New Genetic Variations in RNA-binding Protein Gene and Breast Cancer Risk: A Case-Control Study.

Background: LIN28, a highly conserved RNA-binding protein, regulate a wide variety of post-transcriptional cellular processes. The current study aimed to identify genetic variants of five single nucleotide polymorphisms (SNPs) in the LIN28B gene (rs221634, rs22163, rs314276, rs9404590, and rs12194974) and their association with Breast cancer.

Method: 220 patients and 230 controls were genotyped by the RFLP assay for Lin28B gene variants.

Pharmacoinformatics-based screening and construction of a neutralizing anti-SARS-CoV-2 camelidae nanobody drug conjugate.

Nanobodies or variable antigen-binding domains (VH) derived from heavy chain-only antibodies (HcAb) occurring in the Camelidae family offer certain superior physicochemical characteristics like enhanced stability, solubility, and low immunogenicity compared to conventional antibodies. Their efficient antigen-binding capabilities make them a preferred choice for next-generation small biologics. In the present work, we design an anti-SARS-CoV-2 bi-paratopic nanobody drug conjugate by screening a nanobody database.

In silico screening and immunogenic features of putative tick cement protein PA107 from Ixodes ricinus tick.

Tick salivary proteins are crucial for efficient and successful tick feeding. Most of them are still uncharacterized, especially those involved in the formation of tick cement. Tick salivary protein PA107 is a putative cement protein, which is transcribed in salivary glands during the initial phase of tick feeding.

Cancer risk in carriers of TP53 germline variants grouped into different functional categories.

Li-Fraumeni syndrome is a cancer predisposition syndrome caused by pathogenic TP53 germline variants and associated with a high lifelong cancer risk. We analysed the German LFS registry that contains data on 304 individuals. Cancer phenotypes were correlated with variants grouped according to their ability to transactivate target genes in a yeast assay using a traditional (non-functional, partially-functional) and a novel (clusters A, B, C) classification of variants into different groups.

tRNA m1A modification regulates cholesterol biosynthesis to promote antitumor immunity of CD8+ T cells.

Activation of CD8+ T cells necessitates rapid metabolic reprogramming to fulfill the substantial biosynthetic demands of effector functions. However, the posttranscriptional mechanisms underpinning this process remain obscure. The transfer RNA (tRNA) N1-methyladenine (m1A) modification, essential for tRNA stability and protein translation, has an undefined physiological function in CD8+ T cells, particularly in antitumor responses.

SIRT4 Protects Retina Against Excitotoxic Injury by Promoting OPA1-Mediated Müller Glial Cell Mitochondrial Fusion and GLAST Expression.

Purpose: This study aimed to investigate the role of SIRT4 in retinal protection, specifically its ability to mitigate excitotoxic damage to Müller glial cells through the regulation of mitochondrial dynamics and glutamate transporters (GLASTs).

Methods: A model of retinal excitatory neurotoxicity was established in mice. Proteins related to mitochondrial dynamics, GLAST, and SIRT4 were analyzed on days 0, 1, 3, and 5 following toxic injury.

Temozolomide-Promoted MGMT Transcription Contributes to Chemoresistance by Activating the ERK Signalling Pathway in Malignant Melanoma.

Tumour cells possess a multitude of chemoresistance mechanisms, which could plausibly contribute to the ineffectiveness of chemotherapy. O-methylguanine-DNA methyltransferase (MGMT) is an important effector protein associated with Temozolomide (TMZ) resistance in various tumours. To some extent, the expression level of MGMT determines the sensitivity of cells to TMZ, but the mechanism of its expression regulation has not been fully elucidated.

Vacuolated Parabasal Cells in Papanicolaou Smears Are Cellular Changes Caused by Human Papillomavirus 16 Infection.

In cervical cancer screening, cytology is used as a triage test to refer high-risk human papillomavirus (HR-HPV)-positive women for colposcopy, but its accuracy is inadequate. The present study aimed to demonstrate that the presence of atypical cells with large vacuoles in the cytoplasm of parabasal cells, referred to as vacuolated parabasal cells (VPCs), which are observed in the Pap smears of HPV-positive women, is associated with specific HPV genotypes. Among 2175 patients, 310 with a single HR-HPV infection and cytological diagnosis of high-grade squamous intraepithelial lesions (HSIL) or atypical squamous cells not excluding HSIL (ASC-H) were included, of which 86 were infected with HPV16.

Improving the generalization of protein expression models with mechanistic sequence information.

The growing demand for biological products drives many efforts to maximize expression of heterologous proteins. Advances in high-throughput sequencing can produce data suitable for building sequence-to-expression models with machine learning. The most accurate models have been trained on one-hot encodings, a mechanism-agnostic representation of nucleotide sequences.

Prognostic signature based on mitochondria- and angiogenesis-related genes associated with immune microenvironment of multiple myeloma.

Introduction: Mitochondria and angiogenesis play key roles in multiple myeloma (MM) development, but their interrelated genes affecting MM prognosis are under-studied.

Methods: We analyzed TCGA_MMRF and GSE4581 datasets to identify four genes - CCNB1, CDC25C, HSP90AA1, and PARP1 - that significantly correlate with MM prognosis, with high expression indicating poor outcomes.

