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Simple Summary: The priority of the lactating animal is to provide the mammary gland with nutrients via metabolic changes orchestrated by several mechanisms, and more specifically, by the dynamic crosstalk between steroid hormones and some hematological analytes. The present study provides new evidence that occurs at the onset of lactation and throughout the lactation period in 10 Holstein, 10 Brown Swiss, and 10 Modicana healthy dairy cows, showing that lactation induces significant changes in circulating progesterone, cortisol, sodium, and magnesium concentrations. The breeds showed a significant effect on liver enzyme (AST, ALT, and LDH) activities and the concentration of calcium and magnesium, according to the early, middle, and late phases of lactation. Significant correlations were recorded for progesterone with cortisol, chlorine, and potassium, and for cortisol with calcium and LDH. Understanding the differences among breeds might improve their management, nutrition, and productivity in commercial dairy farms. Lactation in dairy cows implies comprehensive endocrine and metabolic changes including a systemic electrolytic reaction. Previous studies have rarely considered these specific demands due to the influence of lactation periods. Therefore, this study aimed to assess the effects of early, middle, and late lactation phases on the dynamic changes in serum concentrations of progesterone (P4), 17β-oestradiol (E2), cortisol, and some electrolytes (Ca++, Mg++, Na+, K+, Cl−, Pi) and biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), total bilirubin, urea, and iron (Fe++) in 10 Holstein, 10 Brown Swiss, and 10 Modicana multiparous healthy dairy cows (4.2 ± 1.7 years of age) sampled at 60-day intervals throughout lactation. Lactation induced significant changes in the concentrations of P4, which peaked at >120–180 days, decreased at >240–300 days, and increased again after 300 days. Cortisol showed an opposite trend to P4, with concentrations progressively decreasing, except for the phase between >240 and 300 days, and a steep drop at >300 days compared to previous phases. Na+ concentrations showed the lowest values at 0–60 d and the highest ones at >180–240 days, whereas Mg++ showed the highest values at >60–120 d and the lowest at >300 d. Significant correlations were found between P4 with cortisol, Cl− and K+, and cortisol with Ca++ and LDH. Significant differences in average concentrations of AST, ALT, LDH, Ca++, Mg++, and Fe++ were observed among different dairy cow breeds. Understanding the dynamic changes in hormone levels, electrolytes, and biochemical parameters during different lactation phases, while considering breed differences in dairy cows, is crucial for improving herd health management and milk production in commercial dairy farms. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is an aggressive brain cancer with a median survival time of 14.6 months after diagnosis. GBM cells have altered metabolism and exhibit the Warburg effect, preferentially producing lactate under aerobic conditions. After standard-of-care treatment for GBM, there is an almost 100% recurrence rate. Hypoxia-adapted, treatment-resistant GBM stem-like cells are thought to drive this high recurrence rate. We used human T98G GBM cells as a model to identify differential gene expression induced by hypoxia and to search for potential therapeutic targets of hypoxia adapted GBM cells. RNA sequencing (RNAseq) and bioinformatics were used to identify differentially expressed genes (DEGs) and cellular pathways affected by hypoxia. We also examined expression of lactate dehydrogenase (LDH) genes using qRT-PCR and zymography as LDH dysregulation is a feature of many cancers. We found 2630 DEGs significantly altered by hypoxia (p < 0.05), 1241 upregulated in hypoxia and 1389 upregulated in normoxia. Hypoxia DEGs were highest in pathways related to glycolysis, hypoxia response, cell adhesion and notably the endoplasmic reticulum, including the inositol-requiring enzyme 1 (IRE1)-mediated unfolded protein response (UPR). These results, paired with numerous published preclinical data, provide additional evidence that inhibition of the IRE1-mediated UPR may have therapeutic potential in treating GBM. We propose a possible drug repurposing strategy to simultaneously target IRE1 and the spleen tyrosine kinase (SYK) in patients with GBM. [ABSTRACT FROM AUTHOR]

