Ageing on the impact of distribution about preformed anti-HLA and anti-MICA antibody specificities in recipients prior to initial HSCT from East China.

BACKGROUND: With the development of Hematopoietic Stem Cell Transplantation (HSCT) technology, increasing numbers of elderly patients were undergoing allogeneic HSCT and elderly patients with hematologic malignancies could benefit most from it. Preformed donor-specific human leukocyte antigen (HLA) antibodies (DSA) were associated with graft failure in HLA-mismatched allogeneic HSCT and the absence of DSA was the main criterion of selecting the donor. Except for sensitization events such as transfusion, pregnancy or previous transplantation, ageing affects the humoral immune response both quantitatively and qualitatively. To evaluate the prevalence and distribution of anti-HLA and antibodies of MHC class I chain related antigens A (MICA) specificities in different age groups before initial HSCT would provide HLA and MICA specific antibody profiles under the impact of ageing, which could provide meaningful information in the process of selecting suitable HLA-mismatched donors by avoiding preformed DSA. RESULTS: There were no significant differences in the distribution of anti-HLA class I, class II and anti-MICA antibodies among the three age groups in this study except that a significant lower negative ratio of anti-HLA class I, class II antibodies and higher positive rate of MICA antibodies with maximum mean fluorescent intensity (MFI) > 5000 in the elderly than in young age group. The distribution of antibody specificities against HLA -A, -B, -C, -DR, -DQ, -DP and MICA antigens in the three age groups were generally consistent. The anti-HLA class I antibody specificities with higher frequencies were A80,A68;B76,B45;Cw17, which were unlikely to become DSA in Chinese. Anti-HLA class II antibody specificities were more likely to become potential DSA than class I.DR7, DR9, DQ7, DQ8 and DQ9 were most likely to become potential DSA. CONCLUSIONS: The prevalence of anti-HLA and anti-MICA antibodies increased slightly as age increased. While ageing had a small impact on the distribution of antibody specificity frequencies against HLA-A, -B, -C, -DR,-DQ, -DP and MICA antigens in recipients awaiting initial HSCT from East China. The risk of developing preformed DSA was basically consistent in the three age groups and the elderly group might be more favorable in HLA-mismatched HSCT due to higher positive rate of anti-MICA antibody.

Self-assembled albumin nanoparticles as a nanocarrier for aclacinomycin A.

This study aimed to reduce the cytotoxicity and improve the targeting of aclacinomycin (ACM) by covalently coupling it with amino-oxyacetic acid (AOA) to generate an active intermediate, AOA-ACM. AOA-ACM was conjugated with self-assembled human serum albumin (HSA) nanoparticles constructed using tris(2-carboxyethyl)phosphine (TCEP) as disulfide bond breaking molecules in an 'opening stage-intermediate-closing stage' route, in which the hydrophobic interaction, interchange of sulfhydryl and hydrogen bond may be the key factors in the assembling process. Conjugation between ACM and albumin nanoparticles was found to occur at an ACM ketone site using 1H-NMR and 13C-NMR matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass analysis indicated that the drug loading efficiency of ACM conjugated with HSA nanoparticles (NPs-ACM) was 7.4% (molar ratio = 6:1). The release of NPs-ACM was pH dependent. In vivo studies indicated that NPs-ACM exhibited fourfold higher tumor targeting capability on S180-tumor-bearing mice compared with the free ACM (p < 0.05). The cytotoxictiy and cardiotoxicity of NPs-ACM was reduced compared with the free ACM. Albumin carrier altered the blood pharmacokinetics and distribution of ACM. Hence, the NPs-ACM prodrug is ideal tumor targeting drug carriers for ACM, and the easy approach developed in this study for active intermediate and prodrug preparation can be applied to other pharmacological substances containing ketone groups. The method of preparing HSA-blank nanoparticles through TCEP reduction could be adopted to improve the water solubility of lipophilic drugs and their tumor-targeting specificity by fabricating HSA-lipophilic drug nanoparticles.

Curcumin-incorporated albumin nanoparticles and its tumor image.

