Tissue Concentrations Research Articles

Content of Biogenic Elements in Sheep Wool by the Regions of Slovakia.

The quality of nutrition and environmental pollution are crucial chemical indicators influencing animal health, reflected in element concentrations in animal tissues and coats. This study investigates the concentrations of biogenic elements (calcium, potassium, magnesium, sodium, copper, and iron) in sheep wool from various regions of Slovakia to compare concentrations and identify possible correlations between individual elements. Samples were collected from six different regions, and concentrations of elements were measured using flame atomic absorption spectrometry. Statistical analysis revealed significant differences in element levels among the examined regions. Calcium concentrations ranged from 729.2 to 4065ppm, with the highest concentrations in the Kysuce region and the lowest in the Šariš region. Potassium concentrations ranged from 2315 to 3282ppm, with the lowest values in the Zemplín region and the highest in the Liptov region. Magnesium, sodium, copper, and iron also exhibited varying concentrations across the regions. Correlation analysis identified significant associations between several elements. The findings suggest that regional environmental differences influence element concentrations in sheep wool, highlighting the importance of monitoring biogenic elements for assessing environmental pollution and animal health. Further research is warranted to explore the underlying mechanisms driving element accumulation in wool and its implications for animal welfare and environmental management.

Low doses of acetyl trihexyl citrate plasticizer promote adipogenesis in hepatocytes and mice.

Accumulating epidemiological evidence underscores the association between pervasive environmental factors and an increased risk of metabolic diseases. Environmental chemicals, recognized disruptors of endocrine and metabolic processes, may contribute to the global prevalence of metabolic disorders, including obesity. Acetyl tributyl citrate (ATHC), categorized as a citric acid ester plasticizer, serves as a substitute for di-(2-ethylhexyl) phthalate (DEHP) in various everyday products. Despite its widespread use and the increasing risk of exposure in humans and animals due to its high leakage rates, information regarding the safety of exposure to environmentally relevant doses of ATHC remains limited. This study aimed to investigate the potential impact of ATHC exposure on metabolic homeostasis. Both in vivo and in vitro exposure models were used to characterize the effects induced by ATHC exposure. C57BL/6J male mice were subjected to a diet containing ATHC for 12weeks, and metabolism-related parameters were monitored and analyzed throughout and after the exposure period. Results indicated that sub-chronic dietary exposure to ATHC induced an increase in body fat percentage, elevated serum lipid levels, and increased lipid content in the liver tissue of mice. Furthermore, the effect of ATHC exposure on murine hepatocytes were examined and results indicated that ATHC significantly augmented lipid levels in AML12 hepatocytes, disrupting energy homeostasis and altering the expression of genes associated with fatty acid synthesis, uptake, oxidation, and secretion pathways. Conclusively, both in vivo and in vitro results suggest that exposure to low levels of ATHC may be linked to an elevated risk of obesity and fatty liver in mice. The potential implications of ATHC on human health warrant comprehensive evaluation in future studies.

Phytoremediation Potential of Azolla filiculoides: Uptake and Toxicity of Seven Per- and Polyfluoroalkyl Substances (PFAS) at Environmentally Relevant Water Concentrations.

