genetically engineered polypeptide-capped Ag2S quantum dots for second near-infrared fluorescence/photoacoustic imaging and photothermal therapy.

Ag2S quantum dots have received extensive attention as theranostic agents for second near-infrared (NIR-II) fluorescence and photoacoustic dual-mode imaging, and photothermal therapy. However, it is still greatly challenging to synthesize Ag2S quantum dots using aqueous synthesis. In this study, genetically engineered polypeptide-capped Ag2S quantum dots were successfully synthesized. Three cysteines were integrated to the C-terminal and N-terminal of RGDPC10A to enhance the stability and brightness of the synthesized Ag2S quantum dots. The RGDPC10A-capped Ag2S quantum dots exhibited excellent stability, outstanding resistance to photobleaching, and a superior quantum yield of up to 3.78% in the NIR-II biological window. The in vitro and in vivo results showed that the RGDPC10A-capped Ag2S quantum dots possessed typical NIR-II fluorescence, photoacoustic imaging, and photothermal therapeutic effectiveness against tumors. Moreover, the results of toxicity assays suggested that the RGDPC10A-capped Ag2S quantum dots have negligible long-term toxicity. These findings open up the possibility for synthesizing theranostic agents by using this aqueous method.

In vivo Imaging-Guided Nanoplatform for Tumor Targeting Delivery and Combined Chemo-, Gene- and Photothermal Therapy.

Currently, a large number of anti-tumor drug delivery systems have been widely used in cancer therapy. However, due to the molecular complexity and multidrug resistance of tumors, monotherapies remain suboptimal. Thus, this study aimed to develop a multifunctional theranostic nanoplatform for effective cancer therapy. Methods: Folic acid-modified silver sulfide@mesoporous silica core-shell nanoparticle was first modified with desthiobiotin (db) on the surface, then doxorubicin (DOX) was loaded into pore. Avidin was employed as "gatekeeper" to prevent leakage of DOX via desthiobiotin-avidin interaction. Db-modified survivin antisense oligonucleotide (db-DNA) which could inhibit survivin expression was then grafted on avidin at the outer layer of nanoparticle. DOX release and db-DNA dissociation were simultaneously triggered by overexpressing biotin in cancer cells, then combining PTT from Ag2S QD to inhibit tumor growth. Results: This nanoprobe had satisfactory stability and photothermal conversion efficiency up to 33.86% which was suitable for PTT. Due to the good targeting ability and fluorescent anti-bleaching, its signal still existed at the tumor site after tail vein injection of probe into HeLa tumor-bearing nude mice for 48 h. In vitro and in vivo antitumor experiments both demonstrated that drug, gene and photothermal synergistic therapy significantly enhanced antitumor efficacy with minimal systemic toxicity. Conclusion: Our findings demonstrate that this novel nanoplatform for targeted image-guided treatment of tumor and tactfully integrated chemotherapy, photothermal therapy (PTT) and gene therapy might provide an insight for cancer theranostics.

A multifunctional targeting probe with dual-mode imaging and photothermal therapy used in vivo.

BACKGROUND: Ag2S has the characteristics of conventional quantum dot such as broad excitation spectrum, narrow emission spectrum, long fluorescence lifetime, strong anti-bleaching ability, and other optical properties. Moreover, since its fluorescence emission is located in the NIR-II region, has stronger penetrating ability for tissue. Ag2S quantum dot has strong absorption during the visible and NIR regions, it has good photothermal and photoacoustic response under certain wavelength excitation. RESULTS: 200 nm aqueous probe Ag2S@DSPE-PEG2000-FA (Ag2S@DP-FA) with good dispersibility and stability was prepared by coating hydrophobic Ag2S with the mixture of folic acid (FA) modified DSPE-PEG2000 (DP) and other polymers, it was found the probe had good fluorescent, photoacoustic and photothermal responses, and a low cell cytotoxicity at 50 µg/mL Ag concentration. Blood biochemical analysis, liver enzyme and tissue histopathological test showed that no significant influence was observed on blood and organs within 15 days after injection of the probe. In vivo and in vitro fluorescence and photoacoustic imaging of the probe further demonstrated that the Ag2S@DP-FA probe had good active targeting ability for tumor. In vivo and in vitro photothermal therapy experiments confirmed that the probe also had good ability of killing tumor by photothermal. CONCLUSIONS: Ag2S@DP-FA was a safe, integrated diagnosis and treatment probe with multi-mode imaging, photothermal therapy and active targeting ability, which had a great application prospect in the early diagnosis and treatment of tumor.

Nursing effect of personalized traditional Chinese medicine nursing mode for patients with subtotal ;gastrectomy / 中国实用护理杂志

Objective To explore the application effect of individualized traditional Chinese medicine nursing mode in the nursing of patients with subtotal gastrectomy. Methods A total of 60 eligible patients who met the standard were divided into the control group and the intervention group with 30 cases in each group according to the random number table method, the control group received only normal nursing while the intervention group was subjected to the individualized TCM nursing based on the normal nursing. The nursing effect was compared between two groups. Results Scores of negative mood of patients of the intervention group before surgery, electrogastrogram slow wave 3 h, the first day and the second day after the operation, first feeding time after operation, early ambulation time, average length of stay was (16.50 ± 3.20) points, 2.58 ± 0.46, 2.88 ± 0.08, 2.99 ± 0.54, (28.70 ± 4.43) h, (29.09 ± 4.55) h, (8.24 ± 1.38) d. The control group was(16.98 ± 2.61)points, 2.40 ± 0.53, 2.79 ± 0.14, 2.71 ± 0.30,(31.45 ± 3.80)h,(32.91±2.28)h,(10.40±1.99)d, there were significant differences between the two groups (t=2.53-25.19, P 0.05). Conclusions Individualized TCM nursing can effectively alleviate the patients′ negative mood, shorten the recovery time of postoperative electrogastrogram slow wave, first feeding time and early ambulation time, to restore the gastrointestinal function of patients earlier, effectively promote the rehabilitation of patients;at the same time, shorten the hospitalization time.