Albumin is an ideal carrier for hydrophobic drugs. This paper reports a facile route to develop human serum albumin (HSA)-curcumin (CCM) nanoparticles, in which ß-mercaptoethanol (ß-ME) acted as an inducer and CCM acted as a bridge. Fluorescence quenching and conformational changes in HSA-CCM nanoparticles occurred during assembly. Disulfide bonds and hydrophobic interactions may play a key role in assembly. HSA-CCM nanoparticles were about 130 nm in size, and the solubility of CCM increased by more than 500 times. The HSA-CCM nanoparticles could accumulate at the cytoplasm of tumor cells and target the tumor tissues. Therefore, HSA nanoparticles fabricated by ß-ME denaturation are promising nanocarriers for hydrophobic substances from chemotherapy drugs to imaging probes.

Stem cell-based therapies for intracerebral hemorrhage in animal model: a meta-analysis.

Stem cell to be a new intervention for treating intracerebral hemorrhage (ICH) might benefit humans. Therefore, we collected animal studies to find the effect of this innovative treatment. In July 2014, we searched Medline (from 1950), Embase (from 1980), China Biology Medicine disk (from 1978) for studies on stem cells used for treating experimental ICH in animal models that reported neurobehavioral and structural outcome. We evaluated the quality of these studies and used a weighted mean difference random affects model for the meta-analysis. We have collected 30 studies from 650 publications identified through systematic review describing the effects of 5 different type of stem cells on 12 different neurobehavioral scales with 1101 rodents or monkeys. Although there is lack of uniformity of the evaluation methods, these researches showed consistent improvements both in neurobehavioral function and structural outcomes. Besides, the quality of these studies needs to be raised. In conclusion, stem cells hold extensive potential in treating ICH, which should be further evaluated with more evidence-based, high-quality animal studies.

The impact of preformed and de novo HLA-DP antibodies in renal transplantation, a meta-analysis.

The impact of preformed and de novo HLA-DP antibodies after renal transplantation remains controversial and unclear. To address the clinical relevance of HLA-DP antibodies on the outcomes in renal transplantation, we performed a random effect model meta-analysis through a systematic review from inception to December 31, 2021. The outcome was graft loss or acute rejection. Finally five articles were identified as our inclusion criteria. The study which reported 1166 patients included in the final meta-analysis of de novo HLA-DP antibodies after transplantation showed an increased risk of graft loss or acute rejection (OR = 3.6, 95% CI = 1.6-8.10, P = 0.002, I2  = 52%). In the subgroup study, we established that patients with HLA-DP DSA after renal transplantation had a 8.85-fold increased risk of graft loss or acute rejection compared with patients without HLA-DP DSA (p = 0.003).While as for HLA-DP NDSA after renal transplantation, 2.73-fold increased risk of graft loss or acute rejection compared with patients without HLA-DP antibodies (p = 0.04). Besides, the studies which reported 487 patients included in the final meta-analysis of preformed HLA-DP antibodies did not show an increased risk of graft loss or acute rejection (OR = 4.55, 95% CI = 0.79-26.16, P = 0.09, I2  = 57%). The results of our meta-analysis suggested that de novo HLA-DP antibodies especially de novo HLA-DP DSA had a significant deleterious impact on the renal transplant risk of graft loss or acute rejection, while preformed HLA-DP antibodies had a no significant deleterious impact on the risk. The routine detection of HLA-DP antibodies after renal transplantation seems to be very important and may be as one of noninvasive biomarker-guided risk stratification.

Hepar-on-a-sensor-platform with hybridization chain reaction amplification strategy to intuitively monitor the hepatoxicity of natural compounds.

