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American Family Physician Dec 2019Acute kidney injury is a clinical syndrome characterized by a rapid decline in glomerular filtration rate and resultant accumulation of metabolic waste products. Acute...
Acute kidney injury is a clinical syndrome characterized by a rapid decline in glomerular filtration rate and resultant accumulation of metabolic waste products. Acute kidney injury is associated with an increased risk of mortality, cardiovascular events, and progression to chronic kidney disease. Severity of acute kidney injury is classified according to urine output and elevations in creatinine level. Etiologies of acute kidney injury are categorized as prerenal, intrinsic renal, and postrenal. Accurate diagnosis of the underlying cause is key to successful management and includes a focused history and physical examination, serum and urine electrolyte measurements, and renal ultrasonography when risk factors for a postrenal cause are present (e.g., older male with prostatic hypertrophy). General management principles for acute kidney injury include determination of volume status, fluid resuscitation with isotonic crystalloid, treatment of volume overload with diuretics, discontinuation of nephrotoxic medications, and adjustment of prescribed drugs according to renal function. Additional supportive care measures may include optimizing nutritional status and glycemic control. Pharmacist-led quality-improvement programs reduce nephrotoxic exposures and rates of acute kidney injury in the hospital setting. Acute kidney injury care bundles are associated with improved in-hospital mortality rates and reduced risk of progression. Nephrology consultation should be considered when there is inadequate response to supportive treatment and for acute kidney injury without a clear cause, stage 3 or higher acute kidney injury, preexisting stage 4 or higher chronic kidney disease, renal replacement therapy, and other situations requiring subspecialist expertise.
Topics: Acute Kidney Injury; Creatinine; Fluid Therapy; Glomerular Filtration Rate; Humans; Nephrology; Prognosis; Referral and Consultation; Risk Factors
PubMed: 31790176
DOI: No ID Found -
International Journal of Cancer Feb 2021The analysis of tumor cells or tumor cell products obtained from blood or other body fluids ("liquid biopsy" [LB]) provides a broad range of opportunities in the field... (Review)
Review
The analysis of tumor cells or tumor cell products obtained from blood or other body fluids ("liquid biopsy" [LB]) provides a broad range of opportunities in the field of oncology. Clinical application areas include early detection of cancer or tumor recurrence, individual risk assessment and therapy monitoring. LB allows to portray the entire disease as tumor cells or tumor cell products are released from all metastatic or primary tumor sites, providing comprehensive and real-time information on tumor cell evolution, therapeutic targets and mechanisms of resistance to therapy. Here, we focus on the most prominent LB markers, circulating tumor cells (CTCs) and circulating tumor-derived DNA (ctDNA), in the blood of patients with breast, prostate, lung and colorectal cancer, as the four most frequent tumor types in Europe. After a brief introduction of key technologies used to detect CTCs and ctDNA, we discuss recent clinical studies on these biomarkers for early detection and prognostication of cancer as well as prediction and monitoring of cancer therapies. We also point out current methodological and biological limitations that still hamper the implementation of LB into clinical practice.