Multifunctional magnetic-hollow gold nanospheres for bimodal cancer cell imaging and photothermal therapy.

Multifunctional nanocomposites combining imaging and therapeutic functions have great potential for cancer diagnosis and therapy. In this work, we developed a novel theranostic agent based on hollow gold nanospheres (HGNs) and superparamagnetic iron oxide nanoparticles (SPIO). Taking advantage of the excellent magnetic properties of SPIO and strong near-infrared (NIR) absorption property of HGNs, such nanocomposites were applied to targeted magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) of cancer cells. In vitro results demonstrated they displayed significant contrast enhancement for T2-weighted MRI and strong PAI signal enhancement. Simultaneously, the nanocomposites exhibited a high photothermal effect under the irradiation of the near-infrared laser and can be used as efficient photothermal therapy (PTT) agents for selective killing of cancer cells. All these results indicated that such nanocomposites combined with MRI-PAI and PTT functionality can have great potential for effective cancer diagnosis and therapy.

Preventive effects of jujube polysaccharides on fructose-induced insulin resistance and dyslipidemia in mice.

High fructose intake is associated with adverse metabolic syndromes. This study was designed to investigate whether the polysaccharides derived from Zizyphus jujube cv. Shaanbeitanzao (ZSP) could alleviate high fructose-induced insulin resistance and dyslipidemia in mice. ZSP was identified by capillary zone electrophoresis as an acidic heteropolysaccharide with l-arabinose, d-galactose and d-galacturonic acid being the main component monosaccharides. Mice were provided with 20% high-fructose water and ZSP was administered intragastrically at doses of 0, 200 or 400 mg kg(-1) BW for 4 weeks. Fructose-treated mice showed hyperglycemia, hyperinsulinemia and dyslipidemia with impaired insulin sensitivity (p < 0.05). Administration of ZSP at a dose of 400 mg kg(-1) BW significantly reduced the serum levels of glucose, insulin, TC, TG, LDL-C, and VLDL-C (p < 0.01). ZSP also markedly improved the HDL-C level, homeostasis model assessment for insulin resistance (HOMA-IR) and ß-cell function (HOMA-ß), and decreased the atherogenic index (AI) of the mice exposed to high-fructose water. Histopathological test with H&E and oil red O staining confirmed liver steatosis induced by a high-fructose diet and the hepatoprotective effect of ZSP. These findings indicate that the jujube polysaccharides may ameliorate insulin resistance and dyslipidemia in fructose-treated mice.

Effects of scalp acupuncture on acute cerebral ischemia-reperfusion injury in rats / 中西医结合学报

To explore the mechanisms of scalp acupuncture in treating cerebral ischemia in rats.

Effect of herba schizonepetae volatile oil (STO) on activity of 5-lipoxygenase in rat thoracic cavity leukocytes / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of herba schizonepetae volatile oil (STO) on the activity of 5-lipoxygenase (5-LO), so as to elucidate its mechanisms of anti-inflammatory action which is related to the arachidonic acid (AA) metabolism.</p><p><b>METHOD</b>Thoracic cavity leukocytes from the pleurisy model rat induced by injecting 1%-carrageenan into the pleural cavity were collected. Then 0. 4 mL cell suspension including 2 x 10(7) cells per millilitre were used as the reaction system in vitro. STO in different concentrations (final concentration 0.011, 0.022, 0.043, 0.087, 0.179, 0.255, 0.364 g x L(-1)), zileuton (final concentration 0.625 x 10(-3) g x L(-1)), and DMSO in the same volume were added into the reaction tube respectively. The reaction tubes were incubated at 37 degrees C for 20 min and CaCl2 (final concentration 2 mmol x L(-1)), MgCl2 (final concentration 0.5 mmol x L(-1)), exogenous AA (final concentration 200 micromol x L(-1)) and A23187 (final concentration 5 micromol x L(-1)) were added in turns during this period. The reaction tubes were mixed and continuously incubated at 37 degrees C for 30 min. After terminating reaction by adding methanol, the metabolites of 5-LO, leukotriene B4 (LTB4) and 5-hydroxy-6, 8, 11, 14-eicosatetraenoic acid (5-HETE), were extracted, separated and detected by means of RP-HPLC.</p><p><b>RESULT</b>Compared with control group, STO significantly inhibited the biosynthesis of LTB4 and 5-HETE at final concentration between 0. 022 g x L(-1) and 0.364 g x L(-1) (P < 0.05 or 0.001) in dose dependence manner, and its IC50 value was 0.124 g x L(-1) and 0.142 g x L(-1) for LTB4 and 5-HETE, respectively.</p><p><b>CONCLUSION</b>STO can inhibited the activity of 5-LO, which is an important enzyme of AA metabolism, in rat thoracic cavity leukocytes in a dose-dependent manner in vitro. It is suggested that the mechanism of anti-inflammatory action of STO is related to its inhibiting the activity of 5-LO and decreasing the level of major inflammatory mediators LTB4.</p>