Analysis Of Tissue Research Articles

Effects of Gestational and Lactational Lead Exposure and High Fat Diet Feeding on Cerebellar Development of Postnatal Rat Offspring.

Obesity and heavy metals, such as lead (Pb), are detrimental to the adult brain because they impair cognitive function and structural plasticity. However, the effects of co-administration of Pb and a high-fat diet (HFD) on the developing cerebellum is not clearly elucidated. We investigated the effects of Pb exposure (0.3% lead acetate) on developing cerebellum in the pups of an HFD-fed obese rat model. One week before mating, we fed a chow diet (CD) or HFD to the rats for one week and additionally administered Pb to HFD-fed female SD rats. Thereafter, treatment with Pb and a HFD was continued during the gestational and lactational periods. On postnatal day 21, the pups were euthanized to sample the brain tissue and blood for further analysis. Blood Pb levels were significantly higher in HFD-fed rats than in CD-fed rats. Histologically, the prominent degeneration of Purkinje cells was induced by the co-administration of Pb and HFD. The calbindin-28Kd-, GAD67-, NMDAR1-, and PSD95-immunopositive Purkinje cells and inhibitory synapse-forming pinceau structures were significantly decreased following Pb and HFD co-administration. MBP-immunoreactive myelinated axonal fibers were also impaired by HFD but were significantly damaged by the co-administration of HFD and Pb. Oxidative stress-related Nrf2-HO1 signaling was activated by HFD feeding, and Pb exposure further aggravated oxidative stress, as demonstrated by the consumption of endogenous anti-oxidant in HFD-Pb rats. The pro-inflammatory response was also increased by the co-administration of HFD and Pb in the cerebellum of the rat offspring. The present results suggest that HFD and Pb treatment during the gestational and lactational periods are harmful to cerebellar development.

Prognostic fine needle aspiration biopsy of uveal melanoma: Molecular and genetic factors of metastasis risk

Introduction. Molecular genetic testing is actively used for prognostication in patients with uveal melanoma (UM). Tissue for genetic analysis may be obtained either by surgical excision or through fine-needle aspiration biopsy (FNAB). Performing genetic testing and FNAB in each institution can differ in surgical techniques and laboratory methodologies.Aim. To present our own experience of performing FNAB-based molecular genetic testing for prognostication in patients with uveal melanoma.Materials and methods. Prognostic FNAB (n = 151) were combined with brachytherapy or stereotactic surgery. Genetic testing was performed by methods based on polymerase chain reaction (GNAQ, GNA11, EIF1AX and SF3B1 mutations) and fluorescence in situ hybridization (copy numbers of PPARG and MYC genes); cytology of FNAB material was also assessed.Results. Fine-needle aspiration biopsy material was informative in 91 % of cases. At the median follow-up of 36 months, 12 cases of distant metastases were detected. Occurrence of the assessed mutations and copy numbers were related to other representative studies. PPARG deletion was shown to be a significant prognostic factor for metastasis-free survival (p <0,01), which was demonstrated for the first time; EIF1AX and SF3B1 mutations, MYC amplification and cytological class were not shown to be significantly associated with survival in our study.Conclusion. FNAB-based molecular genetic testing for prognostication in patients with uveal melanoma was shown to be a reliable and highly informative approach. Some of the prognostic factors need to be evaluated further with longer follow-up.

Long-term earnings growth forecasts: investor sentiment or valuation difficulty?

PurposeThis article analyzes the hypothesis that analysts issue higher long-term earnings growth (LTG) forecasts following a market-wide investor sentiment.Design/methodology/approachThis study analyzed 193 publicly traded Brazilian firms listed on B3 (Brasil, Bolsa, Balcão), totaling 2,291 observations. To address the potential selection bias resulting from analysts' preference for more liquid firms, this study used the Heckman model in the analysis with samples with only one analyst and the entire sample. The study also applied other robustness tests to ensure the reliability of the findings.FindingsThe results suggest that market-wide investor sentiment influences LTG when the firm's stocks are difficult to value. Market optimism did not reflect five-year profit growth after the forecast issue, suggesting lower forecast accuracy during high investor sentiment values.Practical implicationsVolatile-earnings firms have relevant implications in LTG forecasts during bullish moments. According to the study’s evidence, investors' decisions and policymakers' and regulators' rules should consider analysts' expertise as independent information when considering LTG as input for valuation models, even under market optimism.Originality/valueThis paper contributes to the literature on the influence of investor sentiment on analysts' forecasts by incorporating two crucial elements in the discussion: the scenario free from herding behavior, as usually only one analyst issues LGT forecast for Brazilian firms, and the analysis of research hypotheses incorporates the difficulty of pricing a firm given the uncertainty of its earnings as an explanation to bullish forecast.

