A multifunctional cascade enzyme system for enhanced starvation/chemodynamic combination therapy against hypoxic tumors.

Starvation therapy has shown promise as a cancer treatment, but its efficacy is often limited when used alone. In this work, a multifunctional nanoscale cascade enzyme system, named CaCO3@MnO2-NH2@GOx@PVP (CMGP), was fabricated for enhanced starvation/chemodynamic combination cancer therapy. CMGP is composed of CaCO3 nanoparticles wrapped in a MnO2 shell, with glucose oxidase (GOx) adsorbed and modified with polyvinylpyrrolidone (PVP). MnO2 decomposes H2O2 in cancer cells into O2, which enhances the efficiency of GOx-mediated starvation therapy. CaCO3 can be decomposed in the acidic cancer cell environment, causing Ca2+ overload in cancer cells and inhibiting mitochondrial metabolism. This synergizes with GOx to achieve more efficient starvation therapy. Additionally, the H2O2 and gluconic acid produced during glucose consumption by GOx are utilized by MnO2 with catalase-like activity to enhance O2 production and Mn2+ release. This process accelerates glucose consumption, reactive oxygen species (ROS) generation, and CaCO3 decomposition, promoting the Ca2+ release. CMGP can alleviate tumor hypoxia by cycling the enzymatic cascade reaction, which increases enzyme activity and combines with Ca2+ overload to achieve enhanced combined starvation/chemodynamic therapy. In vitro and in vivo studies demonstrate that CMGP has effective anticancer abilities and good biosafety. It represents a new strategy with great potential for combined cancer therapy.

Konjac glucomannan films incorporated pectin-stabilized Mandarin oil emulsions: Structure, properties, and application in fruit preservation.

To enhance the water-resistance and antibacterial properties of KGM films, mandarin oil (MO), was directly emulsified by pectin and then dispersed to the KGM matrix. The effect of MO concentration (0, 0.5, 1.0, 1.5, and 2 wt%) on the performance of the film-forming emulsions as well as the emulsion films was investigated. The results revealed that pectin could encapsulate and protect MO, and KGM as film matrix could further contributed to the high stability of the film-forming emulsions. The FT-IR, XRD, and SEM suggested that MO stabilized by pectin was uniformly distributed in the KGM matrix. The compatibility and good interaction between KGM and pectin contributed to highly dense and compact structure. Furthermore, increasing the concentration of MO effectively improved water-resistance, oxygen barrier, and antimicrobial activity of the KGM based films. The 1.5 wt% MO loaded KGM film had the highest tensile strength (72.22 MPa) and water contact angle (θ = 95.73°), reduced the WVP and oxygen permeability by about 25.8 % and 32.8 times, respectively, prolonged the shelf life of strawberries for 8 days. As demonstrated, the 1.5 wt% MO-loaded KGM film has considerable potential for high-performance natural biodegradable active films to ensure food safety and reduce environmental impacts.

Konjac glucomannan-based nanocomposite spray coating with antimicrobial, gas barrier, UV blocking, and antioxidation for bananas preservation.

Fruit is prone to rot and deterioration due to oxidative browning and microbial infection during storage, which can cause serious economic losses and food safety problems. It is urgent to develop a multifunctional composite coating to extend the shelf life of fruits. In this work, multifunctional quaternized chitosan nanoparticles (QCs/TA NPs) with excellent antibacterial and antioxidant properties were prepared based on electrostatic interaction using tannic acid instead of conventional cross-linking agents. Meanwhile, konjac glucomannan (KGM) with high viscosity, edible and biodegradable properties was used as a dispersant to disperse and stabilize the nanoparticles, and as a film-forming agent to form a multifunctional composite coating. The composite coating exhibited excellent oxygen and water vapor barrier properties, antioxidant, antibacterial, mechanical properties, hydrophobicity, and UV shielding properties. Surprisingly, the oxygen permeability of the K-NPs-15 composite film was as low as 1.93 × 10-13 (cm3·cm)/(cm2·s·Pa). The banana spray preservation experiments proved that the K-NPs-15 composite coating could effectively prolong the shelf life of bananas. Therefore, this study provides a new idea for designing multifunctional freshness preservation coatings, which has a broad application prospect.

