Aspirin,lysine, mifepristone and doxycycline combined can effectively and safely prevent and treat cancer metastasis: prevent seeds from gemmating on soil

Recent scientific advances have increased our understanding of the cancer metastatic complexities and provided further impetus for new combination therapies to prevent cancer metastasis. Here, we demonstrated that a combination (HAMPT) of aspirin, lysine, mifepristone and doxycycline can effectively and safely prevent cancer metastasis. The pharmaceutically-formulated HAMPT inhibited adhesion of cancer cells to either endothelial cells or extracellular matrix via down-regulating cell adhesion molecules ICAM-1 and α₄-integrin. HAMPT inhibited the cloak effect by activated platelets on cancer cells, thereby interfering adhesion and invasion of cancer cells to the underlying stroma. At the effective concentration, HAMPT induced cancer cells into dormancy with minor inhibition on cell viability. Four-day pretreatment followed by 30-day oral administration of HAMPT (33.5-134 mg/kg) to the mice inoculated with cancer cells produced significant inhibition on cancer metastasis dose-dependently without marked side effects. Fifty-day rat toxicity study with HAMPT at doses (335-1340 mg/kg) 20-fold higher than its therapeutic dose produced no significant toxicity. Interestingly, the acute toxic death could not be reached at the maximum administrable dose (5 g/kg). This proof-of-concept study provides the first conceptual evidence that cancer metastasis can be controlled by using affordable old drugs to restrain circulating tumor cells from gemmating on the metastatic soil without the need for cytotoxicity.     

Effect of topology of poly(L-lactide-co-ε-caprolactone) scaffolds on the response of cultured human umbilical cord Wharton’s jelly-derived mesenchymal stem cells and neuroblastoma cell lines

In this study, for the first time, a biodegradable poly(L-lactide-co-ε-caprolactone), PLC 67:33 copolymer was developed for use as temporary scaffolds in reconstructive nerve surgery. The effect of the surface topology and pore architecture were studied on the biocompatibility for supporting the growth of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs) and human neuroblastoma cells (hNBCs) as cell models. Porous PLC membranes were prepared by electrospinning and phase immersion precipitation with particulate leaching and nonporous PLC membranes were prepared by solvent casting. From the results, the porous PLC membranes can support hWJ-MSCs and hNBCs cells better than the nonporous PLC membrane, and the interconnected pore scaffold prepared by electrospinning exhibited a more significant supporting attachment of the cells than the open pore and nonporous membranes. We can consider that these electrospun PLC membranes with 3-D interconnecting fiber networks and a high porosity warrant a potential use as nerve guides in reconstructive nerve surgery.     

Doxorubicin alters the mitochondrial dynamics machinery and mitophagy in the liver of treated animals

Doxorubicin (Dox) is an effective chemotherapeutic agent, but known to cause cardiac and hepatic toxicity. Mechanisms of toxicity have not been clearly identified, but shown to involve oxidative stress and mitochondrial dysfunction. However, antioxidant supplementation has only shown modest protection from Dox‐induced toxicity in clinical trials. Therefore, further research is required to discern alternative mechanisms that may also play an important role in Dox‐induced toxicity. Thus, we aimed to investigate the role of mitochondrial fusion and fission in Dox‐induced hepatic toxicity, which has not yet been investigated. Six‐week‐old male F344 rats were injected IP with 20 mg/kg of Dox or saline. Once administered, both groups of animals were fasted with no food or water until sacrifice 24 h later. Dox decreased content of primary regulators of mitochondrial fusion (OPA1, MFN1, and MFN2) with no effect on regulators of fission (DRP1 and FIS1), thus shifting the balance favoring mitochondrial fission. Moreover, it was determined that mitochondrial fission was likely not coupled to cell proliferation or cytochrome c release leading to the activation of mitochondrial‐mediated apoptotic signaling. Rather, mitochondrial fission may be coupled to mitophagy and may be an adaptive response to protect against Dox‐induced hepatic toxicity. This is the first study to report the role of altered mitochondrial dynamics and mitophagy machinery in Dox‐induced hepatic injury.     

Adherence to outpatient oral medication regimens in adolescent hematopoietic stem cell transplant recipients

PurposeHematopoietic stem cell transplantation (HSCT) is an increasingly utilized treatment option for adolescents with many life-threatening diagnoses. Suboptimal adherence may result in compromised treatment effectiveness and increased risk of adverse medical outcomes.MethodThis study examined adherence patterns in six adolescents (ages 12–18) who had undergone HSCT. Demographic and clinical information were obtained from caregivers and via chart review. Electronic pill bottles (Medical Event Monitors, MEMS™) were used to track medication adherence. Daily, weekly, and monthly adherence as well as medication interruptions (periods of ≥24 h between doses) were calculated.ResultsParticipants took 73% of doses (SD = 13%) and demonstrated perfect adherence on 56% of days (SD = 18%, Range = 34–88%). Average monthly adherence ranged from 40 to 91% and decreased over time. Participants demonstrated at least two [M(SD) = 4.20(2.28)] medication interruptions. Individual adherence patterns included high sustained adherence, variable adherence, and delayed non-adherence.ConclusionsOverall, participants struggled to adhere to medication schedules, taking less than three-quarters of prescribed doses and demonstrating perfect adherence on fewer than four out of seven days per week. Adherence rates are similar to those observed in other pediatric populations and demonstrate the importance of routinely assessing adherence in adolescents who have undergone HSCT.     

