Microdialysis, a sampling method for pharmacokinetics⁻pharmacodynamics (PK⁻PD) modeling in preclinical and clinical studies, is a convenient in vivo sampling technique. Geniposide (GE), an iridoid glycoside compound, is the major active ingredient of Gardenia jasminoides Ellis fruit which has an anti-inflammatory effect. In this study, an articular cavity microdialysis sampling system for adjuvant arthritic (AA) rats was established to study the effect of GE on the release of prostaglandin E₂ (PGE₂) in AA rats induced by Freund's complete adjuvant (FCA). An UHPLC-MS/MS method was developed to determine the concentrations of GE and PGE₂ in the dialysate. Through the determination of drug concentrations and PGE₂ efficacy levels in the dialysate, the developed methods were successfully applied to set up concentration⁻time and effect⁻time profiles followed by PK⁻PD modeling of GE's effect on decreasing PGE₂ release after oral administration of GE. The effect was well described by the developed PK⁻PD modeling, indicating that GE may play an anti-inflammatory role via decreasing AA-induced elevated PGE₂ levels. In the selection of suitable endogenous small molecules as effect markers, the establishment of AA rat joint-cavity microdialysis is an attractive technique for rational PK⁻PD studies.

The development of small-molecule inhibitors of influenza virus Hemagglutinin could be relevant to the opposition of the diffusion of new pandemic viruses. In this work, we made use of Nuclear Magnetic Resonance (NMR) spectroscopy to study the interaction between two derivatives of sialic acid, Neu5Ac-α-(2,6)-Gal-β-(1⁻4)-GlcNAc and Neu5Ac-α-(2,3)-Gal-β-(1⁻4)-GlcNAc, and hemagglutinin directly expressed on the surface of recombinant human cells. We analyzed the interaction of these trisaccharides with 293T cells transfected with the H5 and H1 variants of hemagglutinin, which thus retain their native trimeric conformation in such a realistic environment. By exploiting the magnetization transfer between the protein and the ligand, we obtained evidence of the binding event, and identified the epitope. We analyzed the conformational features of the glycans with an approach combining NMR spectroscopy and data-driven molecular dynamics simulations, thus obtaining useful information for an efficient drug design.

A novel active Ca-Co dually-doping pyrochlore oxide La2−xCaxSn2−yCoyO₇ catalyst was synthesized by the sol-gel method for catalytic oxidation of soot particulates. The microstructure, atomic valence, reduction, and adsorption performance were investigated by X-ray powder diffraction (XRD), scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), H₂-TPR (temperature-programmed reduction), and in situ diffuse reflection infrared Fourier transformed (DRIFTS) techniques. Temperature programmed oxidation (TPO) tests were performed with the mixture of soot-catalyst under tight contact conditions to evaluate the catalytic activity for soot combustion. Synergetic effect between Ca and Co improved the structure and redox properties of the solids, increased the surface oxygen vacancies, and provided a suitable electropositivity for oxide, directly resulting in the decreased ignition temperature for catalyzed soot oxidation as low as 317 °C. The presence of NO in O₂ further promoted soot oxidation over the catalysts with the ignition temperature decreased to about 300 °C. The DRIFTS results reveal that decomposition of less stable surface nitrites may account for NO₂ formation in the ignition period of soot combustion, which thus participate in the auxiliary combustion process.

The aim of this study was to relate the course of parturition to the condition of piglets at birth, based on umbilical cord blood acid-base values, and relate the condition at birth to neonatal survival and performance up to 10 weeks of life. Data were collected from 37 spontaneous unassisted parturitions, and neonatal performance was based on observations of 516 piglets. Stillbirth rate increased from 2% in the first piglets, to 17% in piglets born 13th in the litter or later. This was aggravated in sows with longer than average stage II of parturition. Umbilical cord blood values also reflected the effect of birth order, with pH decreasing and lactate increasing in the course of parturition. Interestingly, sows that had a long expulsion stage of parturition also took longer to give birth to the first four piglets (r = 0.74), suggesting that sows with complicated parturition were already experiencing problems at the start of expulsion of piglets. Piglets with signs of asphyxia, based on umbilical blood lactate higher than 4.46 mmol/L, were slower to start suckling, had a higher risk of neonatal mortality, and had a slower growth rate over the first 10 weeks of life.

