Search Results (517)

Insulin resistance, stem cell dysfunction, and muscle fiber dystrophy are all age-related events in skeletal muscle (SKM). However, age-related changes in insulin isoforms and insulin receptors in myogenic progenitor satellite cells have not been studied. Since SKM is an extra-pancreatic tissue that does not express mature insulin, we investigated the levels of insulin receptors (INSRs) and a novel human insulin upstream open reading frame (INSU) at the mRNA, protein, and anatomical levels in Baltimore Longitudinal Study of Aging (BLSA) biopsied SKM samples of 27–89-year-old (yrs) participants. Using RT-qPCR and the MS-based selected reaction monitoring (SRM) assay, we found that the levels of INSR and INSU mRNAs and the proteins were positively correlated with the age of human SKM biopsies. We applied RNAscope fluorescence in situ hybridization (FISH) and immunofluorescence (IF) to SKM cryosections and found that INSR and INSU were co-localized with PAX7-labeled satellite cells, with enhanced expression in SKM sections from an 89 yrs old compared to a 27 yrs old. We hypothesized that the SKM aging process might induce compensatory upregulation of INSR and re-expression of INSU, which might be beneficial in early embryogenesis and have deleterious effects on proliferative and myogenic satellite cells with advanced age. Full article

This study was conducted on Klasztorne Małe Lake located in the city of Kartuzy. For about 100 years, the lake served as a receiver of domestic, industrial, and rain sewage. The lake was completely degraded. In addition, excessive sewage inflow caused the accumulation of dense pollution in the area of the lake’s deepest part, which caused the formation of a monimolimnion layer. The bradymictic KML became a meromictic lake. After cutting off the inflow of pollutants, the lake was restored by the P inactivation method using coagulants PIX 111 and PAX 18. Before the restoration process of this lake, concentrations of nutrients in the bottom water layers achieved very high values of TN (total N) 65 mg/L and TP (total P) 30 mg/L. An average concentration of chlorophyll was 65 µg/L and visibility did not exceed 1 m. The method used brought very good results. In the entire volume of water, over 90% reduction in TP and a several-fold decrease in the content of TN were noted. The withdrawal of mineral P from the water limited the production processes in the lake, which was reflected in the reduction in chlorophyll amounts (19 µg/L) and the increase in water visibility (2 m). In addition, oxygen conditions in the lake improved. The application of coagulants caused a decrease in the density of the monimolimnion water, which was indicated by a significant decrease in water conductivity. However, the restoration method did not improve the water dynamics. Full article

Cutaneous metastases from clear cell renal carcinoma (ccRC) are uncommon and often indicate a poor prognosis. These metastases typically occur on the scalp, face, and trunk, and they can be difficult to diagnose due to their resemblance to benign dermatological tumors. We report the case of a 56-year-old patient with a history of ccRC (TNM stage 4) who was referred to our dermatology department with two rapidly enlarging, painful lesions on the left jawline and scalp, which had developed one month and one week earlier, respectively. On examination, the lesions appeared as well-defined, round to oval plaques with a central ulceration and a peripheral red rim, suggestive of an inflammatory appearance. Dermoscopic examination revealed a structureless pink to orange pattern, atypical central vessels, and irregular linear vessels in a corona-like arrangement. Despite the patient’s stable oncological treatment for six months, pain management had recently included paracetamol, tramadol, and NSAIDs. The primary presumptive diagnosis was of cutaneous metastasis, considering the patient’s history of metastatic ccRC. However, given the recent initiation of new pharmacological agents, the rapid progression of the cutaneous lesions, and their clinical presentation, alternative differential diagnoses were considered, including drug-induced reactions such as erythema multiforme or fixed drug eruption. A biopsy of the facial lesion revealed immunohistochemical positivity for CD10, CAIX, and PAX8, confirming the diagnosis of metastatic ccRC with sarcomatoid differentiation. Unfortunately, despite continued targeted therapies and palliative care, the patient’s condition deteriorated rapidly, leading to death two months later. This case highlights the potential for extremely rapidly evolving cutaneous metastases from ccRC and their capacity to occasionally mimic atypical drug eruptions. Additionally, it reaffirms the poor prognosis of such metastases, as evidenced by the patient’s death within two months. Full article