The irrational use of natural compounds in the treatment of diseases can lead to serious side effects, especially hepatoxicity, and its toxic effects are usually cumulative and imperceptible. Therefore, an accurate sensing platform is urgently needed to monitor the hepatotoxicity of natural compounds. Here, we deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and a thorough validation was adopted to evaluate the bioprinted hepatic constructs. The engineered hepar-platform was then employed to access its biological response toward Emodin (EM) and Triptolide (TP), two typical hepatotoxic natural compounds. Subsequently, we integrated it with a robust fluorescent sensor based on hybridization chain reaction amplification strategy (HCR) to monitor the early hepatotoxic biomarker - glutathione-S-transferase-alpha (GST-α) secreted by this 3D constructs. Our study was the first attempt to construct an accurate hepar-on-a-sensor platform that could effectively detect GST-α for monitoring the hepatoxic effects of natural compounds. The limit of detection of the platform was 0.3 ng ml-1 and the accuracy of this platform was verified by enzyme linked immunosorbent assay. Furthermore, the variation of GST-α induced by EM and TP was consistent with hepatotoxicity studies, thus providing an important application value for evaluating the hepatotoxicity of natural compounds. STATEMENT OF SIGNIFICANCE: 1. We deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and elucidated the essential reasons why hybrid bioinks more suitable for 3D extrusion from biomaterials itself. Also, a thorough validation associated with a series of important proteins and genes involved in liver cell metabolism was adopted to evaluate the bioprinted hepatic constructs accurately 2. Glutathione-S-transferase-alpha is a soluble trace biomarker for acute hepatotoxic injury, the hepatotoxic effects of natural compounds on the secretion of GST-α has not been reported to date. We integrated our 3D hepar-platform with recognition molecules-aptamers and HCR amplification strategy to monitor the variation of GST-α, aiming at developing a robust and stable fluorescent biosensing platform to monitor the hepatoxicity of natural compounds.

Molecular switch for the assembly of lipophilic drug incorporated plasma protein nanoparticles and in vivo image.

A strategy to manipulate the disulfide bond breaking triggered unfolding, and subsequently assembly of human serum albumin (HSA) in a lipophilic drug-dependent manner is present. In this study, the hydrophobic region, a molecular switch of the HSA, was regulated to form HSA-paclitaxel (HSA-PTX) nanoparticles by a facile route. High-resolution transmission electron microscopy and fluorescence quenching indicate that HSA coassembled with PTX, which acts as a bridge to form core-shell nanoparticles about 50-240 nm in size, and that PTX might bind to the subdomain IIA sites of HSA. Change of ultraviolet absorption and circular dichroism spectra reveal the formation of HSA-PTX nanoparticles, which is a safety, injectable pharmaceutic nanocarrier system for tumor target. This method to prepare nanocarrier systems for hydrophobic guest molecules reveals a general principle of self-assembly for other plasma proteins and other pharmacologically active substances with poor water solubility. It also provides a basis for developing nanocarrier systems for a wide range of applications in nanomedicine, from drug delivery to bioimaging systems.

A curcumin-induced assembly of a transferrin nanocarrier system and its antitumor effect.

To increase the solubility and targeting efficiency of curcumin (CCM) to tumors, transferrin (Tf)-CCM nanoparticles (NPs-CCM) with a CCM loading capacity of 5.2% were fabricated by Tf denaturation with hydrochloric acid, a denaturing agent, to open the hydrophobic cavity of Tf. The NPs-CCM were approximately 160 nm in size with a spherical shape. The solubility of the CCM in the nanoparticles was approximately 100,000 times greater than that of CCM alone (11 ng mL-1 vs 1.11 mg mL-1, respectively). The changes in the fluorescence spectra of Tf and 1-(anilinon)-aphthalene-8-sulfonic acid (ANS) in the NP-CCM preparation indicated that the polarity of certain hydrophobic and hydrophilic groups of Tf changed. CCM treatment of A549 cells resulted in a decrease in the mitochondrial membrane potential (MMP) and induced apoptosis through mitochondrial dependence. CCM increased the expression of phosphorylated c-Jun N-terminal kinase (JNK), P38, and extracellular signal-regulated kinase (ERK) but had a weak effect on the expression of nonphosphorylated JNK, P38, and ERK, which showed that the mitogen-activated protein kinase signaling (MAPK) transduction pathway is involved in CCM-mediated apoptosis. The half maximal inhibitory concentration (IC50) of NPs-CCM was higher than that of free CCM in A549 (16.41 ± 0.86 vs 12.51 ± 3.9 (µg mL-1), p = 0.036) and MCF-7 (9.31 ± 0.11 vs 2.44 ± 3.76 (µg mL-1), p < 0.0037) tumor cells, however the former had a greater tumor-targeting in vivo. Without the side effects of polyoxyethylene castor oil/ethanol as solvent, the hemolysis effect of NPs-CCM (0.05-1 mg mL-1) was notably lower than that of free CCM (p < 0.05). It was estimated that the half maximal lethal dose (LD50) of NPs-CCM was approximately two times that of CCM (100 mg kg-1 vs 50 mg kg-1), and the former had many advantages over that of free CCM in terms of lower toxicity and better targeting; thus, NPs-CCM can be administered at higher doses to acquire better antitumor effects than CCM alone, indicating that NPs-CCM are an effective and safe carrier for CCM delivery.