Topics: Biomarkers, Tumor; Breast Neoplasms; Circulating Tumor DNA; Colorectal Neoplasms; Early Detection of Cancer; Female; Humans; Liquid Biopsy; Lung Neoplasms; Male; Molecular Targeted Therapy; Neoplasms; Neoplastic Cells, Circulating; Prognosis; Prostatic Neoplasms
PubMed: 32683679
DOI: 10.1002/ijc.33217 -
Frontiers in Molecular Biosciences 2021Cancer-related cognitive impairment (CRCI) is a frequent side effect experienced by an increasing number of cancer survivors with a significant impact on their quality... (Review)
Review
Cancer-related cognitive impairment (CRCI) is a frequent side effect experienced by an increasing number of cancer survivors with a significant impact on their quality of life. Different definitions and means of evaluation have been used in available literature; hence the exact incidence of CRCI remains unknown. CRCI can be described as cognitive symptoms reported by cancer patients in self-reported questionnaires or as cognitive changes evaluated by formal neuropsychological tests. Nevertheless, association between cognitive symptoms and objectively assessed cognitive changes is relatively weak or absent. Studies have focused especially on breast cancer patients, but CRCI has been reported in multiple types of cancer, including colorectal, lung, ovarian, prostate, testicular cancer and hematological malignancies. While CRCI has been associated with various treatment modalities, including radiotherapy, chemotherapy, hormone therapy and novel systemic therapies, it has been also detected prior to cancer treatment. Therefore, the effects of cancer itself with or without the psychological distress may be involved in the pathogenesis of CRCI as a result of altered coping mechanisms after cancer diagnosis. The development of CRCI is probably multifactorial and the exact mechanisms are currently not completely understood. Possible risk factors include administered treatment, genetic predisposition, age and psychological factors such as anxiety, depression or fatigue. Multiple mechanisms are suggested to be responsible for CRCI, including direct neurotoxic injury of systemic treatment and radiation while other indirect contributing mechanisms are hypothesized. Chronic neuroinflammation mediated by active innate immune system, DNA-damage or endothelial dysfunction is hypothesized to be a central mechanism of CRCI pathogenesis. There is increasing evidence of potential plasma (e.g., damage associated molecular patterns, inflammatory components, circulating microRNAs, exosomes, short-chain fatty acids, and others), cerebrospinal fluid and radiological biomarkers of cognitive dysfunction in cancer patients. Discovery of biomarkers of cognitive impairment is crucial for early identification of cancer patients at increased risk for the development of CRCI or development of treatment strategies to lower the burden of CRCI on long-term quality of life. This review summarizes current literature on CRCI with a focus on long-term effects of different cancer treatments, possible risk factors, mechanisms and promising biomarkers.
PubMed: 34970595
DOI: 10.3389/fmolb.2021.770413 -
Frontiers in Immunology 2023Prostatitis is a common urological condition that affects almost half of all men at some point in their life. The prostate gland has a dense nerve supply that... (Review)
Review
Prostatitis is a common urological condition that affects almost half of all men at some point in their life. The prostate gland has a dense nerve supply that contributes to the production of fluid to nourish sperm and the mechanism to switch between urination and ejaculation. Prostatitis can cause frequent urination, pelvic pain, and even infertility. Long-term prostatitis increases the risk of prostate cancer and benign prostate hyperplasia. Chronic non-bacterial prostatitis presents a complex pathogenesis, which has challenged medical research. Experimental studies of prostatitis require appropriate preclinical models. This review aimed to summarize and compare preclinical models of prostatitis based on their methods, success rate, evaluation, and range of application. The objective of this study is to provide a comprehensive understanding of prostatitis and advance basic research.
Topics: Humans; Male; Prostatitis; Semen; Pelvic Pain; Prostate; Spermatozoa
PubMed: 37228599
DOI: 10.3389/fimmu.2023.1183895 -
Molecular Nutrition & Food Research Nov 2022Urolithins, metabolites produced by the gut microbiota from the polyphenols ellagitannins and ellagic acid, are discovered by the research group in humans almost 20... (Review)
Review
Urolithins, metabolites produced by the gut microbiota from the polyphenols ellagitannins and ellagic acid, are discovered by the research group in humans almost 20 years ago. Pioneering research suggests urolithins as pleiotropic bioactive contributors to explain the health benefits after consuming ellagitannin-rich sources (pomegranates, walnuts, strawberries, etc.). Here, this study comprehensively updates the knowledge on urolithins, emphasizing the review of the literature published during the last 5 years. To date, 13 urolithins and their corresponding conjugated metabolites (glucuronides, sulfates, etc.) have been described and, depending on the urolithin, detected in different human fluids and tissues (urine, blood, feces, breastmilk, prostate, colon, and breast tissues). There has been a substantial advance in the research on microorganisms involved in urolithin production, along with the compositional and functional characterization of the gut microbiota associated with urolithins metabolism that gives rise to the so-called urolithin metabotypes (UM-A, UM-B, and UM-0), relevant in human health. The design of in vitro studies using physiologically relevant assay conditions (molecular forms and concentrations) is still a pending subject, making some reported urolithin activities questionable. In contrast, remarkable progress has been made in the research on the safety, bioactivity, and associated mechanisms of urolithin A, including the first human interventions.