The success of rotator cuff tendon repair relies on both tendon healing and muscle recovery. The objective of this descriptive study was to investigate the regenerative potential of the supraspinatus muscle in rotator cuff tear conditions by quantifying the expression of Pax7, MyoD, and myogenin, basic factors that regulate myogenesis. Muscle biopsies were collected from thirty-three patients aged 34 to 73 years who underwent surgery for a rotator cuff tear affecting the supraspinatus muscle. Among these patients, twenty-seven percent were women, and the age of the lesions ranged from 2 to 72 months post-initial trauma. Biopsies were harvested from the supraspinatus muscle at the end closest to the tendon, and control biopsies were harvested from the ipsilateral deltoid muscle. The densities of immunohistochemically stained Pax7⁺, MyoD⁺, and myogenin⁺ nuclei/mm² were used to estimate the myogenic potential of the muscle. Adjustments were made for patient age and lesion age. We found increased density of MyoD⁺ and myogenin⁺ cells in supraspinatus muscles compared to deltoid muscles (p < 0.001 and p = 0.003, respectively). Regression analyses that combined the density of positive nuclei with patient age showed a continuous increase in Pax7 with age but also a reduction of MyoD and myogenin in older patients. When combined with lesion age, there was a decline in the density of all myogenic markers after an initial rise. Pax7 density continued to be higher in supraspinatus compared to the deltoid muscle, but the density of MyoD and myogenin terminally dropped to a density lower than in the deltoid. Our findings suggest that the supraspinatus muscle in tear conditions showed signs of initial activation of muscle regeneration. When compared to the unaffected deltoid muscle, an apparent reduction in capacity to progress to full muscle fiber maturity was also demonstrated. This pattern of inhibited myogenesis seemed to increase with both patient age and lesion age. Our results on muscle regenerative capacity indicate that younger patients with rotator cuff tears have better chances of muscle recovery and may benefit from early surgical reconstruction. Full article

Type 2 diabetes (T2D) is associated with increased inflammation and reactive oxygen species (ROS) in muscles, leading to basal satellite cell (SC) myogenic impairment (i.e., reduction in SC pool), which is critical for maintaining skeletal muscle mass. T2D may contribute to muscle atrophy, possibly due to reductions in the SC pool. Geranylgeraniol (GGOH) and ginger can reduce inflammation and enhance SC myogenesis in damaged muscles, thereby alleviating muscle atrophy; however, their effect on basal SC myogenic state and muscle mass in T2D rats is limited. Rats consumed a control diet (CON), high-fat diet with 35 mg/kg of streptozotocin (HFD), a HFD with 800 mg/kg body weight of GGOH (GG), or a HFD with 0.75% ginger root extract (GRE). In the eighth week, their soleus muscles were analyzed for Pax7, MyoD, and MSTN gene and protein expression, SC myogenic state, and muscle cross-sectional area (CSA). The HFD group had a significantly lower number of Pax7⁺/MyoD⁻ and Pax7⁺/MSTN⁺ cells, less Pax7 and MyoD gene expression, and less MyoD and MSTN protein expression, with a smaller CSA than the CON group. Compared to the GG and GRE groups, the HFD group had a significantly lower number of Pax7⁺/MSTN⁺ cells, less MyoD protein expression, and smaller CSA. The GRE group also had a significantly lower number of Pax7⁻/MyoD⁺ and greater MSTN protein expression than the HFD group. Nevertheless, the CON group had a significantly greater number of Pax7⁺/MyoD⁻ than the GG and GRE groups, and a greater number of Pax7⁻/MyoD⁺ cells than the GRE group with a larger CSA than the GG group. GGOH and ginger persevered muscle CSA, possibly through increased MyoD and the ability to maintain the SC pool in T2D rats. Full article

Background/Objectives:Porphyromonas gingivalis infection has been associated with various systemic diseases and may cause delayed healing of muscle injury. However, the relationship between muscle injury healing and P. gingivalis infection remains unclear. Our hypothesis was that P. gingivalis infection delays the healing of muscle injuries. Methods: Fifty-six 8-week-old male Wistar rats were randomly divided into two groups: sonicated P. gingivalis was intraperitoneally administered in one group (PG group), whereas saline was administered in the other group (CO group). Skeletal muscle injury was induced via cardiotoxin injections in all animals. The cross-sectional area of regenerating muscle cells was evaluated by haematoxylin–eosin staining, and the degree of muscle fibrosis was evaluated by Masson’s trichrome staining. The expression of paired box protein (Pax7) and myoblast determination protein (MyoD) and the identified stages of myocyte regeneration were analysed by immunohistochemical staining. Motion analysis was performed during walking. Results: The cross-sectional area of muscle cells was significantly smaller in the PG group on days 7 and 14 post-injury than in the CO group. The Pax7+/MyoD− ratio was significantly lower in the PG group on day 1 post-injury than in the CO group. Motion analysis of treadmill walking showed that the PG group had a lower minimum calcaneal height on days 3 and 7 post-injury than the CO group. Conclusions: This study suggests that administration of sonicated P. gingivalis in rats can delay the healing process of muscle injury. Further research is needed to understand this mechanism of delay of P. gingivalis. Full article

