Nature Reviews Urology最新文献

A study in Proceedings of the National Academy of Sciences has elucidated the roles of the whey acidic protein four-disulfide core (WFDC) gene cluster in spermatogenesis and sperm function.

The fact that this reproductive-tract-specific cluster — comprising 11 genes in humans (SPINT3, WFDC6, EPPIN, WFDC8, WFDC9, WFDC10A, WFDC11, WFDC10B, WFDC13, SPINT4 and WFDC3) and 13 in rodents — is so well conserved across species suggests combined critical functions of the cluster.

Immune checkpoint inhibitor (ICI) efficacy in patients with metastatic castration-resistant prostate cancer (mCRPC) is hampered by resistance. Understanding the mechanisms underlying ICI resistance is crucial to improve therapeutic efficacy.

A new study published in Nature identified a distinct macrophage subset that shows increasing abundance as the disease progresses and that is responsible for immunotherapy resistance.

Prostate cancer is a multifactorial disease influenced by various molecular features. Over the past decades, epigenetics, which is the study of changes in gene expression without altering the DNA sequence, has been recognized as a major driver of this disease. In the past 50 years, advancements in technological tools to characterize the epigenome have highlighted crucial roles of epigenetic mechanisms throughout the entire spectrum of prostate cancer, from initiation to progression, including localized disease, metastatic dissemination, castration resistance and neuroendocrine transdifferentiation. Substantial advances in the understanding of epigenetic mechanisms in the pathophysiology of prostate cancer have been carried out, but translating preclinical achievements into clinical practice remains challenging. Ongoing research and biomarker-oriented clinical trials are expected to increase the likelihood of successfully integrating epigenetics into prostate cancer clinical management.

Kidney transplantation is a crucial treatment option for older adults (defined as ≥65 years old) with kidney failure, but the evaluation process for transplantation is often complex and burdensome, with many older adults not ultimately receiving a kidney.

In a study published in JAMA Internal Medicine, the authors explored the experiences of older adults and their families during the kidney transplant evaluation process. By using qualitative methods, including semi-structured interviews with 26 older adults and 7 family members, some dominant themes emerged, mostly related to the fact that the evaluation process is complex, lengthy and often leaves patients feeling responsible yet powerless about actively shaping this process.

New data show that bitter taste transduction has an essential role maintaining male reproductive health. This process is key in the inflammatory response to inhalable particulate matter and provides a mechanism by which exposure to particulate matter adversely affects male fertility. Bitter taste molecules could be potential targets for male infertility management.

A particulate matter exposure mouse model was established using intraperitoneal injection of ovalbumin (OVA) and subsequent aerosol inhalation of OVA. In OVA-exposed mice, testis weight, testis coefficient, seminiferous epithelium height, tubular diameter, number of maturing spermatids and Johnsen score were notably reduced and arrangement of spermatogenic cells was disordered. These effects were attenuated in mice who also received oral baicalin, a bitter compound.

The 2-year follow-up results of the OASIS trial, assessing the efficacy of the novel implantable tibial neuromodulation device Revi in treating urgency urinary incontinence (UUI), were published in The Journal of Urology.

The Revi device is powered by an external, battery-operated wearable, which eliminates the need for an implanted battery, in turn providing more freedom margin for patients over other implantable devices, which are associated with high rates of reintervention also due to battery replacement.

Heat shock protein 60 (HSP60), the main chaperone of the mitochondrial unfolded protein response, could be a potential therapeutic target in neuroendocrine prostate cancer (NEPC). Preclinical evidence shows that HSP60 inhibition reduces NEPC growth in vivo.

In the TRAMP mouse model, oxidative phosphorylation complex activity was dysfunctional in mitochondrial fractions from tumour samples. The mitochondrial unfolded protein response, assessed using HSP60 as a surrogate readout, was increased in several models of aggressive prostate cancer and patient sample datasets.

Pain related to percutaneous nephrolithotomy (PCNL) is multifactorial and poorly elucidated. However, understanding the pathophysiology of pain can enable a practical approach to pain management, which can be tailored to each patient. A number of potential mechanisms underlie pain perception in PCNL, and these mechanisms can be leveraged at various points on the perioperative care pathway. These interventions provide opportunities for modulation of pain associated with PCNL but must take into account various technical, pharmacological and patient-related considerations. Technical considerations include the influence of percutaneous access, stone removal and drainage techniques. Pharmacological aspects include the use of various analgesics and anaesthesia approaches. Patient factors include consideration of the biopsychosocial model in pain experience to understand each individual’s response to pain. By understanding the contemporary evidence surrounding the physiology of postoperative pain and identifying tangible intervention points, we can seek to mitigate postoperative pain in patients undergoing PCNL.

Spatial transcriptomics has emerged as a powerful tool for discerning the heterogeneity of the tumour microenvironment across various cancers, including renal cell carcinoma (RCC). Spatial transcriptomics-based studies conducted in clear-cell RCC (the only RCC subtype studied using this technique to date) have given insights into spatial interactions within this disease. These insights include the role of epithelial-to-mesenchymal transitioning, revealing proximity-dependent interactions between tumour cells, fibroblasts, interleukin-2-expressing macrophages and hyalinized regions. Investigations into metabolic programmes have shown high transcriptional heterogeneity within tumours, with a tendency of increased metabolic activity towards the tumour centre. T cell infiltration has been shown to be independent of neoantigen burden, although T cell activity correlates with both metabolic states and various transcripts expressed by tumour cells, fibroblasts and monocytes. The role of tertiary lymphoid structures in both plasma cell maturation and their infiltration of the tumour has been shown through tracks of fibroblasts. Collectively, these findings indicate the potential of spatial transcriptomics to reveal predictive spatial features, supporting its promise in the development of biomarkers for clear-cell RCC management.

Multiple conditions can cause hypoxia in the testis, including exposure to high altitude, sleep apnoea, testicular torsion and varicocele. Varicocele accounts for up to 44% of instances of primary infertility, but the cumulative contribution of hypoxic conditions to male infertility is undefined. Results of controlled hypobaric hypoxia studies have demonstrated a substantial detrimental effect of short-term and long-term exposures on sperm; however, downstream effects on embryo development and offspring health are less well understood. Hypoxia can have direct and indirect effects on the molecular biology and biochemistry of germ cells, including changes to gene expression, metabolism, oxidative stress and to the endocrine environment. Hypoxia also has often-overlooked effects on the epididymis, such as altered composition and gene expression of epithelial cells, with knock-on effects on sperm maturation, including the capacity to acrosome react. Evidence from model species shows that paternal hypoxia exposure results in disrupted embryo development and transgenerational effects on male fertility and offspring physiology. Overall, hypoxia induces a complex, multifaceted subfertility phenotype that is reversible with resolution of the exposure, in part because of a resilient testis stem cell population that thrives in hypoxia. However, the potential for transgenerational effects deserves further exploration, particularly in considering the purported decline in sperm counts over the past 50 years.