Multiple enzyme-mimic polypeptide based carbon nanoparticles by ROP and Fe coordination for ROS regulation and photo-thermal therapy against bacterial infection.

Novel strategy is urgently needed to overcome the bacterial infection all over the world due to unreasonable use of biotics. In recent years, nanozymes have attracted great interests of researchers for their high catalytic efficiency and biocompatibility. In this study, a novel multiple enzyme-mimic polypeptide-based carbon nanoparticle was synthesized by N-carboxyanhydride mediated ring opening polymerization (ROP) and Fe coordination for actualizing ROS regulation and photo-thermal therapy. The multiple enzyme-mimic activities of the nanozyme, such as peroxidase, oxidase, catalase, and glutathione peroxidase, were detailly explored in ROS regulation for potential utilization in bacterial inhibition. The photo-thermal effect of the nanozyme was investigated under 808 nm NIR irradiation. Enhanced inhibition rate of the as prepared nanozyme was observed against Gram-negative Escherichia coli (99.03 %) and Gram positive Staphylococcus aureus (99.78 %) planktonic bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) was chosen as the drug resistant bacteria model to evaluate the efficiency in bacterial biofilm disruption. Improved healing efficacy of 99.05 % against MRSA wound infection and excellent biosafety were observed in mice model experiments for the as prepared nanozyme. In conclusion, the as synthesized nanozyme with ROS regulation, enhanced bacteria inhibition, and excellent biocompatibility could be potentially applied in clinic against bacterial infection.

[Spatial and Temporal Evolution Characteristics of Carbon Emission from Land Use and Influencing Factors in Gansu Province].

Land ecosystems are the largest carbon sink in the world, and land use change is one of the main factors leading to regional carbon emissions. By studying the spatiotemporal evolution characteristics and influencing factors of land use carbon emissions in Gansu Province from 2000 to 2020, this research aimed to provide a scientific basis and reference for promoting low-carbon land use and low-carbon economic development in Gansu Province. Using land use data and the greenhouse gas emission coefficient method, the study analyzed the growth trend of land use carbon emissions at the city-regional scale in Gansu Province, and the spatiotemporal evolution characteristics at the provincial scale, and identified the controlling factors through principal component analysis. The results showed that： ① From 2000 to 2020, land use carbon emissions in Gansu Province showed an overall increasing trend, from 24.289 3 million tons to 57.739 6 million tons. The first stage from 2000 to 2014 was a significant increase period, whereas the second stage from 2014 to 2020 was a stable and slightly decreasing period. Construction land was the main carbon source, and the carbon intensity continued to increase. ② Spatially, there was an "east high, west low" pattern, with carbon emissions in the eastern part of the province significantly higher than those in the western part. ③ Based on emission characteristics, Gansu Province could be divided into five types of carbon emission zones： slow growth, relatively slow growth, moderate growth, relatively fast growth, and rapid growth. ④ The main reasons for the continuous increase in land use carbon emissions in Gansu Province were economic development level, degree of land use, and energy consumption.

Poly-l-lysine modified MOF nanoparticles with pH/ROS sensitive CIP release and CUR triggered photodynamic therapy against drug-resistant bacterial infection.

The challenge of drug resistance in bacteria caused by the over use of biotics is increasing during the therapy process, which has attracted great attentions of the clinicians and scientists around the world. Recently, photodynamic therapy (PDT) triggered by photosensitizer (PS) has become a promising treatment method because of its high efficacy, easy operation, and low side effect. Herein, the poly-l-lysine (PLL) modified metal-organic framework (MOF) nanoparticles, ZIF/PLL-CIP/CUR, were synthesized to allow both reactive oxygen species (ROS) responsive drug release and photodynamic effect for synergistic therapy against drug resistant bacterial infections. The PLL was modified on the shell of the zeolite imidazole framework (ZIF) by the ROS-responsive thioketal linker for controllable CIP release. CUR were encapsulated in ZIF as the photosensitizer for blue light mediated photodynamic effect to produce singlet oxygen (1O2) and superoxide anion radical (O2-) for efficient inhibition towards methicillin-resistant Staphylococcus aureus (MRSA). The charge conversion from negative charge (-4.6 mV) to positive charge (2.6 mV) was observed at pH 7.4 and pH 5.5, and 70.9 % CIP was found released at pH 5.5 in the presence of H2O2, which suggests the good biosafety at physiological pH and ROS-responsive drug release of the as-prepared nanoparticle in the bacterial microenvironment. The as-prepared nanoparticles could effectively kill MRSA and disrupt bacterial biofilm by combination of chemo- and photodynamic therapy. In mice model, the as-prepared nanoparticles exhibited excellent biosafety and synergistic effect with 98.81 % healing rate in treatment of MRSA infection, which is considered as a promising candidate in combating drug resistant bacterial infection.