The pikeperch (Sander lucioperca) is an economically important freshwater fish and a valuable food with high market acceptance. It is undergoing important changes in growth and regulatory metabolism during the ontogeny. Hence, the current study aims to investigate the mRNA expression of the growth hormone (gh)/insulin-like growth factor (igf) axis (ghr, igfI, igfbp, igfr), muscle regulatory factors (pax7, myf5, myod, myogenin, mrf, mymk, mstn), and osteogenesis-related genes (colla1a, fib1a, on, op, ostn) from hatching through day 40th post-hatching (DPH). The average total length (TL) of larvae measured at hatching was 3.6 ± 0.4 mm (67 degree days), and at the end of the experiment (40 DPH, 777 degree days), it was 27.1 ± 1.1 mm. The results showed three phases of gene expression in day 0 (egg), larval, and juvenile stages of pikeperch, which can be a progression or transition from the initial state toward the juvenile state. The expression pattern of myf5, mymk, and fib1a genes showed the highest value at day 0. The growth hormone receptor gene (ghr) and igfbp5 were raised to 1 DPH, whereas increased expression of igfI, igfII, igf1bp4, igf1rb, myod2, and mrf4 was detected at 14 DPH. The myod1, pax7, op, ostc, on, igf1ra, and col1a1a genes were highly expressed at 21 DPH and juvenile stages. According to the PLS-DA model, the most relevant VIPs are myf5 and mymk as best markers of earlier stages and igf1ra, ostc, pax7, and ghr as markers of later stages of ontogeny. Results from this study suggest that basal metabolism, growth of body cells and muscles, and bone proliferation and development can be regulated by the dynamic changes in gene expression patterns in this species. The identified genes will help to understand the basic biological process of pikeperch larvae and development, which is very important in pikeperch farming Full article

Pyrite has natural floatability and thus readily enters valuable mineral flotation concentrates, diluting their quality and decreasing their economic value. Its separation is challenging, depending on process conditions, the presence of activating ions, and water quality, particularly in regions where seawater is used. This study examines the effect of various doses of sodium metabisulfite (SMBS) on pyrite depression in freshwater and seawater under weakly alkaline conditions and with different copper ion concentrations. Without the addition of activators or depressants, pyrite recovery is 40% in freshwater and 60% in seawater, whereas with 10 ppm of SMBS, recoveries drop to 28% and 38%, respectively. The addition of 10 ppm Cu²⁺ increases recovery by 10% in freshwater and by 20% in seawater. In the presence of 75 ppm of PAX, maximum recovery reached 50% in freshwater and 80% in seawater. These results suggest that cationic bridges formed by seawater ions, combined with CaOH⁺ activation, play a critical role in pyrite activation, even in the presence of depressants. Full article

Detecting IgE sensitizations in the serum of allergic dogs is commonly performed using allergen extracts, but these are difficult to standardize. This article details the development and validation of the Pet Allergy Xplorer (PAX; Nextmune, Stockholm, Sweden), the first multiplex macroarray for the detection of IgE sensitization in dogs using allergen extracts and molecular components; the PAX is derived from the Allergy Xplorer (ALEX²; MacroArray Diagnostics, Vienna, Austria). The selection of allergens, cartridge processing, strategy for identifying and blocking IgE directed against cross-reactive carbohydrate determinants (CCDs), and the method used for determining the positivity threshold are described. The validation of the PAX included evaluations of the specificity of its anti-IgE monoclonal antibody, specificity of IgE binding to target allergens, assay precision, and internal consistency. Additionally, the influence of possible confounding factors, such as sample type, the influence of hemolysis, lipemia, bilirubinemia, and elevated CCD-IgE, was tested. Finally, the sensitization rates of 23,858 European dogs to 145 environmental and Hymenoptera venom allergens were summarized. The PAX is accurate and reproducible and has a unique CCD-detection and blocking strategy; its molecular allergens offer a unique window on allergen cross-reactivity. Full article

