Tissue Alterations Research Articles

Powdery mildew pathogen [Erysiphe necator (Schw.) Burrill.] induced physiological and biochemical alterations in leaf tissue of grapevines (Vitis spp.)

Grapevine serves as a host for an array of pathogenic agents, among which powdery mildew (PM), a fungal disease, stands as a major threat under changing climate and erratic weather patterns. The study aimed to examine the physiological, biochemical responses and microscopic examinations of diverse grapevine genotypes including the 42 Vitis species to powdery mildew infection caused by Erysiphe necator (Schw.) Burrill. Significant reductions were observed in leaf gas exchange parameters like net photosynthetic rate (33.09 %) and transpiration rate (32.36 %) in the infected leaves of susceptible genotypes compared to resistant and moderate genotype groups. Susceptible genotypes had higher intercellular CO2 concentration (4.01 %). Chlorophyll fluorescence analysis revealed a decrease in the maximum quantum efficiency of photosystem-II in PM-infected leaves across the genotype groups. Furthermore, PM infection led to a decrease in chlorophyll content, particularly in susceptible plants, along with a notable reduction in total chlorophyll (25.86 %) and total carotenoids (3.58 %) contents. The ascorbic acid/dehydroascorbic ascorbic acid ratio was observed to be increased by 50 % in the susceptible genotypes due to PM infection. The higher potassium content was registered in healthy leaves of resistant genotypes compared to PM infection stage. This clearly demonstrated the genotype-specific ability to withstand biotic stress. Antioxidant enzyme activities, including glutathione reductase (1.27-fold), polyphenol oxidase (1.15-fold), phenylalanine ammonia-lyase (1.02-fold) and peroxidase (1.21-fold), were enhanced in PM infected plants, suggesting the activation of different defence mechanisms against oxidative stress induced due to pathogen. Scanning electron microscopy revealed prominent differences in fungal hyphae growth between susceptible and resistant genotypes, which showed restricted tissue growth and host cell necrosis.

The Radiogenomic Landscape of Clear Cell Renal Cell Carcinoma: Insights into Lipid Metabolism through Evaluation of ADFP Expression.

This study aims to explore the relationship between radiological imaging and genomic characteristics in clear cell renal cell carcinoma (ccRCC), focusing on the expression of adipose differentiation-related protein (ADFP) detected through computed tomography (CT). The goal is to establish a radiogenomic lipid profile and understand its association with tumor characteristics. Data from The Cancer Genome Atlas (TCGA) and the Cancer Imaging Archive (TCIA) were utilized to correlate imaging features with adipose differentiation-related protein (ADFP) expression in ccRCC. CT scans assessed various tumor features, including size, composition, margin, necrosis, and growth pattern, alongside measurements of tumoral Hounsfield units (HU) and abdominal adipose tissue compartments. Statistical analyses compared demographics, clinical-pathological features, adipose tissue quantification, and tumoral HU between groups. Among 197 patients, 22.8% exhibited ADFP expression significantly associated with hydronephrosis. Low-grade ccRCC patients expressing ADFP had higher quantities of visceral and subcutaneous adipose tissue and lower tumoral HU values compared to their high-grade counterparts. Similar trends were observed in low-grade ccRCC patients without ADFP expression. ADFP expression in ccRCC correlates with specific imaging features such as hydronephrosis and altered adipose tissue distribution. Low-grade ccRCC patients with ADFP expression display a distinct lipid metabolic profile, emphasizing the relationship between radiological features, genomic expression, and tumor metabolism. These findings suggest potential for personalized diagnostic and therapeutic strategies targeting tumor lipid metabolism.

Comparative Assessment of Lipid Peroxidase in Oral Cancer and Oral Potentially Malignant Disorders.

