Brief Report: Adenosine A2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function

Chemotherapy-induced cognitive impairment (CICI) has emerged as a significant medical problem without therapeutic options. Using the platinum-based chemotherapy cisplatin to model CICI, we revealed robust elevations in the adenosine A_2A receptor (A_2AR) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A_2AR inhibition by the Food and Drug Administration–approved A_2AR antagonist KW-6002 prevented cisplatin-induced impairments in neural progenitor proliferation and dendrite morphogenesis of adult-born neurons, while improving memory and anxiety-like behavior, without affecting tumor growth or cisplatin’s antitumor activity. Collectively, our study identifies A_2AR signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments.     

Aggressive prolactinomas responsive to temozolomide treatment: Report of two cases

Refractory aggressive prolactinomas are detected after the unresponsiveness to conventional therapies. We report two cases that underwent temozolomide treatment and have been in near‐complete remission ever since. We suggest the pathology techniques for earlier detection and, subsequently, treatment with temozolomide to reduce morbidities and better respond to therapy.     

Modeling and Control of Layer Height in Laser Wire Additive Manufacturing

Laser Wire Additive Manufacturing (LWAM) is a flexible and fast manufacturing method used to produce variants of high metal geometric complexity. In this work, a physics-based model of the bead geometry including process parameters and material properties was developed for the LWAM process of large-scale products. The developed model aimed to include critical process parameters, material properties and thermal history to describe the relationship between the layer height with different process inputs (i.e., the power, the standoff distance, the temperature, the wire-feed rate, and the travel speed). Then, a Model Predictive Controller (MPC) was designed to keep the layer height trajectory constant taking into consideration the constraints faced in the LWAM technology. Experimental validation results were performed to check the accuracy of the proposed model and the results revealed that the developed model matches the experimental data. Finally, the designed MPC controller was able to track a predefined layer height reference signal by controlling the temperature input of the system.     

Immune checkpoints in targeted-immunotherapy of pancreatic cancer: New hope for clinical development

Immunotherapy has been recently considered as a promising alternative for cancer treatment. Indeed, targeting of immune checkpoint (ICP) strategies have shown significant success in human malignancies. However, despite remarkable success of cancer immunotherapy in pancreatic cancer (PCa), many of the developed immunotherapy methods show poor therapeutic outcomes in PCa with no or few effective treatment options thus far. In this process, immunosuppression in the tumor microenvironment (TME) is found to be the main obstacle to the effectiveness of antitumor immune response induced by an immunotherapy method. In this paper, the latest findings on the ICPs, which mediate immunosuppression in the TME have been reviewed. In addition, different approaches for targeting ICPs in the TME of PCa have been discussed. This review has also synopsized the cutting-edge advances in the latest studies to clinical applications of ICP-targeted therapy in PCa.KEY WORDS: Immune checkpoint, Pancreatic cancer, Tumor microenvironment, Immunotherapy, Clinical development     

Incorporation of second‐tier tests and secondary biomarkers to improve positive predictive value (PPV) rate in newborn metabolic screening program

BackgroundNowadays, neonatal screening has become an essential part of routine newborn care in the world. This is a non‐invasive evaluation that evaluated inborn errors of metabolisms (IEMs) using tandem mass spectrometry (LC‐MS/MS) for the evaluation of the baby''s risk of certain metabolic disorders.MethodsThis retrospective study was conducted on 39987 Iranian newborns who were referred to Nilou Medical Laboratory, Tehran, Iran, for newborn screening programs of IEMs. We incorporated second‐tier tests and secondary biomarkers to improve positive predictive value (PPV).ResultsStatistical data were recorded via call interviewing in 6–8 months after their screening tests. The overall prevalence of IEM was 1:975. The mean age of all participants was 3.9 ± 1.1 days; 5.1% of participants were over 13 days and 7.7% were preterm or underweight. A total of 11384 (29.4%) of the cases were born in a consanguineous family. The type of delivery was the cesarean section in 8332 (51.3%) valid cases. The neonatal screening results had an overall negative predictive value (NPV) of 100% and the overall PPV of 40.2%. The false‐positive rate was 0.15%.ConclusionThis study showed a high incidence of metabolic disease due to a high rate of consanguineous marriages in Iran and indicated that incorporation of second‐tier tests and secondary biomarkers improves PPV of neonatal screening programs.     

