Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of ethanolic extract of Caralluma diazielli on serum lipid profiles on fructose induced diabetes in wistar rats

This work was conducted to evaluate the effect of e thanolic extract of Caralluma diazielli on lipid pr ofiles in fructose-induced diabetes in Wistar rats. Induction of diabetes was done by dissolving 20g/100ml (20%) of fructose in distilled water. After which the animals were ra ndomly assigned into 5 groups of 5 rats each. Group 1 as negative control received distilled water( 5mg/kg), Group 2 received positive control received glibenclimide or ally (1mg/kg b w), Group 3 received 200mg/kg b w of extract of C . diazielli orally, Group 4 received 100mg/kg b w of extract of C.diazielli orally Group 5 received 50mg/kg b w of extract of C.diazielli orally. The results obtaine d showed statistical significant reduction (p<0.05) in the level of serum total cholesterol and triglyceride in all groups that received the extract when compared to control group . However, the serum level of high density lipoprot ein was significantly increased in the groups that received the extract when compared to the negative control group. The preliminary phytochemical screening of the extract of C.diazielli revealed the presences of cardenolid es carbohydrate flavonoid and glycosides. Also the Acu te toxicity of the extract was found to be 2.154 mg /kg orally.
Metabolomics signatures in type 2 diabetes: a systematic review and integrative analysis.

OBJECTIVE Metabolic signatures have emerged as valuable signaling molecules in the biochemical process of type 2 diabetes (T2D). To summarize and identify metabolic biomarkers in T2D, we performed a systematic review and meta-analysis of the associations between metabolites and T2D using high-throughput metabolomics techniques. METHODS We searched relevant studies from MEDLINE (PubMed), Embase, Web of Science and Cochrane Library as well as Chinese databases (Wanfang, Vip and CNKI) inception through 31th December 2018. Meta-analysis was conducted using STATA 14.0 under random effect. Besides, bioinformatic analysis was performed to explore molecule mechanism by MetaboAnalyst and R 3.5. 2. RESULTS Finally, 46 articles were included in this review on metabolites involved amino acids, acylcarnitines, lipids, carbohydrates, organic acids and others. Results of meta-analysis in prospective studies indicated that isoleucine, leucine, valine, tyrosine, phenylalanine, glutamate, alanine, valerylcarnitine (C5), palmitoylcarnitine (C16), palmitic acid and linoleic acid were associated with higher T2D risk. Conversely, serine, glutamine and LPC C18:2 decreased risk of T2D. Arginine and glycine increased risk of T2D in western countries subgroup, and betaine was negatively correlated with T2D in nested case-control subgroup. In addition, slight improvements in T2D prediction beyond traditional risk factors were observed when adding these metabolites in predictive analysis. Pathway analysis identified 17 metabolic pathways may alter in the process of T2D and metabolite-related genes were also enriched in functions and pathways associated with T2D. CONCLUSIONS Several metabolites and metabolic pathways associated with T2D have been identified, which provide valuable biomarkers and novel targets for prevention and drug therapy.
Evaluation of the Reactivity and Receptor Competition of HLA-G Isoforms toward Available Antibodies: Implications of Structural Characteristics of HLA-G Isoforms

The human leucocyte antigen (HLA)-G, which consists of seven splice variants, is a tolerogenic immune checkpoint molecule. It plays an important role in the protection of the fetus from the maternal immune response by binding to inhibitory receptors, including leukocyte Ig-like receptors (LILRs). Recent studies have also revealed that HLA-G is involved in the progression of cancer cells and the protection from autoimmune diseases. In contrast to its well characterized isoform, HLA-G1, the binding activities of other major HLA-G isoforms, such as HLA-G2, toward available anti-HLA-G antibodies are only partially understood. Here, we investigate the binding specificities of anti-HLA-G antibodies by using surface plasmon resonance. MEM-G9 and G233 showed strong affinities to HLA-G1, with a nM range for their dissociation constants, but did not show affinities to HLA-G2. The disulfide-linker HLA-G1 dimer further exhibited significant avidity effects. On the other hand, 4H84 and MEM-G1, which can be used for the Western blotting of HLA-G isoforms, can bind to native HLA-G2, while MEM-G9 and G233 cannot. These results reveal that HLA-G2 has a partially intrinsically disordered structure. Furthermore, MEM-G1, but not 4H84, competes with the LILRB2 binding of HLA-G2. These results provide novel insight into the functional characterization of HLA-G isoforms and their detection systems.
Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