Research progress of organic fluorescent probes for lung cancer related biomarker detection and bioimaging application.

As one of the major public health problems, cancers seriously threaten the human health. Among them, lung cancer is considered to be one of the most life-threatening malignancies. Therefore, developing early diagnosis technology and timely treatment for lung cancer is urgent. Recent research has witnessed that measuring changes of biomarkers expressed in lung cancer has practical significance. Meanwhile, we note that bioimaging with organic fluorescent probes plays an important role for its high sensitivity, real-time analysis and simplicity of operation. In the past years, kinds of organic fluorescent probes targeting lung cancer related biomarker have been developed. Herein, we summarize the research progress of organic fluorescent probes for the detection of lung cancer related biomarkers in this review, along with their design principle, luminescence mechanism and bioimaging application. Additionally, we put forward some challenges and future prospects from our perspective.

Properties of konjac glucomannan/curdlan-based emulsion films incorporating camellia oil and the preservation effect as coatings on 'Kyoho' grapes.

The strategy of emulsion coating was used for grape preservation. Camellia oil (CO) was incorporated with KGM/curdlan (KC) to fabricate KC-CO emulsion systems. KC-CO emulsions were analyzed by droplet size distribution and confocal laser scanning microscopy (CLSM), and KC-CO films were investigated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), mechanical properties, dissolution, gas permeability, water contact angle (WCA). KC-CO coating was used for preservation of 'Kyoho' grapes. The results indicated that the addition of CO had a positive effect on KC system. CO could form a uniform emulsion with KC, and the droplets were evenly dispersed in the KC matrix. KC-CO films displayed a continuous microstructure, and elongation at break (EAB) was improved, while tensile strength decreased. The dissolution, water vapor permeability (WVP), and WCA were significantly enhanced, while the permeability of oxygen and carbon dioxide exhibited no advantage compared with KC film. KC-CO-10 possessed optimal properties and was selected as an emulsion coating for preservation. The results suggested that KC-CO-10 significantly maintained the appearance, total solid and acid content of 'Kyoho' grapes, and delayed the weight loss and firmness decrease. This study contributed to the understanding of polysaccharide-lipid emulsion system and the applications.

Effect of Emi1 gene silencing on the proliferation and invasion of human breast cancer cells.

Breast cancer is the most common malignant tumour in women. The early silk-splitting inhibitor protein 1 Emi1 is responsible for mediating ubiquitin protein degradation. The present study investigated the effects of the decreased expression of the Emil gene on the proliferation and invasion of breast cancer cells. The interference efficiency of small interfering ribonucleic acid (siRNA) was quantitatively verified using fluorescence real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting, and the effect of Emi1 gene silencing on cell vitality and invasion was determined using MTT and Transwell assays, respectively. The expression of the proliferation genes programmed cell death receptor 4 (PDCD-4), fatty acid synthase ligand (FasL), PTEN and RhoB, along with the invasive genes Maspin, TIMP3 and RECK, was measured using fluorescence RT-qPCR. In breast cancer cells, siRNA successfully reduced the expression of the Emi1 gene, and the expression level of the cell proliferation genes PDCD-4, FasL, PTEN and RhoB, along with invasive genes Maspin, TIMP3 and RECK, decreased significantly (P < 0.05). Furthermore, Emi1 gene silencing reduced the proliferation and invasion abilities of MDA-MB-231 and SUM149PT cells by reducing the expression of proliferative and invasive genes.

Rutin modified selenium nanoparticles reduces cell oxidative damage induced by H2O2 by activating Nrf2/HO-1 signaling pathway.

