Search Results (64)

Renal function refers to the combined actions of the glomerulus and tubular system to achieve homeostasis in bodily fluids. While the glomerulus is essential in the first step of urine formation through a coordinated filtration mechanism, the tubular system carries out active mechanisms of secretion and reabsorption of solutes and proteins using specific transporters in the epithelial cells. The assessment of renal function usually focuses on glomerular function, so the tubular function is often underestimated as a fundamental part of daily clinical practice. Therefore, it is essential to properly understand the tubular physiological mechanisms and their clinical association with prevalent human pathologies. This review discusses the primary solutes handled by the kidneys, including glucose, amino acids, sodium, potassium, calcium, phosphate, citrate, magnesium and uric acid. Additionally, it emphasizes the significance of physicochemical characteristics of urine, such as pH and osmolarity. The use of a concise methodology for the comprehensive assessment of urine should be strengthened in the basic training of nephrologists when dealing with problems such as water and electrolyte balance disorders, acid-base disorders, and harmful effects of commonly used drugs such as chemotherapy, antibiotics, or diuretics to avoid isolated replacement of the solute without carrying out comprehensive approaches, which can lead to potentially severe complications. Full article

Background: Elevated levels of methylmalonic acid (MMA) are observed in the bodily fluids and tissues of patients with methylmalonic aciduria, a metabolic disorder characterized by manifestations such as vomiting, lethargy, muscle weakness, seizures, and coma. Objectives and Methods: To better understand the neuropathological mechanisms underlying this condition, we investigated the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of MMA on antioxidant defenses, citric acid cycle functioning, and glial reactivity in the cerebral cortex and striatum of Wistar rats. Amino acid levels were also quantified. Results: i.p. and i.c.v. administration of MMA decreased reduced glutathione levels and altered the activities of different antioxidant enzymes in the cortex and striatum. The activity of the citric acid cycle enzyme succinate dehydrogenase was diminished in both brain regions by i.p. and i.c.v. administration. Citrate synthase, isocitrate dehydrogenase, and malate dehydrogenase activities were further inhibited in the striatum. Furthermore, the i.p. administration increased glial fibrillary acidic protein (GFAP) and glucose transporter 1 (GLUT1) levels, whereas i.c.v. administration elevated GFAP and ionized calcium-binding adaptor molecule 1 (IBA1) levels in the striatum, suggesting glial activation. In contrast, no significant changes in glial markers were detected in the cortex. Moreover, synaptophysin levels remained unaltered in both regions. Finally, i.p. administration increased glutamate, glycine, and serine levels and reduced tyrosine concentrations in the striatum. Conclusions: Our findings indicate that oxidative stress, bioenergetic dysfunction, and glial reactivity induced by MMA may contribute to the neurological deficits observed in methylmalonic aciduria. Full article

Triclosan (TCS) is an antimicrobial agent in a wide range of health care products. It has been found in various human bodily fluids and is a potential reproductive toxicant. However, the effect of TCS on early embryo development in mammalian species is limited. We therefore asked whether exposure to TCS affects mammalian cumulus–oocyte complexes (COCs), and if so, whether the effects persist into the early embryo. COCs, isolated from abattoir-derived bovine ovaries, were exposed to two environmentally relevant doses of TCS (1 and 10 nM) during in vitro maturation. When exposed to 1 nM TCS during in vitro maturation, progesterone release from bovine oocytes was elevated. Furthermore, altered pyruvate metabolism and mitochondrial dysfunction were also observed; specifically, O₂ consumption coupled to ATP production was significantly decreased in COCs after acute exposure to TCS prior to maturation, whereas proton leak from the respiratory chain was increased. Subsequently, TCS-exposed COCs were fertilised. Fewer oocytes were able to develop to blastocyst when exposed to 1 nM TCS during maturation compared to the Control group, and those that did reach the blastocyst displayed impaired glycolytic and amino acid metabolic activity. These findings indicate for the first time that oocytes exposed to TCS during the final stages of maturation give rise to embryos with impaired mitochondrial function, altered steroidogenesis, and disrupted metabolic activity. Full article