Introduction Oral potentially malignant disorders (OPMD) are abnormally altered tissues that could potentially develop into oral cancer. From the literature, it is understandable that not all OPMDs develop into oral cancer. Hence, it is essential to identify the high-risk lesions that are more likely to develop into oral cancer. Lipid peroxidase (LPO) is a byproduct of phospholipidmetabolism, and its levels are an oxidative stress marker that can probably help us predict the onset of cancer in OPMDS. This study aimed to assess the levels of LPO in OPMD, oral cancer, and normal patients. Materials and methods The sample size estimated was 15 per group. There were four groups in total. The estimation was done with the Abbkine LPO enzyme-linked immunosorption assay (ELISA) kit (Atlanta, Georgia, USA). An enzyme-substrate reaction was carried out, and the degree of the color change was measured using a microplate reader. The values were tabulated, and statistics were carried out using Statistical Package for Social Sciences(SPSS) version 26.0 (IBM Corp., Armonk, NY, USA). Both descriptive and inferential statistics were carried out. Results LPO levels (nmol/L) in each of the four groups were as follows: Group 1 (oral cancer): 171.86±78.86, Group 2 (controls): 71.66±28.36, Group 3: (oral leukoplakia): 127.50±103.53, and Group 4 (oral submucous fibrosis and oral lichen planus): 100.39±41.06.The results, when compared, were statistically significant (P< 0.05). Discussion From the above results, it is understandable that oral cancer patients experience increased oxidative stress compared to the OPMD group. The current study concluded that the obtained results showed differences in LPO levels, suggesting LPO could be used as a marker and screening tool to assess the rate and severity of cellular damage in patients with oral potentially malignant disorders.

COMPARATIVE EVALUATION OF PERI-IMPLANT TISSUES AROUND EARLY LOADED VERSUS DELAYED LOADEDIMPLANTS

Aims and Objectives: This study compared and evaluated the peri-implant tissue alterations in single-piece implants that were loaded early versus delayed. To evaluate the differences in radiographic results and clinical characteristics between early and delayed loaded implants. Materials and Methods: Using radio visio graphs (RVGs), the current study aims to assess and compare the clinical and radiographic results of early loaded implants versus delayed loaded implants. Twenty sites in all, based on the kind of implant loading techniques, were randomly divided into two groups by flipping a coin, following the first screening and the patients who met the inclusion requirements. Ten sites with an early loading technique (GROUP 1) and ten sites with a delayed loading methodology (GROUP 2) were separated into two groups. In both groups, the Bioline single-piece implants were utilised. Results: The clinical parameters probing pocket depth, clinical attachment level, and width of the keratinized peri-implant mucosa were measured at baseline, 3 &amp; 6 months. Changes in marginal bone loss were measured using RVG. To evaluate the alterations in marginal bone level, AUTO CAD was utilised. SPSS V.23 was employed for the purpose of data analysis. Using the Mann Whitney U test for intergroup comparison and Friedmans Two-way ANOVA for intragroup comparison, groups 1 and 2 were assessed on mesial and distal surfaces. Conclusion: Given the current studys constraints, the findings can be summed up as follows: early loaded implants performed better than delayed loaded implants in all clinical and radiographic measures from baseline to six months.

Biosafety assessment and In vitro antioxidant activity of Musanga cecropioides root sap

The present study evaluated the biosafety and in vitro antioxidant activity of Musanga cecropioides root sap, a traditional remedy known for its health benefits. The sap was found to be rich in bioactive compounds, including alkaloids, tannins, saponins, flavonoids, and phenols, confirming existing literature. Proximate analysis revealed high moisture, fat, and protein content, alongside significant levels of essential vitamins and amino acids, indicating potential nutritional and therapeutic benefits. Acute toxicity assessments in mice demonstrated safety at doses up to 100 ml/kg, while the sub-acute toxicity assessment using rats showed no significant changes in haematological parameters or liver and kidney function markers. Histological examinations showed minor, non-significant alterations in liver and lung tissues. Antioxidant assays (DPPH and ABTS) revealed considerable radical scavenging activities, attributed to the presence of known antioxidant compounds. These findings support the traditional use of Musanga cecropioides root sap, highlighting its potential as a natural therapeutic agent. Further research is recommended to explore its mechanisms and clinical efficacy, paving the way for its development into a standardized natural remedy.

Hepatoprotective activity of Mentha rotundifolia aqueous extract against hepatocellular damage induced by CCL4 in rats

This study aims to assess hepatoprotective properties of M. rotundifolia. Decoction was used to prepare the aqueous extract. The preliminary cytotoxicity evaluated against Caco 2 and RAW 264 cells demonstrate no cytotoxic effect. The preventive impact of the extract against liver damage was evaluated by examining blood levels of AST, ALT, ALP, total proteins, and histological alterations in liver tissues. Thirty albino rats were separated into five groups: the first served as normal group, the second was injected by olive oil (3 ml/kg), and the third was injected by CCL4 (3 ml/kg). However, groups IV and V received daily doses of 250 and 500 mg extract/kg bw, respectively before CCL4 injection. The results showed that the administration of the extract led to a marked improvement in plasma biochemical markers and a reduction in symptoms of CCL4-induced liver damage. The extract exhibits hepatoprotective activity, which may be attributed to its phytochemical components.