Role of SiNx Barrier Layer on the Performances of Polyimide Ga2O3-doped ZnO p-i-n Hydrogenated Amorphous Silicon Thin Film Solar Cells

In this study, silicon nitride (SiN_x) thin films were deposited on polyimide (PI) substrates as barrier layers by a plasma enhanced chemical vapor deposition (PECVD) system. The gallium-doped zinc oxide (GZO) thin films were deposited on PI and SiN_x/PI substrates at room temperature (RT), 100 and 200 °C by radio frequency (RF) magnetron sputtering. The thicknesses of the GZO and SiN_x thin films were controlled at around 160 ± 12 nm and 150 ± 10 nm, respectively. The optimal deposition parameters for the SiN_x thin films were a working pressure of 800 × 10⁻³ Torr, a deposition power of 20 W, a deposition temperature of 200 °C, and gas flowing rates of SiH₄ = 20 sccm and NH₃ = 210 sccm, respectively. For the GZO/PI and GZO-SiN_x/PI structures we had found that the GZO thin films deposited at 100 and 200 °C had higher crystallinity, higher electron mobility, larger carrier concentration, smaller resistivity, and higher optical transmittance ratio. For that, the GZO thin films deposited at 100 and 200 °C on PI and SiN_x/PI substrates with thickness of ~000 nm were used to fabricate p-i-n hydrogenated amorphous silicon (α-Si) thin film solar cells. 0.5% HCl solution was used to etch the surfaces of the GZO/PI and GZO-SiN_x/PI substrates. Finally, PECVD system was used to deposit α-Si thin film onto the etched surfaces of the GZO/PI and GZO-SiN_x/PI substrates to fabricate α-Si thin film solar cells, and the solar cells’ properties were also investigated. We had found that substrates to get the optimally solar cells’ efficiency were 200 °C-deposited GZO-SiN_x/PI.     

Hepatitis B virus e antigen (HBeAg) may have a negative effect on dendritic cell generation

Hepatitis B virus (HBV) continues to be a serious worldwide health problem despite the use of protective HBV vaccines and therapeutic regimens against chronic HBV infection. Chronic HBV patients cannot induce sufficient immune responses against the virus. HBV and its antigens are believed to suppress immune responses during chronic infection. Hence, studying the role of HBV in immune suppression is very important for the development of alternative therapeutic strategies for HBV infections.     

RNA-binding protein CELF1 promotes tumor growth and alters gene expression in oral squamous cell carcinoma

The RNA binding protein CELF1 (also known as CUGBP1) is emerging as a critical regulator of cancer cell proliferation and apoptosis. Here, to provide a global prospective of CELF1 regulation of oral squamous cell carcinoma, we performed RNA-sequencing in oral cancer cells and CELF1 overexpression analysis in non-malignant human oral keratinocytes. Our approaches identified 1283 mRNAs differentially regulated as a function of CELF1 expression and more importantly CELF1 promoted alternative splicing of several target pre-mRNAs, which are known to be involved in various cancer biological processes. Overexpression of CELF1 in non-malignant human oral keratinocytes protected cells against oxidative damage and altered gene expression patterns. Finally, we provide evidence that reduction of CELF1 protein using a xenograft tumorigenesis mouse model decreased tumor growth. Altogether, these data provided a comprehensive view of the CELF1 mRNA regulatory network in oral cancer and suggests that CELF1 and/or its target mRNAs are viable candidates for therapeutic intervention.     

肾移植术后人类微小病毒B19感染致纯红细胞再生障碍性贫血2例并文献复习

目的探讨肾移植术后人类微小病毒(HPV)B19感染致纯红细胞再生障碍性贫血(纯红再障)的诊断和治疗特点。方法总结南方医科大学南方医院器官移植科收治的2例肾移植术后HPV B19感染致纯红再障的病例,结合文献复习讨论该病的临床特点、诊断方法、治疗过程及预后。结果两例肾移植受者术后早发严重贫血且进行性加重,输血治疗无效。排除导致贫血的其他原因,综合骨髓穿刺活检、荧光聚合酶链反应(PCR)检测HPV DNA等方法诊断为HPV B19感染致纯红再障。经调整免疫抑制方案、静脉注射用免疫球蛋白(IVIG)等治疗后2例患者贫血症状明显改善。结论对于肾移植术后早期不明原因、进行性加重的贫血患者,特别是伴随网织红细胞缺乏者,应考虑HPV B19感染致纯红再障的可能性。骨髓穿刺及荧光PCR检测结果是诊断纯红再障的主要依据,免疫抑制剂减量和应用IVIG治疗是主要治疗措施。经治疗后,患者预后较好,但易复发。