Oxidative damage of neurons is one of the key pathological markers of Alzheimer's disease (AD), which eventually leads to neuronal apoptosis and loss. Nuclear factor E2-related factor 2 (Nrf2) is a key regulator of antioxidant response and is considered to be an important therapeutic target for neurodegenerative diseases. In this study, the selenated derivative of antioxidant rutin (Se-Rutin) was synthesized with sodium selenate (Na2SeO3) as raw material by a simple electrostatic-compound in situ selenium reduction method. The effects of Se-Rutin on H2O2 induced oxidative damage in Pheochromocytoma PC12 cells were evaluated by cell viability, apoptosis, reactive oxygen species level and the expression of antioxidant response element (Nrf2). The results showed that H2O2 treatment significantly increased the level of apoptosis and reactive oxygen species, while the level of Nrf2 and HO-1 decreased. However, Se-Rutin significantly reduced H2O2 induced apoptosis and cytotoxicity, and increased the expression of Nrf2 and HO-1, both of which were better than that of pure rutin. Therefore, the activation of Nrf2/HO-1 signaling pathway may be the basis of Se-Rutin's anti-oxidative damage to AD.

Polydopamine nanoparticles coated with a metal-polyphenol network for enhanced photothermal/chemodynamic cancer combination therapy.

Polydopamine nanoparticles (PDA NPs) are commonly used for photothermal therapy (PTT) of cancer because of their good biocompatibility and photothermal conversion capability. However, it is difficult to achieve a good tumor inhibition effect with a single PTT of PDA. Therefore, in this work, we prepared a combined anticancer nanosystem for enhanced chemodynamic therapy (CDT)/PTT by coating PDAs with an (-)-epigallocatechin gallate (EGCG)/iron (Fe) metal-polyphenol network (MPN). The MPN shell of this nanosystem named EGCG@PDA is degraded by the weakly acidic environment intracellular, releasing EGCG and Fe3+. EGCG inhibits the expression of heat shock proteins (HSPs) in cancer cells, thus eliminating their thermal protection against cancer cells for enhanced PTT. Meanwhile, the reductive EGCG can also reduce Fe3+ to Fe2+, to catalyze the decomposition of overexpressed hydrogen peroxide (H2O2) in cancer cells to generate strong oxidative hydroxyl radicals (OH), i.e., catalyzing the Fenton reaction, for CDT. After the Fenton reaction, the re-oxidized Fe ions can be reduced again by EGCG and reused to catalyze the Fenton reaction, which can achieve enhanced CDT. Both in vitro and in vivo studies have shown that EGCG@PDA has low dark toxicity and good anticancer effects. It is expected to be used for precision cancer therapy.

Small-size Ti3C2Tx MXene nanosheets coated with metal-polyphenol nanodots for enhanced cancer photothermal therapy and anti-inflammation.

As a controllable, simple method with few side effects, near-infrared (NIR) light-based photothermal therapy (PTT) has been proven an effective cancer therapeutic approach. However, PTT-induced inflammation is a potential negative factor. And the overexpressed heat shock proteins (HSPs) by cancer cells can protect them from hyperthermia during PTT. In this work, small-size Ti3C2Tx MXene nanosheets with high photothermal conversion efficiency in the region of NIR, high cargo loading capability and good free radical scavenging capability were chosen for cancer PTT and anti-inflammation. And (-)-epigallocatechin gallate (EGCG) was applied to form EGCG/Fe metal-polyphenol nanodots on the nanosheets. EGCG being released in acid cancer cells could reduce the expression of HSPs and could be used for anti-inflammation. As a result, the complex nanosheets named MXene@EGCG could achieve enhanced cancer PTT and be anti-inflammatory. Both in vitro and in vivo studies proved the good photothermal ability of MXene@EGCG and demonstrated that it could inhibit the expression of HSPs in tumor cells and relieve PTT-induced inflammation. Therefore, the nanosheets show good results in tumor ablation with a low level of inflammation, which provides another possibility for cancer therapy. STATEMENT OF SIGNIFICANCE: Photothermal therapy (PTT)-induced inflammation plays an essential role in some important stages of tumor development and is unfavorable for cancer treatment. And hyperthermia leads to the overexpression of heat shock proteins (HSPs) in cancer cells, which limits the therapeutic effect of PTT. Therefore, we coated small-size Ti3C2Tx MXene nanosheets with (-)-epigallocatechin gallate (EGCG)/Fe metal-polyphenol nanodots and named them as MXene@EGCG. This system shows a good photothermal conversion efficiency at 808 nm. And it can release EGCG in cancer cells to inhibit the expression of HSPs, thus achieving an enhanced cancer PTT. Both MXene and EGCG can also diminish the PTT-trigged inflammation. Both in vitro and in vivo studies prove the good anti-cancer PTT effect and anti-inflammation capability of MXene@EGCG.