Chloroquines are 4‐aminoquinoline‐based drugs mainly used to treat malaria. At pharmacological concentrations, they have significant effects on tissue homeostasis, targeting diverse signaling pathways in mammalian cells. A key target pathway is autophagy, which regulates macromolecule turnover in the cell. In addition to affecting cellular metabolism and bioenergetic flow equilibrium, autophagy plays a pivotal role at the interface between inflammation and cancer progression. Chloroquines consequently have critical effects in tissue metabolic activity and importantly, in key functions of the immune system. In this article, we will review the work addressing the role of chloroquines in the homeostasis of mammalian tissue, and the potential strengths and weaknesses concerning their use in cancer therapy.
Effects of Metacognitive Strategies on the Self-Regulated Learning Process: The Mediating Effects of Self-Efficacy

The purpose of this study was to examine the effects of metacognitive strategies on self-regulated learning processes, focusing on the mediating effects of self-efficacy. The surveys were conducted in December 2016 (Time 1) and January 2017 (Time 2). One hundred and five undergraduates enrolled at a Japanese university participated in this survey study, consisting of two surveys conducted one month apart. The questionnaires measured the use of metacognitive strategies (i.e., planning strategy and monitoring strategy), self-efficacy, general learning behaviors (behavioral engagement and persistence), and the use of cognitive strategies (i.e., writing-repetition strategy and deep-processing strategy). First, cross-lagged structure equation modeling revealed that the use of planning strategy enhanced self-efficacy. Second, path analysis examined relationships between metacognitive strategies, general learning behaviors, and cognitive strategies. It revealed that (a) general learning behaviors were promoted by metacognitive strategies mediated by self-efficacy and (b) cognitive strategies were almost directly affected by the monitoring strategy. The current study reveals that general learning behaviors and cognitive strategies involve different processes than metacognitive strategies.
Comparison of the sequences and expression levels of genes related to follicular development and atresia between prolific and nonprolific goat breeds

Abstract This study investigated the variations of the nucleotide sequences and ovarian expression levels of genes related to follicular development and atresia in prolific Jintang black goats and nonprolific Tibetan goats. Eight genes, FSHB, LHB, FSHR, LHCGR, ESR2, B4GANT2, BCL2 and BAX, were examined using reverse transcription‐polymerase chain reaction and quantitative real‐time PCR. The results showed that the nucleotide and deduced amino acid sequences of the LHB and BAX genes were not different, but there was one base change in the FSHR genes between the two breeds. There was one base change in the FSHB gene, which resulted in one amino acid substitution; there were nine base changes in the LHCGR gene, which resulted in five amino acid substitutions; and there were six base changes in the B4GANT2 gene, which resulted in four amino acid substitutions. The expression levels of the FSHR, LHCGR, ESR2, B4GANT2, BCL2 and BAX genes in the ovaries were not different between the two breeds. The plasma concentrations of FSH were not different, but the plasma concentrations of LH, P4 and E2 were lower in prolific Jintang black goats than in nonprolific Tibetan goats (P ˂ 0.05) at 40 hr after removal of the Controlled Internal Drug Release Devices. These results provide some foundations elucidating the endocrine and molecular mechanisms controlling ovulation rate in goats, but these need to be further verified.
AN ANALYSIS OF 102 PATIENTS

