AKR1C3 Promotes AR-V7 Protein Stabilization and Confers Resistance to AR-Targeted Therapies in Advanced Prostate Cancer.

The mechanisms resulting in resistance to next-generation antiandrogens in castration-resistant prostate cancer are incompletely understood. Numerous studies have determined that constitutively active androgen receptor (AR) signaling or full-length AR bypass mechanisms may contribute to the resistance. Previous studies established that AKR1C3 and AR-V7 play important roles in enzalutamide and abiraterone resistance. In the present study, we found that AKR1C3 increases AR-V7 expression in resistant prostate cancer cells through enhancing protein stability via activation of the ubiquitin-mediated proteasome pathway. AKR1C3 reprograms AR signaling in enzalutamide-resistant prostate cancer cells. In addition, bioinformatical analysis of indomethacin-treated resistant cells revealed that indomethacin significantly activates the unfolded protein response, p53, and apoptosis pathways, and suppresses cell-cycle, Myc, and AR/ARV7 pathways. Targeting AKR1C3 with indomethacin significantly decreases AR/AR-V7 protein expression in vitro and in vivo through activation of the ubiquitin-mediated proteasome pathway. Our results suggest that the AKR1C3/AR-V7 complex collaboratively confers resistance to AR-targeted therapies in advanced prostate cancer.

Three novel Cu6S6 cluster-based coordination compounds: synthesis, framework modulation and the sensing of small molecules and Fe(3+) ions.

Three novel Cu6S6 cluster-based coordination compounds formulated as [Cu(mpymt)3]2 (1), {(CuBr4)[Cu(mpymt)6]}n (2), and {(CuI6)[Cu(mpymt)6]}n (3) (Hmpymt = 4-methylpyrimidine-2-thione), have been synthesized under solvothermal conditions and characterized by elemental analysis, infrared (IR) spectroscopy, thermal gravimetric analysis, powder X-ray diffraction and single-crystal X-ray diffraction. Structural analysis reveals that compound 1 shows a distorted octahedral core of six copper atoms (Cu6S6) constructed from four α and two ß type N[double bond, length as m-dash]C-SH parts from six mpymt(-) anions. Compound 2 displays an interesting 3D framework constructed from Cu6S6 and Cu4Br4 Cu(i) clusters simultaneously, interestingly, six mpymt(-) with α type N[double bond, length as m-dash]C-SH parts are involved in the formation of Cu6S6. Compound 3 displays an infinite 1D framework constructed from Cu6S6 and Cu6I6 Cu(i) clusters, notably, four α and two ß type N[double bond, length as m-dash]C-SH parts are involved in the formation of the Cu6S6 cluster, however, only mpymt(-) ligands containing α type N[double bond, length as m-dash]C-SH parts form the bridged Cu6I6 cluster. The experimental results reveal that halogen ions finely modulate the structural features of compounds 1-3. The fluorescent properties of compounds 1-3 in the solid state and in various solvent emulsions were investigated in detail, the results of which indicate that compounds 1-3 are all highly sensitive naked eye colorimetric sensors for NB, 2-NT and Fe(3+) (NB = nitrobenzene and 2-NT = 2-nitrotoluene).

20-(s)-ginsenoside Rg3 induces apoptotic cell death in human leukemic U937 and HL-60 cells through PI3K/Akt pathways.

Leukemia is currently one of the most deadly diseases. Ginseng has been used in Asian countries for the treatment and prevention of various diseases, including leukemia, but the molecular mechanism of its antileukemia activity has not been well defined. The aim of this study was to explore the effect of 20-(s)-ginsenoside Rg3 on apoptosis in human leukemic U937 and HL-60 cells and the underlying mechanism. We found that 20-(s)-ginsenoside Rg3 reduced cell viability and induced apoptosis in U937 and HL-60 cells. The induction of apoptosis was accompanied by the downregulation of PI3K/Akt family proteins. Moreover, we observed that 20-(s)-ginsenoside Rg3 treatment resulted in activation of caspase-3 and caspase-9. Taken together, our findings suggest for the first time that 20-(s)-ginsenoside Rg3 can promote apoptosis in U937 and HL-60 cells, at least partly through the downregulation of PI3K/Akt family proteins. Moreover, the triggering of caspase-3 and caspase-9 activation mediated apoptotic induction. All these findings collectively demonstrate that the natural compound 20-(s)-ginsenoside Rg3 effectively induces apoptosis in human leukemic cells, which suggests that this compound may play a role in future therapies for leukemia.