Metal-polyphenol nanodots loaded hollow MnO2 nanoparticles with a "dynamic protection" property for enhanced cancer chemodynamic therapy.

Chemodynamic therapy (CDT) is a novel cancer therapeutic strategy. However, barriers such as high glutathione (GSH) concentration and low concentration of metal ions intracellular reduce its treatment effect. In this work, a nanosystem named GA-Fe@HMDN-PEI-PEG with a "dynamic protection" property was reported for enhanced cancer CDT. Mesoporous hollow manganese dioxide (MnO2) nanoparticle (HMDN) was prepared to load gallic acid-ferrous (GA-Fe) nanodots fabricated from gallic acid (GA) and ferrous ion (Fe2+). Then the pores of HMDN were blocked by polyethyleneimine (PEI), which was then grafted with methoxy poly(ethylene glycol) (mPEG) through a pH-sensitive benzoic imine bond. mPEG could protect the nanoparticles (NPs) against the nonspecific uptake by normal cells and enhance their accumulation in the tumor. However, in the slightly acidic tumor microenvironment, hydrolysis of benzoic imine led to DePEGylation to reveal PEI for enhanced uptake by cancer cells. The reaction between HMDN and GSH could consume GSH and obtain manganese ion (Mn2+) for the Fenton-like reaction for CDT. GA-Fe nanodots could also offer Fe for the Fenton reaction, and reductive GA could reduce the high-valence ions to low-valence for reusing in Fenton and Fenton-like reactions. These properties allowed GA-Fe@HMDN-PEI-PEG for precise medicine with a high utilization rate and common side effects.

Drug Delivery Systems with a "Tumor-Triggered" Targeting or Intracellular Drug Release Property Based on DePEGylation.

Coating nanosized anticancer drug delivery systems (DDSs) with poly(ethylene glycol) (PEG), the so-called PEGylation, has been proven an effective method to enhance hydrophilicity, aqueous dispersivity, and stability of DDSs. What is more, as PEG has the lowest level of protein absorption of any known polymer, PEGylation can reduce the clearance of DDSs by the mononuclear phagocyte system (MPS) and prolong their blood circulation time in vivo. However, the "stealthy" characteristic of PEG also diminishes the uptake of DDSs by cancer cells, which may reduce drug utilization. Therefore, dynamic protection strategies have been widely researched in the past years. Coating DDSs with PEG through dynamic covalent or noncovalent bonds that are stable in blood and normal tissues, but can be broken in the tumor microenvironment (TME), can achieve a DePEGylation-based "tumor-triggered" targeting or intracellular drug release, which can effectively improve the utilization of drugs and reduce their side effects. In this review, the stimuli and methods of "tumor-triggered" targeting or intracellular drug release, based on DePEGylation, are summarized. Additionally, the targeting and intracellular controlled release behaviors of the DDSs are briefly introduced.

Polysaccharide/mesoporous silica nanoparticle-based drug delivery systems: A review.