Phosphoantigen-activated V gamma 2V delta 2 T cells antagonize IL-2-induced CD4+CD25+Foxp3+ T regulatory cells in mycobacterial infection.

Although Foxp3(+) T regulatory cells (Tregs) are well documented for their ability to suppress various immune cells, T-cell subsets capable of counteracting Tregs have not been demonstrated. Here, we assessed phosphoantigen-activated Vgamma2Vdelta2 T cells for the ability to interplay with Tregs in the context of mycobacterial infection. A short-term IL-2 treatment regimen induced marked expansion of CD4(+)CD25(+)Foxp3(+) T cells and subsequent suppression of mycobacterium-driven increases in numbers of Vgamma2Vdelta2 T cells. Surprisingly, activation of Vgamma2Vdelta2 T cells by adding phosphoantigen Picostim to the IL-2 treatment regimen down-regulated IL-2-induced expansion of CD4(+)CD25(+)Foxp3(+) T cells. Consistently, in vitro activation of Vgamma2Vdelta2 T cells by phosphoantigen plus IL-2 down-regulated IL-2-induced expansion of CD4(+)CD25(+)Foxp3(+) T cells. Interestingly, anti-IFN-gamma-neutralizing antibody, not anti-TGF-beta or anti-IL-4, reduced the ability of activated Vgamma2Vdelta2 T cells to down-regulate Tregs, suggesting that autocrine IFN-gamma and its network contributed to Vgamma2Vdelta2 T cells' antagonizing effects. Furthermore, activation of Vgamma2Vdelta2 T cells by Picostim plus IL-2 treatment appeared to reverse Treg-driven suppression of immune responses of phosphoantigen-specific IFNgamma(+) or perforin(+) Vgamma2Vdelta2 T cells and PPD-specific IFNgamma(+)alphabeta T cells. Thus, phos-phoantigen activation of Vgamma2Vdelta2 T cells antagonizes IL-2-induced expansion of Tregs and subsequent suppression of Ag-specific antimicrobial T-cell responses in mycobacterial infection.

Fabrication of a nanocarrier system through self-assembly of plasma protein and its tumor targeting.

Human serum albumin (HSA) nanoparticles hold great promise as a nanocarrier system for targeted drug delivery. The objective of this study was to explore the possibility of preparing size controllable albumin nanoparticles using the disulfide bond breaking reagent ß-mercaptoethanol (ß-ME). The results showed that the protein concentration and temperature had positive effects on the sizes of the albumin nanoparticles, while pH had a negative effect on the rate of nanoparticle formation. The addition of ß-ME induced changes in HSA secondary structure and exposed the hydrophobic core of HSA, leading to the formation of nanoparticles. Human serum albumin nanoparticles could be internalized by MCF-7 cells and mainly accumulated in cytoplasm. After injection in tumor bearing mice, the HSA nanoparticles accumulated in tumor tissues, demonstrating the targeting ability of the nanoparticles. Therefore, human serum albumin can be fabricated into nanoparticles by breaking the disulfide bonds and these nanoparticles exhibit high tumor targeting ability. Human serum albumin nanoparticles could be ideal for the targeted delivery of pharmacologically active substances.

Targeted Dual Small Interfering Ribonucleic Acid Delivery via Non-Viral Polymeric Vectors for Pulmonary Fibrosis Therapy.

Inhibiting the myofibroblast differentiation of lung-resident mesenchymal stem cells (LR-MSCs) is a promising yet challenging approach for pulmonary fibrosis (PF) therapy. Here, micelles formed by a graft copolymer of multiple PEGs modified branched polyethylenimine are used for delivering runt-related transcription factor-1 (RUNX1) small interfering RNA (siRNA) (siRUNX1) to the lung, aiming to inhibit the myofibroblast differentiation of LR-MSCs. LR-MSC targeting is achieved by functionalizing the micelle surface with an anti-stem-cell antigen-1 antibody fragment (Fab'). Consequently, therapeutic benefits are obtained by successful suppression of myofibroblast differentiation of LR-MSCs in bleomycin-induced PF model mice treated with siRUNX1-loaded micelles. Furthermore, an excellent synergistic effect of PF therapy is achieved for this micelle system loaded siRUNX1 and glioma-associated oncogene homolog-1 (Gli1) small interfering RNA (siGli1), a traditional anti-PF siRNA of glioma-associated oncogene homolog-1. Hence, this work not only provides RUNX1 as a novel PF therapeutic target, but also as a promising dual siRNA-loaded nanocarrier system for the therapy of PF.