Background: Identical translocations involving the TFE3 gene and various partners have been found in both renal and soft tissue tumors, like alveolar soft part sarcoma (ASPSCR1), ossifying fibromyxoid tumor (PHF1), epithelioid hemangioendothelioma, and the clear cell stromal tumor of the lung (YAP1). Methods: Herein, we review in detail the clinicopathologic and molecular data of TFE3-rearranged renal tumors and propose our perspective, which may shed light on this emerging conundrum. Results: Among the kidney tumors carrying TFE3 translocations, most are morphologically heterogeneous carcinomas labeling for the tubular marker PAX8. The others are mesenchymal neoplasms known as PEComas, characterized by epithelioid cells co-expressing smooth muscle actin, cathepsin-K, melanogenesis markers, and sometimes melanin pigment deposition. Over the past 30 years, numerous TFE3 fusion partners have been identified, with ASPL/ASPSCR1, PRCC, SFPQ/PSF, and NONO being the most frequent. Conclusions: It is not well understood why similar gene fusions can give rise to renal tumors with different morpho-immunophenotypes, which may contribute to the recent disagreement regarding their classification. However, as these two entities, respectively, epithelial and mesenchymal in nature, are widely recognized by the pathology community and their clinicopathologic features well established, we overall believe it is still better to retain the names TFE3-rearranged renal cell carcinoma and TFE3-rearranged PEComa. Full article

Background: Oncocytic thyroid carcinoma (OTC) was previously considered a variant of follicular thyroid carcinoma (FTC) but has recently been reclassified as a separate form of thyroid cancer. This study aimed to demonstrate that FTC and OTC are fundamentally distinct entities that can potentially be differentiated preoperatively through cytology and/or molecular testing. Methods: A retrospective chart review of patients diagnosed with FTC and OTC operated upon at two university health centers from January 2016 to September 2023 (n = 3219) was conducted. Molecular testing results were correlated with histopathologic diagnosis. Results: Fifty patients met the inclusion criteria. FTC was identified in 27 (54.0%) patients, and OTC in 23 (46.0%) patients. Patients with OTC were older (61.8 years) than FTC patients (51.2 years) (p = 0.013). Moreover, aggressive tumors were found in 39.1% (9/23) of OTCs compared to 11.1% (3/27) of FTCs (p = 0.021). Amongst Bethesda category III and IV nodules, 17 out of 20 (85.0%) OTC cytology reports demonstrated an oncocytic subtype compared to only 5 out of 24 FTC cytology reports (20.8%) (p = 0.002). On molecular testing, the EIF1AX alteration was exclusively present in OTCs while the PAX8/PPARy and PTEN alterations were exclusively found in FTCs. Copy number alterations (CNAs) were found to be more prevalent in OTC (66.7%) compared to FTC (33.3%), and they were not indicative of tumor aggressiveness. Within the OTC group, all three patients who had a TP53 alteration were diagnosed with aggressive cancer. Lastly, the OTCs exhibited a higher frequency of multiple alterations on molecular testing (66.7%) compared to FTCs (33.3%). Conclusion: To our knowledge, this is the largest study to date comparing the clinical application of abnormalities found on molecular testing for FTC and OTC. It further demonstrates the distinct clinicopathological and molecular characteristics of OTC. Full article

Cranial neural crest cells are implicated in multiple transcriptional events at the different stages of differentiation during development. The alteration of some transcription factors expressed during neural crest development, like PAX7, could be implicated in the etiology of face malformation in murine models. Epigenetic regulation has been shown to be an important mechanistic actor in the control of timing and the level of gene expression at different stages of neural crest development. During this work, we investigated the interconnection between epigenetics and transcription factors across a diversity of human development cranial neural crest cells. Across a diversity of neural cells from human developing cranial tissues, in accordance with their proliferation stage, an alternative balance of regulation between transcription factors and epigenetic factors was identified. Full article

Deciduous tooth agenesis is a severe craniofacial developmental defect because it affects masticatory function from infancy and may result in delayed growth and development. Here, we aimed to identify the crucial pathogenic genes and clinical features of patients with deciduous tooth agenesis. We recruited 84 patients with severe deciduous tooth agenesis. Whole-exome and Sanger sequencing were used to identify the causative variants. Phenotype–genotype correlation analysis was conducted. We identified 54 different variants in 8 genes in 84 patients, including EDA (73, 86.9%), PAX9 (2, 2.4%), LRP6 (2, 2.4%), MSX1 (2, 2.4%), BMP4 (1, 1.2%), WNT10A (1, 1.2%), PITX2 (1, 1.2%), and EDARADD (1, 1.2%). Variants in ectodysplasin A (EDA) accounted for 86.9% of patients with deciduous tooth agenesis. Patients with the EDA variants had an average of 15.4 missing deciduous teeth. Mandibular deciduous central incisors had the highest missing rate (100%), followed by maxillary deciduous lateral incisors (98.8%) and mandibular deciduous lateral incisors (97.7%). Our results indicated that EDA gene variants are major pathogenic factors for deciduous tooth agenesis, and EDA is specifically required for deciduous tooth development. The results provide guidance for clinical diagnosis and genetic counseling of deciduous tooth agenesis. Full article