Electrochemical desulfurative formation of C-N bonds through selective activation of inert C(sp3)-S bonds.

In this study, we introduce an efficient, metal-free electrocatalytic desulfurative protocol for forming C-N bonds by selectively activating inert C(sp3)-S bonds of alkyl thioethers. This method offers a straightforward and environmentally friendly approach for modification of heterocyclic compounds from readily accessible thioethers. Preliminary mechanistic investigations suggest that the reaction proceeds via a carbocation intermediate. Furthermore, successful synthesis on a 10-gram scale was achieved in a continuous flow electrochemical reactor.

Establishment and biological characterization of drug-resistant cells and identification of multidrug resistance in small-cell lung cancer / 中国药理学通报

Aim To establish NCI-H446/EP for small cell lung cancer resistant cells resistant to cisplatin and etoposide, and to evaluate their biological characteristics and multidrug resistance. Methods Nude mice were subcutaneously inoculated with NCI-H446 cells of SCLC to construct an in vivo model of xenograft tumor, and were given first-line EP regimen treatment for SCLC, inducing drug resistance in vivo, and stripping tumor tissue in vitro culture to obtain drug-resistant cells. The resistance coefficient, cell doubling time, cell cycle distribution, expression of multidrug resistance gene (MDR1), and drug resistance-related protein were detected in vitro, and the drug resistance to cisplatin and etoposide in vivo were verified. Results Mice with NCI-H446 tumors acquired resistance after eight weeks' EP regimen treatment, and the drug-resistant cell line NCI-H446/EP was obtained by isolation and culture in vitro. The resistance factors of this cell line to cisplatin, etoposide, SN38 and doxorubicin were 12.01, 18.36, 65.4 and 10.12, respectively. Compared with parental cells, the proportion of NCIH446/EP cells in Q

Metal-free photoinduced C(sp3)-H/C(sp3)-H cross-coupling to access α­tertiary amino acid derivatives.

The cross-dehydrogenative coupling (CDC) reaction is the most direct and efficient method for constructing α-tertiary amino acids (ATAAs), which avoids the pre-activation of C(sp3)-H substrates. However, the use of transition metals and harsh reaction conditions are still significant challenges for these reactions that urgently require solutions. This paper presents a mild, metal-free CDC reaction for the construction of ATAAs, which is compatible with various benzyl C-H substrates, functionalized C-H substrates, and alkyl substrates, with good regioselectivity. Notably, our method exhibits excellent functional group tolerance and late-stage applicability. According to mechanistic studies, the one-step synthesized and bench-stable N-alkoxyphtalimide generates a highly electrophilic trifluoro ethoxy radical that serves as a key intermediate in the reaction process and acts as a hydrogen atom transfer reagent. Therefore, our metal-free and additive-free method offers a promising strategy for the synthesis of ATAAs under mild conditions.

Magnetic ion-imprinted polyacrylonitrile-chitosan electro-spun nanofibrous membrane as recyclable adsorbent with selective heavy metal removal and antibacterial fouling in water treatment.

