KPNB1-mediated nuclear import in cancer.

Dysregulation of nucleocytoplasmic shuttling impairs cellular homeostasis and promotes cancer development. KPNB1 is a member of karyopherin ß family, mediating the transportation of proteins from the cytoplasm to the nucleus. In a variety of cancers, the expression of KPNB1 is upregulated to facilitate tumor growth and progression. Both downregulation of KPNB1 level and inhibition of KPNB1 activity prevent the entry of cancer-related transcription factors into the nucleus, subsequently suppressing the proliferation and metastasis of cancer cells. Currently, five KPNB1 inhibitors have been reported and exhibited good efficacy against cancer. This paper provides an overview of the role and mechanism of KPNB1 in different cancers and KPNB1-targeted anticancer compounds which hold promise for the future.

Dual-Functional Nanofibrous Patches for Accelerating Wound Healing.

Bacterial infections and inflammation are two main factors for delayed wound healing. Coaxial electrospinning nanofibrous patches, by co-loading and sequential co-delivering of anti-bacterial and anti-inflammation agents, are promising wound dressing for accelerating wound healing. Herein, curcumin (Cur) was loaded into the polycaprolactone (PCL) core, and broad-spectrum antibacterial tetracycline hydrochloride (TH) was loaded into gelatin (GEL) shell to prepare PCL-Cur/GEL-TH core-shell nanofiber membranes. The fibers showed a clear co-axial structure and good water absorption capacity, hydrophilicity and mechanical properties. In vitro drug release results showed sequential release of Cur and TH, in which the coaxial mat showed good antioxidant activity by DPPH test and excellent antibacterial activity was demonstrated by a disk diffusion method. The coaxial mats showed superior biocompatibility toward human immortalized keratinocytes. This study indicates a coaxial nanofiber membrane combining anti-bacterial and anti-inflammation agents has great potential as a wound dressing for promoting wound repair.

Design, synthesis and biological evaluation of rhein-piperazine-dithiocarbamate hybrids as potential anticancer agents.

A series of novel rhein-piperazine-dithiocarbamate hybrids 3 were efficiently synthesized from rhein through a catalyst-free and one-pot, three-step sequence involving chlorination and N-acylation followed by dithiocarbamate formation. Hybrids 3 were evaluated for their in vitro cytotoxic potency by MTT assay against several human cancer and non-cancer cells. Five of the hybrids were more cytotoxic to human lung cancer cell line A549 than the parent rhein and the reference, cytarabine (CAR). Structure-activity relationship (SAR) analysis indicated that cytotoxicity was significantly enhanced when ester groups were incorporated into the hybrids (3h-j). In particular, hybrid 3h (IC50 = 10.93 µg/mL), containing a long-chain alkyl ester, was the most potent compound toward A549 tumor cells, being 7- and 5-fold more toxic than rhein (IC50 = 77.11 µg/mL) and CAR (IC50 = 49.27 µg/mL), respectively. Additionally, hybrid 3h was less toxic to the corresponding normal human lung fibroblast cell line, WI-38, with a higher selectivity index (SI, WI-38/A549 ≈ 5) than doxorubicin (DOX, SI ≈ 0), CAR (SI ≈ 2) and rhein (SI ≈ 1). Furthermore, hybrid 3h displayed more toxicity against four types of lung cancer cells (A549, Calu-1, PC-9, and H460; IC50 = 10.81-23.78 µg/mL) than against six other types of cancer cells (Huh-7, 786-O, HCT116, Hela, SK-BR-3, and SK-OV-3; IC50 = 23.85-51.98 µg/mL). Further mechanistic studies showed that hybrid 3h induced apoptosis in a concentration-dependent manner in human lung adenocarcinoma cell line PC-9. In vivo safety studies showed that hybrid 3h had no acute toxicity to the major organs of mice and did not lead to blood biochemical index changes. Our results exhibit prominent anti-cancer cell inhibition ability and no obvious systemic toxicity to normal organs, indicating that hybrid 3h has promising potential for further applications in anti-lung cancer drug development.

Synergistic Effect of Co-Delivering Ciprofloxacin and Tetracycline Hydrochloride for Promoted Wound Healing by Utilizing Coaxial PCL/Gelatin Nanofiber Membrane.