The 5HT4R agonist velusetrag efficacy on neuropathic chronic intestinal pseudo-obstruction in PrP-SCA7-92Q transgenic mice.

Chronic intestinal pseudo-obstruction (CIPO) is a type of intestinal dysfunction with symptoms of intestinal blockage but without the actual mechanical obstruction. Currently, there are no drugs available to treat this disease. Herein, we report the characterization of the PrP-SCA7-92Q transgenic (Tg) line as a valuable CIPO mouse model and investigated the tolerability and efficacy of the 5-hydroxytryptamine type-4 receptor (5HT4R) agonist velusetrag as a promising pharmacological treatment for CIPO. To test the pharmacodynamics of velusetrag, 8-week-old SCA7 Tg mice, which express human mutated Ataxin-7 gene containing 92 CAG repeats under the mouse prion protein promoter, were treated for 5weeks by oral route with velusetrag at 1 and 3mg/kg doses or vehicle. Body weight was monitored throughout the treatment. After sacrifice, the small intestine and proximal colon were collected for whole-mount immunostaining. Untreated, age-matched, C57BL/6J mice were also used as controls in comparison with the other experimental groups. Analysis of SCA7 Tg mice showed tissue damage and alterations, mucosal abnormalities, and ulcers in the distal small intestine and proximal colon. Morphological changes were associated with significant neuronal loss, as shown by decreased staining of pan-neuronal markers, and with accumulation of ataxin-7-positive inclusions in cholinergic neurons. Administration of velusetrag reversed intestinal abnormalities, by normalizing tissue damage and re-establishing the normal level of glia/neuron's count in both the small and large intestines. We demonstrated that the PrP-SCA7-92Q Tg line, a model originally developed to mimic spinocerebellar ataxia, is suitable to study CIPO pathology and can be useful in establishing new therapeutic strategies, such as in the case of velusetrag. Our results suggest that velusetrag is a promising compound to treat patients affected by CIPO or intestinal dysmotility disease.

A study of clinical evaluation of migraine and other seizure related headaches in patients with Epilepsy - a prospective, cross-sectional, observational study

Introduction Epilepsy and Migraine are the chronic disorders with recurrent neurological dysfunction associated with headache and autonomic, abdominal and psychotic features. In some patients it may be difficult to differentiate between migraine and the seizure episodes. Both are having comorbid symptoms and occurrence. Migraine patients can develop seizure and epileptics can have migraine attacks. Epileptologists proposed the hyperexcitability of the altered brain tissue, as the cause of seizure and migraine headache occurrence and vice versa. Enhanced hyperexcitability of cortical neurons and diminished threshold are the pathophysiological mechanisms enumerated in these conditions. Low magnesium in brain and the altered neurotransmitters are responsible for increased cortical excitability. Both the environmental as well as the genetic factors might cause these changes.

Angiogenesis-elicited spectral responses of early invasive skin melanoma: Implications for the evaluation of lesion progression.

Early invasive skin melanoma (EISM) associated with partial tumor invasion to the thin and optically complex papillary dermis (PD) represents a critical stage before the onset of metastasis. EISM lesions may be accompanied by angiogenesis, which can alter the PD's blood and fibril contents. A comprehensive understanding about these interconnected processes is essential for enhancing the efficacy of EISM optical evaluation methodologies. Employing a first-principles computational approach supported by measured data, we systematically assess the impact that angiogenesis can have on the EISM's spectral responses. Our findings indicate that these responses are discernibly affected by angiogenesis under distinct physiological conditions, with more substantial tissue alterations leading to accentuated spectral changes in the 550-600 nm region. Accordingly, we propose the use of a customized low-cost spectral index to monitor these processes. Furthermore, our investigation provides a high-fidelity in silico platform for interdisciplinary research on the photobiology of evolving skin melanomas.