Ginkgolide attenuates memory impairment and neuroinflammation by suppressing the NLRP3/caspase-1 pathway in Alzheimer's disease.

The NLRP3 inflammasome is involved in the neuroinflammatory pathway of Alzheimer's disease (AD). The aim of this study is to explore the roles and underlying mechanisms of ginkgolide (Baiyu®) on amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and a murine microglial cell line, BV-2. In the present study, the APP/PS1 mice were administered with ginkgolide, followed by a Morris water maze test. The mice were then euthanized to obtain brain tissue for histological and Aβ analysis. Additionally, BV-2 cells were pretreated with ginkgolide and then incubated with Aβ1-42 peptide. NLRP3, ASC, and caspase-1 mRNA and protein expression in brain tissue of mice and BV-2 cells were quantified by real-time PCR and western blotting, as well as reactive oxygen species (ROS) production, interleukin (IL)-1β and IL-18 levels by lucigenin technique and ELISA. Compared with the APP/PS1 mice, ginkgolide-treated mice demonstrated the shortened escape latency, reduced plaques, less inflammatory cell infiltration and neuron loss in the hippocampi of APP/PS1 mice. The levels of NLRP3, ASC, caspase-1, ROS, IL-1β, and IL-18 were also decreased in the brain tissue of APP/PS1 mice or Aβ1-42-treated BV-2 cells following ginkgolide treatment. Ginkgolide exerted protective effects on AD, at least partly by inactivating the NLRP3/caspase-1 pathway.

Earnings guidance stoppage and the value of financial analysts' research

AbstractWe examine the relation between voluntary disclosure and the value of analysts' research by studying the change in the informativeness of analysts' research after managers stop providing quarterly guidance to investors. We find that the market reaction to analysts' recommendation revisions increases significantly after guidance stoppage, controlling for confounding factors as well as for firm and time fixed effects. The increase in market reaction is greater for firms with more opaque information environments and for firms that previously provided disaggregated guidance. Further, the effect of guidance stoppage on the informativeness of analysts' research reverses after managers resume guidance. Finally, textual analyses of analysts' reports before and after guidance stoppage reveal that analysts issue longer, more frequent, and more detailed reports that convey more forward‐looking information after stoppages. These findings collectively shed light on the relation between the supply of voluntary disclosure and the value that sell‐side analysts add to price discovery in capital markets.

A Multi-Institutional Analysis of MRI-Based Brachytherapy for Medically Inoperable Endometrial Cancer