Intervertebral disc degeneration (IDD) is an important cause of low back pain. Recent evidence suggests that in addition to abnormal and excessive mechanical loading, inflammation may be a key driver for both IDD and low back pain. Obesity, a known mechanical risk factor of IDD, is now increasingly being recognized as a systemic inflammatory state with adipokines being postulated as likely inflammatory mediators. The aim of this review was to summarize the current literature regarding the inflammatory role of adipokines in the pathophysiology of IDD. A systematic literature search was performed using the OVID Medline, EMBASE and PubMed databases to identify all studies assessing IDD and adipokines. Fifteen studies were included in the present review. Leptin was the most commonly assessed adipokine. Ten of 15 studies were conducted in humans; three in rats and two in both humans and rats. Studies focused on a variety of topics ranging from receptor identification, pathway analysis, genetic associations, and proteonomics. Currently, data from both human and animal experiments demonstrate significant effects of leptin and adiponectin on the internal milieu of intervertebral discs. However, future studies are needed to determine the molecular pathway relationships between adipokines in the pathophysiology of IDD as avenues for future therapeutic targets.

The interactions between implants and host tissues depend on several factors. In particular, a growing body of evidence has demonstrated that the surface texture of an implant influences the response of the surrounding cells. The purpose of this study is to develop new implant materials aiming at the regeneration of periodontal tissues as well as hard tissues by coating nano-modified titanium with amelogenin, which is one of the main proteins contained in Emdogain®. We confirmed by quartz crystal microbalance evaluation that amelogenin is easy to adsorb onto the nano-modified titanium surface as a coating. Scanning electron microscopy, scanning probe microscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy analyses confirmed that amelogenin coated the nano-modified titanium surface following alkali-treatment. In vitro evaluation using rat bone marrow and periodontal ligament cells revealed that the initial adhesion of both cell types and the induction of hard tissue differentiation such as cementum were improved by amelogenin coating. Additionally, the formation of new bone in implanted surrounding tissues was observed in in vivo evaluation using rat femurs. Together, these results suggest that this material may serve as a new implant material with the potential to play a major role in the advancement of clinical dentistry.

Nowadays, quantitative structure⁻activity relationship (QSAR) methods have been widely performed to predict the toxicity of compounds to organisms due to their simplicity, ease of implementation, and low hazards. In this study, to estimate the toxicities of substituted aromatic compounds to Tetrahymena pyriformis, the QSAR models were established by the multiple linear regression (MLR) and radial basis function neural network (RBFNN). Unlike other QSAR studies, according to the difference of functional groups (−NO₂, −X), the whole dataset was divided into three groups and further modeled separately. The statistical characteristics for the models are obtained as the following: MLR: n = 36, R² = 0.829, RMS (root mean square) = 0.192, RBFNN: n = 36, R² = 0.843, RMS = 0.167 for Group 1; MLR: n = 60, R² = 0.803, RMS = 0.222, RBFNN: n = 60, R² = 0.821, RMS = 0.193 for Group 2; MLR: n = 31 R² = 0.852, RMS = 0.192; RBFNN: n = 31, R² = 0.885, RMS = 0.163 for Group 3, respectively. The results were within the acceptable range, and the models were found to be statistically robust with high external predictivity. Moreover, the models also gave some insight on those characteristics of the structures that most affect the toxicity.

The large neutral amino acid transporter 1 (LAT1, or SLC7A5) is a sodium- and pH-independent transporter, which supplies essential amino acids (e.g., leucine, phenylalanine) to cells. It plays an important role at the Blood⁻Brain Barrier (BBB) where it facilitates the transport of thyroid hormones, pharmaceuticals (e.g., l-DOPA, gabapentin), and metabolites into the brain. Moreover, its expression is highly upregulated in various types of human cancer that are characterized by an intense demand for amino acids for growth and proliferation. Therefore, LAT1 is believed to be an important drug target for cancer treatment. With the crystallization of the arginine/agmatine antiporter (AdiC) from Escherichia Coli, numerous homology models of LAT1 have been built to elucidate the substrate binding site, ligand⁻transporter interaction, and structure⁻function relationship. The use of these models in combination with molecular docking and experimental testing has identified novel chemotypes of ligands of LAT1. Here, we highlight the structure, function, transport mechanism, and homology modeling of LAT1. Additionally, results from structure⁻function studies performed on LAT1 are addressed, which have enhanced our knowledge of the mechanism of substrate binding and translocation. This is followed by a discussion on ligand- and structure-based approaches, with an emphasis on elucidating the molecular basis of LAT1 inhibition. Finally, we provide an exhaustive summary of different LAT1 inhibitors that have been identified so far, including the recently discovered irreversible covalent inhibitors.

Ambulance personnel who witness trauma experienced by patients have been reported to experience positive changes, known as vicarious posttraumatic growth (VPTG). We examined VPTG and its relationship with social support and resilience among ambulance personnel.

To evaluate the incidence of incisional hernia (IH) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and its impact on health-related quality of life (HRQoL).