Forecasting the Post-Pandemic Effects of the SARS-CoV-2 Virus Using the Bullwhip Phenomenon Alongside Use of Nanosensors for Disease Containment and Cure

The COVID-19 pandemic has the tendency to affect various organizational paradigm alterations, which civilization hasyet to fully comprehend. Personal to professional, individual to corporate, and across most industries, the spectrum of transformations is vast. Economically, the globe has never been more intertwined, and it has never been subjected to such widespread disruption. While many people have felt and acknowledged the pandemic’s short-term repercussions, the resultant paradigm alterations will certainly have long-term consequences with an unknown range and severity. This review paper aims at acknowledging various approaches for the prevention, detection, and diagnosis of the SARS-CoV-2 virus using nanomaterials as a base material. A nanostructure is a material classification based on dimensionality, in proportion to the characteristic diameter and surface area. Nanoparticles, quantum dots, nanowires (NW), carbon nanotubes (CNT), thin films, and nanocomposites are some examples of various dimensions, each acting as a single unit, in terms of transport capacities. Top-down and bottom-up techniques are used to fabricate nanomaterials. The large surface-to-volume ratio of nanomaterials allows one to create extremely sensitive charge or field sensors (electrical sensors, chemical sensors, explosives detection, optical sensors, and gas sensing applications). Nanowires have potential applications in information and communication technologies, low-energy lightning, and medical sensors. Carbon nanotubes have the best environmental stability, electrical characteristics, and surface-to-volume ratio of any nanomaterial, making them ideal for bio-sensing applications. Traditional commercially available techniques have focused on clinical manifestations, as well as molecular and serological detection equipment that can identify the SARS-CoV-2 virus. Scientists are expressing a lot of interest in developing a portable and easy-to-use COVID-19 detection tool. Several unique methodologies and approaches are being investigated as feasible advanced systems capable of meeting the demands. This review article attempts to emphasize the pandemic’s aftereffects, utilising the notion of the bullwhip phenomenon’s short-term and long-term effects, and it specifies the use of nanomaterials and nanosensors for detection, prevention, diagnosis, and therapy in connection to the SARS-CoV-2.     

Distribution of single wall carbon nanotubes in the Xenopus laevis embryo after microinjection

Single wall carbon nanotubes (SWCNTs) are advanced materials with the potential for a myriad of diverse applications, including biological technologies and large‐scale usage with the potential for environmental impacts. SWCNTs have been exposed to developing organisms to determine their effects on embryogenesis, and results have been inconsistent arising, in part, from differing material quality, dispersion status, material size, impurity from catalysts and stability. For this study, we utilized highly purified SWCNT samples with short, uniform lengths (145 ± 17 nm) well dispersed in solution. To test high exposure doses, we microinjected > 500 µg ml^–1 SWCNT concentrations into the well‐established embryogenesis model, Xenopus laevis, and determined embryo compatibility and subcellular localization during development. SWCNTs localized within cellular progeny of the microinjected cells, but were heterogeneously distributed throughout the target‐injected tissue. Co‐registering unique Raman spectral intensity of SWCNTs with images of fluorescently labeled subcellular compartments demonstrated that even at regions of highest SWCNT concentration, there were no gross alterations to subcellular microstructures, including filamentous actin, endoplasmic reticulum and vesicles. Furthermore, SWCNTs did not aggregate and localized to the perinuclear subcellular region. Combined, these results suggest that purified and dispersed SWCNTs are not toxic to X. laevis animal cap ectoderm and may be suitable candidate materials for biological applications. Copyright © 2015 John Wiley & Sons, Ltd.     

4-羟基壬烯醛在糖尿病大鼠白内障中的代谢及发病中的作用

目的 研究脂质过氧化代谢产物4-羟基壬烯醛(HNE)在糖尿病性白内障中的代谢过程以及发病中的作用.方法 实验研究.采用两因素析因设计:处理因素为两水平(正常对照组和糖尿病组),时间因素为三水平(30、45、70 d).对于不同时期的正常与糖尿病大鼠晶状体采用下列方法进行处理:(1)使用一定晕的带有放射活性的HNE与这些晶状体一起培养,测定HNE在晶状体的代谢;(2)分光光度计法测定醛脱氢酶(ALDH)活性;(3)免疫印迹法检测ALDH和HNE-蛋白质加合物的表达.采用两因素析因设计定量资料方差分析对资料进行统计学处理.结果 HNE在正常对照组的晶状体的代谢主要是与谷胱甘肽(GSH)结合形成GS-HNE(约45%),其次为经ALDH氧化成HNA(约9.1%);但糖尿病组晶状体的HNE与GSH结合径路受到抑制,GS-HNE形成减少,与正常组相比30 d时减少约64%(F=49.59,P＜0.001);而糖尿病组晶状体的ALDH氧化径路代偿增强,HNA形成增多,70 d比30 d增多约1.7倍(F=11.51,P=0.0442).糖尿病组的晶状体ALDH活性增高,免疫印迹法显示ALDH较正常对照组增多,HNE-蛋白质加合物较对照组减少.结论糖尿病性白内障中HNE与GSH的结合径路受到抑制,而氧化径路代偿性增强,揭示了结合径路的损伤可能与白内障发生有密切关系,氧化径路的代偿增强可能对防止糖尿病性白内障的发生有一定的意义.(中华眼科杂志,2009,45:248-253)