Structural and molecular alterations in murine tissue due to far-field radiofrequency exposure

Public concern over exposure to radiofrequency electromagnetic fields has prompted several studies to determine possible health outcomes. However, studies on low level far-field radiofrequency (RF) exposure remain inconclusive on whether it can alter biological systems. Our study's aim was to evaluate structural and molecular modifications such as apoptosis and gene expression in murine brain, liver and kidney tissues exposed to a far-field RF of 915 MHz at a whole-body specific absorption rate of 1.17 W/kg. Forty (40) Swiss male mice were equally and randomly divided into 2 groups: a control group and an RF-exposed group. Each were further equally subdivided (n=5 per subgroup) based on different time points: baseline or no exposure, 3-day exposure, 6-day-exposure and 9-day exposure subgroups. Biometric parameters such as body temperature, body weight, and organ weight were obtained. Tissue samples were collected and analyzed using light and electron microscopy, followed by qPCR assay for both the p53 and Hsp-70 genes. Statistical analysis was performed using ANOVA. There was evidence of both structural and molecular modification beginning Day 3 from continuous-wave far-field RF exposure. The study established multi-level alterations in the murine system due to far field RF exposure providing a glimpse of possible biological effects, and therefore, a need for further studies to translate such evidence in a larger biological perspective.

Histopathological Alterations in Nilaparvata lugens (Hemiptera: Delphacidae) after Exposure to Cordyceps javanica.

The brown planthopper (BPH), Nilaparvata lugens (Stål, 1854), is a pest of rice plants worldwide. Cordyceps javanica is a destructive entomopathogenic fungus known to attack leafhoppers or BPHs specifically. Live adult BPH samples were inoculated with isolated C. javanica PSUC002, and their interaction was morpho-histologically examined from 0 to 120 h post-inoculation (pi). We observed that the mortality of BPH continuously increased until 120 h pi (Day 5). Tissue alterations in the host were examined after infection using morphological and histological methods, including the Grocott Methenamine Silver stain test (GMS). Filamentous fungi were first found on the external integument at 12 h pi, and fungal conidia attached to the integument at 24 h pi. However, the initial degeneration of BPHs was identified by histology at 6 h pi especially in the integument and adipose tissue. We identified the degeneration and loss of integument and adipose tissue of infected BPHs at 12 h pi, and their necrosis was completed at 96 h pi. The enzymatic index of the sampled fungi (chitinase and protease) peaked at 7 days of incubation. This study demonstrated that C. javanica PSUC002 is useful to control the BPHs as an eco-friendly practice and will possibly be applied in agriculture.

Metabolomic Profiling of Adipose Tissue in Type 2 Diabetes: Associations with Obesity and Insulin Resistance.

The global prevalence of Type 2 Diabetes (T2D) poses significant public health challenges due to its associated severe complications. Insulin resistance is central to T2D pathophysiology, particularly affecting adipose tissue function. This cross-sectional observational study investigates metabolic alterations in subcutaneous adipose tissue (SAT) associated with T2D to identify potential therapeutic targets. We conducted a comprehensive metabolomic analysis of SAT from 40 participants (20 T2D, 20 ND-T2D), matched for sex, age, and BMI (Body Mass Index). Metabolite quantification was performed using GC/MS and LC/MS/MS platforms. Correlation analyses were conducted to explore associations between metabolites and clinical parameters. We identified 378 metabolites, including significant elevations in TCA cycle (tricarboxylic acid cycle) intermediates, branched-chain amino acids (BCAAs), and carbohydrates, and a significant reduction in the nucleotide-related metabolites in T2D subjects compared to those without T2D. Obesity exacerbated these alterations, particularly in amino acid metabolism. Adipocyte size negatively correlated with BCAAs, while adipocyte glucose uptake positively correlated with unsaturated fatty acids and glycerophospholipids. Our findings reveal distinct metabolic dysregulation in adipose tissue in T2D, particularly in energy metabolism, suggesting potential therapeutic targets for improving insulin sensitivity and metabolic health. Future studies should validate these findings in larger cohorts and explore underlying mechanisms to develop targeted interventions.

Baicalin promotes migration and angiogenesis of endothelial progenitor cells but impedes thrombus formation via SIRT1/NF-κB signaling in a rat model of deep vein thrombosis.