The exceptionally high prevalence of diastrophic dysplasia in Finland has enabled us to analyse the foot deformities of 102 patients at their first orthopaedic evaluation and classify 204 feet into five categories. The most common finding (43%) was a foot with tarsal valgus deformity and metatarsus adductus; 37% showed either equinovarus adductus (29%) or equinus(8%) deformities. At the first examination 13% showed metatarsus adductus deformity alone, and 7% were clinically normal. The expression ‘club foot’, generally used for the foot deformity in diastrophic dysplasia is a misnomer. There is a wide spectrum of deformities, some of them specific for the condition.
Influence of fitting approaches in LCModel on MRS quantification focusing on age‐specific macromolecules and the spline baseline

Quantification of neurochemical concentrations from 1H MR spectra is challenged by incomplete knowledge of contributing signals. Some experimental conditions hinder the acquisition of artifact‐free spectra and impede the acquisition of condition‐specific macromolecule (MM) spectra. This work studies differences caused by fitting solutions routinely employed to manage resonances from MM and lipids. High quality spectra (free of residual water and lipid artifacts and for which condition‐specific MM spectra are available) are used to understand the influences of spline baseline flexibility and noncondition‐specific MM on neurochemical quantification. Fitting with moderate spline flexibility or using noncondition‐specific MM led to quantification that differed from when an appropriate, fully specified model was used. This occurred for all neurochemicals to an extent that varied in magnitude among and within approaches. The spline baseline was more tortuous when less constrained and when used in combination with noncondition‐specific MM. Increasing baseline flexibility did not reproduce concentrations quantified under appropriate conditions when spectra were fitted using a MM spectrum measured from a mismatched cohort. Using the noncondition‐specific MM spectrum led to quantification differences that were comparable in size with using a fitting model that had moderate freedom, and these influences were additive. Although goodness of fit was better with greater fitting flexibility, quantification differed from when fitting with a fully specified model that is appropriate for low noise data. Notable GABA and PE concentration differences occurred with lower estimates of measurement error when fitting with greater spline flexibility or noncondition‐specific MM. These data support the need for improved metrics of goodness of fit. Attempting to correct for artifacts or absence of a condition‐specific MM spectrum via increased spline flexibility and usage of noncondition‐specific MM spectra cannot replace artifact‐free data quantified with a condition‐specific MM spectrum.
HMGCS2 Mediates Ketone Production and Regulates the Proliferation and Metastasis of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor worldwide; however, the traditional therapeutic approaches and survival rates are still limited. To improve current therapies, it is necessary to investigate the molecular mechanisms underlying liver cancer and to identify potential therapeutic targets. The aims of this study were to verify the mechanisms and therapeutic potential of the ketogenesis rate-limiting enzyme 3-Hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) in HCC. Immunohistochemical staining of human liver disease tissue arrays showed that HMGCS2 is abundantly expressed in normal liver tissues but is downregulated in cirrhosis and HCC tissues. In HCC patients, lower HMGCS2 expression was correlated with higher pathological grades and clinical stages. In our investigation of the molecular mechanisms of HMGCS2 in HCC, we showed that knockdown of HMGCS2 decreased ketone production, which promoted cell proliferation, cell migration, and xenograft tumorigenesis by enhancing c-Myc/cyclinD1 and EMT signaling and by suppressing the caspase-dependent apoptosis pathway. Ketone body treatment reduced the proliferation- and migration-promoting effects of HMGCS2 knockdown in cells. In contrast, HMGCS2 overexpression increased the intracellular ketone level and inhibited cell proliferation, cell migration, and xenograft tumorigenesis. Finally, ketogenic diet administration significantly inhibited liver cancer cell growth in mice. Our studies highlight the potential therapeutic strategy of targeting HMGCS2-mediated ketogenesis in liver cancer.
Randomised controlled trial of gradual antipsychotic reduction and discontinuation in people with schizophrenia and related disorders: the RADAR trial (Research into Antipsychotic Discontinuation and Reduction)

