Association between Ureaplasma urealyticum colonization and bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis.

Background: Bronchopulmonary dysplasia (BPD) is the most prevalent chronic lung disease in preterm infants. Studies have shown that Ureaplasma urealyticum (UU) infection is linked to its pathogenesis. However, it remains controversial whether UU colonization in preterm infants increases the risk of developing BPD. Objective: This study aimed to conduct a systematic review and meta-analysis to summarize the correlation between UU and BPD. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, Wanfang Database, Chinese National Knowledge Infrastructure Database, Chinese Science and Technique Journal Database, and the China Biology Medicine disc from their inception to March 15, 2024. We included cohort and case-control studies investigating the association between UU infections and BPD in preterm infants, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Newcastle-Ottawa Scale was used for quality assessment. The outcome was defined as the continued need for oxygen or respiratory support at 28 days after birth (BPD28) or at 36 weeks postmenstrual age (BPD36). Considering the potential publication bias in observational studies, we used a random-effects meta-analysis model, assessed heterogeneity (I2), performed subgroup analyses, evaluated publication bias, and graded the quality of evidence. Results: The meta-analysis included 36 cohort studies encompassing 5,991 participants. Among these, 20 reported on BPD28, 13 on BPD36, and 3 on both. The results indicated a significant association between UU colonization and BPD28 (odds ratio (OR): 2.26, 95% confidence interval (CI): 1.78-2.85, P < 0.00001, 23 studies, very low certainty of evidence) and BPD36 (OR: 2.13, 95% CI: 1.47-3.07, P < 0.0001, 16 studies, very low certainty of evidence). Conclusion: There is a correlation between UU colonization and the development of BPD in preterm infants. Future research should prioritize well-designed, large-scale, high-quality randomized controlled trials (RCTs) to comprehensively assess the risk of BPD in neonates following UU infection and to provide stronger evidence for clinical screening and prevention strategies to improve the prognosis of affected newborns. Systematic Review Registration: https://www.crd.york.ac.uk/, identifier (CRD42024524846).

Colorectal cancer initiation: Understanding early-stage disease for intervention.

How tumors arise or the cause of precancerous lesions is a fundamental question in cancer biology. It is generally accepted that tumors originate from normal cells that undergo uncontrolled proliferation owing to genetic alterations. At the onset of adenoma formation, cancer driver mutations confer clonal growth advantage, enabling mutant cells to outcompete and eliminate the surrounding healthy cells. Hence, the development of precancerous lesions is not only attributed to the expansion of pre-malignant clones, but also relies on the relative fitness of mutated cells compared to the neighboring cells. Colorectal cancer (CRC) is an excellent model to investigate cancer origin as it follows a stereotypical process from mutant cell hyperplasia to adenoma formation and progression. Here, we review the evolving understanding of colonic tumor development, focusing on how cell intrinsic and extrinsic factors impact cell competition and the "clone war" between cancer-initiating cells and normal stem cells. We also discuss the promises and limitations of targeting cell competitiveness in cancer prevention and early intervention. The field of tumor initiation is currently in its infancy, elucidating the adenoma origin is crucial for designing effective prevention strategies and early treatments before cancer becomes incurable.

Targeting miRNAs associated with surface expression of death receptors to modulate TRAIL resistance in breast cancer.

Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is capable of inducing apoptosis upon engagement of its death receptors (DRs) 4 and 5. TRAIL therapy has garnered intense interest as one of the most promising agents for cancer therapy, for its selective induction of tumor-cell apoptosis while low toxicity to most normal cells. However, a variety of breast cancer cell lines could be resistant to TRAIL-induced apoptosis. Absence of DR4 and DR5 on the breast cancer cell surface has been proposed to be critically involved in resistance to TRAIL and its agonistic antibodies. Moreover, endocytosis and autophagy in breast cancer cells could induce TRAIL resistance through downregulation of surface DR4/5. MicroRNAs (miRNAs), as endogenously expressed small non-coding RNAs, function as regulators of gene expression and involve tremendous biological processes including drug resistance. In this review, we highlight recent advances in the functional role of miRNAs in endocytosis and autophagy pathways. This review aims to present that, through regulation of critical molecules involved in autophagy and endocytosis, miRNAs could lead to mislocalization of DR4/5 in breast cancer cells and therefore play an important role in TRAIL-mediated apoptosis and TRAIL resistance.