Patients with medically inoperable endometrial cancer (MIEC) are curable with brachytherapy (BT)-based treatment yet have competing comorbidities making definitive treatment challenging. MRI demonstrates superior soft tissue anatomy and target volume delineation but with limited data in MIEC patients. We aim to report disease and toxicity outcomes with MRI-based BT and identify dose-volume relationships for toxicities in the treatment of MIEC patients treated with MRI-based BT. We conducted a retrospective multi-institutional analysis of MIEC patients undergoing definitive MRI-based BT (+/- EBRT). MRI-based BT was delivered with the applicator in situ or coregistered to a planning CT. We identified patient, tumor, and dosimetric factors associated with disease and toxicity outcomes. Kaplan-Meier method was used for survival estimates. Log rank test and Cox proportional hazards were used for univariate and multivariate analyses, respectively. T-test was used for dose-volume toxicity analysis. A total of 120 patients were included with a median follow up of 28.0 months. Median age was 68.5 years. ECOG PS was 0-1 in 70%. Clinical stage I was 83.3% and II-IV, 16.7%. Most patients (91.7%) were node negative. Endometrioid and high risk histologies comprised 83.3%, and 16.7%, respectively. EBRT + BT was delivered in 97 patients (80.8%) and BT alone in 23 patients (19.2%). Chemotherapy or hormonal therapy was delivered during treatment in 10 (8.3%) and 11 (9.2%) patients, respectively. Estimated 3-year freedom from local, nodal, and distant recurrence were 88.0%, 96.0%, and 89.1% respectively. Estimated 3-year PFS and OS were 60.9% and 62.9%, respectively. On UVA, older age, PS ≥2, high risk histology, higher grade, and larger GTV at BT were significant (p<0.1). On MVA, older age, higher grade, and larger GTV at BT (p<0.05) predicted for inferior PFS. Fifteen late grade ≥3 toxicities were experienced in 14 (11.6%) patients, 13 of whom received EBRT and BT and 1 who received BT alone. Grade ≥3 toxicities were rectal (2, 1.7%), sigmoid (8, 6.7%), bowel (1, 0.8%), bladder (3, 2.5%), and osseous (1, 0.8%). EBRT was delivered in 7 of 8 sigmoid toxicities. Median sigmoid doses (EQD2a/b = 3Gy) for patients with and without late grade ≥3 sigmoid toxicity were 69.6 Gy and 64.3 Gy, respectively (p = 0.009). MRI-based BT for MIEC patients results in high rates of local control and favorable rates of late grade ≥3 morbidity. Older age, higher grade, and larger GTV at BT predicted for poorer PFS. Sigmoid colon was the predominant organ at risk for grade ≥3 toxicity with a dose -volume relationship observed. Attention to the location of the sigmoid throughout the treatment course may add insight into its predilection for risk. Future work will include additional institutions and dose-volume relationships of target volumes and normal tissues for further disease control and toxicity analysis.

Castration promotes the browning of the prostate tumor microenvironment

BackgroundAdipose tissue has gained attention due to its potential paracrine role. Periprostatic adipose tissue surrounds the prostate and the prostatic urethra, and it is an essential player in prostate cancer progression. Since obesity is directly related to human tumor progression, and adipose tissue depots are one of the significant components of the tumor microenvironment, the molecular mediators of the communication between adipocytes and epithelial cells are in the spotlight. Although periprostatic white adipose tissue contributes to prostate cancer progression, brown adipose tissue (BAT), which has beneficial effects in metabolic pathologies, has been scarcely investigated concerning cancer progression. Given that adipose tissue is a target of androgen signaling, the actual role of androgen removal on the periprostatic adipose tissue was the aim of this work.MethodsSurgical castration of the transgenic adenocarcinoma of the mouse prostate (TRAMP) was employed. By histology examination and software analysis, WAT and BAT tissue was quantified. 3T3-like adipocytes were used to study the role of Casodex® in modifying adipocyte differentiation and to investigate the function of the secretome of adipocytes on the proliferation of androgen-dependent and independent prostate cancer cells. Finally, the role of cell communication was assayed by TRAMP-C1 xenograft implanted in the presence of 3T3-like adipocytes.ResultsAndrogen removal increases brown/beige adipose tissue in the fat immediately surrounding the prostate glands of TRAMP mice, concomitant with an adjustment of the metabolism. Castration increases body temperature, respiratory exchange rate, and energy expenditure. Also, in vitro, it is described that blocking androgen signaling by Casodex® increases the uncoupling protein 1 (UCP1) marker in 3T3-like adipocytes. Finally, the effect of brown/beige adipocyte secretome was studied on the proliferation of prostate cancer cells in vivo and in vitro. The secretome of brown/beige adipocytes reduces the proliferation of prostate cancer cells mediated partly by the secretion of extracellular vesicles.ConclusionsConsequently, we concluded that hampering androgen signaling plays a crucial role in the browning of the periprostatic adipose tissue. Also, the presence of brown adipocytes exhibits the opposite effect to that of white adipocytes in vitro regulating processes that govern the mechanisms of cell proliferation of prostate cancer cells. And finally, promoting the browning of adipose tissue in the periprostatic adipose tissue might be a way to handle prostate cancer cell progression.EECkevEGf-HMwkJP3j4bZsVideo

JS01.3.A EPIGENETICALLY DEFINED ANGIOCENTRIC GLIOMAS MAY LACK ANGIOCENTRIC GROWTH AND INSTEAD SHOW A VARIETY OF GROWTH PATTERNS