Deep vein thrombosis (DVT) is the third most prevalent vascular disease worldwide, seriously threatening human health. Baicalin, a flavonoid isolated from the roots of Scutellaria baicalensis, has been identified to play a crucial role in various vascular diseases. The study aimed to explore the efficacy and underlying mechanisms of baicalin in DVT. Endothelial progenitor cells (EPCs) were differentiated from peripheral blood mononuclear cells isolated from rat bone marrow. Dil-ac-LDL/FITC-UEA-1 double staining and flow cytometry analysis were conducted for the identification of EPCs. The angiogenesis and migration of EPCs in vitro were tested by a tube formation assay and Transwell assay, respectively. DVT rat models were established by stenosis of the inferior vena cava (IVC). After the euthanasia of rats, thrombi in the IVC were collected and weighed, and histological alterations in IVC tissue were measured by H&E staining. The protein levels of SIRT1, p-P65, and p65 in rat IVC tissues were quantified via western blotting. EPCs used in this study displayed a spindle-like shape and were positive for endothelial cell-specific markers, suggesting the phenotypic characteristics of EPCs. Baicalin enhanced the migratory and angiogenetic abilities of EPCs in vitro. For in vivo experiments, baicalin reduced thrombus weight and mitigated DVT formation in model rats. Moreover, baicalin activated SIRT but repressed NF-κB signaling in IVC tissues of DVT rats. Baicalin facilitates migration and angiogenesis of EPCs but impedes thrombus formation via regulation of SIRT1/NF-κB signaling in DVT model rats.

Assessment for acceleration and transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma using histologic and immunohistochemical features: a case series

Morphologic features of aggressive/ “accelerated” chronic lymphocytic leukemia/small lymphocytic lymphoma (aCLL/SLL) have been described. Richter transformation (RT) also occurs in a subset of CLL/SLL cases. This case series examined inter-observer variability when assessing for aCLL/SLL and RT, with attention to how immunohistochemical (IHC) markers may assist in this evaluation. Twelve cases of CLL/SLL with available FFPE tissue were identified. H&E staining and IHC (CD3, CD20, CD5, CD23, LEF1, LAG3, C-MYC, PD-1, MUM1, Cyclin D1, BCL-6, p53, and Ki-67) were performed. Three hematopathologists reviewed each case. The pathologists provided a final interpretation of (1) CLL/SLL, (2) CLL/SLL with expanded and/or confluent proliferation centers or increased Ki-67 (aCLL/SLL), or (3) large cell transformation/DLBCL. The pathologists lacked consensus in the diagnosis in 6/12 cases (50%). The reviewers disagreed on the presence of expanded/confluent proliferation centers in 8/12 cases (67%). With the exception of Ki-67, no IHC marker showed a difference in the staining profile in aCLL/SLL or RT compared to low-grade cases. This series showed inter-observer variability in the evaluation for aCLL/SLL and RT. A study that serially examines genetic alterations in FFPE tissue and correlates the features with histology and IHC, at diagnosis and throughout the disease course, may help refine indicators of aggressive disease.

Predicting major adverse cardiac events using radiomics nomogram of pericoronary adipose tissue based on CCTA: A multi-center study.

The evolution of coronary atherosclerotic heart disease (CAD) is intricately linked to alterations in the pericoronary adipose tissue (PCAT). In recent epochs, characteristics of the PCAT have progressively ascended as focal points of research in CAD risk stratification and individualized clinical decision-making. Harnessing radiomic methodologies allows for the meticulous extraction of imaging features from these adipose deposits. Coupled with machine learning paradigms, we endeavor to establish predictive models for the onset of major adverse cardiovascular events (MACE). To appraise the predictive utility of radiomic features of PCAT derived from coronary computed tomography angiography (CCTA) in forecasting MACE. We retrospectively incorporated data from 314 suspected or confirmed CAD patients admitted to our institution from June 2019 to December 2022. An additional cohort of 242 patients from two external institutions was encompassed for external validation. The endpoint under consideration was the occurrence of MACE after a 1-year follow-up. MACE was delineated as cardiovascular mortality, newly diagnosed myocardial infarction, hospitalization (or re-hospitalization) for heart failure, and coronary target vessel revascularization occurring more than 30days post-CCTA examination. All enrolled patients underwent CCTA scanning. Radiomic features were meticulously extracted from the optimal diastolic phase axial slices of CCTA images. Feature reduction was achieved through a composite feature selection algorithm, laying the groundwork for the radiomic signature model. Both univariate and multivariate analyses were employed to assess clinical variables. A multifaceted logistic regression analysis facilitated the crafting of a clinical-radiological-radiomic combined model (or nomogram). Receiver operating characteristic (ROC) curves, calibration, and decision curve analyses (DCA) were delineated, with the area under the ROC curve (AUCs) computed to gauge the predictive prowess of the clinical model, radiomic model, and the synthesized ensemble. A total of 12 radiomic features closely associated with MACE were identified to establish the radiomic model. Multivariate logistic regression results demonstrated that smoking, age, hypertension, and dyslipidemia were significantly correlated with MACE. In the integrated nomogram, which amalgamated clinical, imaging, and radiomic parameters, the diagnostic performance was as follows: 0.970 AUC, 0.949 accuracy (ACC), 0.833 sensitivity (SEN), 0.981 specificity (SPE), 0.926 positive predictive value (PPV), and 0.955 negative predictive value (NPV). The calibration curve indicated a commendable concordance of the nomogram, and the decision curve analysis underscored its superior clinical utility. The integration of radiomic signatures from PCAT based on CCTA, clinical indices, and imaging parameters into a nomogram stands as a promising instrument for prognosticating MACE events.

