Mcelroychristian7679

To date, the underlying mechanisms involved intervertebral disc degeneration (IDD) remain unclear, which has hindered the development of molecular biological therapy for IDD. Autophagy is vital for intracellular quality control and metabolic balance in intervertebral disc cells. Hence, autophagy homeostasis is important. Emerging evidence has implicated vitamin D (VD) and the vitamin D receptor (VDR) in IDD progression because of their effects on different autophagy steps. However, the results of clinical trials in which VD supplementation was assessed as a treatment for IDD are controversial. Furthermore, experimental studies on the interplay between VD/VDR and autophagy are still in their infancy. In view of the significance of the crosstalk between VD/VDR and autophagy components, this review focuses on the latest research on VD/VDR modulation in autophagy and investigates the possible regulatory mechanisms. This article will deepen our understanding of the relationship between VD/VDR and autophagy and suggests novel strategies for IDD prevention and treatment.Liver injury is a major public health problem all over the world that raises the demand of developing novel effective and safe remedies. Traditionally, Thyme (Thymus fontanesii) has a therapeutic potential against different organs toxicity due to its antioxidant activity. The present study aimed to evaluate the antioxidant activities in vitro and the possible hepato-protective effects of T. fontanesii aqueous extract (TFAE) against CCl4 induced liver damage (mild fibrosis) in male albino mice and annotate its phytochemical constituents as well. The extract displayed substantial antioxidant activities in vitro and high content of flavonoids and other phenolic compounds. Oral administration of TFAE (especially high dose) significantly suppressed (but with different degrees) the incidence and severity of CCl4 liver toxicity by activating the hepatic antioxidant defense mechanisms, modulating hepatic functions, and decreasing the production of lipid peroxidation, pro-inflammatory mediators, and pro-fibrotic proteins expression including COL1A1, Fn, and TGF-β1. These activities might be attributed to the presence of 58 secondary metabolites (identified by LC-MS), mainly phenolic acids, flavonoids and diterpenoids that were able, according to molecular docking, to bind to the inhibitor's binding site of three protein targets involved in liver inflammation and fibrosis. These results showcase the antioxidant and anti-inflammatory properties of Thyme (Thymus fontanesii), illustrate the protective and beneficial effects of the plant against CCl4-induced hepatic toxicity in mice, and support its consumption, traditional uses and promotes its valorization as nutraceutical product.BN82002 is well-known as an inhibitor of the CDC25 phosphatase. However, it was recently reported that BN82002 also selectively suppressed AKT2 and reduced inflammatory responses in lipopolysaccharide (LPS)-stimulated macrophage-like RAW264.7 cells. Therefore, in this study, we evaluated the alleviating efficacy of BN82002 in sepsis in vivo. BN82002 (50 μM) suppressed the mRNA levels of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in LPS-treated peritoneal macrophages without cytotoxicity. The septic in vivo mouse model was established on the basis of the endotoxin model using poly(IC) (10 mg/kg) and LPS (54 mg/kg). In histological analysis, peritoneal injection of BN82002 (20 mg/kg) significantly reduced lung, kidney, and liver damage. Lung edema and serum alanine transaminase (ALT), aspartate transaminase (AST), TNF-α, IL-1β, and nitric oxide (NO) levels also were decreased by BN82002 (20 mg/kg). A2ti-1 inhibitor In addition, BN82002 (20 mg/kg) suppressed the mRNA levels of TNF-α in lung and liver tissues. Gene expression levels of IL-1β and IL-6 were decreased in lung, kidney, and liver in the BN82002 (20 mg/kg) group. Furthermore, p-AKT2 and p-IκBα levels were reduced by BN82002 (20 mg/kg). Finally, all septic mice died 7 days after poly(IC)/LPS-injection, whereas 4 mice in the BN82002 (20 mg/kg) group, survived strongly suggesting that BN82002 reduces sepsis mortality. In conclusion, we verified that pre-treatment with BN82002 protects against tissue damage and increases survival by inhibiting AKT2-NF-κB signaling in septic mice. These results suggest that BN82002 could be utilized in the treatment of sepsis.Oral squamous cell carcinoma (OSCC) is the most common form of malignant tumor in the head and neck region worldwide. Hence, the identification of biological signatures with high diagnostic and therapeutic potential for OSCC will be of great clinical importance. Epithelial to mesenchymal transition (EMT) is a key driver of malignant transformation of human tumors including OSCC. Loss of epithelial properties and gain of mesenchymal cell properties is one of the most important hallmarks of malignant tumors. Although much has been reported on the protein components of the EMT process, studies on the non-protein coding components are quite limited. Consequently, here we sought to explore biological significance of VIM antisense RNA 1 (VIM-AS1) in OSCC. A total of 36 patients diagnosed with oral cancer were recruited for the study. Formalin-fixed paraffin embedded (FFPE) tissue samples of patients were obtained from pathology archive. For the gene expression analysis, quantitative RT-PCR was used. We also analyzed the expression levels of E-cadherin and Vimentin. Notably, it was found that the expression levels of VIM-AS1 and Vimentin were significantly elevated, while the expression of E-cadherin was downregulated in OSCC. Deregulation of VIM-AS1 was associated with the clinicopathological features of OSCC patients. ROC analysis also showed that VIM-AS1 is an independent diagnostic biomarker for OSCC. Consequently, our findings suggest a chief role for VIM-AS1 in oral cancers.After the accident at the Fukushima Daiichi Nuclear Power Plant (FDNPP), Japan, in March 2011, 137Cs in demersal fish had, between 2011 and 2015, a prolonged ecological half-life when compared to pelagic fish. Using stable isotope mixing models combined with gut content analysis and 137Cs activity concentrations, this study investigated the hypothesis that an unexplored food web structure could be a contributing factor explaining the ecological half-life of 137Cs in benthic flatfish. Benthic invertebrates and demersal fish species sampled in 2015 still showed 137Cs activity concentrations higher than pre-accident. The mixing models of stable N and C isotopes and gut content analysis identified deposit, suspension and filter feeders to be the main flatfish food items in the benthos. There was a significant correlation between 137Cs activity concentrations in specific flatfish species and benthos, and between 137Cs activity concentrations in benthos and surface sediment. The results of this study partially explained the 137Cs activity concentrations found in the analysed demersal fish, suggesting that the benthos can be a continuous source of 137Cs for the demersal fish during this period of time. Extending monitoring programmes to include invertebrates that are not food species for humans would greatly improve our ability to understand the role of trophic transfer pathways and take appropriate management actions.