The common deletion of the glutathione S-transferase Mu 1 (GSTM1) gene in humans has been shown to be involved in xenobiotic metabolism and associated with bladder cancer. However, the evolution of this deletion has not been investigated.

Globally, adolescent girls' physical activity (PA) levels are low. The 'Girls Active' secondary school-based programme, developed by the Youth Sport Trust, aims to increase PA in adolescent girls. This paper explores the effectiveness of the 'Girls Active' school-based PA programme.

Dyslipidemia and hyper-homocysteinemia are the major independent risk factors of cardio vascular disease. Deficiency of folate and vitamin B-12 are associated with both hyper-homocysteinemia and dyslipidemia. The aim of the study is to evaluate the relationship of homocysteine and its associated dietary determinant levels (Folate and Vitamin B-12) with lipids and obesity parameters (WC, BMI, WHR) in North Indian population.

Glutaraldehyde fixed xenogeneic heart valve prosthesis are hindered by calcification and lack of growth potential. The aim of tissue decellularization is to remove tissue antigenicity, avoiding the use of glutaraldehyde and improve valve integration with low inflammation and host cell recolonization. In this preliminary study, we investigated the efficacy of a NaOH-based process for decellularization and biocompatibility improvement of porcine pulmonary heart valves in comparison to a detergent-based process (SDS-SDC0, 5%).

The dysregulated host immune response that defines sepsis varies as a function of both the immune status of the host and the distinct nature of the pathogen. The degree to which immunocompromising comorbidities or immunosuppressive medications affect the immune response to infection is poorly understood because these patients are often excluded from studies about septic immunity. The objectives of this study were to determine the immune response to a single pathogen (Staphylococcus aureus) among a diverse case mix of patients and to determine whether comorbidities affect immune and clinical outcomes.

Base substitution catalogues represent historical records of mutational processes that have been active in a cell. Such processes can be distinguished by various characteristics, like mutation type, sequence context, transcriptional and replicative strand bias, genomic distribution and association with (epi)-genomic features.

Transmission dynamics of mosquito-borne viruses such as dengue, Zika and chikungunya are affected by the longevity of the adult female mosquito. Environmental conditions influence the survival of adult female Aedes mosquitoes, the primary vectors of these viruses. While the association of temperature with Aedes mortality has been relatively well-explored, the role of humidity is less established. The current study's goals were to compile knowledge of the influence of humidity on adult survival in the important vector species Aedes aegypti and Ae. albopictus, and to quantify this relationship while accounting for the modifying effect of temperature.

Variations in HPV LCR/E6/E7 have been shown to be associated with the viral persistence and cervical cancer development. So far, there are few reports about the polymorphisms of the HPV-58 LCR/E6/E7 sequences in Southwest China. This study aims to characterize the gene polymorphisms of the HPV-58 LCR/E6/E7 sequences in women of Southwest China, and assess the effects of variations on the immune recognition of viral E6 and E7 antigens.

Atypical iron overload without variation in the five clinically associated hereditary hemochromatosis genes is now recognized; however, their etiology remains unknown. Since the identification of iron overload in the bone morphogenetic protein 6 (Bmp6) knockout mouse, the search has been on for clinically pathogenic variants in the BMP6 gene. A recent report proposes that variants in the pro-peptide region of BMP6 are the underlying cause of several cases of iron overload. We performed targeted next-generation sequencing on three cases of atypical iron overload with Asian ethnicity and identified a p.Q118dup (aka p.E112indelEQ, p.Q115dup, p.Q118_L119insQ) variant in BMP6. The purpose of this study was to characterize the molecular function of the identified BMP6 variant. Molecular characterization by immunofluorescence microscopy and Western blotting of transfected cells, bioinformatics, and population analyses was performed.

Environmental factors have a large influence on the composition of the human gut microbiota. One of the most influential and well-studied is host diet. To assess and interpret the impact of non-dietary factors on the gut microbiota, we endeavoured to determine the most appropriate method to summarise community variation attributable to dietary effects. Dietary habits are multidimensional with internal correlations. This complexity can be simplified by using dietary indices that quantify dietary variance in a single measure and offer a means of controlling for diet in microbiota studies. However, to date, the applicability of different dietary indices to gut microbiota studies has not been assessed. Here, we use food frequency questionnaire (FFQ) data from members of the TwinsUK cohort to create three different dietary measures applicable in western-diet populations: The Healthy Eating Index (HEI), the Mediterranean Diet Score (MDS) and the Healthy Food Diversity index (HFD-Index). We validate and compare these three indices to determine which best summarises dietary influences on gut microbiota composition.