Topics: Male; Humans; Gastrointestinal Microbiome; Coumarins; Hydrolyzable Tannins; Feces; Ellagic Acid; Juglans
PubMed: 35118817
DOI: 10.1002/mnfr.202101019 -
Human Reproduction (Oxford, England) Apr 2022Are epididymosomes implicated in protein transfer from the epididymis to spermatozoa?
STUDY QUESTION
Are epididymosomes implicated in protein transfer from the epididymis to spermatozoa?
SUMMARY ANSWER
We characterized the contribution of epididymal secretions to the sperm proteome and demonstrated that sperm acquire epididymal proteins through epididymosomes.
WHAT IS KNOWN ALREADY
Testicular sperm are immature cells unable to fertilize an oocyte. After leaving the testis, sperm transit along the epididymis to acquire motility and fertilizing abilities. It is well known that marked changes in the sperm proteome profile occur during epididymal maturation. Since the sperm is a transcriptional and translational inert cell, previous studies have shown that sperm incorporate proteins, RNA and lipids from extracellular vesicles (EVs), released by epithelial cells lining the male reproductive tract.
STUDY DESIGN, SIZE, DURATION
We examined the contribution of the epididymis to the post-testicular maturation of spermatozoa, via the production of EVs named epididymosomes, released by epididymal epithelial cells. An integrative analysis using both human and mouse data was performed to identify sperm proteins with a potential epididymis-derived origin. Testes and epididymides from adult humans (n = 9) and adult mice (n = 3) were used to experimentally validate the tissue localization of four selected proteins using high-resolution confocal microscopy. Mouse epididymal sperm were co-incubated with carboxyfluorescein succinimidyl ester (CFSE)-labeled epididymosomes (n = 4 mice), and visualized using high-resolution confocal microscopy.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Adult (12-week-old) C57BL/CBAF1 wild-type male mice and adult humans were used for validation purposes. Testes and epididymides from both mice and humans were obtained and processed for immunofluorescence. Mouse epididymal sperm and mouse epididymosomes were obtained from the epididymal cauda segment. Fluorescent epididymosomes were obtained after labeling the epididymal vesicles with CFSE dye followed by epididymosome isolation using a density cushion. Immunofluorescence was performed following co-incubation of sperm with epididymosomes in vitro. High-resolution confocal microscopy and 3D image reconstruction were used to visualize protein localization and sperm-epididymosomes interactions.
MAIN RESULTS AND THE ROLE OF CHANCE
Through in silico analysis, we first identified 25 sperm proteins with a putative epididymal origin that were conserved in both human and mouse spermatozoa. From those, the epididymal origin of four sperm proteins (SLC27A2, EDDM3B, KRT19 and WFDC8) was validated by high-resolution confocal microscopy. SLC27A2, EDDM3B, KRT19 and WFDC8 were all detected in epithelial cells lining the human and mouse epididymis, and absent from human and mouse seminiferous tubules. We found region-specific expression patterns of these proteins throughout the mouse epididymides. In addition, while EDDM3B, KRT19 and WFDC8 were detected in both epididymal principal and clear cells (CCs), SLC27A2 was exclusively expressed in CCs. Finally, we showed that CFSE-fluorescently labeled epididymosomes interact with sperm in vitro and about 12-36% of the epididymosomes contain the targeted sperm proteins with an epididymal origin.
LARGE SCALE DATA
N/A.
LIMITATIONS, REASONS FOR CAUTION
The human and mouse sample size was limited and our results were descriptive. The analyses of epididymal sperm and epididymosomes were solely performed in the mouse model due to the difficulties in obtaining epididymal luminal fluid human samples. Alternatively, human ejaculated sperm and seminal EVs could not be used because ejaculated sperm have already contacted with the fluids secreted by the male accessory sex glands, and seminal EVs contain other EVs in addition to epididymosomes, such as the abundant prostate-derived EVs.
