Parenterally administered ascorbic acid modulates sepsis-induced inflammation and coagulation in experimental animal models. The objective of this randomized, double-blind, placebo-controlled, phase I trial was to determine the safety intravenously infused patients with severe sepsis. Twenty-four sepsis medical intensive care unit were randomized 1:1:1 receive intravenous infusions every six hours for four days acid: Lo-AscA (50 mg/kg/24 h, n = 8), or Hi-AscA (200 Placebo (5% dextrose/water,...

Cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in neutral pathway of bile acid biosynthesis, is feedback-inhibited at transcriptional level by hydrophobic acids. Recent studies show that acids are physiological ligands for farnesoid X receptor (FXR). Activated FXR indirectly repressesCYP7A1 transcription through induction small heterodimer protein (SHP-1). In this study, we provide evidence rapidly down-regulate CYP7A1 via activation JNK/c-Jun pathway. Furthermore, demonstrate...

Previous studies have argued that enhanced activity of the epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK) pathway can promote tumor cell survival in response to cytotoxic insults. In this study, we examined impact MAPK signaling on primary hepatocytes exposed low concentrations deoxycholic acid (DCA, 50 μM). Treatment with DCA caused activation, which was dependent upon ligand independent activation EGFR, downstream through Ras PI 3 kinase. Neither...

Previously, we have demonstrated that deoxycholic acid (DCA)-induced signaling of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in primary hepatocytes is a protective response. In the present study, examined roles ERK c-Jun NH(2)-terminal kinase (JNK) pathways, downstream transcription factors, survival response hepatocytes. DCA caused activation ERK1/2 JNK1/2 pathways. Inhibition either DCA-induced or enhanced apoptotic Further analyses JNK2 was cytoprotective whereas JNK1...

The mechanisms by which bile acids induce apoptosis in hepatocytes and the signaling pathways involved control of cell death are not understood fully. Here, we examined impact mitogen-activated protein kinase (MAPK) phosphatidyl inositol 3-kinase (PI3K) on survival primary exposed to acids. Treatment with deoxycholic acid (DCA), chenodeoxycholic (CDCA) or ursodeoxycholic (UDCA) caused sustained MAPK activation that was dependent epidermal growth factor receptor (EGFR). Activation partially...

Platelet factor 4 (PF-4) is an archetype of the "chemokine" family low molecular weight proteins that play important role in injury responses and inflammation. From activated human leukocyte culture supernatants, we have isolated a form PF-4 acts as potent inhibitor endothelial cell proliferation. The derivative generated by peptide bond cleavage between Thr-16 Ser-17, site located downstream from highly conserved structurally CXC motif. unique leads to loss one large loops molecule...

Previous studies have demonstrated in hepatocytes that deoxycholic acid (DCA) promotes inactivation of protein tyrosine phosphatases (PTPases) and activation ERBB1 the extracellular-regulated kinase (ERK) 1/2 pathway. The present determined biochemical mechanism(s) through which these events occur. DCA taurodeoxycholic (TDCA) (100 μmol/L) caused ERBB1, insulin receptor, ERK1/2 AKT pathways primary rodent hepatocytes. DCA- TDCA-induced receptor signaling pathway activations were blocked by...

Several studies have argued that G-protein–coupled receptors (GPCR) the capacity to promote activation of receptor tyrosine kinases. The current were performed examine regulation extracellular regulated kinase (ERK)1/2 and AKT pathways by conjugated unconjugated bile acids in primary hepatocytes. Deoxycholic acid (DCA), chenodeoxycholic (CDCA), taurodeoxycholic (TDCA), glycodeoxycholic (GDCA), taurochenodeoxycholic (TCDCA), glycochenodeoxycholic (GCDCA), taurocholic (TCA), glycocholic (GCA),...

Modulation of endothelial cell proliferation and cycle progression by the "chemokine" platelet factor-4 (PF-4) was investigated. PF-4 inhibited DNA synthesis, as well cells derived from large small blood vessels. Inhibition independent type concentration stimuli used for induction proliferation. growth reversible. The effects were antagonized heparin. Cell analysis using [3H]thymidine pulse labeling during traverse synchronous G0/G1 to S phase revealed that addition G1 completely abolished...

