Current State of the Art in DNA Vaccine Delivery and Molecular Adjuvants: Bcl-xL Anti-Apoptotic Protein as a Molecular Adjuvant

DNA vaccines (nucleic acid vaccines) have been gaining importance as promising therapeutics against infectious diseases, cancer, autoimmune disorders and allergy for the past two decades. However, the immune responses elicited by the DNA vaccines are not at the desired level to stimulate a protective immune response. Thus, studies are focused on the enhancement of DNA vaccine-induced immune response by different approaches. The most common approach is to use biomaterial-based adjuvants for enhanced antigen delivery and uptake by antigen-presenting cells. Some of these adjuvants are alum, saponins, microspheres, nanoparticles, liposomes, polymers, etc. used in vaccine formulations. In addition, molecular adjuvants like cytokines, chemokines and heat shock proteins have been shown to be promising in designing DNA vaccines. In this chapter, molecular adjuvants to improve DNA vaccination-induced immune responses will be summarized with a special focus on Bcl-xL anti-apoptotic protein

Conducting Informal Discovery of a Party\u27s Former Employees: Legal and Ethical Concerns and Constraints

This Article identifies and critiques existing sources of confusion in the law and proposes revised and alternative discovery procedures to provide equal access to information possessed by ex-employees, while simultaneously safeguarding the integrity of that information. Its primary emphasis is on federal jurisprudence, although important points of consensus and departure between state and federal law are noted, as appropriate. Part I explains the issues that arise in informal discovery, and the difficulties with clearly resolving those issues given the conflicting state of the law. Part II discusses application of the attorney-client privilege to communications between corporate counsel and former employees, concluding that the privilege should not shield the content of such communications from discovery by opposing counsel. Because the attorney-client privilege issue and the debate over ex parte contact both turn on whether a former employee is a party to the litigation, an exposition of the ethical concerns of ex parte contact follows in Part III, which concludes that ex parte contact by opposing counsel should be allowed. Part IV examines the applicability of the work product doctrine in shielding from discovery certain tangible materials related to the interview. This Article advocates absolute immunity from discovery for attorney notes and memoranda, and for collections of documents selected by counsel for discussion with former employees; limited discovery of signed witness statements generated pursuant to the interview; and fairly broad discovery of the content of counsel\u27s questions and statements during the interview. The proposed discovery guidelines in the Conclusion are offered with the ambitious, if not elusive, goal of reconciling the competing interests and policies that rouse litigants to battle when informal discovery is conducted of former employees, while simultaneously giving due regard to the pragmatic impact that new or revised rules may have on the litigants and the adversarial process. The overriding objective is to provide equal access by all parties to the information possessed by former employees, while at the same time providing mechanisms to deter, and if necessary to reveal, inappropriate manipulation of these potential witnesses by counsel

Nano-vesicular formulation of propolis and cytotoxic effects in a 3D spheroid model of lung cancer

BACKGROUND: Propolis exhibits therapeutic properties due to the presence of phenolic acids, esters, and flavonoids. The scope of this study was to develop a nano-vesicular formulation and establish a three-dimensional (3D) spheroid model in which lung cancer is recapitulated. RESULTS: Niosome vesicles doped with galangin-rich propolis extract were synthesized by the ether injection method using a cholesterol : surfactant mass ratio of 1 : 3 at 40 °C for 1 h. Formulated niosomes were administered to 3D lung cancer spheroid model and the cytotoxicity was compared with that of a two-dimensional (2D) setting. The galangin content was determined as 86 μg mg–1 propolis extract by ultra-performance liquid chromatography (UPLC). The particle size of loaded niosome was 151 ± 2.84 nm with a polydispersity index (PDI) of about 0.232, and an encapsulation efficiency of 70% was achieved. CONCLUSION: The decrease in cell viability and the scattering in the 3D spheroids of A549 lung cancer cells treated with propolis-loaded niosomes were notable, indicating a profound cytotoxic effect and suggesting that they can be utilized as an effective nano-vesicle. © 2020 Society of Chemical Industry. © 2020 Society of Chemical Industr

Non-Penetrating Wounds of the Chest

The heart may be seriously injured by compression of the chest by a steering wheel in automobile accidents or in other injuries by non-penetrating blows to the chest. These injuries vary from a simple bruise of the heart to actual laceration of heart muscle and heart valves. The changes may be identified by electrocardiograph and changes in heart rhythm. Attorneys should make certain that any injury by a blow to the chest is studied by a cardiologist, using not one but a series of electrocardiographs, as even seemingly harmless blows to the chest may result in injuries equivalent to heart attacks

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Cytoprotective effect of a functional antipollutant blend through reducing B[a] P-induced intracellular oxidative stress and UVA exposure

Benzo[a]pyrene (B[a]P) is a ubiquitous environmental pollutant that reacts with skin and induces intracellular oxidative stress through reactive oxygen species (ROS) accumulation. the antipollution properties of natural extracts, especially including antioxidants, for inhibiting ROS in cells are gaining importance, in addition to the anticancer effects attributed to them. in this study, a commercial functional antipollutant blend of plant extracts consisting of ellagic acid standardized Punica granatum peel extract, Sambucus nigra fruit extract, Prunus cerasus seed extract, and hydrolyzed wheat protein with high antioxidant properties and UV damage-protective properties attributed to each one was investigated. the cytoprotective effect of this functional antipollutant blend was determined by ROS assay through reducing the level of intracellular ROS induced by B[a]P as an oxidative stress factor in human neonatal keratinocytes and fibroblast cells. in addition, the cytoprotective effect of the functional antipollutant blend after UVA exposure was also determined. It is shown that the oxidative damage induced by B[a]P and UVA, which are the most abundant factors of chemical and physical pollution, would be prevented by the functional antipollutant blend. Thus, it can be concluded that this antipollutant functional blend may offer a promising ingredient for the cosmetic industry’s skincare products

The biomarker features of miR-145-3p determined via meta-analysis validated by qRT-PCR in metastatic cancer cell lines

WOS: 000483423500041PubMed ID: 31195093MicroRNAs (miRNAs) play important roles in the cancer biology such as proliferation, differentiation, and apoptosis. The pivotal roles that miRNA expression plays, make them ideal candidates for detection of cancer progression as well as cancer metastasis. Especially for breast, lung and prostate cancer which are originated from soft tissues and prone to metastasis. Thus, the aim of this study is to evaluate the expression level of miR145-3p which is a shared potential biomarker identified by meta-analysis of breast, prostate and lung cancer data sets. Six different data sets representative of three different cancer types were analyzed. These data sets are pooled together to have a master metamiRNA list while getting rid of the platform differentiations between them. As a result, 24 common differentially expressed miRNAs are determined in which miR-145-3p has the topmost rank. To mimic in vivo cancer microenvironment, hypoxia and serum deprivation were used to induce metastasis in breast (MCF-7, MDA-MB-231, MDA-MB-453), prostate (PC3, LNCaP, DU145), lung (A549, NCIH82,) cancer cell lines and noncancerous cell lines of the coresponding tissues (MCF10A, RWPE-1, MRC-5). miR-145-3p expression levels were determined by qRT-PCR. It has been shown that it is down regulated by the induction of metastasis in cancer cell lines while it is up regulated in normal cell lines to suppress the tumor formation. As a conclusion, as representing the same results in three different cancer cell types, miR-145-3p will be a promising biomarker to follow up its expression to detect cancer metastasis