To investigate whether chemically modified non-anticoagulation heparin derivate (periodate oxidation/borohydride reduction-modified heparin (OR-heparin)) could inhibit high glucose-induced human mesangial cell apoptosis and to explore its possible mechanism.Methods:Mesangial cells were exposed to high glucose or high glucose with OR-heparin for 24 h.Apoptosis was evaluated by Hoechst 33258 staining and Fluorescent activated cell sorting analysis.The expressions of apoptosis-related proteins ( p53,Bcl-2,Bax,cytosolic cytochrome C) were determined by Western blotting.NF-kB translocation was observed under fluorescence microscopy by using Cy3-1abeled antibody.Caspase-3 activity was detected by colorimetry.Results:OR-heparin significantly inhibited high glucose-induced mesangial cell apoptosis and the expression of apoptosis-related proteins.It also blocked NF-kB translocation induced by high glucose.Conclusion:OR-heparin inhibits high glucose-induced mesangial cell apoptosis through inhibiting the expression of apoptosis-related proteins and it may be due to the blockage of the translocation of NF-kB.

Objective To analyze the risk factors of 30-day mortality in patients with malignant hilar obstruction (MHO) after percutaneous transhepatic biliary metal stent deployment. Methods One hundred and fifty-nine consecutive patients with MHO caused by cholangiocarcinoma or gallbladder carcinoma were enrolled in this study. Percutaneous transhepatic biliary stent (PTBS) implantation was carried out in all the patients. Independent predictors for 30-day mortality were evaluated by logistic regression analysis. Covariates that were incorporated into the multivariate analysis were the variables that reached statistical significance (P < 0.1) in univariate analysis. Two-tailed, P value of less than 0.05 was considered to be statistically significant. Results The 30-day mortality of patient with MHO after metal stent deployment was 9.4%. Univariate analysis indicated that the differences in WBC (OR = 1.224.95%CI [1.07 - 1.44], P < 0.01), INR (OR=78.75, 95%CI [5.02-1 235.70], P<0.01), PT(OR=1.55, 95%CI [1.18-2.04], P<0.01), BUN (OR=1.19, 95%CI [1.02- 1.38], P < 0.05), CRE(OR = 1.02, 95%CI [1.000 - 1.041], P < 0.1) and lymph nodes metastasis(OR = 0.334. 95%CI[0.105 - 1.131], P < 0.1) were statistically significantly between 30-day mortality group and non-30-day mortality group. Multivariate analysis showed that statistically significant differences in WBC (OR = 1.19, 95%CI[1.026 - 1.380], P < 0.05), INR(OR = 151.5, 95%CI [3.13 - 5 440.7], P < 0.05) and CRE (OR = 1.025, 95%CI [1.002 - 1.048], P < 0.05) also existed palliative treatment for patients with malignant hilar obstruction. Active preoperative measures to improve hepatic and renal functions as well as to control infection are necessary in order to reduce 30-day mortality.

The assay method of GLP-1 receptor binding affinity for a long-acting hypoglycemic peptide—PEgylated Exendin-4 analogue(PE)was optimized and established based on the luciferase reporter gene approach. CHO-GLP-1R-CRE-Luc+ cells were previously constructed in our lab followed by the verification of methodology. This assay method showed good specificity and robustness as well as high accuracy and precision when PE was incubated with the cell for 4 h, the luminescent substrate reacted with cell lysates for 15 min and the concentration for PE ranged 5. 7×10-3-1. 5×103 nmol/L, on which condition this developed method is in accordance with General Principles of Analytical Method Validation Techniques for Biological Products Quality Control. This study also lays the foundations for rapid evaluation and screening of GLP-1 receptor agonist drugs.

Peptide and protein biologics possess high specificity and high biological activity, but their poor stability and short plasma half-life have limited clinical application. One established strategy to increase half-life of therapeutic proteins is chemical conjugation of the biologic with PEG. Nevertheless, PEGylation technology has some drawbacks, so recombinant polypeptide mimetics of PEG have gradually developed in recent years. Pharmaceutically active protein can be fused with specific amino acid sequences using recombinant DNA technology, and then increase hydrodynamic volume or produce charge effect, which retards kidney filtration and eventually prolongs the half-life. This article mainly reviews kinds of polypeptides and the research progress in half-life extension of therapeutic proteins.

