Activity

In post-partum dairy cows, the energy needs to satisfy high milk production induces a status of more or less pronounced Negative Energy Balance (NEB). NEB associated with fat mobilization impairs reproductive function. In a companion paper, we described constitutive gene expression in the three main endometrial cell types (stromal, glandular and luminal epithelial cells) isolated by laser capture micro-dissection (LCM) showing the specificities of their transcriptomic profiles. This study investigates the specific impact of NEB on gene expression in these cells around 80 days after parturition at day 15 of the oestrus cycle and describes their specific response to NEB.

Following the description of their constitutive expression, the transcriptome profiles obtained by RNA sequencing of the three cells types revealed that differences related to the severity of NEB altered mainly specific patterns of expression related to individual cell types. Number of differentially expressed genes between severe NEB (SNEBhe establishment of pregnancy.

The severity of NEB after calving is associated with changes in gene expression around 80 days after parturition corresponding to the time of breeding. Specific alterations in GEs are associated with activation of pro-inflammatory mechanisms. Concomitantly, changes in the expression of genes encoding proteins involved in cell interactions and maternal recognition of pregnancy takes place in ST. The combination of these effects possibly altering the uterine environment and embryo maternal interactions may negatively influence the establishment of pregnancy.Sodium-glucose co-transporter 2 (SGLT2) inhibitors are an emerging group of therapeutic agents that showcase their tremendous glucose-lowering activity without causing hypoglycemia, which is one of the major drawbacks of existing antidiabetic therapy. Comprehensive literature was searched in English language using electronic databases, including PubMed, ScienceDirect, Medline, Scopus, and Embase. SGLT2 inhibitors reduce blood glucose levels by causing glucosuria via an insulin-independent pathway. The major mechanism by which SGLT2 inhibitors are involved in glucose homeostasis is to prevent the reabsorption of glucose in the proximal convoluted tubule and increase glucose excretion in the urine. Deterioration of β-cells, impairment of functions, and development of insulin resistance do not affect the efficacy of SGLT2 inhibitors. SGLT2 inhibitors significantly reduce HbA1c, ameliorate glycemic control, and control body weight. SGLT2 inhibitors can block Na+/H+ exchanger (NHE) 1 and play a significant role inic patients.

Cancer is a complex disease that is derived from the uncontrolled proliferation of cells. Bone cancer is a type of prevalent cancer that occurs both in youngsters and adults. Bone cancer is mostly common in the long bones of the pelvis, arms, and legs. Statistically, more than 200 cases of osteosarcoma have been reported annually in our country. Classical treatment with chemotherapeutics remains ineffective for the cure of this cancer. Recent studies have shown that ceramide induces apoptosis due to its increased levels in the cells. Thus, many studies have been conducted for the accumulation of ceramide molecules in the cell by different ways to induce apoptosis. NOE (N-oleoylethanolamine) is a specific inhibitor of ceramidase enzymes that hydrolyse intracellular ceramides and prevent apoptosis.

This study investigates the cytotoxic and apoptosis-inducing activities of NOE on human osteosarcoma Saos-2 cells.

Cytotoxic effects were investigated by MTT colorimetric assay. For the detection of morphological and ultrastructural indicators of apoptosis, confocal and TEM techniques were used, respectively.

Our finding indicated that NOE is effective in the inhibition of the growth of Saos-2 cells. Confocal and TEM findings showed morphological and ultrastructural changes as chromatin condensation, fragmentations of nuclei and mitochondria, as well as damaged cytoskeleton and cell shrinkage.

The results revealed that NOE exhibits its cytotoxicity on Saos-2 cells by changing the ultrastructure and morphology of cells with clear apoptotic sparks.

The results revealed that NOE exhibits its cytotoxicity on Saos-2 cells by changing the ultrastructure and morphology of cells with clear apoptotic sparks.The ‘gold standard’ in the management of left main coronary artery disease has historically been coronary artery bypass surgery. Recent innovations in drug-eluting stent technology coupled with the increasing utility of physiology and imaging guidance for procedures has led to an evolving role for percutaneous coronary intervention in left main disease of low and intermediate anatomical complexity. This revascularization modality carries the clear advantage of being less invasive and significantly reducing recovery times. This practice is currently supported by international guidelines. However, it remains a controversial topic in the field of interventional cardiology, and the longer-term outcomes from a percutaneous strategy have been questioned. This review describes the current evidence base for the assessment and choice of intervention in left main coronary artery disease. The percutaneous revascularization techniques and use of imaging to optimize procedures and improve clinical outcomes will be discussed.

Dapsone (4,4′-diamino-diphenyl sulfone) is a synthetic derivative of sulfones, with the antimicrobial activity described since 1937. It is also a drug traditionally used in dermatological therapies due to its anti-inflammatory effect. In recent years its antioxidant, antiexcitotoxic, and antiapoptotic effects have been described in different ischemic damage models, traumatic damage, and models of neurodegenerative diseases, such as Parkinson’s (PD) and Alzheimer’s diseases (AD). Finally, dapsone has proven to be a safe and effective drug as a protector against heart, renal and pulmonary cells damage; that is why it is now employed in clinical trials with patients as a neuroprotective therapy by regulating the main mechanisms of damage that lead to cell death.