Abstract BACKGROUND Angiocentric glioma mainly occurs in children and young adults. It is associated with a good prognosis (CNS WHO grade 1). Molecularly, most angiocentric gliomas have a MYB-QKI fusion. Histologically, angiocentric gliomas were initially defined by angiocentric growth of the tumor cells. However, we noticed that epigenetically defined angiocentric gliomas often get different diagnoses based on their histology as they may lack this angiocentric growth pattern. We therefore wanted to further analyze epigenetically defined angiocentric gliomas and evaluate how reliable these gliomas are histologically diagnosed based on the criteria defined by the WHO. MATERIAL AND METHODS We collected 48 epigenetically defined angiocentric gliomas (37 supratentorial, 11 infratentorial) from 46 patients with sufficient tissue for histological and molecular analyses (DNA methylation analyses; RNA sequencing of a subset). The classification was done using unsupervised hierarchical cluster analyses from DNA methylation data and the brain tumor classifiers v11b4 and v12.5 (www.molecularneuropathology.org). RESULTS Angiocentric gliomas were epigenetically distinct from other gliomas including the diffuse astrocytomas, MYB- or MYBL1-altered. A MYB-QKI fusion was detected in 69% (n = 18/26) of angiocentric gliomas, confirming the diagnosis. Other fusions detected were fusions of MYB with intergenic sites, mainly close to QKI (19%; n = 5/26), and MYBL1-QKI (8%; n = 2/26). Histological workup revealed that 75% of the cases included in this study showed the typical angiocentric growth pattern. However, in many of these tumors this was not very pronounced. Many angiocentric gliomas displayed an unspecific growth pattern or resembled pilocytic astrocytoma or ependymoma. Hence, about 59% of angiocentric gliomas were initially misdiagnosed without molecular analyses (supratentorial 50%, infratentorial 100%). We obtained similar results expanding the cohort with further epigenetically defined angiocentric gliomas for which no tissue for a histological re-evaluation was available (total 68 cases; 50 supratentorial, 12 infratentorial; 65 patients). In this expanded cohort, 54% of cases were initially misdiagnosed (45% of supratentorial and 100% of infratentorial cases). CONCLUSION In summary, we show that angiocentric glioma often does not show the typical angiocentric growth pattern, resulting in different diagnoses in more than 50% of the cases without molecular analyses. Thus, DNA methylation analyses are needed for a reliable diagnosis of this tumor type.

Lipid Correction for Carbon Stable Isotope Analysis of Yellowfin Tuna

Carbon stable isotopes (δ13C) are widely used in ecological studies to understand diet, food web dynamics, and movements of marine fishes. Still, δ13C is influenced by lipid content and often requires chemical extraction or mathematical correction. Here, we developed a species-specific mathematical lipid correction for white muscle tissue of yellowfin tuna (Thunnus albacares), a highly migratory finfish of considerable economic and ecological value. Lipid extraction was conducted on yellowfin tuna white muscle tissue (C:N range: 2.96–6.49), and both linear and non-linear lipid correction models for δ13C were fitted and assessed. Lipid extraction increased δ13C, and to a lesser extent, δ15N values in yellowfin tuna white muscle tissue, but had no effect on δ34S. Both non-linear models provided better fits to the data than the linear model, suggesting an asymptotic relationship between C:N and ∆δ13C. Results support the growing body of evidence that C:N ratios can be used to predict lipid corrected δ13C and highlight the value of mathematical correction approaches. We provide species-specific parameter estimates that can be used for lipid correction of white muscle tissue for δ13C analysis in yellowfin tuna and similar species for which species-specific models have yet to be developed.

Prophylactic feeding of neomycin to Holstein calves alters gut microbiota, bile acid metabolism, and expression of genes involved in immunometabolic regulation.