Environmental contamination of aquatic systems by per- and polyfluoroalkyl substances (PFAS) has generated significant health concerns. Remediation of contaminated sites such as the fire-fighting emergency training grounds that use aqueous film-forming foams is a high priority. Phytoremediation may help play a part in removing PFAS from such contaminated waters. We investigated the potential of the water fern Azolla filiculoides, which is used for phytoremediation of a wide range of contaminants, to uptake seven common PFAS (perfluorobutanoic acid [PFBA], perfluorobutane sulfonic acid [PFBS], perfluoroheptanoic acid [PFHpA], perfluorohexanoic acid [PFHxA], perfluorohexane sulfonic acid [PFHxS], perfluorooctanoic acid [PFOA], and perfluoropentanoic acid [PFPeA]), during a 12-day exposure to environmentally relevant concentrations delivered as equimolar mixtures: low (∑PFAS = 0.0123 ± 1.89 μmol L-1), medium (∑PFAS = 0.123 ± 2.88 μmol L-1), and high (∑PFAS = 1.39 μmol L-1) treatments, equivalent to approximately 5, 50, and 500 µg L-1 total PFAS, respectively. The possible phytotoxic effects of PFAS were measured at 3-day intervals using chlorophyll a content, photosystem II efficiency (Fv/Fm), performance index, and specific growth rate. The PFAS concentrations in plant tissue and water were also measured every 3 days using ultra-high-performance liquid chromatography-tandem mass spectrometry. Treatments with PFAS did not lead to any detectable phytotoxic effects. All seven PFAS were detected in plant tissue, with the greatest uptake occurring during the first 6 days of exposure. After 12 days of exposure, a maximum bioconcentration factor was recorded for PFBA of 1.30 and a minimum of 0.192 for PFBS. Consequently, the application of Azolla spp. as a stand-alone system for phytoremediation of PFAS in aquatic environments is not sufficient to substantially reduce PFAS concentrations. Environ Toxicol Chem 2024;00:1-12. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Drug and biomarker tissue levels in a randomized presurgical trial on exemestane alternative schedules.

The drug's activity at the target tissue could help to define the minimal effective dose to promote cancer preventive therapy. Here we present exemestane and sex hormone concentrations within breast tissue from a pre-surgical study of alternative exemestane schedules. Postmenopausal women candidate for breast surgery for estrogen receptor-positive breast cancer were randomized to exemestane 25 mg once daily (QD), 25 mg three times/week (TIW), or 25 mg per/week (QW) for 4-6 weeks before surgery. Drug and sex hormones were analyzed from homogenized frozen tissue using a QTRAP 6500+ LC-MS/MS System. Tissue drug concentrations were detectable only in the QD arm with higher concentrations in non-malignant tissue. Estradiol was nearly suppressed in all groups in the non-malignant tissue (QD vs TIW p = .364 and QD vs QW p = .693). In contrast, a dose-response trend was observed in cancer tissue. Based on estradiol suppression in non-malignant tissue, lower exemestane schedules should be explored for breast cancer preventive therapy.

Drying the mystery: a novel electronic sensor to quantify soft-tissue desiccation and natural mummification for forensic taphonomy

This study investigates the desiccation process of soft-tissue in South Africa, analyzing its interaction with environmental parameters and its implications for estimating the post-mortem interval. Through the examination of four decomposing porcine bodies across two summer seasons and one winter season, the research quantifies desiccation patterns using custom-designed and constructed printed circuit boards to measure the moisture content of body tissue over time. Generalized additive models were used to determine the environmental forces driving desiccation. Tissue resistivity was tested against the environmental predictor variables to determine the amount of variation they account for, and predicted values of the region-specific tissue resistivity variables were measured for each decomposing body. Results reveal distinct desiccation trajectories between summer and winter, with summer conditions conducive to precocious natural mummification. Environmental factors, particularly temperature and solar radiation, emerge as significant drivers of desiccation. This study represents the first quantitative analysis of deep tissue desiccation internationally, but also the first quantitative assessment of desiccation and natural precocious mummification in the Western Cape, South Africa. The exploration of desiccation as a potential indicator for estimating PMI opens new avenues for research and the integration of innovative methodologies and technologies promises to revolutionize forensic taphonomy practices.

Ivermectin toxicokinetics in rainbow trout (Oncorhynchus mykiss) following P-glycoprotein inhibition.