Water pollution has become one of the most concerned environmental issues on the worldwide scale. Due to the harmfulness of the heavy metal ions and microorganisms in wastewater, novel filtration membranes for water treatment are expected to simultaneously clear these pollutants. Herein, the electro-spun polyacrylonitrile (PAN) based magnetic ion-imprinted membrane (MIIM) were fabricated to achieve both selective removal of Pb(II) ions and excellent antibacterial efficiency. The competitive removal experiments showed that the MIIM displayed efficiently selective removal of Pb(II) (45.4 mg·g-1). Pseudo-second-order mode and Langmuir isotherm equation is well matched with the equilibrium adsorption. The MIIM showed sustained removal performance (~79.0 %) against Pb(II) ions after 7 adsorption-desorption cycles with negligible Fe ions loss of 7.3 %. Moreover, the MIIM exhibited excellent antibacterial properties that >90 % of E. coli and S. aureus were killed by the MIIM. In conclusion, the MIIM provides a novel technological platform for integration of multi-function with selective metal ions removal, excellent cycling reusability, and enhanced antibacterial fouling property, which can be potentially utilized as a promising adsorbent in actual treatment of polluted water.

Phase-change composite filled natural nanotubes in hydrogel promote wound healing under photothermally triggered drug release.

It is of great importance to treat a bacterial-infected wound by a smart dressing capable of delivering antibiotics in a smart manner without causing drug resistance. The construction of smart release nanocontainers responsive to near-infrared (NIR) laser irradiation in an on-demand and stepwise way is a promising strategy for avoiding the emergence of multidrug-resistant bacteria. Here, we develop a hydrogel composite made of alginate and nanotubes with an efficient NIR-triggered release of rifampicin and outstanding antibacterial ability. This composite hydrogel is prepared through co-encapsulating antibacterial drug (rifampicin), NIR-absorbing dye (indocyanine green), and phase-change materials (a eutectic mixture of fatty acids) into halloysite nanotubes, followed by incorporation into alginate hydrogels, allowing the in-situ gelation at room temperature and maintaining the integrity of drug-loaded nanotubes. Among them, the eutectic mixture with a melting point of 39 °C serves as the biocompatible phase-change material to facilitate the NIR-triggered drug release. The resultant phase-change material gated-nanotubes exhibit a prominent photothermal efficiency with multistep drug release under laser irradiation. In an in vitro assay, composite hydrogel provides good antibacterial potency against Staphylococcus aureus, one of the most prevalent microorganisms of dangerous gas gangrene. A bacterial-infected rat full-thickness wound model demonstrates that the NIR-responsive composite hydrogel inhibits the bacteria colonization and suppresses the inflammatory response caused by bacteria, promoting angiogenesis and collagen deposition to accelerate wound regeneration. The NIR-responsive composite hydrogel has a great potential as an antibacterial wound dressing functionalized with controlled multistep treatment of the infected sites.

NDFIP1 limits cellular TAZ accumulation via exosomal sorting to inhibit NSCLC proliferation

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.

Pricking and cupping at Jianbo area combined with conventional acupuncture for scapulohumeral periarthritis of frozen stage: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect of conventional acupuncture combined with pricking and cupping at Jianbo area and conventional acupuncture in the treatment of scapulohumeral periarthritis of frozen stage.@*METHODS@#A total of 66 patients with scapulohumeral periarthritis of frozen stage were randomly divided into a combination group (31 cases) and an acupuncture group (35 cases, 1 case dropped off). Both groups were given functional exercise. Patients in the acupuncture group were treated with acupuncture at Jianyu (LI 15), Jianliao (TE 14), Binao (LI 14) and ashi point on the affected side, once every other day, three times a week, for a total of 4 weeks. On the basis of treatment in the acupuncture group, the patients in the combination group were treated with pricking and cupping at Jianbo area (the area surrounded by the 3 acupoints of Tianzong [SI 11], Naoshu [SI 10] and Jianzhen [SI 9]), once a week for 4 weeks. The University of California-Los Angeles (UCLA) shoulder joint score, visual analogue scale (VAS) score before treatment, after treatment and after 6 months of treatment completion (follow-up) and tenderness threshold before and after treatment, and the clinical effects of the two groups after treatment and in follow-up were evaluated.@*RESULTS@#In the two groups, after treatment and in follow-up, the UCLA shoulder joint scores were higher than those before treatment (P<0.05), and the VAS scores were lower than those before treatment (P<0.05). In the combination group, after treatment and in follow-up, the UCLA shoulder joint score was higher than that of the acupuncture group (P<0.05), and the VAS score was lower than that of the acupuncture group (P<0.05). After treatment, the tenderness thresholds of the two groups were higher than those before treatment (P<0.05), and the tenderness threshold in the combination group was higher than that in the acupuncture group (P<0.05). After treatment and in follow-up, the cured and markedly effective rate of the combination group was 48.4% (15/31) and 51.6% (16/31) respectively, which was higher than 23.5% (8/34) and 23.5% (8/34) of the acupuncture group (P<0.05).@*CONCLUSION@#Pricking and cupping in Jianbo area combined with conventional acupuncture can improve shoulder joint function and relieve shoulder joint pain in patients with scapulohumeral periarthritis of frozen stage, and the curative effect is better than that of single conventional acupuncture.