Transcription factors control genes to maintain normal hemopoiesis, and dysregulation of some factors can lead to acute lymphoblastic leukemia (ALL). Mycoviruses are known to alter the genetics of their fungal host. The present study evaluates the effects of the products of a mycovirus-containing Aspergillus flavus (MCAF), isolated from the home of a patient with ALL, on certain transcription factors of normal and ALL cell lines. Our published studies have shown that ALL patients have antibodies to MCAF, and that exposure of the mononuclear leukocytes of patients in complete remission to its products, unlike controls, results in the re-development of genetic and cell surface phenotypes characteristic of ALL. For the present study, normal, pre-B, and B-cell leukemia cell lines were exposed to the culture of MCAF. Pre- and post-exposure levels of PAX5, Ikaros, and NF-κB were assessed. Exposure to MCAF resulted in apoptosis, cell cycle changes, and complete downregulation of all transcription factors in normal cell lines. In acute leukemia cell lines, cellular apoptosis and alterations in the cell cycle were also noted; however, while there was downregulation of all tested transcription factors, residual levels were retained. The noted alterations in the transcription factors caused by MCAF are novel findings. The possible role of MCAF in leukemogenesis needs to be further investigated. Mycovirus-containing Aspergillus flavus was initially isolated from a leukemia patient’s home. Our prior published studies have illuminated intriguing associations of this organism with leukemia. Unlike controls, patients diagnosed with acute lymphoblastic leukemia (ALL) harbor antibodies to this organism. Furthermore, the exposure of mononuclear cells from patients with ALL in complete remission to the products of this organism reproduced genetic and cell phenotypes characteristic of ALL. These findings underscore the potential role of environmental factors in leukemogenesis and hint at novel avenues for therapeutic intervention and preventive strategies. Full article

In this research, we aimed to determine the antioxidant activity of an atomized extract of Cnidoscolus diacanthus (Pax & K. Hoffm.) J.F. Macbr., known in Peru as “huanarpo hembra”, and its effect on sex hormone levels. Its phytochemical profile was determined using liquid chromatography–mass spectrometry (LC–MS), while its total phenol content (TPC) and total flavonoids (TFs) were determined using the Folin–Ciocalteu method and the aluminum chloride method. Its antioxidant activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), the radical 2,2-azino-bis-3-ethylbenzthiazolin-6 sulfonic acid (ABTS), and ferric-reducing antioxidant power (FRAP). The biological activity of C. diacanthus and its effect on sexual hormones were determined in Holtzman rats of both sexes. Phytochemical analysis revealed the presence of flavonoids and phenolic compounds in its leaves and stems, mainly rutin, quercetin, chlorogenic acid, and genistein. However, the stem extract contained higher total phenol (464.38 ± 4.40 GAE/g) and flavonoid (369.17 ± 3.16 mg QE/g of extract) contents than the leaf extract (212.38 ± 3.19 mg GAE/g and 121.49 ± 2.69 mg QE/g). For DPPH, ABTS, and FRAP, the Trolox-equivalent antioxidant capacity (TEAC) was 597.20 ± 5.40 µmol/g, 452.67 ± 5.76 µmol/g, and 535.91 ± 1.56 µmol/g, respectively, for the stems, while for the leaves, it was 462.39 ± 3.99 µmol/g, 202.32 ± 5.20 µmol/g, and 198.13 ± 1.44 µmol/g, respectively. In terms of the values for hormonal levels, at a dose of 100 mg/kg of the extract, testosterone levels of 1.430 ng/mL (with the leaf extract) and 1.433 ng/mL (with the stem extract), respectively, were found in the male rats. Regarding estradiol levels, in the female rats, these were 10.425 ng/mL (leaf extract) and 8.775 ng/mL (stem extract), while their levels of luteinizing hormone were 0.320 mIU/mL (leaf extract) and 0.273 mIU/mL (stem extract). For the follicle-stimulating hormone, levels of 0.858 mIU/mL (leaf extract) and 0.840 mIU/mL (stem extract) were found in the female rats, and levels of 0.220 mIU/mL (leaf extract) and 0.200 mIU/mL (stem extract) were found in the male rats. It is concluded that the C. diacanthus stem extract had a greater antioxidant capacity than the leaf extract, while both extracts had a superior effect on the sex hormone levels in the female rats compared to the male rats. Full article