Mesoporous silica nanoparticles (MSNs) have been well-researched in the design and fabrication of advanced drug delivery systems (DDSs) due to their advantages such as good biocompatibility, large specific surface area and pore volume for drug loading, easily surface modification, adjusted size and good thermal/chemical stability. For MSN-based DDSs, gate materials are also necessary. And natural polysaccharides, one kind of the most abundant natural resource, have been widely applied as the "gatekeepers" in MSN-based DDSs. Polysaccharides are cheap and rich in sources with good biocompatibility, and some of them have important biological functions. In this review article, polysaccharides including chitosan, hyaluronic acid, sodium alginate and dextran, et al. are briefly introduced. And the preparation processes and properties such as controlled drug release, cancer targeting and disease diagnosis of functional polysaccharide/MSN-based DDSs are discussed.

Anti-atopic effect of Viola yedoensis ethanol extract against 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Viola yedoensis Makiho (VY, Violaceae) is a well-known medicinal herb in Chinese medicine, which is traditionally used to treat inflammation-related disorders, including allergic skin reactions. Although studies have uncovered its anti-inflammatory effects and corresponding bioactive constituents, the exact mechanism of action is still unclear in treating allergic skin reactions. OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by severe pruritus, dry, edema and inflamed skin. It affects people's quality of life seriously and causes huge economic losses to society. This study proposes VY as a possible remedy for atopic dermatitis since its traditional usage and superior anti-inflammatory effects. MATERIALS AND METHODS: Atopic dermatitis-like skin lesion was induced by topical application of 2,4-dinitrochlorobenzene (DNCB) in ICR mice. After treatment with Viola yedoensis Makiho ethanol extract (VYE) or dexamethasone (positive control) for 3 weeks, skin pathological observation and the molecular biological index were performed for therapeutic evaluation, including visual inspection in the change of the stimulated skin, scar formation, pathological morphology by hematoxylin and eosin (HE) staining, the measurement of interleukin IL-1ß, IL-6 and tumor necrosis factor-alpha (TNF-α) levels in serum as well as spleen index. The expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were analyzed by western blot. The ratio of CD4+/CD8+ T lymphocyte in the spleen was detected by flow cytometry. Meanwhile, immunohistochemistry staining for CD68 identified the number of activated macrophages in skin lesions. Additionally, a reliable ultrahigh-performance liquid chromatography coupled with a Q exactive hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Orbitrap-MS) method was established for the systematic identification and characterization of main components in VYE. RESULTS: VYE alleviated DNCB-stimulated AD-like lesions symptoms as evidenced by a significant decrease in hypertrophy, hyperkeratosis, and infiltration of inflammatory cells in dorsal skin. The levels of IL-1ß, IL-6, and TNF-α in serum were suppressed in mice treated with VYE as compared to the DNCB-induced model group. Also, the administration of VYE reduced the ratio of CD4+/CD8+ T lymphocyte in the spleen and the number of activated macrophages stimulated by DNCB. Besides, the expression of iNOS and COX-2 were down-regulated in the dorsal skin. CONCLUSIONS: VYE showed therapeutic effects on atopic dermatitis in DNCB-induced AD-like lesion mouse models by inhibiting the T cell-mediated allergic immune response. Our results indicated that VY could act as a potential remedy for atopic dermatitis.

A chitosan/mesoporous silica nanoparticle-based anticancer drug delivery system with a "tumor-triggered targeting" property.