Efficacy of secuchiumab in the treatment of active psoriatic arthritis in a real-world situation / 中华风湿病学杂志

Objective:To observe the clinical efficacy of secukinumab in the treatment of active psoriatic arthritis (PsA).Methods:Thirty active PsA patients in the out-patient clinic of the First Affiliated Hospital of the PLA Air Force Military Medical University between July 2020 to December 2021 were included in this study. Patients were categorized into one group with axial involvement ( n=17, 57%) and the other group with peripheral joint involvement ( n=13, 43%) according to arthritis subtypes. Patients in both groups received a subcutaneous injection of 300 mg of secukinumab at 0, 1, 2, 3, and 4 weeks, and then every 4 weeks. The CRP, ESR, VAS pain score (VAS-pain, 0~10 cm), physician comprehensive assessment of disease activity by VAS score (VAS-gh, 0~10 cm), psoriasis involvement area and severity index (PASI), skin quality of life index (DLQI), psoriatic arthritis disease activity index (DAPSA), psoriatic arthritis activity score (PASDAS), Bath ankylosing spondylitis activity index (BASDAI) were recorded at week 0, week 12, and week 24. DAP-SA response (score ≤4) and minimum disease activity (MDA) were also used to assess the proportion of overall patients who responded to secukinumab treatment. The measurement data with normal distribution were analyzed by repeated measure analysis of variance. Non-normally distributed data were expressed as median (IQR). Count data were expressed as frequency and percentage (%) and analyzed by Fisher exact probability method. Results:The mean duration of skin disease in both axial involvement and peripheral joint involvement groups was (14±8)years and (12±7)years ( t=0.70, P=0.256), respectively. The mean duration of arthritis symptoms in both groups was (3.2±3.7)years and (1.8±2.1)years ( t=1.17, P=0.125), respectively. All patients completed 24 weeks of secukinumab treatment. At 24 weeks, VAS-pain, VAS-gh, PASI, DLQI, DAPSA, PASDAS and BASDAI were all decreased significantly ( P<0.05). Patients with axial involvement seemed more likely to benefit in CRP [2.4 (1.7, 3.5) mg/L vs 8.0 (5.3, 14.0) mg/L, Z=-2.69, P=0.007] and VAS-pain[1.0 (0, 2.0) vs (5.0, 6.0), Z=-3.47, P<0.001]improvement ( P<0.005). Both groups achieved PASI 100, which meant achieving clearance of skin dis-ease. The DAPSA remission rate and MDA of the patients with axial involvement were 88% and 82%, re-spectively, and the DAPSA remission rate and MDA were 92% and 92%, respectively. Secukinumab was found to be safe and well tolerated with no adverse event reported or observed during 24-week treatment. Conclusion:In real-world observations, secukinumab is proven to be safe and effective for the treatment of PsA, with rapid relieving of skin and joint symptoms and reduction of disease activity. Patients with axial involvement may benefit more notably than patients with peripheral arthritis subtype.