Combining multiple drugs or biologically active substances for wound healing could not only resist the formation of multidrug resistant pathogens, but also achieve better therapeutic effects. Herein, the hydrophobic fluoroquinolone antibiotic ciprofloxacin (CIP) and the hydrophilic broad-spectrum antibiotic tetracycline hydrochloride (TH) were introduced into the coaxial polycaprolactone/gelatin (PCL/GEL) nanofiber mat with CIP loaded into the PCL (core layer) and TH loaded into the GEL (shell layer), developing antibacterial wound dressing with the co-delivering of the two antibiotics (PCL-CIP/GEL-TH). The nanostructure, physical properties, drug release, antibacterial property, and in vitro cytotoxicity were investigated accordingly. The results revealed that the CIP shows a long-lasting release of five days, reaching the releasing rate of 80.71%, while the cumulative drug release of TH reached 83.51% with a rapid release behavior of 12 h. The in vitro antibacterial activity demonstrated that the coaxial nanofiber mesh possesses strong antibacterial activity against E. coli and S. aureus. In addition, the coaxial mats showed superior biocompatibility toward human skin fibroblast cells (hSFCs). This study indicates that the developed PCL-CIP/GEL-TH nanofiber membranes hold enormous potential as wound dressing materials.

[Affected Factors of Separating Erythrocytes by Discontinuous of Density Gradient Centrifugation].

OBJECTIVE: To study the affected factors of the separation of red blood cells by discontinuous density gradient method, and to establish the optimal operating conditions of percoll for the separation of erythrocytes. METHODS: The osmolality of different ratio of Percoll and 1.5 mol/L NaCl were 9:1, 10:1, 11:1, 12:1, 13:1 ratio, was detected respectively. The isotonic osmolality ratio was selected as optimum stock isotonic Percoll solution(SIP). Evaluation criteria: All the different density cells were separated sufficiently by centrifugation, there is little red cell retention and entrainment phenomena. The separation efficacy of different red cell suspension concentration, different centrifugal force, different centrifugal speed, different temperature and different time were compared. RESULTS: The separation efficacy of red cell suspension concentration which not exceed 50% was better than above 50%, efficacy of 4 000×g was superior to 3 000×g and 2 000×g, 2-8 centrifugal acceleration and deceleration centrifugal could obtain the satisfactory efficacy, the 4 °C layered effect was more stable than room temperature, the separation effect of 20 min was better than 15 min and 10 min. CONCLUSION: Percoll and 1.5 mol/L NaCl 12:1 to 11:1 can be used as stock isotonic percoll solution, preferentially selected 4 °C as centrifugal conditions. When conditions of separation was satisfied, the centrifugal acceleration and deceleration is 2-8, the optimal centrifugal effect can be obtained with the decrease of erythrocyte suspension concentration, with centrifugation time prolonging and centrifugal force increasing.

[Anti-A/B Antibody Titers in Group O Healthy Donors in Hainan Province Area].

OBJECTIVE: To detect the IgM anti-A (B) and IgG anti-A (B) antibody titers of group O healthy donors in Hainan province area, to understand the distribution of O-type blood donor IgM and IgG antibody titers and to analyze the relationship between antibody titers, so as to provide experimental evidences for the safety and feasibility of urgent transfusion of uncrossmatched group O RBCs. METHODS: Group O whole blood sample was collected from 80 volunteers blood donors. IgM antibody titrations was performed using the immediate spin (IS) tube, and IgG antibody titration were performed using the column agglutination technique with anti-human globulin (AHG). Using two-way ANOVA, paired t-test and correlation analysis, the different types of antibodies were compared. RESULTS: The IgM antibody titers distributed in 4-1 024, IgG antibody titer distributed in 2-2 048. Anti-A antibody titers of IgG were significantly higher than that of IgM anti-B, IgG anti-B and IgM anti-A titers (P < 0.05). There was a positive correlation bewteen IgM anti-A and anti-B, IgM anti-B and IgG anti-B, IgG anti-A and anti-B (P < 0.05). CONCLUSION: Group O blood donors have high antibody titers in Hainan province area, type O RBC suspensions should be first screened through screening the anti-A titer of IgG, so that can significantly improve the pass rate of O-type universal blood and reduce testing costs.