Changes to ivermectin (IVM [22,23-dihydro avermectin B1a + 22,23-dihydro avermectin B1b]) toxicokinetics (TK) with and without P-glycoprotein (P-gp) inhibition by cyclosporin A (CsA) were examined in rainbow trout (Oncorhynchus mykiss). Rainbow trout were injected with 175μg/kg 3H-IVM (8.6μCi/mg IVM) with or without co-administration of 480μg/kg CsA into the caudal vasculature. Fish were sacrificed at various time points (0.25, 0.5, 1, 3, 24, 48, 96, and 168h) for organ and tissue sampling (blood, liver, kidney, gill, intestines, brain [5 regions], eye, gonad, and fat) which were analyzed for IVM-derived radioactivity. The IVM concentration decreased over time in blood, liver, kidney, and gill, while concentrations in other tissues remained constant. The highest maximum IVM concentration (Cmax) was found in kidney, followed by liver; the lowest Cmax was found in eye, followed by brain and adipose tissue. The highest % of the administered dose was found in the blood 15min post-IVM administration, followed by the intestine at 60min post-IVM administration. P-gp inhibition by CsA did not significantly affect calculated TK parameters (AUC [7.33 ± 0.73 - 11.5 ± 2.5mg•h/kg], mean residence time [84.7 ± 21 - 125 ± 55h], T1/2 [58.7 ± 15 - 86.8 ± 38h], clearance rate [0.0152 ± 0.0033 - 0.0239 ± 0.0024 L/kg•h], or volume of distribution [1.91 ± 0.47 - 2.02 ± 0.33 L/kg]), but resulted in small but significant changes in the % administered dose found in blood and medulla. These results suggest that P-gp plays a limited role in overall IVM TK, and that its role in xenobiotic protection may be much less robust in fish than it is in mammals.

Phase Preparation of Xiao-chai-hu Decoction and its Pharmacodynamics of Acute Liver Injury.

Self-emulsifying nano-phase of traditional Chinese medicine are a research hotspot. Xiao-Chai-Hu decoction is a commonly used compound decoction in clinical practice, which is of great research significance. The aim of this study was to isolate and characterize the self-emulsifying nano-phase and other phases of Xiao-Chai-Hu decoction, and to study the effects of each phase on acute liver injury. The liquid medicine was prepared employing centrifugation followed by dialysis. Single- factor investigation methodology was utilized to optimize the preparation parameters for both phases. Characterization of the formulated phase involved analyses such as surface morphology assessment, measurement of nanoparticle size and Zeta potential using an analyzer, observation of the Tyndall effect, conducting diffusion and dilution tests, examination under a microscope, and structural visualization via transmission electron microscopy (TEM). Furthermore, an acute liver injury model was established in rats through intraperitoneal injection of D-Galactosamine (D-Gal- N). To assess hepatic function and oxidative stress status, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content in liver tissue were quantified. The liver coefficients for each group were calculated as an additional parameter. For histopathological evaluation, liver tissue sections from the experimental group were stained with Hematoxylin and Eosin (H&E) and examined microscopically under light conditions. These revisions aim to enhance clarity, correct minor grammatical errors (such as capitalization of "HE" to "H&E"), and ensure a smoother flow of information without altering the scientific content of your original text. Successful establishment and separation of four distinct phases were achieved, including the self-emulsifying nano-phase, precipitation phase, suspension phase, and true solution phase. The self-emulsifying nano-phase was characterized as spherical particles with an average diameter of approximately 100 nm. Pharmacodynamic assessments revealed that both Xiao-Chai-Hu decoction and its self-emulsifying nano-phase significantly reduced liver coefficients and alanine aminotransferase (ALT) levels compared to controls (P<0.05). However, no statistically significant differences were observed in regards to aspartate aminotransferase (AST) concentrations, malondialdehyde (MDA) content, or superoxide dismutase (SOD) activity between the treatment groups and control (P>0.05). These findings indicate that both Xiao-Chai-Hu decoction and its self-emulsifying nano-formulation ameliorated D-GalN-induced acute liver injury, albeit without statistically distinguishable efficacy between them (P>0.05). The presence of a self-emulsifying nano-phase within Xiao-Chai-Hu decoction is confirmed, and this nano-phase emerges as a therapeutically efficacious component in mitigating acute liver injury.