Bone metastases (BM) are related to worse outcome in patients with neuroendocrine neoplasms (NENpts).

Assess utility of serum tumor markers (STM) for detection of BM in lung NENpts.

Diagnostic metrics of STM, such as ferritin, carbohydrate antigens 19-9 (CA19-9), cancer antigen 125 (CA125), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and beta-2 microglobulin (BMG) were assessed in 62 Lung NEN patients (LNENpts), both with BM (BM-LNENpts) and without BM (non-BM-LNENpts) and 40 controls.

Except AFP, the mean circulating STM levels in LNENpts were significantly increased vs controls (p<0.04), but the most significant difference was in CA19-9 and CEA. BM-LNENpts exhibited an elevated level only for ferritin (n=6; 180.75±53.73 ng/ml; [182.68] compared to non-BM-LNENpts (n=56; 94.33±98.80 ng/ml; [70.35], p<0.001). Three from all used STM (ferritin, BMG and CA125) could differentiate BM-LNENpts from nonBM-LNENpts (area under the curve (AUC)=0.884 for ferritin, 0.74 for BMG and 0.658 for CA 125, p<0.05). These all three STM showed significant sensitivity (100%) by lower specificity in the detection of BM.

Some of the STM seem to have clinical utility for detection of BM-LNEN. The single good marker was ferritin (the high AUC, sensitivity and specificity) and fair biomarker was BMG. BM-LNENpts could be diagnosed by using CEA. The follow-up with combinations of STM (ferritin, BMG) could increase the diagnostic efficacy of BM-LNENpts. This requires further studies with larger patient groups.

Some of the STM seem to have clinical utility for detection of BM-LNEN. The single good marker was ferritin (the high AUC, sensitivity and specificity) and fair biomarker was BMG. BM-LNENpts could be diagnosed by using CEA. The follow-up with combinations of STM (ferritin, BMG) could increase the diagnostic efficacy of BM-LNENpts. This requires further studies with larger patient groups.There are numerous reports of seizure exacerbation related to specific anti-seizure medications (ASMs); however, a quantitative analysis with clearly defined parameters for seizure exacerbation in an outpatient setting is lacking. This retrospective study examines adult patients starting a single ASM and follows patient outcomes over the course of treatment, with quantitative evaluation of the incidence of paradoxical seizure exacerbation. In this study, outpatient encounters with five epileptologists at the Baylor College of Medicine Comprehensive Epilepsy Center were evaluated over a 10-month period. Seizure exacerbation was defined as an increase in seizure frequency at least 2 times greater than the baseline seizure frequency after initiation of an ASM, with return to baseline after ASM discontinuation. Patients were stratified into four categories (1) probable ASM-induced seizure exacerbation; (2) possible ASM-induced seizure exacerbation; (3) non-ASM induced seizure exacerbation; or (4) no seizure exacerbation. Out of a total of 236 encounters where an ASM was initiated, we found that 5.5% of patients experienced some form of seizure exacerbation. However, only 1.3% of patients had probable ASM-induced seizure exacerbation. Consistent with prior studies, our data indicate seizure exacerbation in adults is rare with the initiation of ASMs. However, further studies with a larger sample size are necessary to better understand what factors may predispose patients to potential medication-induced seizure exacerbation.

Characteristics of the audiological performance of children with auditory neuropathy spectrum disorder (ANSD) have been identified; however, studies regarding factors influencing their language development, especially those related to aural-oral rehabilitation, are relatively few. This study aimed to investigate classification functions among the factors regarding audiological, interventional (rehabilitation) and demographic variables that can help determine group membership in language performance for Mandarin-speaking preschoolers with ANSD.

Children with ANSD aged 3-6 years (n=27) enrolled in an auditory-verbal therapy were recruited. The combination of factors that could be used to predict memberships of children regarding whether they achieved age-appropriate language performance or were at risk of language delay were explored using discriminant function analysis.

Maternal education level, age at initial hearing aid fitting, and duration of rehabilitation were all significant factors in predicting the membership of children with ANSD and whether they could achieve an age-appropriate language level or were at risk for language delay.