Synthesis and Evaluation of Cytocompatible Alkyne-Containing Poly(ß-amino ester)-Based Hydrogels Functionalized via Click Reaction.

Although poly(ß-amino esters) (PAEs) have been widely applied in nonviral gene transfection, drug delivery systems, and regenerative medicine, the multifunctional modification of PAEs and bio-orthogonal strategies of PAE-based hydrogel functionalization is still a challenge. Herein, a strategy of poly(ß-amino ester)-based hydrogel functionalization was developed via bio-orthogonal reactions in this study. Acrylate-terminated poly(ß-amino esters) containing alkyne groups were synthesized by Michael addition reaction. Alkyne groups on poly(ß-amino esters) could conjugate bioactive molecules with azide of K(N3)RGD via copper-catalyzed azide-alkyne cycloaddition, and terminal acrylate groups could in situ polymerize to prepare a hydrogel. A biomimetic peptide K(N3)RGD functionalized hydrogel was prepared by polymerization of acrylate-terminated poly(ß-amino esters) containing conjugated peptide and polyethylene glycol diacrylate (PEGDA). The storage modulus and mechanical properties exhibited an increased trend with the increased concentration; nevertheless, swelling ratio and surface wetting properties demonstrated a decreased tendency by increased concentrations. Cell proliferation and live/dead staining showed that Schwann cells plated on the hydrogel with an elastic modulus of 25.39 KPa are more suitable for proliferation and function exertion of Schwann cells compared with that of 42.11 and 57.86 KPa, and KRGD-conjugated hydrogel could increase the elongation of Schwann cells relative to nonconjugated hydrogels. This azide-alkyne strategy may be a promising candidate for hydrogel functionalization in tissue engineering and other biomedical applications.

Natural skin-whitening compounds for the treatment of melanogenesis (Review).

Melanogenesis is the process for the production of melanin, which is the primary cause of human skin pigmentation. Skin-whitening agents are commercially available for those who wish to have a lighter skin complexions. To date, although numerous natural compounds have been proposed to alleviate hyperpigmentation, insufficient attention has been focused on potential natural skin-whitening agents and their mechanism of action from the perspective of compound classification. In the present article, the synthetic process of melanogenesis and associated core signaling pathways are summarized. An overview of the list of natural skin-lightening agents, along with their compound classifications, is also presented, where their efficacy based on their respective mechanisms of action on melanogenesis is discussed.

Clinical study for external washing by traditional Chinese medicine in the treatment of multiple infectious wounds of diabetic foot: Study protocol clinical trial (SPIRIT compliant).

BACKGROUND: Diabetic foot (DF) is among the most serious complications of type 2 diabetes. DF infection (DFI) is a key factor in the deterioration and development of DF, so controlling infection plays an important role in the treatment of the disease. Traditional Chinese medicine foot bath has been widely used in China as a complementary and alternative therapy to improve circulation and infection control of DF. However, the existing evidence shows that its efficacy and safety are still insufficient. We report a study protocol about a multicenter, double-blind, randomized, placebo controlled trial which aims to make well-designed clinical trials to evaluate the efficacy and safety of herbal medicine foot bath decoction (FBD) and explore the mechanism of external washing of Chinese herbs in DFI. METHODS: This study is a multicenter, double-blind, randomized, placebo controlled clinical trial in which 60 eligible participants were randomly divided into an experimental group and control group at a 1:2 ratio. Both groups received the same basic treatment for DF disease, the experimental group used FBD and ordinary dressing changes, while half of the patients in the control group received placebo and ordinary dressings, and the other half received placebo and silver ion dressings. Patients in both groups will be evaluated weekly for efficacy during the intervention. The primary efficacy indicators include the types of wound pathogens, interleukin 6 and tumor necrosis factor α. Secondary efficacy indicators included blood glucose, blood lipids, wound area, lower extremity blood vessel diameter, blood flow speed, walking speed, walking distance, and traditional Chinese medicine syndrome scores. We will also conduct a safety evaluation of the drug at the end of the trial. DISCUSSION: This multicenter, double-blind, randomized, placebo clinical trial not only provides data on the efficacy and safety of FBD, but also provides a novel treatment strategy for clinicians and DF patients.