Penicillin concentrations in bone and subcutaneous tissue: A porcine microdialysis study comparing oral and intravenous treatment.

Penicillin is available in both an oral (penicillin V) and intravenous formulation (penicillin G), theoretically allowing for a safe transition between the two. However, the use of oral penicillin remains a topic of debate due to low and variable bioavailability. This study aimed to assess the time for which the free penicillin concentration exceeded targeted minimum inhibitory concentrations for Staphylococcus aureus and Streptococcus species (0.125, 0.25, and 0.5 mg/L) in cancellous bone and subcutaneous tissue after intravenous penicillin and oral penicillin administration. 12 female pigs (68-75 kg) were assigned, according to local standard clinical regimes, to either intravenous penicillin (1.2 g) or oral penicillin (0.8 g) treatment every 6 h over an 18 h period. Microdialysis catheters were placed for sampling in tibial cancellous bone and adjacent subcutaneous tissue. Data was dynamic/continually collected in the first dosing interval (0-6 h), simulating a prophylactic situation, and the third dosing interval (12-18 h), simulating a therapeutic setting. Plasma samples were collected for reference. For all investigated targets, intravenous treatment resulted in a longer mean time above relevant minimum inhibitory concentrations in cancellous bone during the first dosing interval, and in both cancellous bone and subcutaneous tissue during the third dosing interval compared to oral treatment. With clinically relevant dosing, intravenous penicillin provides superior exposure compared to oral penicillin in both a prophylactic and therapeutic setting.

Bioaccumulation of Aluminium Chloride in Different Organs of Freshwater Fish Labeo rohita (Ham.)

The present research work was carried out to determine the bioaccumulation of aluminium chloride in the gills, liver, Kidney and muscles of Labeo rohita. Sub-lethal concentration (LC50) for 96 hours of exposure was found to be 32.5 ppm. The accumulation of heavy metal gradually increases in liver during the heavy metal exposure period. In the present study the accumulation of aluminium chloride was not found in tissues like gill, liver, kidney and muscle in control fish, whereas in treated fish the accumulation was found in the following order of liver&gt;kidney&gt;gill&gt;muscle. Changes in the aluminium chloride content of muscle tissue in treated fish against the control fish were statistically significant at P&lt;0.05. In all heavy metal, the bioaccumulation of aluminium chloride proportion was significantly increased in the tissues of Labeo rohita. This study revealed the accumulation of heavy metals in fish Labeo rohita which may act as an indicative measure to address the production, bioaccumulation and health hazardous issues of heavy metals.

Histological Changes in Dental Pulp During the Aging Process: Implications for Endodontic Treatment

on the results of endodontic treatment. Knowledge of these changes is essential in order to design treatment strategies that allow aging people a life with constant dental health. Objective: The objective of this study sought to perform an analysis of the histological changes that occur within dental pulp as a result of aging. Study Design: This is a cross-sectional study. Duration and Place of the Study: This study was conducted at Department Anatomy of General Hospital and Research Centre, Peshawar, from 3rd November 2022 to 2nd December 2023. Material and Methods: A total of 220 patients aged between 20-80 years, were admitted to this survey. According to age, they were classified into 20-29 years (n=41), 30-39 years (n=39),40-49 years (n=48), 50-59 years (n=45 ) and 60 -80 years( n=47). Extraction of dental pulp samples Pulp tissues were harvested from teeth that had been extracted for non-dental reasons. Histological analysis for cellularity, vascularity and fibrous content of the pulp tissue. Results: A total of 220 patients aged between 20 and 80 Years were included in this study. The biggest group of people was participants 40-49 years old (21.8%), and the smallest one is for 30-39-year-olds with (17.7%). The study found that Participants of the age groups 20–29 years showed a mean cellularity (1500 cells/mm²), with standard deviation of ±200, while those in the 60-80 years group had the lowest mean cellularity at 800 cells/mm² with a standard deviation of ±160. Conclusion: The histological changes in dental pulp with ageing have as consequences implications on endodontic treatment. Keywords: Dental Pulp, Histological Changes, Endodontic Treatment Implications