Introduction Antipsychotic medication is effective in reducing acute symptoms of psychosis, but it has a range of potentially serious and debilitating adverse effects and is often disliked by patients. It is therefore essential it is only used when benefits outweigh harms. Although multiple trials conducted with people with schizophrenia indicate an increased risk of relapse in the short-term following abrupt antipsychotic discontinuation, there is little evidence about the long-term outcome of a gradual process of reduction and discontinuation on social functioning, relapse and other outcomes. Methods and analysis This is a multicentre, randomised controlled trial involving people with schizophrenia and related disorders who have had more than one episode. Participants are randomised to have a clinically-supervised, gradual reduction of antipsychotic medication, leading to discontinuation when possible, or to continue with maintenance treatment. Blinded follow-up assessments are conducted at 6, 12 and 24 months and the primary outcome is social functioning, measured by the Social Functioning Scale at 24 months. A minimum of 134 evaluable participants provides 90% power to detect a five-point difference, and 206 to detect a four-point difference. Secondary outcomes include severe relapse (admission to hospital) and the study is also intended to detect a minimum 10% difference in severe relapse, which requires 402 participants, assuming a 15% loss to follow-up. Other secondary outcomes include all relapses, as identified by an independent and blinded endpoint committee, symptoms measured by the Positive and Negative Syndrome Scale, quality of life, adverse effects, self-rated recovery and neuropsychological measures. Enrolment started in 2016. The trial is scheduled to finish in June 2022. Ethics and dissemination Ethical approval was initially obtained on 27 October 2016 (UK Research Ethics Committee reference 16/LO/1507). Results will be published in peer-reviewed journals and disseminated to the public. Trial registration number ISRCTN90298520. EudraCT: 2016-000709-36. Pre-results.
Role of Fibronectin in Primary Open Angle Glaucoma

Primary open angle glaucoma (POAG) is the most common form of glaucoma and the 2nd most common cause of irreversible vision loss in the United States. Nearly 67 million people have the disease worldwide including >3 million in the United States. A major risk factor for POAG is an elevation in intraocular pressure (IOP). The increase in IOP is believed to be caused by an increase in the deposition of extracellular matrix proteins, in particular fibronectin, in a region of the eye known as the trabecular meshwork (TM). How fibronectin contributes to the increase in IOP is not well understood. The increased density of fibronectin fibrils is thought to increase IOP by altering the compliance of the trabecular meshwork. Recent studies, however, also suggest that the composition and organization of fibronectin fibrils would affect IOP by changing the cell-matrix signaling events that control the functional properties of the cells in the trabecular meshwork. In this article, we will discuss how changes in the properties of fibronectin and fibronectin fibrils could contribute to the regulation of IOP.
Poly(methylmethacrylate) Microwave Processing: A Technique Paper.

Microwave processing of a wax trial denture into a poly(methylmethacrylate) provides a viable alternative to conventional compression, injection and digital techniques. This article briefly describes a processing technique that yields a complete dental prosthesis in under two hours using a combination of modern materials designed to reduce working and setting times without compromising the quality of the final prosthesis. This article is protected by copyright. All rights reserved.
Antibody prodrugs for cancer

ABSTRACT Introduction: The toxicity of potent new biological therapies for cancer has limited their utility. By improving tumor specificity, antibody prodrugs can widen or even create a therapeutic window for anticancer agents that are difficult or impossible to use otherwise because of poor tolerability. Areas covered: This review will describe the current status of the field of antibody prodrugs, focusing on ProbodyTM therapeutics, including the principles behind their design, application to a variety of different antibody-based therapies, preclinical examples of their activity and safety, and early results of Phase 1 trials. Expert opinion: Proof of concept for the antibody prodrug approach, which is defined as demonstration of potent antitumor activity with improved safety, has been extensively established preclinically as well as preliminarily in early clinical trials in human patients. However, experience with antibody prodrugs is limited, and important challenges remain. Principal among them are how to design the molecules to provide the most effective protection from toxicities while preserving efficacy, how to optimize clinical pharmacology, and how to determine which among the many possible clinical applications is the best use of this promising technology.
Factors predicting poor glycemic control in the first two years of childhood onset type 1 diabetes in a cohort from East London, UK: Analyses using mixed effects fractional polynomial models

Poor early glycemic control in childhood onset type 1 diabetes (T1D) is associated with future risk of acute and chronic complications. Our aim was to identify the predictors of higher glycated hemoglobin (HbA1c) within 24 months of T1D diagnosis in children and adolescents.
Relationships between corneal biomechanics and the structural and functional parameters of glaucoma damage.