Efficacy and safety of Xiyanping for COVID-2019: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by the severe acute respiratory syndrome coronavirus-2.COVID-19 is highly pathogenic and infectious. COVID-19 epidemic is still spreading all over the world, and there is no sign of stopping at present. There is no specific cure for this disease, and the clinical management mainly depends on supportive treatment. Xiyanping is widely used in treating COVID-19 in China. However, there is no evidence that Xiyanping is effective and safe for COVID-19. METHODS: A comprehensive literature search will be conducted. Two methodological trained researchers will read the title, abstract, and full texts and independently select the qualified literature according to inclusion and exclusion criteria. After assessment of the risk of bias and data extraction, we will conduct meta-analysis for outcomes related to COVID-19. The heterogeneity of data will be investigated by Cochrane X and I tests. Then publication bias assessment will be conducted by funnel plot analysis and Egger test. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: Our study aims to systematically present the clinical evidence of Xiyanping in the treatment of COVID-19, which will be of guiding significance for further research and clinical practice. OPEN SCIENCE FRAMEWORK REGISTRATION NUMBER: 10.17605/OFS.IO/SW75F.

Huangqi Guizhi Wuwu decoction for diabetic peripheral neuropathy: Protocol for a systematic review.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common causes of disability in diabetic population, and its pathogenesis is related to a variety of factors. There is currently no effective treatment for such chronic disease. Traditional Chinese medicine has a long clinical history for the prevention and treatment of diabetes and chronic complications, and it also shows certain advantages in the treatment of DPN. Many clinical studies have confirmed that Chinese medicine Huangqi Guizhi Wuwu decoction (HGWD) can reduce the clinical symptoms and improve neuronal function of patients with DPN. So we intend to conduct a systematic review further clarified the effectiveness and safety of HGWD for DPN. METHODS: We will search each database from the built-in until June 2019. The English literature mainly searches Cochrane Library, PubMed, EMBASE, and Web of Science, while the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Simultaneously we will retrieval clinical registration tests and grey literatures. This study only screen the clinical randomized controlled trials (RCTs) about HGWD for DPN to assess its efficacy and safety. The 2 researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is represented by relative risk (RR), and the continuous is expressed by mean difference (MD) or standard mean difference (SMD), eventually the data is synthesized using a fixed effect model (FEM) or a random effect model (REM) depending on whether or not heterogeneity exists. The clinical efficacy, median sensory nerve conduction velocity, median motor nerve conduction velocity, peroneal sensory nerve conduction velocity, and peroneal motor nerve conduction velocity were evaluated as the main outcomes. Fasting blood glucose, 2 hours postprandial blood glucose, hemorheology, and adverse reactions were secondary outcomes. Finally, meta-analysis was conducted by RevMan software version 5.3. RESULTS: This study will synthesize and provide high-quality evidence based on the data of the currently published HGWD for the treatment of DPN, especially in terms of clinical efficacy, neurological function, blood glucose, hemorheology, and safety. CONCLUSION: This systematic review aims to provide new options for HGWD treatment of DPN in terms of its efficacy and safety. PROSPERO REGISTRATION NUMBER: PROSPERO 2019 CRD42019132031.

A novel nanoparticle drug delivery system based on PEGylated hemoglobin for cancer therapy.

Proteins such as albumin, gelatin, casein, transferrin, and collagen are widely used as drug delivery systems. However, only albumin-based paclitaxel (PTX) formulation Abraxane® (PTX-albumin NPs prepared by nab-technology) has been successfully developed for treating metastatic breast cancer clinically due to abundant materials, simple industrial scale-up process, and well tumor-targeting ability. Hemoglobin (Hb) is another protein used for drug delivery with similar advantages. In this study, we successfully synthesized PEG-Hb nanoparticles loading with PTX based on previously well-established acid-denatured method. PEG-Hb-PTX NPs showed enhanced cellular uptake and great cellular inhibition ability in vitro. Moreover, our animal study showed that PEGylated NPs greatly accumulated in tumor tissues and exhibited excellent anticancer activity in vivo. We found that PEG-Hb-PTX NPs possess a better in vivo antitumor effect than the commercially available Taxol® formulation. We believe that PEG-Hb has great potential as an efficient drug delivery system for further clinic study.

