Diagnostic biomarkers for active tuberculosis: progress and challenges.

Tuberculosis (TB) is a leading cause of morbidity and mortality from a single infectious agent, despite being preventable and curable. Early and accurate diagnosis of active TB is critical to both enhance patient care, improve patient outcomes, and break Mycobacterium tuberculosis (Mtb) transmission cycles. In 2020 an estimated 9.9 million people fell ill from Mtb, but only a little over half (5.8 million) received an active TB diagnosis and treatment. The World Health Organization has proposed target product profiles for biomarker- or biosignature-based diagnostics using point-of-care tests from easily accessible specimens such as urine or blood. Here we review and summarize progress made in the development of pathogen- and host-based biomarkers for active TB diagnosis. We describe several unique patient populations that have posed challenges to development of a universal diagnostic TB biomarker, such as people living with HIV, extrapulmonary TB, and children. We also review additional limitations to widespread validation and utilization of published biomarkers. We conclude with proposed solutions to enhance TB diagnostic biomarker validation and uptake.

The Emerging Role of PIWI-Interacting RNAs (piRNAs) in Gastrointestinal Cancers: An Updated Perspective.

Gastrointestinal (GI) cancers produce ~3.4 million related deaths worldwide, comprising 35% of all cancer-related deaths. The high mortality among GI cancers is due to late diagnosis, the presence of metastasis and drug resistance development. Additionally, current clinical markers do not adequately guide patient management, thereby new and more reliable biomarkers and therapeutic targets are still needed for these diseases. RNA-seq technology has allowed the discovery of new types of RNA transcripts including PIWI-interacting RNAs (piRNAs), which have particular characteristics that enable these molecules to act via diverse molecular mechanisms for regulating gene expression. Cumulative evidence has described the potential role of piRNAs in the development of several tumor types as a likely explanation for certain genomic abnormalities and signaling pathways' deregulations observed in cancer. In addition, these piRNAs might be also proposed as promising diagnostic or prognostic biomarkers or as potential therapeutic targets in malignancies. This review describes important topics about piRNAs including their molecular characteristics, biosynthesis processes, gene expression silencing mechanisms, and the manner in which these transcripts have been studied in samples and cell lines of GI cancers to elucidate their implications in these diseases. Moreover, this article discusses the potential clinical usefulness of piRNAs as biomarkers and therapeutic targets in GI cancers.

Sepsis-induced acute kidney injury: biomarkers for diagnosis

Sepsis is a major global health problem leading to the increased incidence of death in intensive care units. In recent years, despite technological advances, the number of cases has grown significantly. Among the main complications presented by septic patients, acute renal dysfunction is largely responsible for the high mortality rate. Initially, the reduction of renal function is associated with focal tubular injury with preserved glomerular morphology and systemic hemodynamic alterations. During sepsis development, the progressive decrease in urinary volume and reduction of the glomerular filtration rate associated with increased serum levels of urea and creatinine are considered classic markers of severe kidney injury. Despite the valuable role of these serum markers regarding renal function, these data provide an incomplete scenario of the patient, since many renal disorders may occur in individuals with increased plasma concentrations of urea and creatinine. Taking into account the important role of systemic inflammatory processes in the development of acute kidney injury induced by sepsis, the search for new markers presenting high sensitivity and specificity capable of detecting early renal injury is still necessary. Thus, the present review summarizes important aspects of pathophysiology of acute kidney dysfunction induced by sepsis and presents an updated view of possible new biomarkers associated with the development of acute kidney injury. Understanding these markers allows important advances leading to new therapeutic approaches, indicating a new horizon in the diagnosis and treatment of acute kidney injury in sepsis

Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

The aim of the present study was to identify specific markers that mirror liver fibrosis progression as an alternative to biopsy when biopsy is contraindicated, especially in children. After liver biopsies were performed, serum samples from 30 hepatitis C virus (HCV) paediatric patients (8-14 years) were analysed and compared with samples from 30 healthy subjects. All subjects were tested for the presence of serum anti-HCV antibodies. Direct biomarkers for liver fibrosis, including transforming growth factor-β1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), hyaluronic acid (HA), procollagen type III amino-terminal peptide (PIIINP) and osteopontin (OPN), were measured. The indirect biomarkers aspartate and alanine aminotransferases, albumin and bilirubin were also tested. The results revealed a significant increase in the serum marker levels in HCV-infected children compared with the healthy group, whereas albumin levels exhibited a significant decrease. Significantly higher levels of PIIINP, TIMP-1, OPN and HA were detected in HCV-infected children with moderate to severe fibrosis compared with children with mild fibrosis (p < 0.05). The diagnostic accuracy of these direct biomarkers, represented by sensitivity, specificity and positive predictive value, emphasises the utility of PIIINP, TIMP-1, OPN and HA as indicators of liver fibrosis among HCV-infected children.