To enhance drug utilization and reduce their side effects, the strategy of "tumor-triggered targeting" was introduced to fabricate dual-pH-sensitive chitosan (CHI)/mesoporous silica nanoparticle (MSN)-based anticancer drug delivery system (DDS) in this work. Model drug doxorubicin hydrochloride (DOX) was loaded in MSN, which was modified with benzimidazole (Bz) group. Then chitosan-graft-ß-cyclodextrin (CHI-g-CD) was applied as the "gatekeeper" to cover MSN through host-guest interaction between ß-CD and Bz. After being coated with targeting peptide adamantane-glycine-arginine-glycine-aspartic acid-serine (Ad-GRGDS), methoxy poly(ethylene glycol) benzaldehyde (mPEG-CHO) was finally grafted on CHI through the pH-sensitive benzoic imine bond. Due to the dynamic protection of PEG, the obtained carriers were "stealthy" at pH 7.4, but could reveal the shielded targeting peptide and the positive charge of CHI in the weakly acidic environment achieved a "tumor-triggered targeting". Inside cancer cells, the interaction between ß-CD and Bz group could be destroyed due to the lower pH, resulted in DOX release. Both in vitro and in vivo studies proved the DDS could targeting induce cancer cell apoptosis, inhibit tumor growth, and reduce the cytotoxicity of DOX against normal cells. It is expected that the system named DOX@MSN-CHI-RGD-PEG could be a potential choice for cancer therapy.

Multi-stimuli responsive hollow MnO2-based drug delivery system for magnetic resonance imaging and combined chemo-chemodynamic cancer therapy.

The exploration and application of hollow manganese dioxide nanoparticle (HMDN) for biosensing and biomedicine has gained significant research attention in the past decade. In this study, a type of biodegradable HMDN is prepared for multi-stimuli responsive tumor-targeted drug delivery, which was successfully loaded with doxorubicin hydrochloride (DOX). Then, the drug-loaded HMDN is functionalized with polyethyleneimine (PEI) as a gatekeeper followed by citraconic anhydride (cit) functionalized poly-L-lysine (PLL(cit)) as a charge reversal moiety successively to yield the resultant DOX@HMDN-PEI-PLL(cit) nanoparticles. In vitro study showed that DOX@HMDN-PEI-PLL(cit) exhibited a ''stealthy'' property under physiological conditions and enhanced cellular uptake activity in response to the mild acidic tumor microenvironment due to the departure of cit. In vitro release profiles proved that the decomposition of HMDN to Mn2+ under acidic condition/high glutathione (GSH) concentration triggered the release of DOX and Fenton-like reaction for improved therapeutic effect. And Mn2+ could also act as a T1-weighted magnetic resonance imaging (MRI) contrast agent. In vivo studies further proved with both the charge reversal and combined therapy properties, DOX@HMDN-PEI-PLL(cit) showed a good tumor enrichment ability and therapeutic effect with few side effects to the mice. These results demonstrate that DOX@HMDN-PEI-PLL(cit) nanoparticles are promising drug delivery systems for targeted cancer therapy. STATEMENT OF SIGNIFICANCE: Traditional chemotherapy based on anticancer drugs such as doxorubicin hydrochloride (DOX) shows limited efficacy with serious side effects. We employed hollow manganese dioxide nanoparticle (HMDN) to loaded DOX and coated it with polyethyleneimine and then citraconic anhydride functionalized poly-L-lysine to endow it with a charge reversal property to obtain a multi-stimuli responsive drug delivery system named DOX@HMDN-PEI-PLL(cit). It was ''stealthy'' with low cellular uptake capability by normal cells, but could be "acid-activated" in tumors for endocytosis by cancer cells to reduce side effects. HMDN could be decomposed to Mn2+ under acidic conditions/high glutathione concentration to release DOX intracellular. DOX and Mn2+ catalyzed Fenton-like reaction could achieve a combined chemo-chemodynamic therapy. And Mn2+ could be used for T1-weighted magnetic resonance imaging.

