Immune checkpoint inhibitors, namely anti-CTLA-4, anti-PD-1 and anti-PD-L1 monoclonal antibodies, have emerged in the last decade as a novel form of cancer treatment, promoting increased survival in patients. As they tamper with the immune response in order to destroy malignant cells, a new type of adverse reactions has emerged, known as immune-related adverse events (irAEs), which frequently target the endocrine system, especially the thyroid and hypophysis. Thyroid irAEs include hyperthyroidism, thyrotoxicosis, hypothyroidism and a possibly life-threatening condition known as the “thyroid storm”. Early prediction of occurrence and detection of the thyroid irAEs should be a priority for the clinician, in order to avoid critical situations. Moreover, they are recently considered both a prognostic marker and a means of overseeing treatment response, since they indicate an efficient activation of the immune system. Therefore, a multidisciplinary approach including both oncologists and endocrinologists is recommended when immune checkpoint inhibitors are used in the clinic.

Cancer is a leading cause of death worldwide, with increasing numbers of new cases each year. For the vast majority of cancer patients, surgery is the most effective procedure for the complete removal of the malignant tissue. However, relapse due to the incomplete resection of the tumor occurs very often, as the surgeon must rely primarily on visual and tactile feedback. Intraoperative near-infrared imaging with pafolacianine is a newly developed technology designed for cancer detection during surgery, which has been proven to show excellent results in terms of safety and efficacy. Therefore, pafolacianine was approved by the U.S. Food and Drug Administration (FDA) on 29 November 2021, as an additional approach that can be used to identify malignant lesions and to ensure the total resection of the tumors in ovarian cancer patients. Currently, various studies have demonstrated the positive effects of pafolacianine’s use in a wide variety of other malignancies, with promising results expected in further research. This review focuses on the applications of the FDA-approved pafolacianine for the accurate intraoperative detection of malignant tissues. The cancer-targeting fluorescent ligands can shift the paradigm of surgical oncology by enabling the visualization of cancer lesions that are difficult to detect by inspection or palpation. The enhanced detection and removal of hard-to-detect cancer tissues during surgery will lead to remarkable outcomes for cancer patients and society, specifically by decreasing the cancer relapse rate, increasing the life expectancy and quality of life, and decreasing future rates of hospitalization, interventions, and costs.

Human immunodeficiency virus (HIV) poses a major health problem around the globe, resulting in hundred-thousands of deaths from AIDS and over a million new infections annually. Although the standard treatment of HIV infection, antiretroviral therapy, has proven effective in preventing HIV transmission, it is unsuitable for worldwide use due to its substantial costs and frequent adverse effects. Besides promoting HIV/AIDS awareness through education, there is hardly an alternative for inhibiting the spread of the disease. One promising approach is the development of an HIV vaccine. Unfortunately, the high variability of envelope proteins from HIV subtypes, their frequency of mutation and the lack of fully understanding the mechanisms of protection against the virus constitute an obstacle for vaccine development. Efforts for developing successful anti-HIV vaccines have been underway for decades now, with little success. Lately, significant progress has been made in adopting the novel mRNA vaccine approach as an anti-HIV strategy. mRNA vaccines received a great thrust during the COVID-19 pandemic. Now, several mRNA-based HIV vaccines are undergoing clinical trials to evaluate their safety and efficacy. This review offers an overview of the pathogenesis and treatment of HIV / AIDS, previous efforts of HIV vaccine development and introduces mRNA vaccines as a promising and potential game changing platform for HIV vaccination.

DNA methylation is an essential epigenetic mechanism for regulation of gene expression, through which many physiological (X-chromosome inactivation, genetic imprinting, chromatin structure and miRNA regulation, genome defense, silencing of transposable elements) and pathological processes (cancer and repetitive sequences-associated diseases) are regulated. Nanopore sequencing has emerged as a novel technique that can analyze long strands of DNA (long-read sequencing) without chemically treating the DNA. Interestingly, nanopore sequencing can also extract epigenetic status of the nucleotides (including both 5-Methylcytosine and 5-hydroxyMethylcytosine), and a large variety of bioinformatic tools have been developed for improving its detection properties. Out of all genomic regions, long read sequencing provides advantages in studying repetitive elements, which are difficult to characterize through other sequencing methods. Transposable elements are repetitive regions of the genome that are silenced and usually display high levels of DNA methylation. Their demethylation and activation have been observed in many cancers. Due to their repetitive nature, it is challenging to accurately estimate DNA methylation levels within transposable elements using short sequencing technologies. The advantage to sequence native DNA (without PCR amplification biases or harsh bisulfite treatment) and long and ultra long reads coupled with epigenetic states of the DNA allows to accurately estimate DNA methylation levels in transposable elements. This is a big step forward for epigenomic studies, and unsolved questions regarding gene expression and transposable elements silencing through DNA methylation can now be answered.