Results: A prognostic signature based on these genes stratified patients into high- and low-risk groups, with the latter showing better survival.

Model construction and clinical therapeutic potential of engineered cardiac organoids for cardiovascular diseases.

Cardiovascular diseases cause significant morbidity and mortality worldwide. Engineered cardiac organoids are being developed and used to replicate cardiac tissues supporting cardiac morphogenesis and development. These organoids have applications in drug screening, cardiac disease models and regenerative medicine.

Multiomics characterization of breast angiosarcoma from an Asian cohort reveals enrichment for angiogenesis signaling pathway and tumor-infiltrating macrophages.

Introduction: Recent epidemiological data suggests a rising incidence of breast angiosarcoma (AS-B) in the Western population, with over two-thirds related to irradiation or chronic lymphedema. However, unlike head and neck angiosarcoma (AS-HN), AS-B disease characteristics in Asia remain unclear.

Methods: We examined clinical patterns of angiosarcoma patients (n = 176) seen in an Asiantertiary cancer center from 1999 to 2021, and specifically investigated the molecular and immune features of AS-B in comparison to AS-HN.

DNA vaccines as promising immuno-therapeutics against cancer: a new insight.

Cancer is one of the leading causes of mortality around the world and most of our conventional treatments are not efficient enough to combat this deadly disease. Harnessing the power of the immune system to target cancer cells is one of the most appealing methods for cancer therapy. Nucleotide-based cancer vaccines, especially deoxyribonucleic acid (DNA) cancer vaccines are viable novel cancer treatments that have recently garnered significant attention.

Early transcriptomic changes at the skin interface during Powassan virus transmission by ticks.

Introduction: Powassan virus (POWV), a vector-borne pathogen transmitted by ticks in North America, is the causative agent of Powassan encephalitis. As obligate hematophagous organisms, ticks transmit pathogens like POWV at the tick bite site, specifically during the initial stages of feeding. Tick feeding and salivary factors modulate the host's immunological responses, facilitating blood feeding and pathogen transmission.

Construction of an anaplastic thyroid cancer stratification signature to guide immune therapy selection and validation of the pivotal gene HLF through experiments.

Introduction: While most thyroid cancer patients have a favorable prognosis, anaplastic thyroid carcinoma (ATC) remains a particularly aggressive form with a median survival time of just five months. Conventional therapies offer limited benefits for this type of thyroid cancer. Our study aims to identify ATC patients who might bene t from immunotherapy.

Tracing TMEM106B fibril deposition in aging and Parkinson's disease with dementia brains.

Transmembrane protein 106B (TMEM106B), previously identified as a risk factor in frontotemporal lobar degeneration, has recently been detected to form fibrillar aggregates in the brains of patients with various neurodegenerative diseases (NDs) and normal elders. While the specifics of when and where TMEM106B fibrils accumulate in human brains, as well as their connection to aging and disease progression, remain poorly understood. Here, we identified an antibody (NBP1-91311) that directly binds to TMEM106B fibrils extracted from the brain and to Thioflavin S-positive TMEM106B fibrillar aggregates in brain sections.

Racial Disparities in Time to Huntington Disease Diagnosis in North America: An ENROLL-HD Analysis.

Background And Objectives: There are well-documented racial and ethnic disparities in access to neurologic care and disease-specific outcomes. Although contemporary clinical and neurogenetic understanding of Huntington disease (HD) is thanks to a decades-long study of a Venezuelan cohort, there are a limited number of studies that have evaluated racial and ethnic disparities in HD. The goal of this study was to evaluate disparities in time from symptom onset to time of diagnosis of HD.

Metabolomics insights into doxorubicin and 5-fluorouracil combination therapy in triple-negative breast cancer: a xenograft mouse model study.

Background: Breast cancer is one of the most prevalent malignancies and a leading cause of death among women worldwide. Among its subtypes, triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive behavior and limited treatment options. This study aimed to investigate the effects of doxorubicin (DOX) and 5-fluorouracil (5-FU) as monotherapies and in combination using an established MDA-MB-231 xenograft model in female BALB/C nude mice employing advanced metabolomics analysis to identify molecular alterations induced by these treatments.

Uncovering somatic mosaic variants of -related overgrowth disorders - three cases with different clinical presentations.

Introduction: related disorders (PRD, OMIM: *171834) are genetic disorders resulting from pathogenic somatic mosaic variants in the gene, which encodes a protein crucial for regulating cell growth and division. PRD typically manifest during the post-zygotic phase, leading to a broad spectrum of overgrowth and vascular malformations affecting various body regions.

Methods: Conventional diagnostic methods struggle to detect and confirm pathogenic PIK3CA gene variants due to the mosaic nature of these disorders and the limited accessibility of affected tissues.

Unlocking the Potential of miRNAs in Sepsis Diagnosis and Prognosis: From Pathophysiology to Precision Medicine.

The clinical syndrome appears as a dysregulated host response to infection that results in life-threatening organ dysfunction known as Sepsis. Sepsis is a serious public health concern where for every five deaths in ICU there is one patient who dies with sepsis worldwide. Sepsis is featured as unbalanced inflammation and immunosuppression which is sustained and profound, increasing patient susceptibility to secondary infections and mortality.