Involvement of phosphatidylinositol 3-Kinase/Akt signaling pathway in ß1 integrin-mediated internalization of Staphylococcus aureus by alveolar epithelial cells.

The invasion of Staphylococcus aureus into alveolar epithelial cells is regarded as the key step for S. aureus lung infection. However, the mechanism of internalization of S. aureus by alveolar epithelial cells is not clear, and was the aim of this investigation Human lung adenocarcinomic epithelial cells and A549 cells were used. Human ß1 integrin and rat ß1 integrin were detected by real-time reverse transcription (RT)-PCR. The expressions of ß1 integrin, Akt and p-Akt were detected by Western blot analysis. To further investigate the role of ß1 integrin in S. aureus internalization by alveolar epithelial cells, we next performed siRNA-mediated knockdown of ß1 integrin expression. In this study, we found that S. aureus invades human alveolar epithelial cells and rat primary alveolar epithelial cells. The ß1 integrin ligand competitive inhibitor, GRGDS-peptide, blocked the internalization of S. aureus by A549 cells. Knockdown of ß1 integrin also inhibited the internalization of S. aureus. In addition, the PI3K/Akt signaling pathway in alveolar epithelial cells was activated by the infection with S. aureus. Furthermore, Akt phosphorylation was abolished by transient transfection with ß1 integrin siRNA in A549 cells challenged with S. aureus. Our results suggest that the phosphatidylinositol 3-kinase/Akt signaling pathway plays an important role in ß1 integrin-mediated internalization of S. aureus by alveolar epithelial cells.

Primary lung lymphoma involving the superior vena cava.

Primary lung lymphoma (PLL) presenting as a primary pulmonary lesion is rare and usually affects elderly people. Here we describe a 25-year-old Chinese man diagnosed with primary lung lymphoma, which presented as a huge lung tumor mimicking a primary lung cancer and involving the superior vena cava. He underwent double-sleeve reconstructions of bronchus and pulmonary arteries with right upper- and middle-lobe lobectomy along with replacement of the superior vena cava with a graft, and was then given standard chemotherapy of CHOP plus Rituximab. The patient has been well, showing no local recurrence or distal metastasis during a 27-month follow-up.

Primary endobronchial plasmacytoma involving local lymph nodes and presenting with rare immunoglobulin G lambda monoclonal gammopathy.

Extramedullary plasmacytoma occurring as a primary pulmonary lesion is rare. The present report describes a 42-year-old Chinese man diagnosed with primary pulmonary plasmacytoma following left lower lobectomy. Of note, an extremely rare immunoglobulin G lambda paraprotein was documented in the patient's serum by immunofixation electrophoresis. The patient has been well, showing no local recurrence or multifocal disease during a 15-month follow-up.

[Association of body mass index with diabetes in the elderly in Foshan].

OBJECTIVE: To study the correlation between body mass index (BMI) and diabetes in the elderly residents in Foshan. METHODS: A total of 3 382 people above 60 years old participated in this questionnaire-based survey, with their blood pressure, height, body weight, and blood glucose measured and oral glucose tolerance test performed. RESULTS: The prevalence rates of diabetes in the elderly subjects with obesity, overweight, normal weight, and underweight were 31.58%, 22.84%, 15.65% and 9.40%, respectively. The prevalence rate of impaired glucose tolerance (IGT) in relation to obesity, overweight, normal weight, and underweight were 67.94%, 56.14%, 46.58% and 38.35%, respectively. A higher mean BMI was accompanied by a greater prevalence of diabetes. The average BMI was 23.9+/-3.3 kg/m(2) in diabetic subjects, 23.4+/-3.4 kg/m(2) in subjects with IGT, and 22.6+/-3.2 kg/m(2) in normal elderly subjects. CONCLUSION: There is a close correlation between BMI and diabetes.