Evaluation of the wound healing potential of Sophora alopecuroides in SD rat's skin.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora alopecuroides Linn. (Leguminosae) has been largely used in traditional folk medicine in China as an anti-inflammatory agent and to treat various skin wounds, including sore furunculosis and ulcer (a common type of non-healing wound). The present study aimed to evaluate the effects of S. alopecuroides gel on skin wound healing in rats. MATERIALS AND METHODS: When the rats were anesthetized, full-thickness skin wound was performed on dorsal area by using biopsy punch with 8 mm diameter. Then, wounds received treatment with different doses of S. alopecuroides gel (1.25%, 2.5% and 5%, w/w) once a day with the gel base used as vehicle control and rb-FGF as positive control. Every five animals were sacrificed after 7, 12 days after surgery for histopathology and relevant biochemical indexes analysis. Besides, after RAW 264.7 cells exposure to LPS (1 µg/ml) with or without total extract (25 and 50 µg/ml) for 24 h, the culture supernatant was used for detection of IL-1ß and TNF-α levels using ELISA kits and the protein lysate for western blot analysis. RESULTS: A remarkable wound closure was observed after administration with 5% S. alopecuroides gel with the wound area of 30% and 8.5% as compared to 42% and 19% in the control group on day 7 and 12, respectively. Histological and immunostaining analysis for the wound tissues also revealed that S. alopecuroides promoted the growth of granulation tissue, collagen deposition, cell proliferation and angiogenesis. Meanwhile, it was able to ameliorate inflammatory response and promote the production of TGF-ß. In addition, we also demonstrated that S. alopecuroides inhibited the release of inflammatory mediators and expression of iNOS as well as up-regulated the expression of Arg-1 in LPS-triggered RAW 264.7 cells. CONCLUSIONS: The present study confirmed that S. alopecuroides had a great potential for accelerated wound healing by regulating the over expression of inflammatory response for the first time and provided theoretical basis for the traditional use. It can be used as candidate drug for the treantment of chronic non-healing wounds.

A review on traditional usages, chemical constituents and pharmacological activities of periploca forrestii schltr.

ETHNOPHARMACOLOGICAL RELEVANCE: Periploca forrestii Schltr. was listed as a classical medicinal plant in "Miao medicine", which is a branch of traditional Chinese medicine (TCM). According to the theory of TCM, P. forrestii has the efficacy of relaxing tendons and activating collaterals, and dispelling wind and eliminating dampness. Hence, it was often used for the therapy of rheumatoid arthritis and traumatic injury in clinical practice. AIMS OF THE REVIEW: This review aims to present comprehensive information for the research progress of P. forrestii. The researches on botany, traditional uses, phytochemistry, pharmacology and toxicology of the plant are summarized. We mainly focus on the phytochemical and pharmacological investigations. As a representative class of phytochemicals in P. forrestii, more attention is paid to cardiac glycosides. The insights into potential action of mechanisms and possible future studies on P. forrestii are also discussed. MATERIALS AND METHODS: Relevant literature was acquired from scientific databases including Google Scholar, Web of Science, Scifinder, Baidu Scholar, PubMed and Chinese national knowledge infrastructure. Monographs and Chinese pharmacopoeia were also utilized as references. RESULTS: To date, all kinds of phytochemical constituents have been isolated and identified from this plant including cardiac glycosides, steroids, terpenoids, flavonoids, phenylpropanoids, quinones, organic phenolic acids and others. Among these, cardiac glycosides were considered as the major ingredients and bioactive materials. Modern pharmacological studies demonstrated that the plant possessed extensive bioactivity, such as anti-inflammatory and analgesic effects, immunosuppressive action, wound healing activity, antioxidant, anti-tumor and, cardiotonic properties. CONCLUSIONS: As an important medicinal plant, lots of studies have proved that P. forrestii has significant therapeutical effects, especially on rheumatoid arthritis and traumatic injury. These results provide modern scientific evidence for traditional use and contribute to the development of novel remedies for chronic diseases. However, the exact mechanism of action remains to be elucidated. Furthermore, the long-term in vivo toxicity and clinical efficacy also require in-depth exploration in the future.