Transdermal pilocarpine on the skin over salivary glands to increase salivation: an in vivo study

BackgroundHyposalivation is treated using oral cholinergic drugs; however, systemic side effects occasionally lead to discontinuation of treatment. We aimed to investigate the effects of transdermal pilocarpine on the salivary gland skin on saliva secretion and safety in rats.MethodsPilocarpine was administered to rats orally (0.5 mg/kg) or topically on the salivary gland skin (5 mg/body). Saliva volume, the number of sweat dots, and fecal weight were measured along with pilocarpine concentration in plasma and submandibular gland tissues.ResultsSaliva volume significantly increased 0.5 h after oral administration and 0.5, 3, and 12 h after topical administration. Fecal weight and sweat dots increased significantly 1 h after oral administration; however, no changes were observed after topical application. The pilocarpine concentration in the submandibular gland tissues of the topical group was higher than that in the oral group at 0.5, 3, and 12 h of administration.ConclusionsPilocarpine application to salivary gland skin persistently increased salivary volume in rats without inducing sweating or diarrhea. Transdermal pilocarpine applied to the skin over the salivary glands may be an effective and safe treatment option for hyposalivation.

Effect of carvedilol on pharmacokinetics of sofosbuvir and its metabolite GS-331007: role of P-glycoprotein.

Sofosbuvir (SOF) is a P-glycoprotein (P-gp) substrate, and carvedilol (CAR) is an inhibitor of P-gp, suggesting that it may affect the oral pharmacokinetics and safety of SOF. The current study investigated the pharmacokinetic interaction of CAR with SOF and its metabolite, GS-331007, and the possible consequent toxicities in rats. To assess the pharmacokinetics of SOF and GS-331007, rats were divided into three groups; all received a single oral dose of SOF preceded with saline (SAL), verapamil (VER) as a standard P-gp inhibitor, or CAR, respectively. The serosal, plasma, and hepatic tissue contents of SOF and GS-331007 were assessed using LC-MS/MS. Renal and hepatic toxicities were assessed using biochemical and histopathological tests. Serosal and plasma concentrations of SOF and GS-331007 were increased in the presence of CAR, suggesting a significant inhibitory effect of CAR on intestinal P-gp. Simultaneously, the pharmacokinetic profile of SOF showed a significant increase in the Cmax, AUC(0-t), AUC (0-∞), t1/2, and a reduction in its apparent oral clearance. While the pharmacokinetic profile of GS-331007 was not significantly affected. However, this notable elevation in drug oral bioavailability was corroborated by a significant alteration in renal functions. Hence, further clinical investigations are recommended to ensure the safety and dosing of CAR/SOF combination.

A New Methodology for the Oxygen Measurement in Lung Tissue of an Aged Ferret Model Proves Hypoxia during COVID-19.

Oxygen as a key element has a high impact on cellular processes. Infection with a pathogen such as SARS-CoV-2 and after inflammation may lead to hypoxic conditions in tissue that impact cellular responses. To develop optimized translational invitro models for a better understanding of physiologic and pathophysiologic oxygen conditions, it is a prerequisite to determine oxygen concentrations generated invivo. Our study objective was the establishment of an invasive method for oxygen measurements using a luminescence-based microsensor to determine the dissolved oxygen in the lung tissue of ferrets as animal models for SARS-CoV-2 research. By way of analogy to humans, aged ferrets are more likely to show clinical signs after SARS-CoV-2 infection than are young animals. To investigate oxygen concentrations during a respiratory viral infection, we intratracheally infected nine aged (3-yr-old) ferrets with SARS-CoV-2. The aged SARS-CoV-2-infected ferrets showed mild to moderate clinical signs associated with prolonged viral RNA shedding until 14 days postinfection. SARS-CoV-2-infected ferrets showed histopathologic lung lesion scores that significantly negatively correlated with oxygen concentrations in lung tissue. At 4 days postinfection, oxygen concentrations in lung tissue were significantly lower (mean percentage O2, 3.89 ≙ ≈ 27.78 mm Hg) than in the negative control group (mean percentage O2, 8.65 ≙ ≈ 61.4 mm Hg). In summary, we succeeded in determining the pathophysiologic oxygen conditions in the lung tissue of aged SARS-CoV-2-infected ferrets.