Mid-term efficacy of surface knee prosthesis combined with bionic block in joint reconstruction after resection of giant cell tumor in proximal tibia / 中华骨科杂志

A total of 6 patients were treated with surface knee joint prosthesis combined with 3D-printed customized bionic tibial block for reconstruction of bone defect after giant cell tumor (GCT) in proximal tibia (1 male and 5 females, aged 50, 40, 68, 53, 35, 42, respectively). 3 patients with primary and 3 patients with recurrence of GCT. After resection of the tumor, the bone defect was filled with 3D-printed block combined with surface knee prosthesis, the surrounding ligaments were reconstructed with microporous structure and artificial mesh. All cases were followed up for 60, 90, 60, 60, 75, and 50 months, respectively. During the follow-up, there was no local recurrence, no radiolucent lines around prosthesis, and no signs of loosening. The clinical scores of the American Knee Society Score (KSS) were 87, 92, 85, 90, 95 and 78. The functional scores were 70, 100, 70, 100, 100 and 80 respectively. Musculoskeletal Tumor Society Score (MSTS) were 27, 28, 26, 26, 26, 27, respectively. Surface knee prosthesis combined with bionic block can effectively fill the bone defect after resection of GCT in proximal tibia, achieve anatomical and functional reconstruction of knee joint.

Association between appendicular skeletal muscle mass and ankle-brachial index in patients with type 2 diabetes / 中华健康管理学杂志

Objective:To assess the relationship between appendicular skeletal muscle mass (ASM) and ankle brachial index (ABI) among patients with type 2 diabetes.Methods:In this cross-sectional study, from July 2018 to March 2019, a total of 278 patients with type 2 diabetes treated in Zhongda Hospital were enrolled in this study, and there were 158 males and 120 females. General information and clinical biochemical parameters and ABI in the patients were collected. The appendicular muscle mass was quantitatively measured with body composition analyzer to achieve ASM. And the appendicular skeletal muscle mass index (ASMI), skeletal muscle index (SMI), and appendicular skeletal muscle mass/body mass index (ASM/BMI) were calculated respectively. Correlation analysis and multiple linear regression analyses with different adjustment models were conducted to analyze the correlation between ABI and above-mentioned indexes.Results:The Pearson correlation analysis showed that ABI had significant positive correlation with ASM, ASMI and ASM/BMI ( r=0.14, 0.13, 0.13, all P<0.05), but a marginal relation with SMI ( r=0.116, P=0.053). Multiple linear regression analysis suggested that ASMI ( β=0.053, 95% CI: 0.006-0.101, P=0.027) and AMI/ABI ( β=0.347, 95% CI: 0.040-0.654, P=0.027) were significantly related to ABI. Conclusion:ASM is positively associated with ABI in patients with type 2 diabetes.

Dietary ß-carotene and vitamin A and risk of Parkinson disease: A protocol for systematic review and meta-analysis.

BACKGROUND: The beneficial effects of dietary ß-carotene and vitamin A on Parkinson disease (PD) have been confirmed, but some studies have yielded questionable results. Therefore, this meta-analysis investigated the effect of dietary ß-carotene and vitamin A on the risk of PD. METHODS: The following databases were searched for relevant paper: PubMed, Embase, Medline, Scopus, Cochrane Library, CNKI, Wanfang Med online, and Weipu databases for the relevant paper from 1990 to March 28, 2022. The studies included were as follows: ß-carotene and vitamin A intake was measured using scientifically recognized approaches, such as food frequency questionnaire (FFQ); evaluation of odds ratios using OR, RR, or HR; ß-carotene and vitamin A intake for three or more quantitative categories; and PD diagnosed by a neurologist or hospital records. RESULTS: This study included 11 studies (four cohort studies, six case-control studies, and one cross-sectional study). The high ß-carotene intake was associated with a significantly lower chance of developing PD than low ß-carotene intake (pooled OR = 0.83, 95%CI = 0.74-0.94). Whereas the risk of advancement of PD was not significantly distinctive among the highest and lowest vitamin A intake (pooled OR = 1.08, 95%CI = 0.91-1.29). CONCLUSIONS: Dietary ß-carotene intake may have a protective effect against PD, whereas dietary vitamin A does not appear to have the same effect. More relevant studies are needed to include into meta-analysis in the further, as the recall bias and selection bias in retrospective and cross-sectional studies cause misclassifications in the assessment of nutrient intake.

Zwitterionic meso-silica/polypeptide hybrid nanoparticles for efficient azithromycin delivery and photodynamic therapy for synergistic treatment of drug-resistant bacterial infection.