Exploration of the Effect and Mechanism of ShenQi Compound in a Spontaneous Diabetic Rat Model.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a world-wide metabolic disease with no cure from drugs and treatment. In China, The Traditional Chinese Medicine (TCM) herbal formulations have been used to treat T2DM for centuries. METHODS: In this study, we proposed a formula called ShenQi Compound (SQC), which has been used in clinical therapeutics in China for several years. We evaluated the effect of SQC in a spontaneous diabetic rat model (GK rats) by detecting a series of blood indicators and performing histological observations. Meanwhile, the gene microarray and RT-qPCR experiments were used to explore the molecular mechanism of SQC treatment. In addition, western medicine, sitagliptin was employed as a comparison. RESULTS: The results indicated that SQC and sitagliptin could effectively improve the serum lipid (blood Total Cholesterol (TC) and blood Triglycerides (TG)), hormone levels (serum insulin (INS), Glucagon (GC) and Glucagon-Like Peptide-1 (GLP-1)), alleviated the inflammatory response (hypersensitive C-Reactive Protein (hsCRP)), blood glucose fluctuation (Mean Blood Glucose (MBG), standard deviation of blood glucose (SDBG) and Largest Amplitude of plasma Glucose Excursions (LAGE)), pancreatic tissue damage and vascular injury for T2DM. Compared with sitagliptin, SQC achieved a better effect on blood glucose fluctuation (p<0.01). Meanwhile, the gene microarray and RT-qPCR experiments indicated that SQC and sitagliptin may improve the T2DM through affecting the biological functions related to apoptosis and circadian rhythm. Moreover, SQC might be able to influence the mTOR signaling pathway by regulating Pik3r1, Ddit4 expression. CONCLUSION: All these results indicate that SQC is an effective therapeutic drug on T2DM. Notably, SQC presents an obvious blood glucose fluctuation-preventing ability, which might be derived from the regulation of the mTOR signaling pathway.

A single center study of protective and susceptible HLA alleles and haplotypes with end-stage renal disease in China.

Chronic kidney disease (CKD) is becoming a global public health problem and usually cause End-Stage Renal Disease (ESRD) in the end of progression. To analyze the associations of HLA-A, -B, -C, -DRB1 and -DQB1 alleles at high resolution with ESRD in Jiangsu province of China, a total of 499 unrelated patients with ESRD from the First Affiliated Hospital with Nanjing Medical University and 1584 healthy controls from Jiangsu Branch of Chinese Marrow Donor Program (CMDP) were genotyped at HLA-A, -B, -C, -DRB1 and -DQB1 loci. Statistical analysis was applied to compare the differences of HLA allele frequencies between patients with ESRD and healthy controls. As results, no protective allele at A locus was found and the susceptible alleles were A*11:01 and A*31:01. At B locus, B*15:01, B*55:02 and B*39:05 emerged as susceptible alleles, whereas no protective allele was found. At C locus, C*06:02 and C*07:01 emerged as protective alleles and no susceptible allele was found. At DRB1 locus, six alleles including DRB1*03:01, DRB1*04:03, DRB1*04:04, DRB1*04:05, DRB1*11:01 and DRB1*12:02 emerged as susceptible alleles, while DRB1*15:01 emerged as a protective allele. At DQB1 locus, DQB1*02:01, DQB1*03:01, DQB1*03:02 and DQB1*04:01 emerged as susceptible alleles, while DQB1*06:02 and DQB1*06:09 emerged as protective alleles. Haplotype A*11:01-C*03:03-B*15:01-DRB1*11:01-DQB1*03:01 containing four susceptible alleles was regarded as the most susceptible haplotype. The susceptible alleles and haplotypes might be used as some important risk classification markers. Besides, in the consanguineous renal transplantation, it would be very beneficial for the long-term survival of renal transplant patients to avoid the susceptible alleles and haplotypes in selecting optimal donors.