Chronic pain significantly impacts quality of life and is often accompanied by inflammation, a natural bodily response that can become harmful when excessive. The orofacial region is commonly affected, making effective treatment crucial. However, current drugs often cause undesirable side effects, highlighting the need for new pharmacological alternatives. 4-hydroxycoumarin (4-HC), a natural compound, has shown promising antinociceptive and anti-inflammatory effects, but studies confirming its specific properties are limited. In silico analyses suggest that 4-HC exhibits favorable pharmacokinetic characteristics, not interacting with P-glycoprotein and successfully crossing the blood–brain barrier. Molecular docking studies indicate that its effects may be mediated through NMDA_R or by inhibiting iNOS. Our study assessed the antinociceptive and anti-inflammatory effects of 4-HC in animal models at doses of 25, 50, and 75 mg/kg. 4-HC significantly reduced abdominal contortions induced by acetic acid and decreased nociceptive rubbing in orofacial pain models induced by formalin, glutamate, and capsaicin. Interactions with opioid receptors were not observed, suggesting that 4-HC’s antinociceptive effect does not involve this pathway. Additionally, 4-HC reduced paw edema induced by carrageenan and significantly decreased leukocyte migration and TNF-α levels. These findings highlight the therapeutic potential of 4-HC and warrant further investigation into its mechanisms. Full article

Extracellular nanoparticles (EPs) are a subject of increasing interest for their biological role as mediators in cell–cell communication; however, their harvesting and assessment from bodily fluids are challenging, as processing can significantly affect samples. With the aim of minimizing processing artifacts, we assessed the number density (n) and hydrodynamic diameter (D_h) of EPs directly in diluted plasma and blood using the following recently developed technique: interferometric light microscopy (ILM). We analyzed 613 blood and plasma samples from human patients with inflammatory bowel disease (IBD), collected in trisodium citrate and ethylenediaminetetraacetic acid (EDTA) anticoagulants, and 163 blood and plasma samples from canine patients with brachycephalic obstructive airway syndrome (BOAS). We found a highly statistically significant correlation between n in the plasma and n in the blood only in the human (i.e., but not canine) blood samples, between the samples with trisodium citrate and EDTA, and between the respective D_h for both species (all p < 10⁻³). In the human plasma, the average <D_h> was 139 ± 31 nm; in the human blood, <D_h> was 158 ± 11 nm; in the canine plasma, <D_h> was 155 ± 32 nm; and in the canine blood, <D_h> was 171 ± 33 nm. The differences within species were statistically significant (p < 10⁻²), with sufficient statistical power (P > 0.8). For <n>, we found no statistically significant differences between the human plasma and blood samples or between the samples with trisodium citrate and EDTA. Our results prove that measuring n and D_h of EPs in minimally processed fresh blood and in diluted fresh plasma by means of ILM is feasible for large populations of samples. Full article

Ebola virus (EBOV) is one of three filovirus members of the Orthoebolavirus genus that can cause severe Ebola disease (EBOD) in humans. Transmission predominantly occurs from spillover events from wildlife but has also happened between humans with infected bodily fluids. Specifically, the sexual route through infectious male survivors could be the origin of flare up events leading to the deaths of multiple women. More studies are needed to comprehend this route of infection which has recently received more focus. The use of microbicides prior to intercourse is of interest if neither of the Ebola vaccines are an option. These experimental products have been used against sexually transmitted diseases, and recently polyphenylene carboxymethylene (PPCM) showed efficacy against EBOV in vitro. Shortly after, the first animal model of EBOV sexual transmission was established using type I interferon receptors (IFNAR^−/−) knockout female mice in which mortality endpoint could be achieved. Here, we investigated PPCM efficacy against a mouse-adapted (ma)EBOV isolate in IFNAR^−/− mice and demonstrated that 4% PPCM gel caused a 20% reduction in mortality in two distinct groups compared to control groups when inoculated prior to virus challenge. Among animals that succumbed to disease despite PPCM treatment, we report an increase in median survival time as well as a less infectious virus, and fewer virus positive vaginal swabs compared to those from vehicle-treated animals, altogether indicating the beneficial effect of using PPCM prior to exposure. A post-study analysis of the different gel formulations tested indicated that buffering the gels would have prevented an increase in acidity seen only in vehicles, suggesting that PPCM antiviral efficacy against EBOV was suboptimal in our experimental set-up. These results are encouraging and warrant further studies using optimized stable formulations with the goal of providing additional safe protective countermeasures from sexual transmission of EBOV in humans. Full article