Yellow mealworm frass: A promising organic fertilizer for common sowthistle (Sonchus oleraceus L.) and bristly oxtongue (Helminthotheca echioides (L.) Holub) cultivation

Common sowthistle (Sonchus oleraceus L.) and bristly oxtongue [Helminthotheca echioides (L.) Holub] are winter broad-leaved weeds that have gained interest for cultivation as leafy vegetables. The aim of this study was to examine the effects of frass from the yellow mealworm (Tenebrio molitor L.) on nutrient content in soil, growth parameters, and nutrient content in above-ground plant tissues of common sowthistle and bristly oxtongue. Thus, two pot experiments were carried out with 5 treatments [control, calcium ammonium nitrate (CAN) applied at a dose of 100 kg N ha−1, and insect frass applied at a rate of 3500 kg ha−1 (0.5 % w/w) 7000 kg ha−1 (1 % w/w), and 14,000 kg ha−1 (2 % w/w)]. Our results showed that the lowest values of growth parameters for both plant species were recorded in the control treatment. At the final rosette growth stage [e.g., 152 days after sowing (DAS)], the CAN treatment exhibited the highest values of rosette diameter and above-ground dry weight, followed by the highest rate of insect frass. Similarly, at 152 DAS the SPAD index values in the CAN treatment were 28.4–41.5 % higher compared to the control treatment in both species. Regarding root dry weight, the highest values were found in the CAN and insect frass 2 % treatments. In addition, the application of insect frass significantly enhanced soil fertility, with the highest levels of P and K recorded in the insect frass 2 % treatment. In contrast, the CAN treatment resulted in the highest NO3–N content in the soil (15.83 and 19.26 mg kg−1 in common sowthistle and bristly oxtongue, respectively). Moreover, both P and K content in the above-ground plant tissues had the highest values in the insect frass 2 % treatment, while the content of Mg, Mn, and Cu in plant tissues was not affected by the fertilization sources. Therefore, our findings indicate that insect frass can be an additional option in crop fertilization programs as it can improve both the soil fertility and growth of crops compared to conventional inorganic fertilizer sources. However, the effects of insect frass in mixtures with inorganic fertilizers needs to be taken into consideration in future studies.

Enhancement of growth media for extreme iron limitation in Escherichia coli.

Iron is an essential nutrient for microbial growth and bacteria have evolved numerous routes to solubilize and scavenge this biometal, which is often present at very low concentrations in host tissue. We recently used a MOPS-based medium to induce iron limitation in Escherichia coli K-12 during the characterization of novel siderophore-conjugated antibiotics. In this study we confirm that growth media derived from commercially available M9 salts are unsuitable for studies of iron-limited growth, probably through the contamination of the sodium phosphate buffer components with over 100 µM iron. In contrast, MOPS-based media that are treated with metal-binding Chelex resin allow the free iron concentration to be reduced to growth-limiting levels. Despite these measures a small amount of E. coli growth is still observed in these iron-depleted media. By growing E. coli in conditions that theoretically increase the demand for iron-dependent enzymes, namely by replacing the glucose carbon source for acetate and by switching to a microaerobic atmosphere, we can reduce background growth even further. Finally, we demonstrate that by adding an exogeneous siderophore to the growth media which is poorly used by E. coli, we can completely prevent growth, perhaps mimicking the situation in host tissue. In conclusion, this short study provides practical experimental insight into low iron media and how to augment the growth conditions of E. coli for extreme iron-limited growth.

