Stem Cells in Clinical Trials on Neurological Disorders: Trends in Stem Cells Origins, Indications, and Status of the Clinical Trials.

Neurological diseases can significantly reduce the quality and duration of life. Stem cells provide a promising solution, not only due to their regenerative features but also for a variety of other functions, including reducing inflammation and promoting angiogenesis. Although only hematopoietic cells have been approved by the FDA so far, the number of trials continues to expand. We analyzed 492 clinical trials and illustrate the trends in stem cells origins, indications, and phase and status of the clinical trials. The most common neurological disorders treated with stem cells were injuries of brain, spinal cord, and peripheral nerves (14%), stroke (13%), multiple sclerosis (12%), and brain tumors (11%). Mesenchymal stem cells dominated (83%) although the choice of stem cells was highly dependent on the neurological disorder. Of the 492 trials, only two trials have reached phase 4, with most of all other trials being in phases 1 or 2, or transitioning between them (83%). Based on a comparison of the obtained results with similar works and further analysis of the literature, we discuss some of the challenges and future directions of stem cell therapies in the treatment of neurological diseases.

Exploring dendritic cell subtypes in cancer immunotherapy: unraveling the role of mature regulatory dendritic cells.

Dendritic cells (DCs) possess a specialized function in presenting antigens and play pivotal roles in both innate and adaptive immune responses. Their ability to cross-present antigens from tumor cells to naïve T cells is instrumental in generating specific T-cell-mediated antitumor responses, crucial for controlling tumor growth and preventing tumor cell dissemination. However, within a tumor immune microenvironment (TIME), the functions of DCs can be significantly compromised. This review focuses on the profile, function, and activation of DCs, leveraging recent studies that reveal insights into their phenotype acquisition, transcriptional state, and functional programs through single-cell RNA sequence (scRNA-seq) analysis. Additionally, the therapeutic potential of DC-mediated tumor antigen sensing in priming antitumor immunity is discussed.

The exposure to UV filters: Prevalence, effects, possible molecular mechanisms of action and interactions within mixtures.

Substances that can absorb sunlight and harmful UV radiation such as organic UV filters are widely used in cosmetics and other personal care products. Since humans use a wide variety of chemicals for multiple purposes it is common for UV filters to co-occur with other substances either in human originating specimens or in the environment. There is increasing interest in understanding such co-occurrence in form of potential synergy, antagonist, or additive effects of biological systems. This review focuses on the collection of data about the simultaneous occurrence of UV filters oxybenzone (OXYB), ethylexyl-methoxycinnamate (EMC) and 4-methylbenzylidene camphor (4-MBC) as well as other classes of chemicals (such as pesticides, bisphenols, and parabens) to understand better any such interactions considering synergy, additive effect and antagonism. Our analysis identified >20 different confirmed synergies in 11 papers involving 16 compounds. We also highlight pathways (such as transcriptional activation of estrogen receptor, promotion of estradiol synthesis, hypothalamic-pituitary-gonadal (HPG) axis, and upregulation of thyroid-hormone synthesis) and proteins (such as Membrane Associated Progesterone Receptor (MAPR), cytochrome P450, and heat shock protein 70 (Hsp70)) that can act as important key nodes for such potential interactions. This article aims to provide insight into the molecular mechanisms on how commonly used UV filters act and may interact with other chemicals.

The effect of sunscreen 4-methylbenzylidene camphor in different and reproductive models, its bioaccumulation and molecular effects on ligand-receptor interaction, and protein expression.

4-Methylbenzylidene camphor (4-MBC) is a photo-absorbing UV filter prevalently used in cosmetics, which can be absorbed into circulation and cause systemic effects. 4-MBC is continued to be released in the environment despite the growing knowledge about its bioaccumulation and endocrine disrupting effects. Previous reviews have mentioned UV-filter together but this review considers 4-MBC alone, due to its prevalence and concerning health effects. This review considers 4-MBC's potential effects on human health regarding systemic and molecular effects, with the main focus on reproduction. Also, the potential bioaccumulation and interactions with receptor systems such as the oestrogen receptors ß and α, and progesterone receptor are covered. Additionally, previous studies about 4-MBC's effects on mRNA and protein expression, especially in the prostate and the brain are analysed. Furthermore, 4-MBC is reported to act with inflammatory pathways by activating p38 MAPK and NF-κB, leading to the production of inflammatory TNF-α and IL-6. 4-MBC was also found to induce apoptosis and inhibit cell proliferation and DNA repair. In conclusion, 4-MBC has wide-ranging effects in many different models interacting with multiple pathways causing long-term effects even at low doses and this knowledge can guide governmental risk assessment, regulation divisions and chemical industries.

Neoantigen Vaccines; Clinical Trials, Classes, Indications, Adjuvants and Combinatorial Treatments.

Personalized neoantigen vaccines are a highly specific cancer treatment designed to induce a robust cytotoxic T-cell attack against a patient's cancer antigens. In this study, we searched ClinicalTrials.gov for neoantigen vaccine clinical trials and systematically analyzed them, a total of 147 trials. Peptide vaccines are the largest neoantigen vaccine type, comprising up to 41% of the clinical trials. However, mRNA vaccines are a growing neoantigen vaccine group, especially in the most recent clinical trials. The most common cancer types in the clinical trials are glioma, lung cancer, and malignant melanoma, being seen in more than half of the clinical trials. Small-cell lung cancer and non-small-cell lung cancer are the largest individual cancer types. According to the results from the clinical trials, neoantigen vaccines work best when combined with other cancer treatments, and popular combination treatments include immune checkpoint inhibitors, chemotherapy, and radiation therapy. Additionally, half of the clinical trials combined neoantigen vaccines with an adjuvant to boost the immune effects, with poly-ICLC being the most recurrent adjuvant choice. This study clarifies the rapid clinical trial development of personalized neoantigen vaccines as an emerging class of cancer treatment with increasingly diversified opportunities in classes, indications, and combinatorial treatments.