The aim of this study was to develop a material capable of rapidly absorbing bodily fluids and forming a resilient, adhesive, viscoelastic hydrogel in situ to prevent post-surgical adhesions. This material was formulated using O-carboxymethyl chitosan (O-CMCS), oxidized hyaluronic acid (OHA), and a crosslinking pigment derived from genipin and glutamic acid (G/GluP). Both crosslinked (O-CMCS/OHA-G/GluP) and non-crosslinked hydrogels (O-CMCS/OHA) were evaluated using a HAAKE™ MARS™ rheometer for their potential as post-surgical barriers. A rheological analysis, including dynamic oscillatory measurements, revealed that the crosslinked hydrogels exhibited significantly higher elastic moduli (G′), indicating superior gel formation and mechanical stability compared to non-crosslinked hydrogels. The G/GluP crosslinker enhanced gel stability by increasing the separation between G′ and G″ and achieving a lower loss tangent (tan δ < 1.0), indicating robustness under dynamic physiological conditions. The rapid hydration and gelation properties of the hydrogels underscore their effectiveness as physical barriers. Furthermore, the O-CMCS/OHA-G/GluP hydrogel demonstrated rapid self-healing and efficient application via spraying or spreading, with tissue adherence and viscoelasticity to facilitate movement between tissues and organs, effectively preventing adhesions. Additionally, the hydrogel proved to be both cost effective and scalable, highlighting its potential for clinical applications aimed at preventing post-surgical adhesions. Full article

The absorption of dietary phosphorus typically begins with the digestive phase, where various chemical processes take place. These include the solubilization of calcium phosphates by gastric acid in the stomach, as well as the enzymatic breakdown of various organic phosphorus compounds within the intestinal lumen. Enhancing the digestive phase can be achieved by pre-digesting diets or designing them to be readily digestible, which can be especially advantageous for fish with limited digestive capabilities. This improvement may involve supplementing the diets with phytase and organic acids, fermenting feed ingredients, and selecting highly digestible ingredients. Following the digestive phase, solubilized inorganic phosphates and small organic phosphates are absorbed across the intestinal epithelium. This absorptive process is governed by numerous bodily mechanisms that are not easily altered or enhanced. Nonetheless, comprehending these absorptive mechanisms of dietary phosphorus may pave the way for the development of novel methods to increase dietary phosphorus absorption. Full article

Liquid biopsy has emerged as a promising noninvasive approach for colorectal cancer (CRC) management. This review focuses on technologies detecting circulating nucleic acids, specifically circulating tumor DNA (ctDNA) and circulating RNA (cfRNA), as CRC biomarkers. Recent advancements in molecular technologies have enabled sensitive and specific detection of tumor-derived genetic material in bodily fluids. These include quantitative real-time PCR, digital PCR, next-generation sequencing (NGS), and emerging nanotechnology-based methods. For ctDNA analysis, techniques such as BEAMing and droplet digital PCR offer high sensitivity in detecting rare mutant alleles, while NGS approaches provide comprehensive genomic profiling. cfRNA detection primarily utilizes qRT-PCR arrays, microarray platforms, and RNA sequencing for profiling circulating microRNAs and discovering novel RNA biomarkers. These technologies show potential in early CRC detection, treatment response monitoring, minimal residual disease assessment, and tumor evolution tracking. However, challenges remain in standardizing procedures, optimizing detection limits, and establishing clinical utility across disease stages. This review summarizes current circulating nucleic acid detection technologies, their CRC applications, and discusses future directions for clinical implementation. Full article