Cuproptosis associated cytoskeletal destruction contributes to podocyte injury in chronic kidney disease.

The podocyte cytoskeleton determines the stability of podocyte structure and function, and their imbalance plays a pathogenic role in podocyte diseases. However, the underlying mechanism of podocyte cytoskeleton damage is not fully understood. Here, we investigate the specific role of cuproptosis in inducing podocyte cytoskeleton injury. In in vitro and in vivo studies, exposure to high levels of copper and adriamycin (ADR) caused significant increases in copper concentration in intracellular and renal tissue. Moreover, excessive accumulation of copper induced cuproptosis, resulting in the destruction of the podocyte cytoskeleton. However, inhibition of copper accumulation to reduce cuproptosis also significantly alleviated the damage of podocyte cytoskeleton. In addition, inhibition of cuproptosis mitigated ADR-induced mitochondrial damage as well as the production of reactive oxygen species and depolarization of mitochondrial membrane potential, and restored adenosine triphosphate (ATP) synthesis. Among the transcriptome sequencing data, the difference of CXCL5 (C-X-C motif chemokine ligand 5) was the most significant. Both high copper and ADR exposure can cause upregulation of CXCL5, and CXCL5 deletion inhibits the occurrence of cuproptosis, thereby alleviating the podocyte cytoskeleton damage. This suggests that CXCL5 may act upstream of cuproptosis that mediates podocyte cytoskeleton damage. In conclusion, cuproptosis induced by excessive copper accumulation may induce podocyte cytoskeleton damage by promoting mitochondrial dysfunction, thereby causing podocyte injury. This indicates that cuproptosis plays an important role in the pathogenesis of podocyte injury and provides a basis for seeking potential targets for the treatment of chronic kidney disease.NEW & NOTEWORTHY Cuproptosis induced by excessive copper accumulation leads to podocyte cytoskeleton damage by promoting mitochondrial dysfunction, and CXCL5 acts as an upstream signal mediating the occurrence of cuproptosis.

Exploring the underlying mechanism by transcriptome sequencing in rats with high-voltage electrical burns and the role of iron metabolism

BackgroundClinically, the condition of skeletal muscle injury is the key to the process of high voltage electrical burn (HVEB) wound repair. The aim of this study was to identify the potential mechanisms and intervention targets of skeletal muscle injury after HVEB. MethodsA skeletal muscle injury model in SD rats with HVEB was made. Pathological examination and transcriptome sequencing of injured skeletal muscles were performed, and the expression levels of key proteins and genes in related signaling pathways were verified. ResultsSkeletal muscle injury was progressively aggravated within 48h, then the injury was gradually repaired with scar formation occurring within 1 week. The mechanism of skeletal muscle injury is complex and varied, and ferroptosis is one of the mechanisms. The ferrous iron content in the injured skeletal muscle tissue of model rats increased significantly at 24h after injury. After 24h, damage to injured skeletal muscle tissue could be alleviated by increasing iron storage and blocking lysosomal phagocytosis of autophagy. ConclusionsSkeletal muscle injury caused by HVEB is characterized by progressive progression after injury. Ferroptosis is involved in the mechanism of HVEB, and iron metabolism-related proteins may be potential targets for preventing progressive skeletal muscle injury.

Surface-Enhanced Raman Scattering Nanosensing and Imaging in Neuroscience.