WIDER IMPLICATIONS OF THE FINDINGS
Our findings indicate that epididymosomes are capable of providing spermatozoa with a new set of epididymis-derived proteins that could modulate the sperm proteome and, subsequently, participate in the post-testicular maturation of sperm cells. Additionally, our data provide further evidence of the novel role of epididymal CCs in epididymosome production. Identifying mechanisms by which sperm mature to acquire their fertilization potential would, ultimately, lead to a better understanding of male reproductive health and may help to identify potential therapeutic strategies to improve male infertility.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by the Spanish Ministry of Economy and Competitiveness (Ministerio de Economía y Competividad; fondos FEDER 'una manera de hacer Europa' PI13/00699 and PI16/00346 to R.O.; and Sara Borrell Postdoctoral Fellowship, Acción Estratégica en Salud, CD17/00109 to J.C.), by National Institutes of Health (grants HD040793 and HD069623 to S.B., grant HD104672-01 to M.A.B.), by the Spanish Ministry of Education, Culture and Sports (Ministerio de Educación, Cultura y Deporte para la Formación de Profesorado Universitario, FPU15/02306 to F.B.), by a Lalor Foundation Fellowship (to F.B. and M.A.B.), by the Government of Catalonia (Generalitat de Catalunya, pla estratègic de recerca i innovació en salut, PERIS 2016-2020, SLT002/16/00337 to M.J.), by Fundació Universitària Agustí Pedro i Pons (to F.B.), and by the American Society for Biochemistry and Molecular Biology (PROLAB Award from ASBMB/IUBMB/PABMB to F.B.). Confocal microscopy and transmission electron microscopy was performed in the Microscopy Core facility of the Massachusetts General Hospital (MGH) Center for Systems Biology/Program in Membrane Biology which receives support from Boston Area Diabetes and Endocrinology Research Center (BADERC) award DK57521 and Center for the Study of Inflammatory Bowel Disease grant DK43351. The Zeiss LSM800 microscope was acquired using an NIH Shared Instrumentation Grant S10-OD-021577-01. The authors have no conflicts of interest to declare.
Topics: Animals; Epididymis; Humans; Male; Mice; Mice, Inbred C57BL; Sperm Maturation; Spermatozoa; Testis
PubMed: 35137089
DOI: 10.1093/humrep/deac015 -
Cell Reports Dec 2021The prostate gland produces prostatic fluid, high in zinc and citrate and essential for the maintenance of spermatozoa. Prostate cancer is a common condition with...
The prostate gland produces prostatic fluid, high in zinc and citrate and essential for the maintenance of spermatozoa. Prostate cancer is a common condition with limited treatment efficacy in castration-resistant metastatic disease, including with immune checkpoint inhibitors. Using single-cell RNA-sequencing to perform an unbiased assessment of the cellular landscape of human prostate, we identify a subset of tumor-enriched androgen receptor-negative luminal epithelial cells with increased expression of cancer-associated genes. We also find a variety of innate and adaptive immune cells in normal prostate that were transcriptionally perturbed in prostate cancer. An exception is a prostate-specific, zinc transporter-expressing macrophage population (MAC-MT) that contributes to tissue zinc accumulation in homeostasis but shows enhanced inflammatory gene expression in tumors, including T cell-recruiting chemokines. Remarkably, enrichment of the MAC-MT signature in cancer biopsies is associated with improved disease-free survival, suggesting beneficial antitumor functions.
Topics: Aged; Animals; Epithelial Cells; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Macrophages; Male; Mice; Mice, Inbred C57BL; Middle Aged; Prostate; Prostatic Neoplasms; RNA-Seq; Receptors, Androgen; Single-Cell Analysis; Transcriptome; Zinc
PubMed: 34936871
DOI: 10.1016/j.celrep.2021.110132