The treatment of drug-resistant bacterial infections attributed to the overuse of antibiotics still remains a serious challenge globally. Herein, zwitterionic charge switchable meso-silica/polypeptide hybrid nanoparticles (MSPNs) were prepared for the synergistic chemo-photodynamic therapy in the treatment of drug-resistant bacterial infections. Subsequently, azithromycin (AZT) and methylene blue (MB) were loaded in the MSPNs to form the combined chemo-photodynamic therapeutic nanoparticles (MSPNs-AZT/MB) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, the as-prepared MSPNs-AZT/MB exhibited a negative surface charge of -5.2 mV at physiological pH while switching into positive surface charge of 24.7 mv in an acidic environment, leading to enhanced binding with bacterial surface. The lipase-triggered AZT release up to 77.9 % was achieved, and the loaded MB demonstrated efficient singlet oxygen (1O2) generation for photodynamic therapy. The in vitro experimental results displayed an excellent antibacterial effect against MRSA in both planktonic and biofilm phenotypes. Additionally, the as-prepared MSPNs-AZT/MB exhibited synergistic and enhanced antibacterial infection effect up to 94 % comparing to monotherapy in a mice model. Considering the above advantages, the as-prepared combined chemo-photodynamic therapeutic nanoparticles showed promising biocompatibility and clinical potential for the efficient therapy of drug-resistant bacteria.

Cs2CO3 catalyzed direct aza-Michael addition of azoles to α,ß-unsaturated malonates.

A highly efficient method for the synthesis of azole derivatives via a direct aza-Michael addition of azoles to α,ß-unsaturated malonates using Cs2CO3 as a catalyst, has been successfully developed. A series of azole derivatives have been obtained in up to 94% yield and the reaction could be amplified to gram scale in excellent yield in the presence of 10 mol% of Cs2CO3.

Highly selective cross-coupling reactions of 1,1-dibromoethylenes with alkynylaluminums for the synthesis of aryl substituted conjugated enediynes and unsymmetrical 1,3-diynes.

A highly efficient method for the synthesis of aryl substituted conjugated enediynes and unsymmetrical 1,3-diynes via selective cross-coupling reactions of 1,1-dibromoethylenes with alkynylaluminums using the Pd(OAc)2-DPPE and Pd2(dba)3-TFP complexes as catalysts, respectively, has been successfully developed. Though the alkyl substituted conjugated enediynes and unsymmetrical 1,3-diynes were not obtained, this case is also remarkable as the same starting materials could selectively produce either aryl substituted conjugated enediynes or unsymmetrical 1,3-diynes in moderate to excellent yields (up to 99%) in the different Pd-phosphine catalytic systems.

Surface charge switchable nano-micelle for pH/redox-triggered and endosomal escape mediated co-delivery of doxorubicin and paclitaxel in treatment of lung adenocarcinoma.

Recently, the stimulus-sensitive drug co-delivery system has gained increasing attentions in the clinic and exhibits improved efficiency rather than the mono-chemotherapy in anti-tumor therapy. Herein, the smart charge switchable nano-micelles (NMs) were fabricated for the endosomal escape mediated co-delivery of doxorubicin (DOX) and paclitaxel (PTX) in treatment of lung adenocarcinoma. The disulfide bonds were facilitated as the linker of the polymer backbone to achieve the redox-sensitive degradation by high intracellular GSH, and acid-liable DMMA was grafted onto DOX molecules for pH-triggered drug release under acidic tumoral microenvironment. Folic acid (FA) was utilized as targeting molecule for facilitating entry of the as prepared NMs into cancer cells. Remarkably, the as fabricated NMs exhibited surface charge-switch from negative to positive during transmitting from physiological pH to the tumor extracellular pH, which can improve the cellular internalization towards cancer cell. Subsequently, the "proton-sponge" effect mediated endosome escape of the NMs was facilitated in the acidic endo/lysosome environment. By the cell assay, the NMs possessed good biocompatibility, excellent cellular uptake, and improved inhibition rate against cancer cell. Moreover, the co-delivery of DOX/PTX exhibited synergistic and enhanced solid tumor inhibition efficiency comparing to mono-chemotherapy in A-549 tumor bearing mice model. Based on above experimental results, the as prepared drug co-delivery system showed promising biosafety and potentials for efficient lung adenocarcinoma treatment in clinic.