Tumor immunotherapy is currently the new direction for the treatment of cancer. Bispecific antibody can bind two different antigens, so the development prospect in the field of tumor treatment is very attractive. The most compelling trifunctional antibody and bispecific T-cell engager in bispecific antibodies have been marketed separately, with representative drugs as catumaxomab and blinatumomab, respectively. So far, nearly 100 antitumor bispecific antibody drugs are undergoing clinical trials and in-depth understanding of their mechanisms of action will provide more powerful solutions for cancer treatment. This review summarizes the progress of catumaxomab, blinatumomab and current highly promising bispecific antibody drugs, for the further development and application of tumor therapy.

Antitumor drugs usually have deficiencies such as poor water solubility, low targeting, poor stability, and difficulty in being taken up by tumor cells. The development of an ideal drug delivery vehicle is still an urgent problem to be solved in the field of cancer therapy. Due to their excellent sequence programmability, biocompatibility and biodegradability, DNA-based nanomaterials have been widely used as drug delivery vehicles for cancer treatment. Numerous studies have shown that DNA nanomaterials can effectively load cancer therapeutic agents, and achieve tumor targeted delivery, efficient cellular internalization as well as stimuli-responsive drug release. Starting from the history and development of DNA nanotechnology, this review illustrates the application progress of DNA nanomaterial as drug delivery vehicle in chemotherapy, gene therapy, immunotherapy and photodynamic therapy, and the future development is prospected so as to provide some reference for other researchers in this field.

As numerous connections between oncogenic signalling pathways and metabolic activities emerge, the importance of metabolic reprogramming in cancer is being increasingly recognized. During tumorigenesis, breast cancer cells undergo metabolic reprogramming, which generally includes enhanced glycolysis, tricarboxylic acid cycle activity, glutaminolysis and fatty acid biosynthesis. The extension and functional importance of these metabolic alterations may diverge according to breast cancer subtypes.Besides, aberrant metabolism of breast cancer cells remodels tumor microenvironment, promoting cancer vascularization and inhibiting anti-tumor immunity, and thus accelerates tumor progression.This review addresses current knowledge on the metabolic reprogramming and breast cancer microenvironment, which provides some reference for the development of metabolic target drugs for each breast cancer subtype.

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia ( n=4), fatigue ( n=3), fever ( n=2), abdominal discomfort ( n=2), osteolytic lesions ( n=2), dizziness ( n=1), skin flushing ( n=1), and weight loss ( n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

Mushroom-derived cyathane-type diterpenes possess unusual chemical skeleton and diverse bioactivities. To efficiently supply bioactive cyathanes for deep studies and explore their structural diversity,

Although high-efficiency targeted delivery is investigated for years, the efficiency of tumor targeting seems still a hard core to smash. To overcome this problem, we design a three-step delivery strategy based on streptavidin-biotin interaction with the help of c(RGDfK), magnetic fields and lasers. The ultrasmall superparamagnetic iron oxide nanoparticles (USIONPs) modified with c(RGDfK) and biotin are delivered at step 1, followed by streptavidin and the doxorubicin (Dox) loaded nanosystems conjugated with biotin at steps 2 and 3, respectively. The delivery systems were proved to be efficient on A549 cells. The co-localization of signal for each step revealed the targeting mechanism. The external magnetic field could further amplify the endocytosis of USPIONs based on c(RGDfK), and magnify the uptake distinctions among different test groups. Based on photoacoustic imaging, laser-heating treatment could enhance the permeability of tumor venous blood vessels and change the insufficient blood flow in cancer. Then, it was noticed that only three-step delivery with laser-heating and magnetic fields realized the highest tumor distribution of nanosystem. Finally, the magnetism/laser-auxiliary cascaded delivery exhibited the best antitumor efficacy. Generally, this study demonstrated the necessity of combining physical, biological and chemical means of targeting.