The objective of this study was to evaluate the effects of prophylactic neomycin administration on Holstein bull calves' intestinal microbiota, bile acid (BA) metabolism, and transcript abundance of genes related to BA metabolism. A total of 36 calves were blocked by body weight and assigned to either non-medicated milk replacer (CTL), or neomycin for 14 days (ST) or 28 days (LT) in their milk replacer. At the end of the study, calves were euthanized to collect tissue and digesta samples from the gastrointestinal tract, liver, and adipose tissue for analysis of intestinal microbial diversity, bile acid concentration and profile in various body tissues, and gene expression related to bile acid, lipid, carbohydrate metabolism, and inflammation. Calves that received prophylactic administration of neomycin for 28 d (LT) had reduced species richness (chao1 index), and tended to have reduced phylogenetic diversity in the ileum tissue. The relative abundance of Lactobacillus, and Bifidobacterium in ileum and colon digesta were decreased in LT compared with CTL. Concentrations of primary, secondary, and total BA were increased by ST in ileal tissue. In plasma, ST and LT treatments had lower concentrations of secondary BA. Gene expression of the BA receptor FXR was increased in ileum and liver by LT compared to CTL. The expression of FXR and TGR5 in the liver was increased in the ST group compared with CTL, and in adipose tissue, 5 genes related to triglyceride, gluconeogenesis, and immune activation were differentially expressed between CTL and ST. In conclusion, we provide evidence that prophylactic administration of neomycin leads to aberrant changes in BA concentration and profile in different compartments of the enterohepatic system through a process that possibly entails antimicrobial disruption of key bacterial groups, which persists even after cessation of neomycin administration. Additionally, we uncovered an apparent link between dysregulated BA metabolism and changes in lipid metabolism and immune activation in adipose tissue and liver.

The Wnt pathway regulates wing morph determination in Acyrthosiphon pisum

Wing dimorphism occurs in insects as a survival strategy to adapt to environmental changes. In response to environmental cues, mother aphids transmit signals to their offspring, and the offspring either emerge as winged adults or develop as wingless adults with degeneration of the wing primordia in the early instar stage. However, how the wing morph is determined in the early instar stage is still unclear. Here, we established a surgical sampling method to obtain precise wing primordium tissues for transcriptome analysis. We identified Wnt as a regulator of wing determination in the early second instar stage in the pea aphid. Inhibiting Wnt signaling via knockdown of Wnt2, Wnt11b, the Wnt receptor-encoding gene fz2 or the downstream targets vg and omb resulted in a decreased proportion of winged aphids. Activation of Wnt signaling via knockdown of miR-8, an inhibitor of the Wnt/Wg pathway, led to an increased proportion of winged aphids. Furthermore, the wing primordia of wingless nymphs underwent apoptosis in the early second instar, and cell death was activated by knockdown of fz2 under the wing-inducing condition. These results indicate that the developmental plasticity of aphid wings is modulated by the intrinsic Wnt pathway in response to environmental challenges.

An integrated multi-omics analysis of identifies distinct molecular characteristics in pulmonary infections of Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) can cause severe acute infections, including pneumonia and sepsis, and cause chronic infections, commonly in patients with structural respiratory diseases. However, the molecular and pathophysiological mechanisms of P. aeruginosa respiratory infection are largely unknown. Here, we performed assays for transposase-accessible chromatin using sequencing (ATAC-seq), transcriptomics, and quantitative mass spectrometry-based proteomics and ubiquitin-proteomics in P. aeruginosa-infected lung tissues for multi-omics analysis, while ATAC-seq and transcriptomics were also examined in P. aeruginosa-infected mouse macrophages. To identify the pivotal factors that are involved in host immune defense, we integrated chromatin accessibility and gene expression to investigate molecular changes in P. aeruginosa-infected lung tissues combined with proteomics and ubiquitin-proteomics. Our multi-omics investigation discovered a significant concordance for innate immunological and inflammatory responses following P. aeruginosa infection between hosts and alveolar macrophages. Furthermore, we discovered that multi-omics changes in pioneer factors Stat1 and Stat3 play a crucial role in the immunological regulation of P. aeruginosa infection and that their downstream molecules (e.g., Fas) may be implicated in both immunosuppressive and inflammation-promoting processes. Taken together, these findings indicate that transcription factors and their downstream signaling molecules play a critical role in the mobilization and rebalancing of the host immune response against P. aeruginosa infection and may serve as potential targets for bacterial infections and inflammatory diseases, providing insights and resources for omics analyses.

Isolation and Flow Cytometry Analysis of Intestinal Macrophages.

The intestinal macrophage pool represents the largest population of macrophages present within the body. Nevertheless, flow cytometry analysis of intestinal macrophages remains challenging due to historical lack of consensus on surface markers, variations in sample preparation, and a certain capriciousness of the isolation procedure itself. Furthermore, recent studies have uncovered a hitherto unknown heterogeneity of intestinal macrophages, accompanied by a vast increase of subset-identifying surface markers. Here, the isolation procedure for intestinal tissue for flow cytometry analysis is laid out, with particular attention toward the procedures for isolated intestinal layers, and a trouble-shooting section with strategies to avoid common pitfalls and mistakes.