PURPOSE To investigate the relationships between (i) thickness of the retinal nerve fiber layer, optic nerve head topography, and visual field parameters and (ii) corneal biomechanical properties in normal controls and patients with ocular hypertension and primary open-angle glaucoma. METHODS This observational, cross-sectional study included 68 eyes with primary open-angle glaucoma, 99 eyes with ocular hypertension and 133 control eyes. Corneal biomechanical properties, optic nerve head topographic features, retinal nerve fiber layer thickness, and visual fields were assessed in all cases. Corneal biomechanical properties, retinal nerve fiber layer thicknesses, and optic nerve head topographic features were compared among the groups. The associations between structural and functional measures of glaucomatous damage and corneal biomechanical factors were also evaluated. RESULTS Significantly lower corneal hysteresis and corneal resistance factor values were observed in the primary open-angle glaucoma and ocular hypertension groups as compared with the control group, but there were no significant differences between the primary open-angle glaucoma and ocular hypertension groups. In the ocular hypertension group, no associations were observed between the corneal hysteresis and corneal resistance factor with values and the structural and functional parameters. In the primary open-angle glaucoma group, positive correlations were observed between the corneal hysteresis values and the global retinal nerve fiber layer thickness (p<0.01, r=0.27), mean retinal nerve fiber layer thickness (p<0.01, r=0.33), and mean deviation (p<0.01, r=0.26), and negative correlations were observed between the corneal resistance factor values, and the cup area (p<0.01, r=-0.39), cup-to-disk ratio (p=0.02, r=-0.28), linear cup-to-disk ratio (p=0.02, r=-0.28), and cup shape (p=0.03, r=-0.26). In the control group, weak correlations were detected between the corneal hysteresis and the cup area (p=0.03, r=0.19), cup-to-disk ratio (p=0.01, r=0.21), and linear cup-to-disk ratio (p=0.01, r=0.22). CONCLUSIONS Distinct correlations were identified between the corneal hysteresis and corneal resistance factor values and the functional and structural parameters in the primary open-angle glaucoma and control groups. Corneal hysteresis and corneal resistance factor may have different roles in the pathophysiology of glaucoma.
Radical Scavenging Activity of Puerarin: A Theoretical Study

Puerarin is a C-glycoside of daidzein, one of the major bioactive ingredients isolated from the root of Pueraria lobata, which has a wide spectrum of pharmacological effects. Although puerarin is well-known for its effective antioxidant activity, there is seldom a systematic theoretical study on its radical scavenging activity. Herein, the free radical scavenging ability of puerarin was investigated systematically by density functional theory (DFT) calculations. The reaction activity was compared with daidzein as well. Three reaction pathways: hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET) were discussed and compared by thermodynamic parameters such as bond dissociation enthalpy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), proton affinity (PA), and electron transfer enthalpy (ETE). The reaction kinetics of puerarin with special radicals •OH and •OOH were also studied. The results obtained may be of great significance for better understanding the relationship between the antioxidant properties and structural design of puerarin, as well as other antioxidants.
Comparing the Severity of Coronary Artery Stenosis in Diabetic and Nondiabetic Patients

Results: Based on data found in our study, 93.8% of diabetic and 83.4% of nondiabetic patients were shown to suffer coronary artery stenosis. Severe involvement (grade 3VD) of coronary artery stenosis was observed in 44.6% and 28.8% of diabetic and nondiabetic patients, respectively. Statistically, a significant difference was found between two groups regarding the rate and severity of CAD (P 0.05). Conclusions: Our findings revealed that the severity of coronary artery stenosis is common in diabetic patients compared to nondiabetics. Early diagnosis and treatment of CAD in diabetic patients is recommended.