Monitoring neurochemicals and imaging the molecular content of brain tissues in vitro, ex vivo, and in vivo is essential for enhancing our understanding of neurochemistry and the causes of brain disorders. This review explores the potential applications of surface-enhanced Raman scattering (SERS) nanosensors in neurosciences, where their adoption could lead to significant progress in the field. These applications encompass detecting neurotransmitters or brain disorders biomarkers in biofluids with SERS nanosensors, and imaging normal and pathological brain tissues with SERS labeling. Specific studies highlighting in vitro, ex vivo, and in vivo analysis of brain disorders using fit-for-purpose SERS nanosensors will be detailed, with an emphasis on the ability of SERS to detect clinically pertinent levels of neurochemicals. Recent advancements in designing SERS-active nanomaterials, improving experimentation in biofluids, and increasing the usage of machine learning for interpreting SERS spectra will also be discussed. Furthermore, we will address the tagging of tissues presenting pathologies with nanoparticles for SERS imaging, a burgeoning domain of neuroscience that has been demonstrated to be effective in guiding tumor removal during brain surgery. The review also explores future research applications for SERS nanosensors in neuroscience, including monitoring neurochemistry in vivo with greater penetration using surface-enhanced spatially offset Raman scattering (SESORS), near-infrared lasers, and 2-photon techniques. The article concludes by discussing the potential of SERS for investigating the effectiveness of therapies for brain disorders and for integrating conventional neurochemistry techniques with SERS sensing.

The hepatoprotective potential of tannic acid against doxorubicin-induced hepatotoxicity: Insights into its antioxidative, anti-inflammatory, and antiapoptotic mechanisms.

Doxorubicin (DOX), which is frequently used in cancer treatment, has limited clinical use due to adverse effects on healthy tissues, especially the liver. Therefore, it is necessary to research the molecular basis of DOX-induced organ and tissue damage and protective agents. In this study, we aimed to examine the protective effects of tannic acid (TA) against DOX-induced hepatoxicity in experimental rat models. Rats were randomly divided into four experimental groups: the untreated control, DOX, TA, and cotreatment (DOX + TA) groups. We investigated the antioxidant system's main components and oxidative stress indicators. Moreover, we examined alterations in the mRNA expression of critical regulators that modulate apoptosis, inflammation, and cell metabolism to better understand the underlying factors of DOX-induced liver toxicity. The results showed that DOX exposure caused an increase in MDA levels and a significant depletion of GSH content in rat liver tissues. Consistent with oxidative stress-related metabolites, DOX was found to significantly suppress both mRNA expression and enzyme activities of antioxidant system components. Moreover, DOX exposure had significant adverse effects on regulating the other regulatory genes studied. However, it was determined that TA could alleviate many of the negative changes caused by DOX. The results of the present study indicated that TA might be considered a versatile candidate that could prevent DOX-induced hepatotoxicity, possibly by preserving cell physiology, viability, and especially redox balance.

Cytokinin oxidase2-deficient mutants improve panicle and grain architecture through cytokinin accumulation and enhance drought tolerance in indica rice.

The Osckx2 mutant accumulates cytokinin thereby enhancing panicle branching, grain yield, and drought tolerance, marked by improved survival rate, membrane integrity, and photosynthetic function. Cytokinins (CKs) are multifaceted hormones that regulate growth, development, and stress responses in plants. Cytokinins have been implicated in improved panicle architecture and grain yield; however, they are inactivated by the enzyme cytokinin oxidase (CKX). In this study, we developed a cytokinin oxidase 2 (Osckx2)-deficient mutant using CRISPR/Cas9 gene editing in indica rice and assessed its function under water-deficit and salinity conditions. Loss of OsCKX2 function increased grain number, secondary panicle branching, and overall grain yield through improved cytokinin content in the panicle tissue. Under drought conditions, the Osckx2 mutant conserved more water and demonstrated improved water-saving traits. Through reduced transpiration, Osckx2 mutants showed an improved survival response than the wild type to unset dehydration stress. Further, Osckx2 maintained chloroplast and membrane integrity and showed significantly improved photosynthetic function under drought conditions through enhanced antioxidant protection systems. The OsCKX2 function negatively affects panicle grain number and drought tolerance, with no discernible impact in response to salinity. The finding suggests the utility of the beneficial Osckx2 allele in breeding to develop climate-resilient, high-yielding cultivars for future food security.