The promoting effect of modified Dioscorea pills on vascular remodeling in chronic cerebral hypoperfusion via the Ang/Tie signaling pathway.

The objective of this study was to investigate the effect of modified Dioscorea pills (MDP) on microcirculatory remodeling in the hippocampus of rats with chronic cerebral hypoperfusion (CCH) through the angiopoietin (Ang)/tyrosine kinase receptor tyrosine kinase with immunoglobulin-like and EGF-like domains (Ang receptor) 2 (Tie-2) signaling pathways, which may underlie the cognitive improvement observed in CCH rats. Forty male Sprague-Dawley rats raised under specific pathogen-free conditions were randomly divided into three groups: control group (10 rats), model group (15 rats), and MDP group (15 rats). The rats in the model group and MDP group underwent bilateral common carotid artery occlusion using the 2-vessel occlusion (2-VO) method to induce CCH. Rats in the control group underwent the same surgical procedures as those in the model group, except for ligation and occlusion of the carotid arteries. After 1 week of 2-VO, rats in the MDP group were administered MDP condensed decoction intragastrically at a dose of 1 ml/100 g body weight (prepared by the Preparation Room of Hubei Provincial Hospital of Traditional Chinese Medicine) for 45 days, while rats in the other two groups received normal saline intragastrically with the same dose and duration as the MDP group. After the intervention, all rats were euthanized, and brain perfusion was performed to obtain the hippocampal tissue for analysis. Immunohistochemical staining for CD43 was performed to assess microvessel density (MVD); western blot and the reverse transcription-polymerase chain reaction (RT-PCR) were used to analyze the expression of proteins and genes in angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), Tie-2, and vascular endothelial growth factor (VEGF) proteins and genes in the hippocampal tissue and compute the Ang-1/Ang-2 ratio. MDP treatment reduced neuronal loss and promoted restoration of the damaged hippocampal structure in CCH rats. The model group showed significantly higher MVD (14.93 ± 1.92) compared to the control group (5.78 ± 1.65) (P < 0.01), whereas MDP treatment further increased MVD (21.19 ± 2.62). Western blot and RT-PCR analysis revealed that CCH significantly increased the expression of Ang-1, Ang-2, Tie-2, and VEGF proteins and genes, while MDP treatment further significantly upregulated the expression of these proteins and genes. In addition, MDP significantly elevated the gene and protein expression of the Ang-1/Ang-2 ratio compared to the control group (P = 0.041, P = 0.029). CCH induces microvascular neogenesis in the hippocampus, and MDP promotes angiogenesis and microcirculation remodeling in CCH rats via the Ang/Tie signaling pathway, which may be an important mechanism for its restorative effects on hippocampal perfusion and improvement of cognitive function in CCH rats.

Pre-Clinical Models to Study Human Prostate Cancer.

Prostate cancer is a common cancer among men and typically progresses slowly for several decades before becoming aggressive and spreading to other organs, leaving few treatment options. While large animals have been studied, the dog's prostate is anatomically similar to humans and has been used to study spontaneous prostate cancer. However, most research currently focuses on the mouse as a model organism due to the ability to genetically modify their prostatic tissues for molecular analysis. One milestone in this research was the identification of the prostate-specific promoter Probasin, which allowed for the prostate-specific expression of transgenes. This has led to the generation of mice with aggressive prostatic tumors through overexpression of the SV40 oncogene. The Probasin promoter is also used to drive Cre expression and has allowed researchers to generate prostate-specific loss-of-function studies. Another landmark moment in the process of modeling prostate cancer in mice was the orthoptic delivery of viral particles. This technology allows the selective overexpression of oncogenes from lentivirus or the use of CRISPR to generate complex loss-of-function studies. These genetically modified models are complemented by classical xenografts of human prostate tumor cells in immune-deficient mice. Overall, pre-clinical models have provided a portfolio of model systems to study and address complex mechanisms in prostate cancer for improved treatment options. This review will focus on the advances in each technique.