[Curcumin targeting miR-155-5p/TP53INP1 axis induced oxidative stress to regulate salivary gland tumor cell proliferation and apoptosis].

PURPOSE: To investigate the mechanism of curcumin targeting miR-155-5p/TP53INP1 axis to induce oxidative stress to regulate salivary gland tumor cell proliferation and apoptosis. METHODS: A253 cells were cultured by adding curcumin and transfected with miR-155-5p mimic and/or pcDNA3.1-TP53INP1. Cell proliferation was detected by CCK-8 assay cell apoptosis was detected by flow cytometry, cell migration ability was detected by scratch test. The targeting relationship between miR-155-5p and TP53INP1 was verified by dual luciferase reporter assay. miR-155-5p, TP53INP1 mRNA expression was detected by qRT-PCR. Western blot was performed to detect expression of TP53INP1, Caspase8, Caspase3, Bcl-2, Bax protein; and ELISA was used to determine SOD, Gpx, and MDA content. Statistical analysis was performed using SPSS 22.0 software package. RESULTS: Dual luciferase reporter assay confirmed that TP53INP1 was a downstream target regulatory molecule of miR-155-5p. Compared with DMSO group, cell apoptosis, Caspase8, Caspase3, Bax protein expression and TP53INP1 expression were significantly increased in curcumin group, while Bcl-2 protein expression, miR-155-5p mRNA and number of cell migration were significantly decreased(P<0.05). Compared with curcumin + miR-155-5p mimic group, cell apoptosis, Caspase8, Caspase3, Bax protein expression was significantly increased in curcumin + pcDNA3.1-TP53INP1 group and curcumin + miR-155-5p mimic + pcDNA3.1-TP53INP1 group; Bcl-2 protein expression was significantly increased(P<0.05), SOD, GSH-PX activities and number of cell migration were significantly decreased and MDA content was significantly increased in curcumin+pcDNA3.1-TP53INP1 group (P<0.05). CONCLUSIONS: Curcumin inhibited A253 cell proliferation and promoted A253 cell apoptosis. The mechanism may be related to targeting miR-155-5p/TP53INP1 axis to induce oxidative stress regulation.

Lycium barbarum Polysaccharides Promotes Mitochondrial Biogenesis and Energy Balance in a NAFLD Cell Model.

OBJECTIVE: To explore the protective effect and underlying mechanism of Lycium barbarum polysaccharides (LBP) in a non-alcoholic fatty liver disease (NAFLD) cell model. METHODS: Normal human hepatocyte LO2 cells were treated with 1 mmol/L free fatty acids (FFA) mixture for 24 h to induce NAFLD cell model. Cells were divided into 5 groups, including control, model, low-, medium- and high dose LBP (30,100 and 300 µg/mL) groups. The monosaccharide components of LBP were analyzed with high performance liquid chromatography. Effects of LBP on cell viability and intracellular lipid accumulation were assessed by cell counting Kit-8 assay and oil red O staining, respectively. Triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), adenosine triphosphate (ATP) and oxidative stress indicators were evaluated. Energy balance and mitochondrial biogenesis related mRNA and proteins were determined by quantitative real-time polymerase chain reaction and Western blot, respectively. RESULTS: Heteropolysaccharides with mannose and glucose are the main components of LBP. LBP treatment significantly decreased intracellular lipid accumulation as well as TG, ALT, AST and malondialdehyde levels (P<0.05 or P<0.01), increased the levels of superoxide dismutase, phospholipid hydroperoxide glutathione peroxidase, catalase, and ATP in NAFLD cell model (P<0.05). Meanwhile, the expression of uncoupling protein 2 was down-regulated and peroxisome proliferator-activated receptor gamma coactivator-1α/nuclear respiratory factor 1/mitochondrial transcription factor A pathway was up-regulated (P<0.05). CONCLUSION: LBP promotes mitochondrial biogenesis and improves energy balance in NAFLD cell model.