SPP1 could be an immunological and prognostic biomarker: From pan-cancer comprehensive analysis to osteosarcoma validation.

Secreted phosphoprotein 1 (SPP1), also known as osteopontin, is a phosphorylated protein. High SPP1 expression levels have been detected in multiple cancers and are associated with poor prognosis and reduced survival rates. However, only a few pan-cancer analyses have targeted SPP1. We conducted a comprehensive analysis using multiple public databases, including TIMER and TCGA, to investigate the expression levels of SPP1 in 33 different tumor types. In addition, we verified the effect of SPP1 on osteosarcoma. To assess the impact of SPP1 on patient outcomes, we employed univariate Cox regression and Kaplan-Meier survival analyses to analyze overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in these tumor patients. We also explored SPP1 gene alterations in various tumor tissues using cBioPortal. We then examined the relationship between SPP1 and clinical characteristics, TME, immune regulatory genes, immune checkpoints, TMB, and MSI using R language. In addition, we used GSEA to investigate the molecular mechanisms underlying the role of SPP1. Bioinformatics analysis indicated that SPP1 was upregulated in 17 tumors. Overexpression of SPP1 results in poor OS, DSS, and PFI in CESC, ESCA, GBM, LGG, LIHC, PAAD, PRAD, and skin cutaneous melanoma. SPP1 expression was positively associated with immunocyte infiltration, immune regulatory genes, immune checkpoints, TMB, MSI, and drug sensitivity in certain cancers. We found that high expression of SPP1 in osteosarcoma was related to drug resistance and metastasis and further demonstrated that SPP1 can stimulate osteosarcoma cell proliferation via CCND1 by activating the PI3K/Akt pathway. These findings strongly suggest that SPP1 is a potential prognostic marker and novel target for cancer immunotherapy.

Perfluorooctanesulfonic acid (PFOS) induced cancer related DNA methylation alterations in human breast cells: A whole genome methylome study

DNA methylation plays a pivotal role in cancer. The ubiquitous contaminant perfluorooctanesulfonic acid (PFOS) has been epidemiologically associated with breast cancer, and can induce proliferation and malignant transformation of normal human breast epithelial cells (MCF-10A), but the information about its effect on DNA methylation is sparse. The aim of this study was to characterize the whole-genome methylome effects of PFOS in our breast cell model and compare the findings with previously demonstrated DNA methylation alterations in breast tumor tissues. The DNA methylation profile was assessed at single CpG resolution in MCF-10A cells treated with 1 μM PFOS for 72 h by using Enzymatic Methyl sequencing (EM-seq). We found 12,591 differentially methylated CpG-sites and 13,360 differentially methylated 100 bp tiles in the PFOS exposed breast cells. These differentially methylated regions (DMRs) overlapped with 2406 genes of which 494 were long non-coding RNA and 1841 protein coding genes. We identified 339 affected genes that have been shown to display altered DNA methylation in breast cancer tissue and several other genes related to cancer development. This includes hypermethylation of GACAT3, DELEC1, CASC2, LCIIAR, MUC16, SYNE1 and hypomethylation of TTN and KMT2C. DMRs were also found in estrogen receptor genes (ESR1, ESR2, ESRRG, ESRRB, GREB1) and estrogen responsive genes (GPER1, EEIG1, RERG). The gene ontology analysis revealed pathways related to cancer phenotypes such as cell adhesion and growth. These findings improve the understanding of PFOS's potential role in breast cancer and illustrate the value of whole-genome methylome analysis in uncovering mechanisms of chemical effects, identifying biomarker candidates, and strengthening epidemiological associations, potentially impacting risk assessment.