The molecular diagnostic yield of frame-based stereotactic biopsies in the age of precision neuro-oncology: a cross-sectional study

PurposeWith the increasing role of molecular genetics in the diagnostics of intracranial tumors, delivering sufficient representative tissue for such analyses is of paramount importance. This study explored the rate of successful diagnosis after frame-based stereotactic biopsies of intracranial lesions.MethodsConsecutive patients undergoing frame-based stereotactic biopsies in 2020 and 2021 were included in this retrospective analysis. Cases were classified into three groups: conclusive, diagnosis with missing molecular genetics (MG) data, and inconclusive neuropathological diagnosis.ResultsOf 145 patients, a conclusive diagnosis was possible in n = 137 cases (94.5%). For 3 cases (2.0%), diagnosis was established with missing MG data. In 5 cases (3.5%), an inconclusive (tumor) diagnosis was met. Diagnoses comprised mainly WHO 4 glioblastomas (n = 73, 56%), CNS lymphomas (n = 23, 16%), inflammatory diseases (n = 14, 10%), and metastases (n = 5, 3%). Methylomics were applied in 49% (n = 44) of tumor cases (panel sequencing in n = 28, 30% of tumors). The average number of specimens used for MG diagnostics was 5, while the average number of specimens provided was 15. In a univariate analysis, insufficient DNA was associated with an inconclusive diagnosis or a diagnosis with missing MG data (p < 0.001). Analyses of planned and implemented trajectories of cases with diagnosis with missing MG data or inconclusive diagnosis (n = 8) revealed that regions of interest were reached in almost all cases (n = 7).ConclusionAlthough stereotactic frame-based biopsies deliver a limited amount of tissue, they bear high histopathological and molecular genetic diagnostic yields. Given the proven surgical precision of the planned biopsy trajectories, optimizing surveyed lesion regions could help improve the rate of conclusive diagnoses.

Evaluation of the Possible Ameliorative Effects of Anemarrhena asphodeloides Extract on Liver Cirrhosis by Combining Biochemical Analysis and Electrical Tissue Conductivity

Anemarrhena asphodeloides extract (AAE) has been used for the treatment of inflammatory diseases and its anti-inflammatory effects have been reported. In this feasibility study, the hepato-protective effect of AAE was evaluated in a rat liver cirrhosis model by a combination of biochemical analysis and electrical tissue conductivity. Liver cirrhosis was induced by dimethylnitrosamine (DMN) injection. A total of 32 Sprague–Dawley rats were divided into four groups such as normal liver, cirrhotic liver, cirrhotic liver with AAE treatment, and cirrhotic liver with lactulose treatment. Effects of AAE were compared with those of lactulose. Cirrhotic liver with both AAE and lactulose treatments showed increased body weight, decreased levels of aspartate aminotransferase and alanine aminotransferase, and increased albumin level compared with cirrhotic liver (p &lt; 0.05). The expression levels of α-smooth muscle actin (α-SMA) and cyclooxygenase-2 (COX-2) in immunohistochemical analysis showed reduced fibrosis and inflammatory response in both AAE and lactulose treatments compared with cirrhotic liver (p &lt; 0.05). The levels of AAE treatment were relatively lower than those of lactulose. The western blot analysis of α-SMA and COX-2 protein in both AAE and lactulose treatments was similar to that of normal liver. When comparing electrical conductivity to normal liver, difference in conductivity was 21.2%, 11.5%, and 7.7% in cirrhotic liver, lactulose treatment, and AAE treatment, respectively. These results suggest that the anti-inflammatory effect of AAE may delay or prevent the progress from liver fibrosis to cirrhosis. In summary, a more precise analysis of tissue conditions following the induction of liver cirrhosis was possible by combining electrical tissue conductivity with conventional biochemical analysis.

Temporal correlations of ferroptosis, inflammation and oxidative stress under acute ammonia exposure in brain tissue of yellow catfish (Pelteobagrus fulvidraco)

Ammonia is one of the most serious environmental stressors which severely affect fishery production. Ammonia toxicity to fish has a tight relationship with oxidative stress, inflammation and ferroptosis (a type of programmed cell death characterized by iron-dependent lipid peroxidation), but the temporal response of the above three in brain remains unclear. In the present study, yellow catfish were exposed to three concentrations of ammonia: low concentration (TA-N ˂ 0.01 mg L−1, LA), middle concentration (TA-N 5.70 mg L−1, MA), high concentration (TA-N 28.50 mg L−1, HA) for 96 h. Brain was selected as target tissues for analysis. Results showed that ammonia stress resulted in firstly increased contents of hydroxyl radical at 1 h, total iron at 12 h, malondialdehyde at 48 h, respectively, and decreased contents of GSH at 3 h. The initial high expression levels of ferroptosis (GPX4, system xc−, TFR1) and inflammatory-related factors (NF-ƙB p65, TNF, COX-2, and LOX-15B), antioxidant enzymes genes (SOD and CAT) were observed at first hour upon MA or HA stress. Combining all, it suggested that brain ferroptosis and inflammation were the first to be activated at the initial stage of ammonia stress, and then that provoked oxidative stress.