To what extent should the intestinal be resected proximally after radiotherapy: hint from a pathological view.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is associated with post-operative anastomotic complications in rectal-cancer patients. Anastomosis involving at least one non-irradiated margin reportedly significantly reduces the risk of post-operative anastomotic complications in radiation enteritis. However, the exact scope of radiotherapy on the remaining sigmoid colon remains unknown. METHODS: We evaluated the radiation damage of proximally resected colorectal segments in 44 patients with rectal cancer, who received nCRT followed by conventional resection (nCRT-C, n = 21) or proximally extended resection (nCRT-E, n = 23). The segments from another 13 patients undergoing neoadjuvant chemotherapy (nCT) were used as control. We dissected these samples at a distance of 2 cm between the two adjacent sections. Radiation damage in proximally resected colorectal segments was evaluated using the radiation injury score (RIS) and the concentration and distribution patterns of angiostatin. RESULTS: Compared to those in the nCT group, the nCRT group showed higher RIS, levels of angiostatin, and proportion of diffuse pattern of angiostatin. With increasing distance from the tumor site, these parameters all gradually decreased; and the differences came to be not significant at the site that is over 20 cm from the tumor. The nCRT-E group showed lower RIS (median: 2 vs 4, P = 0.002) and a greater proportion of non-diffuse angiostatin (87% vs 55%, P = 0.039) at the proximal margins compared with the nCRT-C group. CONCLUSIONS: The severity of the radiation damage of the proximal colon is inversely proportional to the proximal-resection margin length. Little damage was left on the proximal margin that was over 20 cm from the tumor. Removal of an initial length of ≥20 cm from the tumor may be beneficial for rectal-cancer patients after nCRT.

Association between diabetes mellitus and lung cancer: Meta-analysis.

BACKGROUND: This study aimed to summarize the association between diabetes mellitus (DM) and the incidence of lung cancer using a meta-analysis of cohort studies. MATERIALS AND METHODS: We systematically searched PubMed, Embase and the Cochrane Library to identify potential cohort studies. Relative risk (RR) was used to calculate the association between DM and the risk of lung cancer. Subgroup analysis, sensitivity analysis and test for publication bias were performed. Twenty cohort studies were selected. RESULTS: The participants with DM showed little or no significant effect on the risk of lung cancer (RR: 1.10; 95% CI: 0.99-1.23; P = .087). DM was not associated with the risk of lung cancer in men (RR: 1.11; 95%CI: 0.92-1.35; P = .270), but a significant association was observed in women (RR: 1.18; 95%CI: 1.10-1.28; P < .001). Subgroup analysis suggested that smoker status was confounding variables that could bias the relationship between DM and the incidence of lung cancer. CONCLUSIONS: This meta-analysis suggests that DM has no significant impact on the incidence of lung cancer in men but has a harmful effect on women.

A novel intratumoral pH/redox-dual-responsive nanoplatform for cancer MR imaging and therapy.

The integration of diagnostic and therapeutic functions in a nanoplatform has been a rapidly emerging method in the management of cancer. The application of imaging technology paves the way to track the pharmacokinetics of the nanoplatforms, to guide the treatment, and to monitor the therapeutic processes and outcomes. Herein, we reported a novel type of monodisperses mesoporous silica-coated superparamagnetic iron oxide-based multifunctional nanoplatform (DOX@MMSN-SS-PEI-cit) for the diagnosis and treatment of cancer. The fabrication process included the surface modification of monodisperses mesoporous silica nanoparticle (MMSN) with branched polyethyleneimine (PEI) via disulfide bonds and the further coupling of citraconic anhydride to PEI. Typically, the hydrolysis of amide bonds in the tumor microenvironment (TME) could lead to a negative-to-positive charge reversion, which can enhance the endosomal escape of the resulting nanoplatform. The rapid release of doxorubicin hydrochloride (DOX) directly killed the cancer cells. Due to the superparamagnetic iron oxide-based high-resolution T2-weighted MR imaging contrast agents, this novel multifunctional nanoplatform successfully realized MR imaging, targeted drug delivery and controlled release in one system, and achieved significant improvement in tumor diagnosis and therapy. In summary, the therapeutic nanoplatform is a promising option in precise cancer treatment.