Raman-guided exploration of placental microplastic exposure: Unraveling the polymeric tapestry and assessing developmental implications

The prevalence of microplastics in human tissues and their potential reproductive toxicity have been increasingly documented, yet their appearance in the placenta and the impact of microplastic exposure on human fertility and pregnancy remains uncertain. Utilizing an inVia™ confocal Raman microspectroscopy by Renishaw equipped with a detection threshold as low as 0.25 µm, our study examined the microplastics in the placentas of 50 women post-delivery and investigated their correlations with gestational age, and neonatal length and weight. We found that 40 microplastic particles were identified across 31 of 50 placentas, averaging 2.35 ± 1.25 µm in size and ranging from 1.03 to 6.84 µm. Seven distinct polymer types were detected, with PTFE, PS, and ABS being the most prevalent. Notably, no significant difference across the normal, PTFE, and PS groups for all demographic variables examined was identified, nor as pathological alterations of placental tissues. In conclusion, our findings demonstrate the presence of seven microplastic polymers in human placentas, with PTFE, PS, and ABS being the most prevalent. However, maternal and neonatal parameters were not affected, and further studies are necessary to elucidate the effects of microplastics on developmental outcomes and fetal health.

Quercetin alleviates kidney damage caused by mercury Chloride: The protective effects of quercetin on autophagy and inflammation were studied based on TRIM32/TLR4/LC3 pathway

ObjectiveMercury is one of the heavy metal pollutants causing serious harm to human health. Quercetin was observed to repair kidney damage through the TLR4/TRIM32 pathway, and the detoxification effect of quercetin on heavy metal poisoning was observed. MethodsFor the study, the researchers divided 40 male mice from the KM strain into five groups: control, HgCl2, QU30, HgCl2+QU15, and HgCl2+QU30. The biological effects of those mice in each group were detected by the biochemical experiment, histopathology experiment and protein expression experiment respectively. ResultsHgCl2 had effects in increasing the level of malondialdehyde (MDA) and decreasing the activity of antioxidant enzymes (P < 0.05). HgCl2 induced inflammation by increasing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and Toll Like Receptor 4 (TLR-4) (P < 0.05). The expression of creatinine (CRE) and urea nitrogen (BUN) showed that HgCl2 promoted kidney injury. HgCl2 altered renal tissue integrity and TRIM32 expression which resulted in the increased autophagy associated protein levels of LC3. In contrast, quercetin reduced oxidative stress, autophagy, inflammation and histopathological changes (P < 0.05). ConclusionQuercetin has the renal protection effects of anti-inflammation, anti-oxidation and anti-autophagy.

Hydroethanolic extracts from Bauhinia guianensis: a study on acute toxicity in Zebrafish embryos and adults

Context The botanical species Bauhinia guianensis Aublet (Leguminosae-Cercidoideae) is traditionally used in the Amazon for medicinal purposes. Objective The acute toxicity of the hydroethanolic extracts from B. guianensis leaves and stems (HELBg and HESBg) was evaluated in zebrafish (Danio rerio), with emphasis on the embryonic developmental stage and adult alterations. Materials and methods Extracts were analyzed on LC-DAD-MS/MS. Zebrafish eggs were inoculated individually with concentrations of HELBg and HESBg (0.25, 0.5, 0.75, 1.0, and 1.5 µg/mL), observed for 96 h. Adult zebrafish were treated with a single oral dose (100, 200, 500, 1000, and 2000 mg/kg) of HELBg and HESBg, observed for 48 h. Results HELBg and HESBg analysis detected 55 compounds. Both extracts exhibited toxicity, including embryo coagulation at higher doses of HELBg and absence of heartbeats in embryos at all doses of HESBg. Behavioral variations were observed; tissue alterations in adult zebrafish were found at the highest doses, primarily in the liver, intestine, and kidneys because of HELBg and HESBg effects. The LD50 of HESBg was 1717 mg/kg, while HELBg exceeded the limit dose of 2000 mg/kg. Conclusions The study on acute toxicity of B. guianensis extracts exhibits significant toxic potential, emphasizing effects on embryonic and adult zebrafish. The results suggest relative safety of the species preparations, encouraging further clinical trials on potential biological activities.