P53 gene mutations among patients involved with breast cancer: types of detection

A significant transcription factor that is involved in the regulation of numerous cellular functions is the tumor suppressor p53. In disease, p53 weakens cell expansion in light of different boosts, including DNA harm, supplement hardship, hypoxia, and hyperproliferative signs, along these lines forestalling growth arrangement. It was detailed that the proficiency of Microarray and ABI 310 framework in distinguishing proof a wide range of p53 quality transformations. Microarray and ABI 310 analysis were used in this study to find p53 gene mutations in archived breast cancer tissues. Breast tissues from cancer patients who had been diagnosed with breast cancer were collected for this purpose and paraffin-embedded after being formalin-fixed. DNA was removed by the Microdissection technique and was cleaned with Microcon 50 channels (Millipore) prior to performing PCR. Twelve of the samples that were analyzed had ABI 310 system mutations in the p53 gene, the genomic DNA was acquired from micro-dissected tests without laser. The ABI 310 system identified p53 gene mutations in three of the nine ESCC specimens from patients who were examined by microarray. In laser-miniature analyzed examples changes were distinguished by ABI 310 framework. The extricated DNA obtained from laser miniature took apart examples was deficient for the evaluation of p53 quality changes with Microarray. It was resolved that Microarray was reliant upon how much tissues were utilized in DNA extraction. The resulting data of this study showed that selecting the appropriate method for extracting DNA from test samples in order to evaluate the p53 gene mutation is crucial. The ABI 310 system and Microarray were able to detect p53 gene mutations (for exons 5-8) with an efficiency of 99.6% and 27%, respectively. Consequently, involving new tissues for Microarray analysis is suggested. In conclusion, the application of Microarray to identify mutation for p53 gene, in breast cancer tissues, will be necessary for central hospitals, where fresh tissue samples are available easily.

Dietary intake of xylose impacts the transcriptome and proteome of tissues involved in xylose metabolism in swine

Xylose is a primary component of arabinoxylan in swine diets. As arabinoxylan is a significant component of fiber, and fiber is generally rising in practical pig diets globally, the study of arabinoxylan and xylose is of increasing interest. However, the mechanisms by which free xylose may be absorbed and the pathways impacted by xylose have yet to be elucidated in pigs. The objective of this study was to determine the impact of xylose supplementation on gene expression and protein abundance in jejunum, kidney, liver, and muscle tissues which have previously been identified as possible sites of xylose absorption or metabolism. This study aimed to expand the preliminary understanding of dietary xylose metabolism and utilization in pigs. One study, replicated twice with 24 crossbred gilts, was used to assess two dietary treatments: a xylose-free (0%) control and 8% D-xylose. The impact of xylose on growth was monitored by measuring initial and final body weight, serum IGF-1, and liver glycogen concentrations. The rate and efficiency of weight gain were reduced on the xylose diet but not to a level that would occur if xylose was not used at all; the detection of xylose systemically further supports this conclusion. This study confirmed that pigs can utilize dietary xylose. To determine the impact of xylose on tissue metabolism, samples were collected from all four tissues for gene expression analysis by RNA-sequencing, and kidney and liver samples were subjected to proteomic analysis using 2D-DIGE and mass spectrometry. The majority of differentially expressed (DE) genes were identified in the kidney samples (n = 157), with a few identified in the jejunum (n = 16), liver (n = 1), and muscle (n = 20) samples. The DE genes in the kidney were mainly identified as being involved in lipid biosynthesis and fatty acid metabolism. Proteomic results corroborated these findings. Although the inclusion of xylose in a diet at practical levels is shown to impact energy metabolic processes, it has been confirmed that this five-carbon sugar can support levels of growth only slightly below those of glucose, a six-carbon sugar that is more commonly utilized as an energy source in pig diets.