Background: Lactate dehydrogenase (LDH) and creatine kinase (CK) have differential tissue activity and isoenzyme profiles. LDH and CK exist as 5 and 3 isoenzymes, respectively, in both serum and cerebrospinal fluid (CSF). Studies have demonstrated that measuring LDH, CK, and their isoenzymes in CSF has diagnostic and prognostic values for dogs and people with neurologic disorders. Objectives: Iatrogenic blood contamination can distort the results of CSF analysis. The purpose of this study was to determine allowable thresholds of blood contamination (RBC/μL) for accurate measurement of LDH, CK, and their isoenzymes in canine CSF. Methods: Venous blood and CSF were collected from healthy dogs. Total LDH and CK activity were measured spectrophotometrically. Isoenzyme profiles were determined using gel electrophoresis and densitometric scanning. All samples were analyzed within 6 hours of collection. A nonlinear mixed effects regression model was used to estimate the allowable thresholds of blood contamination for accurate measurement of LDH, CK, and their isoenzymes in canine CSF. Results: The threshold of iatrogenic blood contamination for total LDH and total CK in healthy dogs are 6696 RBC/μL (95% CI 3879–11 187) and 5961 RBC/μL (95% CI 2939–12 085), respectively. LDH‐1 is the most sensitive isoenzyme to iatrogenic blood contamination, while LDH‐4 is the least sensitive. Conclusions: These results are important for the interpretation of LDH, CK, and their isoenzymes in canine CSF. Additionally, our methodology is translatable for determining thresholds of acceptable iatrogenic blood contamination in CSF for other diagnostic and prognostic biomarkers of neurologic disease. [ABSTRACT FROM AUTHOR]

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Simple Summary: Periodontal disease is one of the most prevalent disorders observed in dogs requiring primary-care veterinary services. Traditional methods for its diagnosis involve clinical measurements requiring sedation or general anesthesia. The aim of this study was to evaluate whether quantified salivary biochemistry parameters can be used as markers of periodontal disease in dogs. Seventy-nine dogs were allocated into three groups according to the severity of periodontal disease: none (Group 1), moderate (Group 2), and severe (Group 3). A blood sample and a saliva sample were collected from each dog to quantify biochemical parameters that included alpha-amylase, lysozyme, lactate dehydrogenase (LDH), calcium, and phosphorus. LDH and phosphorus showed the highest values in Group 3 whereas calcium, amylase, and lysozyme did not differ among groups. The salivary phosphorus cut-off value of 4.04 mg/dl that was established signified that above such value, periodontal disease could be predicted with fairly high probability. Although further studies are needed to confirm these preliminary results, this study offers a valid starting point for further investigation into the role of saliva as a non-invasive tool for detecting periodontal disease in dogs. This study evaluated whether salivary alpha-amylase, lysozyme, lactate dehydrogenase (LDH), calcium, and phosphorus can be used as markers of periodontal disease in dogs. Plaque, calculus, and gingivitis indexes were used to allocate 79 dogs in three groups: none (Group 1), moderate (Group 2), and severe (Group 3) periodontal disease. A blood sample and a saliva sample were collected from each dog to quantify biochemical parameters. LDH and phosphorus showed the highest values in Group 3 (LDH: Group 1, 2559.85 ± 676.95; vs. Group 2: 1636.76 ± 597.36 vs. Group 3: 4099.18 ± 545.45 U.I./l, p = 0.016; phosphorus: Group 1, 3.02 ± 0.76 vs. Group 2: 5.34 ± 0.67 vs. Group 3: 5.85± 0.61 mg/dl, p = 0.049) whereas calcium, amylase, and lysozyme did not differ among groups. A ROC curve analysis permitted the establishment of a salivary phosphorus cut-off value of 4.04 mg/dl, above which periodontal disease could be predicted (70% sensitivity (95% CI: 50.6–85.3%) and 72.41% specificity (95% CI: 52.8–87.3%)). Only salivary calcium was higher in males; no other salivary parameters appeared affected by gender or age. Although further results on a larger population are needed, this study shows that salivary LDH and phosphorus increase in dogs affected by plaque, supragingival calculus, and gingivitis, and this suggests their potential use as markers of periodontal disease in canine species. [ABSTRACT FROM AUTHOR]