To provide a descriptive review of the evidence demonstrating the safety and therapeutic benefit of dapsone treatment, evaluated in animal studies and various human clinical trials.

We conducted a review of PubMed databases looking for scientific research in animals and humans, oriented to demonstrate the effect of dapsone on regulating and reducing the main mechanisms of damage that lead to cell death.

The evidence presented in this review shows that dapsone is a safe and effective neuro and cytoprotective treatment that should be considered for translational therapy.

The evidence presented in this review shows that dapsone is a safe and effective neuro and cytoprotective treatment that should be considered for translational therapy.

Typically, in situ forming implants utilize Poly (lactide-co-glycolide) (PLGA) as a carrier and N-methyl-2-pyrrolidone (NMP) as a solvent. However, it is essential to develop different carriers to release various drugs in a controlled and sustained manner with economic and safety considerations.

The present study aims to evaluate the in-vitro release of Bupivacaine HCl from in situ forming systems as post-operative local anesthesia.

We used Sucrose acetate isobutyrate (SAIB), PLGA 5050, and a mixture of them as carriers to compare the release behavior. Besides, the effect of PLGA molecular weight (RG 502H, RG 503H, and RG 504H), solvent type, and solvent concentration on the drug release profile was evaluated. The formulations were characterized by investigating their in-vitro drug release, rheological properties, solubility, and DSC, in addition to their morphological properties. Furthermore, the Korsmeyer-Peppas and Weibull models were applied to the experimental data. The results revealed that a mixtrug release is predicted to be non-Fickian diffusion.

Etomidate is commonly used in the induction of anesthesia. We have previously confirmed that etomidate requirements are significantly reduced in patients with obstructive jaundice and that etomidate anesthesia during endoscopic retrograde cholangiopancreatography (ERCP) results in more stable hemodynamics when compared with propofol. The aim of the present study is to investigate whether obstructive jaundice affects the pharmacokinetics of etomidate in patients who underwent bile duct surgery.

18 patients with obstructive jaundice and 12 non-jaundiced patients scheduled for bile duct surgery were enrolled in the study. Etomidate 0.333 mg/kg was administered by IV bolus for anesthetic induction. Arterial blood samples were drawn before, during, and up to 300 minutes after the bolus. Plasma etomidate concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry assay. VTX-27 molecular weight A population nonlinear mixed-effects modeling approach was used to characterize etomidate (95% CI, 1.19-1.41, L/min), Cl2= 1.21 (95%CI, 0.95-1.47, L/min), and Cl3=0.584 (95%CI, 0.95-1.21, L/min), respectively.

A 3-compartment open model might best describe the concentration profile of etomidate after bolus infusion for anesthesia induction. The pharmacokinetics of etomidate were not changed by the presence of obstructive jaundice.

A 3-compartment open model might best describe the concentration profile of etomidate after bolus infusion for anesthesia induction. The pharmacokinetics of etomidate were not changed by the presence of obstructive jaundice.Artificial intelligence is an emerging sector in almost all fields. It is not confined only to a particular category and can be used in various fields like research, technology, and health. AI mainly concentrates on how computers analyze data and mimic the human thought process. As drug development involves high R & D costs and uncertainty in time consumption, artificial intelligence can serve as one of the promising solutions to overcome all these demerits. Due to the availability of enormous data, there are chances of missing out on some crucial details. For solving these issues, algorithms like machine learning, deep learning, and other expert systems are being used. On successful implementation of AI in the pharmaceutical field, the delays in drug development, and failure at the clinical and marketing level can be reduced. This review comprises information regarding the development of AI, its subfields, its overall implementation, and its application in the pharmaceutical sector and provides insights on challenges and limitations concerning AI.

This study discussed the mechanism affecting the malignant progression of LUAD and the potential therapeutic targets to provide more effective therapeutic strategies for LUAD patients.

Expression data from TCGA-LUAD were extracted to identify target miRNA, with its downstream target mRNA predicted using bioinformatics analysis. Gene expression in transcript level and protein level were separately examined by qRT-PCR and western blot analysis. Cell malignant phenotypes were assessed via MTT and Transwell assays. Luciferase reporter plasmids carrying target gene sequences were constructed to verify the targeting association between the target miRNA and its downstream mRNA.

miR-1-3p showed decreased expression in LUAD. Over-expressing miR-1-3p suppressed cancer cells to proliferate, migrate and invade. CELSR3, directly regulated by miR-1-3p, presented significantly elevated expression in LUAD and could foster LUAD cells to proliferate, migrate and invade. The rescue experiment identified that miR-1-3p-induced inhibition on LUAD cell malignant phenotypes could be reversed by over-expressing CELSR3.