Bile acids have been reported to activate several different cell signaling cascades in rat hepatocytes. However, the mechanism(s) of activation these pathways not determined. This study aims determine which bile Raf-1/MEK/ERK cascade and mechanism this pathway. Taurodeoxycholic acid (TDCA) stimulated (+235%) phosphorylation p 74 Raf-1 a time (5 20 minutes) concentration-dependent (10 100 μmol/L) manner. ERK activities were both significantly increased by most tested. Deoxycholic (DCA) was...

We have shown previously that bile acids can activate the JNK pathway and down-regulate cholesterol 7α-hydroxylase (CYP7A1), rate-limiting enzyme in neutral of acid biosynthesis. In this study, mechanism(s) by which deoxycholic (DCA) activates were examined. FAS receptor (FAS-R) acidic sphingomyelinase (ASM)-deficient hepatocytes resistant to DCA-induced activation pathway. Activation (2-3-fold) response tumor necrosis factor-α was similar both wild-type FAS-R-/- hepatocytes. hepatocytes,...

Mycobacterium tuberculosis faces various stressful conditions inside the host and responds to them through a coordinated regulation of gene expression. We had previously reported identification virS M. (Rv3082c) belonging AraC family transcriptional regulators. In current study, we show that seven genes (Rv3083–Rv3089) which are present divergently constitute an operon designated mymA operon. Further investigation on this showed transcription is dependent presence VirS protein. A four-fold...

The maxillary canine plays a pivotal role in dental aesthetics, occlusion, and function because of its strategic anatomical positioning. However, the eruption canines is complex process that often leads to impaction. morphological characteristics adjacent teeth, particularly lateral incisors (MLIs), are believed influence canines. This study aimed investigate association between morphology MLI unilateral impacted (IMCs) while also identifying potential predictors such impactions....

Introduction: Dental implants provide a durable solution for missing teeth and improve mastication, speech, quality of life (QoL). However, systemic conditions, such as type 2 diabetes mellitus (T2DM), may affect implant success. This study evaluated patient satisfaction (PS) QoL patient-reported outcome measures (PROMs) following dental therapy in T2DM patients. Materials methods: A cross-sectional was conducted the Department Prosthodontics on 90 patients who had undergone single-unit at...

Anatomical education serves as the cornerstone of medical and dental training, cadaveric dissection is traditionally regarded gold standard for teaching human anatomy. This study explored attitudes perceptions first-year Bachelor Medicine Surgery (MBBS) Dental (BDS) students toward its impact on their academic performance professional development. A cross-sectional survey was conducted in Department Anatomy. structured questionnaire comprising 10 questions assessed students' attitudes,...

Marginal microleakage is a significant factor that contributes to the failure of cavity restorations, ultimately leading recurrent caries. These failures are primarily attributed properties restorative materials, which often influenced by various environmental factors. Gamma radiation has been shown have deleterious effects not only on dental hard tissues but also composite potentially increasing microleakage. A viable approach mitigate these implementation protective shielding for...

Endodontic therapy aims to eliminate microbial infections from the root canal system and prevent reinfection, thus ensuring periapical tissue healing. Persistent bacterial contamination, particularly Staphylococcus aureus Streptococcus mutans, is a major cause of endodontic treatment failure. Owing complexity anatomy, conventional mechanical chemical disinfection methods may be insufficient bacteria. sealers with antimicrobial properties play crucial role in enhancing preventing...

Achieving an impervious seal in root canal treatment is crucial for preventing bacterial infiltration and ensuring long-term success. Various sealers are available, each with different compositions sealing abilities. This vitro study aimed to compare the abilities of four using dye penetration scanning electron microscopy (SEM). Sixty-two extracted single-rooted human teeth were prepared a standardized rotary instrumentation technique. One tooth served as positive control, one negative...

Introduction: Orthodontic stability depends on the balance between soft tissue forces and skeletal structures. The tongue, which is a key component of oral musculature, influences dental arch dimensions occlusal relationships. An abnormal tongue posture linked to malocclusion altered craniofacial development. This study aimed evaluate morphology its correlation with length (AL), width (AW), palatal height (PH) in Class I II patients. Materials methods: A prospective, observational...

Salinity poses a danger to the production of wheat (Triticum aestivum L.), by impacting plant growth and productivity. Deficits in vital minerals like potassium (K⁺) calcium (Ca²⁺) result from buildup sodium (Na⁺) chloride (Cl⁻) ions salty soils, which impairs nutrient absorption. To mitigate salinity-induced decrease mineral content seedlings, this study examines ameliorative effects regulators, specifically gibberellins (GA) cytokinins, combination with supplementation. It was discovered...