Role of the Synergistic Interactions of Environmental Pollutants in the Development of Cancer.

There is a growing awareness that the large number of environmental pollutants we are exposed to on a daily basis are causing major health problems. Compared to traditional studies that focus on individual pollutants, there are relatively few studies on how pollutants mixtures interact. Several studies have reported a relationship between environmental pollutants and the development of cancer, even when pollutant levels are below toxicity reference values. The possibility of synergistic interactions between different pollutants could explain how even low concentrations can cause major health problems. These intricate that molecular interactions can occur through a wide variety of mechanisms, and our understanding of the physiological effects of mixtures is still limited. The purpose of this paper is to discuss recent reports that address possible synergistic interactions between different types of environmental pollutants that could promote cancer development. Our literature studies suggest that key biological pathways are frequently implicated in such processes. These include increased production of reactive oxygen species, activation by cytochrome P450, and aryl hydrocarbon receptor signaling, among others. We discuss the need to understand individual pathological vulnerability not only in relation to basic genetics and gene expression, but also in terms of measurable exposure to contaminants. We also mention the need for significant improvements in future studies using a multitude of disciplines, such as the development of high-throughput study models, better tools for quantifying pollutants in cancer patients, innovative pharmacological and toxicological studies, and high-efficiency computer analysis, which allow us to analyze the molecular mechanisms of mixtures.

Child sexual abuse - Initial suspicion and legal outcome.

OBJECTIVES: To evaluate the association of primary reason to suspect child sexual abuse with the legal end-point in medically examined, police reported cases. STUDY DESIGN: Observational post hoc analysis of retrospective review of records of 155 medically examined, police reported alleged child sexual abuse (CSA) cases during 2001-2009. Primary referral indications for medical examinations or criminal investigations were analyzed with an end-point in the legal process. The data consists of official investigation documents from University Hospital records, police, crime laboratories, state prosecutor, and courts of Law. RESULTS: The median age of the children was 7.1 years (range 11 months-17.5 years) at the time when suspicion of sexual abuse was reported to police. Conviction of the alleged perpetrator was significantly more likely in cases where the child's disclosure was the reason for the initial suspicion of CSA, compared to cases with referrals for "suspicious circumstances" (39/92, 42.4% vs. 7/37, 19%, p<0.001). In 92 (59.5%) cases the initial suspicion of CSA arose from child's disclosure. The forensic interviewer's report supported more likely CSA allegations where the suspicion of CSA arose by child's clear, detailed and credible disclosure of what had happened, compared to the other initial reasons of suspicion (35/61, 57.4% vs. 13/42, 31.0%, p=0.001). In child's age category of 4-9 years conviction was significantly more likely where the initial suspicion of CSA arose with child's disclosure, compared to other reasons of suspicion (21.45, 46.7% vs. 5/27, 16.7%, p=0.001). No association was found regarding to whom the initial suspicion of CSA arose and legal outcome. Forensic interviewer's report supported the allegation of CSA more often if the suspicion was arose first to a neutral person (p=0.019). Legal outcome of conviction was associated with child's disclosure of perpetrator's physical contact regardless of how the suspicion arose (45/99, 45.5% vs. 10/46, 21.7%, p<0.001). CONCLUSION: The reason which initially arise a suspicion of child sexual abuse plays an important role in the criminal investigation. Initial suspicion of CSA by child's disclosure, an eyewitness or objective material may lead to higher conviction rates. If a concerning physical symptom or finding arise the suspicion of CSA, referral to expert consultation is recommended to prevent unnecessary allegations and investigations. Other possible differential diagnostic medical conditions need to be evaluated. Furthermore, when child's disclosure arise a suspicion of CSA, it needs to be thoroughly investigated, regardless to whom the child discloses to.

Child sexual abuse--Medical statement conclusions in criminal legal process.

OBJECTIVES: To evaluate medical statement conclusions in the criminal-legal process in suspected cases of child sexual abuse (CSA). STUDY DESIGN: An observational study of a random sample of 130 medically examined, police reported CSA suspected cases during 2001-2009. Medical statements were evaluated and their conclusions were analyzed with an end-point in the legal process. The data consists of official investigation documents from the University Hospital records, the Police, crime laboratories, the State Prosecutor, and the Courts of Law. RESULTS: The median age of the children was 5.3 years (range 11 months-17.3 years) at the time of the suspected sexual abuse. In most cases (76.2%, 99/130) medical statement conclusions neither supported nor excluded the suspicion of CSA. Twenty-one (16.2%) medical statements supported and in 10 cases (7.7%) the conclusion did not support the suspected CSA. Of the suspected CSA cases a hundred (76.9%) proceeded to the Prosecutor. The charge filing rate was 41.5% (54/130). The final conviction rate was 30.8% (40/130) and 74% in the charged cases. Medical statements were mentioned as evidence in the Prosecutor's decision to file charges in 18 (33.3%) of suspected CSA cases and in 15 (36%) of verdicts. A child's clear disclosure of CSA (p<0.001) and medical statements (p=0.037) had a significant role in decision making on convictions. CONCLUSION: In medical statement conclusions, physical findings with proper documentation and interpretation are needed to avoid misunderstandings in the legal process. The present study supports a routine medical statement peer review to minimize the risk of neglect caused by lack of knowledge among authorities working with sexually abused children.