Patients with diabetes, the elderly, and those who have certain inherited conditions are particularly vulnerable to atypical wound healing with lingering repercussions. Remarkably, the current remedies are insufficient since, despite the plethora of wound healing options, only limited efficacy is observed. This review is a bibliographic survey on eicosapentaenoic acid and its healing effects. It has been investigated in terms of its source of origin, structure, physico-chemical properties, and studies where healing action is demonstrated. Fatty acids, found in all layers of the skin, modify cell function and the synthesis of eicosanoids, reactive oxygen species, and cytokines, which affects skin structure and immunological condition. As a result, fatty acids influence both the inflammatory response and the wound-healing process. EPA is one of the dietary lipids that has a variety of health advantages. It functions in anti-inflammatory processes and the firmness of cell membranes and is integrated into numerous bodily parts. EPA has a crucial role in healthy fetal development and aging. It is a precursor to numerous metabolites that are powerful lipid mediators and are regarded by many researchers as being helpful in the treatment or prevention of several disorders. EPA supplement is used after surgery to lessen infections, accelerate wound healing, and speed up recovery, although, according to other researchers, the oral administration of omega-3 fatty acids, particularly the DHA and EPA combination, significantly slows down the healing of wounds and disrupts the structure of collagen through several mechanisms. The controversy in the reported literature is discussed and new technologies useful for the improvement of the wound healing process are also reported. Full article

Dental erosion represents the gradual and irreversible depletion of dental hard tissues due to a chemical process, independent of bacterial influence. It has emerged as a notable clinical concern in recent years, primarily attributed to substantial lifestyle shifts resulting in the heightened intake and frequency of acid-containing foods and beverages. Apart from the extrinsic erosive agents derived from external sources, such as dietary habits or medication, intrinsic erosive agents may exist due to pathological reasons with the contents of the stomach including gastric juice, mainly composed of hydrochloric acid, being their sole source. Currently, bioactive materials are used in various forms for the prevention of dental erosion. Such materials include, among others, bioactive glasses (BAGs). BAGs are a type of glass that, when in contact with biological fluids, can elicit a specific biological response. When they come into contact with bodily fluids, they can initiate a series of processes, including the formation of a hydroxyapatite layer on the glass surface. This bioactivity is particularly advantageous in medical and dental applications, where BAGs are used for bone regeneration, tissue repair, and dental restorative or preventive techniques. The aim of this literature review was to analyze and discuss the role of BAGs in protecting the tooth structures from dental erosion. The analysis of the existing literature regarding this topic indicated that the use of BAGs in preventive treatments against tooth erosion can be useful in dental practice. Further clinical evidence is necessary to confirm the effectiveness of the particular preventive measures. Full article

Aging is an irreversible process of natural degradation of bodily function. The increase in the aging population, as well as the rise in the incidence of aging-related diseases, poses one of the most pressing global challenges. Hemp seed oil, extracted from the seeds of hemp (Cannabis sativa L.), possesses significant nutritional and biological properties attributed to its unique composition of polyunsaturated fatty acids and various antioxidant compounds. However, there is limited knowledge regarding the anti-aging mechanism of hemp seed oil. This study aimed to evaluate the beneficial effects and potential mechanisms of hemp seed oil in a D-galactose (D-gal)-induced aging rat model through a combined analysis of metabolomics and 16S rRNA gene sequencing. Using nuclear magnetic resonance (NMR)-based metabolomics, significant alterations in serum and urine metabolic phenotypes were observed between the D-gal-induced aging rat model and the healthy control group. Eight and thirteen differentially expressed metabolites related to aging were identified in serum and urine, respectively. Treatment with hemp seed oil significantly restored four and ten potential biomarkers in serum and urine, respectively. The proposed pathways primarily included energy metabolism, amino acid metabolism, one-carbon metabolism, and lipid metabolism. Furthermore, 16S rRNA gene sequencing analysis revealed significant changes in the gut microbiota of aged rats. Compared to the model group, the hemp seed oil group exhibited significant alterations in the abundance of 21 bacterial taxa at the genus level. The results indicated that hemp seed oil suppressed the prevalence of pathogenic bacterial genera such as Streptococcus, Rothia, and Parabacteroides. Additionally, it facilitated the proliferation of the genera Lachnospirace_NK4B4_group and Lachnospirace_UCG_001, while also enhancing the relative abundance of the genus Butyricoccus; a producer of short-chain fatty acids (SCFAs). These findings provided new insights into the pathogenesis of aging and further supported the potential utility of hemp seed oil as an anti-aging therapeutic agent. Full article

