Periprosthetic joint infection (PJI) is a significant issue in orthopedic surgery. Urinary tract infections (UTIs) and asymptomatic bacteriuria (ASB) have been identified as potential causes of PJI; however, evidence is inconclusive. Understanding these relationships is critical for improving therapy and patient outcomes. A systematic review was performed by conducting searches from PubMed, EBSCO, ProQuest, and manual searching with adherence to the Preferred Reporting Items for Systematic Review and Meta-Analysis 2020 guideline. Studies that reported UTI/ASB and PJI were included. Meta-analysis was conducted using a random-effects model using RevMan 5.4 software. A total of 14 studies were included with UTIs and ASB showed an overall association with increased risk of PJI (odds ratio [OR]: 1.84, 95% confidence interval [CI]: 1.14-2.99, P = 0.01). However, subgroup analysis for UTIs and ASB was not significant. Further analysis of UTIs in total hip arthroplasty (THA) surgery showed a significant association (OR: 1.76, 95% CI: 1.57-1.96) with PJI. Preoperative UTIs timing between 0 and 2 weeks before surgery showed an increased risk of PJI (OR: 1.45, 95% CI: 1.35-1.55). Antibiotic treatment in ASB did not significantly impact PJI rates. Urine and PJI sample cultures in four studies showed no correlation of microorganisms between the two sites. According to recent evidence, a statistically significant association was found between UTIs and PJI in patients who underwent THA surgery. However, ASB did not yield significant results in relation to PJI. These results should be supported by larger and well-designed studies to make proper clinical suggestion in future. For further research, it is recommended to adopt standardized criteria for outcome measurement and to involve larger sample sizes to enhance the reliability and generalizability of findings.
Chemokines are small, secreted cytokines crucial in the regulation of a variety of cell functions. The binding of chemokine C-X-C motif chemokine ligand 12 (CXCL12) (stromal cell-derived factor 1) to a G-protein-coupled receptor C-X-C chemokine receptor type 4 (CXCR4) triggers downstream signaling pathways with effects on cell survival, proliferation, chemotaxis, migration, and gene expression. Intensive and extensive investigations have provided evidence suggesting that the CXCL12-CXCR4 axis plays a pivotal role in tumor development, survival, angiogenesis, metastasis, as well as in creating tumor microenvironment, thus implying that this axis is a potential target for the development of cancer therapies. The structures of CXCL12 and CXCR4 have been resolved with experimental methods such as X-ray crystallography, NMR, or cryo-EM. Therefore, it is possible to apply structure-based computational approaches to discover, design, and modify therapeutic molecules for cancer treatments. Here, we summarize the current understanding of the roles played by the CXCL12-CXCR4 signaling axis in cellular functions linking to cancer progression and metastasis. This review also provides an introduction to protein structures of CXCL12 and CXCR4 and the application of computer simulation and analysis in understanding CXCR4 activation and antagonist binding. Furthermore, examples of strategies and current progress in CXCL12-CXCR4 axis-targeted development of therapeutic anticancer inhibitors are discussed.
Extracellular vesicles (EVs) have emerged as key players in intercellular communication, disease pathology, and therapeutic innovation. Initially overlooked as cellular debris, EVs are now recognized as vital mediators of cell-to-cell communication, ferrying a cargo of proteins, nucleic acids, and lipids, providing cellular resilience in response to stresses. This review provides a comprehensive overview of EVs, focusing on their role as biomarkers in disease diagnosis, their functional significance in physiological and pathological processes, and the potential of bioengineering for therapeutic applications. EVs offer a promising avenue for noninvasive disease diagnosis and monitoring, reflecting the physiological state of originating cells. Their diagnostic potential spans a spectrum of diseases, including cancer, cardiovascular disorders, neurodegenerative diseases, and infectious diseases. Moreover, their presence in bodily fluids such as blood, urine, and cerebrospinal fluid enhances their diagnostic utility, presenting advantages over traditional methods. Beyond diagnostics, EVs mediate crucial roles in intercellular communication, facilitating the transfer of bioactive molecules between cells. This communication modulates various physiological processes such as tissue regeneration, immune modulation, and neuronal communication. Dysregulation of EV-mediated communication is implicated in diseases such as cancer, immune disorders, and neurodegenerative diseases, highlighting their therapeutic potential. Bioengineering techniques offer avenues for manipulating EVs for therapeutic applications, from isolation and purification to engineering cargo and targeted delivery systems. These approaches hold promise for developing novel therapeutics tailored to specific diseases, revolutionizing personalized medicine. However, challenges such as standardization, scalability, and regulatory approval need addressing for successful clinical translation. Overall, EVs represent a dynamic frontier in biomedical research with vast potential for diagnostics, therapeutics, and personalized medicine.