Extracellular collagen remodeling is one of the central mechanisms responsible for the structural and compositional coherence of myocardium in patients undergoing myocardial infarction (MI). Activated primary cardiac fibroblasts following myocardial infarction are extensively investigated to establish anti-fibrotic therapies to improve left ventricular remodeling. To systematically assess vitamin C functions as a potential modulator involved in collagen fibrillogenesis in an in vitro model mimicking heart tissue healing after MI. Mouse primary cardiac fibroblasts were isolated from wild-type C57BL/6 mice and cultured under normal and profibrotic (hypoxic + transforming growth factor beta 1) conditions on freshly prepared coatings mimicking extracellular matrix (ECM) remodeling during healing after an MI. At 10 μg/mL, vitamin C reprogramed the respiratory mitochondrial metabolism, which is effectively associated with a more increased accumulation of intracellular reactive oxygen species (iROS) than the number of those generated by mitochondrial reactive oxygen species (mROS). The mRNA/protein expression of subtypes I, III collagen, and fibroblasts differentiations markers were upregulated over time, particularly in the presence of vitamin C. The collagen substrate potentiated the modulator role of vitamin C in reinforcing the structure of types I and III collagen synthesis by reducing collagen V expression in a timely manner, which is important in the initiation of fibrillogenesis. Altogether, our study evidenced the synergistic function of vitamin C at an optimum dose on maintaining the equilibrium functionality of radical scavenger and gene transcription, which are important in the initial phases after healing after an MI, while modulating the synthesis of de novo collagen fibrils, which is important in the final stage of tissue healing.

Myocardial infarction is remains the leading cause of death in developed countries. Recent data show that the composition of the extracellular matrix might differ despite similar heart function and infarction sizes. Because collagen is the main component of the extracellular matrix, we hypothesized that changes in inflammatory cell recruitment influence the synthesis of different collagen subtypes in myofibroblasts, thus changing the composition of the scar. We found that neutrophils sustain the proliferation of fibroblasts, remodeling, differentiation, migration and inflammation, predominantly by IL-1 and PPARγ pathways (n = 3). They also significantly inhibit the mRNA expression of fibrillar collagen, maintaining a reduced stiffness in isolated myofibroblasts (n = 4–5). Reducing the neutrophil infiltration in CCR1^−/− resulted in increased mRNA expression of collagen 11, moderate expression of collagen 19 and low expression of collagen 13 and 26 in the scar 4 weeks post infarction compared with other groups (n = 3). Mononuclear cells increased the synthesis of all collagen subtypes and upregulated the NF-kB, angiotensin II and PPARδ pathways (n = 3). They increased the synthesis of collagen subtypes 1, 3, 5, 16 and 23 but reduced the expression of collagens 5 and 16 (n = 3). CCR2^−/− scar tissue showed higher levels of collagen 13 (n = 3), in association with a significant reduction in stiffness (n = 4–5). Upregulation of the inflammation-related genes in myofibroblasts mostly modulated the fibrillar collagen subtypes, with less effect on the FACIT, network-forming and globular subtypes (n = 3). The upregulation of proliferation and differentiation genes in myofibroblasts seemed to be associated only with the fibrillar collagen subtype, whereas angiogenesis-related genes are associated with fibrillar, network-forming and multiplexin subtypes. In conclusion, although we intend for our findings to deepen the understanding of the mechanism of healing after myocardial infarction and scar formation, the process of collagen synthesis is highly complex, and further intensive investigation is needed to put together all the missing puzzle pieces in this still incipient knowledge process.