Early detection of neurological conditions is critical for timely diagnosis and treatment. Identifying cellular-level changes is essential for implementing therapeutic interventions prior to symptomatic disease onset. However, monitoring brain tissue directly through biopsies is invasive and poses a high risk. Bodily fluids such as blood or cerebrospinal fluid contain information in many forms, including proteins and nucleic acids. In particular, cell-free DNA (cfDNA) has potential as a versatile neurological biomarker. Yet, our knowledge of cfDNA released by brain tissue and how cfDNA changes in response to deleterious events within the brain is incomplete. Mapping changes in cfDNA to specific cellular events is difficult in vivo, wherein many tissues contribute to circulating cfDNA. Organoids are tractable systems for examining specific changes consistently in a human background. However, few studies have investigated cfDNA released from organoids. Here, we examined cfDNA isolated from cerebral organoids. We found that cerebral organoids release quantities of cfDNA sufficient for downstream analysis with droplet-digital PCR and whole-genome sequencing. Further, gene ontology analysis of genes aligning with sequenced cfDNA fragments revealed associations with terms related to neurodevelopment and autism spectrum disorder. We conclude that cerebral organoids hold promise as tools for the discovery of cfDNA biomarkers related to neurodevelopmental and neurological disorders. Full article

This comprehensive review delves into the world of hyaluronic acid (HA) hydrogels, exploring their creation, characteristics, research methodologies, and uses. HA hydrogels stand out among natural polysaccharides due to their distinct features. Their exceptional biocompatibility makes them a top choice for diverse biomedical purposes, with a great ability to coexist harmoniously with living cells and tissues. Furthermore, their biodegradability permits their gradual breakdown by bodily enzymes, enabling the creation of temporary frameworks for tissue engineering endeavors. Additionally, since HA is a vital component of the extracellular matrix (ECM) in numerous tissues, HA hydrogels can replicate the ECM’s structure and functions. This mimicry is pivotal in tissue engineering applications by providing an ideal setting for cellular growth and maturation. Various cross-linking techniques like chemical, physical, enzymatic, and hybrid methods impact the mechanical strength, swelling capacity, and degradation speed of the hydrogels. Assessment tools such as rheological analysis, electron microscopy, spectroscopy, swelling tests, and degradation studies are employed to examine their attributes. HA-based hydrogels feature prominently in tissue engineering, drug distribution, wound recovery, ophthalmology, and cartilage mending. Crafting HA hydrogels enables the production of biomaterials with sought-after qualities, offering avenues for advancements in the realm of biomedicine. Full article

Aging is characterized by the progressive degeneration of bodily tissues and decline in physiological functions, a process that may be exacerbated by imbalances in intestinal flora. Soluble dietary fiber (PSDF) from Citrus unshiu peel has demonstrated strong free radical scavenging ability to regulate intestinal flora in vitro. However, further evidence is required to ascertain the effectiveness of PSDF in vivo. In our study, 8-week-old mice were artificially aged through subcutaneous injections of a 200 mg/kg/d D-galactose solution for 42 days, followed by a 28-day dietary intervention with varying doses of PSDF, insoluble dietary fiber (PIDF), and vitamin C. After the intervention, we observed a significant mitigation of D-galactose-induced oxidative stress, as evident by weight normalization and reduced oxidative damage. 16S rRNA gene sequencing revealed that PSDF significantly altered the composition of intestinal flora, increasing Firmicutes and reducing Bacteroidota percentages, while also enriching colonic short-chain fatty acids (SCFAs). Spearman correlation analysis further identified a positive correlation between Firmicutes and isovaleric acid, and negative correlations between Muribaculaceae and acetic acid, and between Lachnospiraceae_NK4A136_group and caproic acid. These findings support the potential of Citrus PSDF to alleviate oxidative stress. Full article