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Neurology and Therapy Dec 2023Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on...
INTRODUCTION
Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2 years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression.
METHODS
This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4 weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6 months for 2 years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and the Treatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed.
RESULTS
A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2 years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2 years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18 months (p = 0.004) and 29.0 (24.6) at 24 months (p = 0.002). Levels of fatigue and depression were also reduced. After 2 years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14-0.21) from the baseline of 0.42 (95% CI 0.38-0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12 months, which increased to 61.4% during months 12-24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not.
CONCLUSION
Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2 years is effective in reducing ARR and disability progression.
PubMed: 37861931
DOI: 10.1007/s40120-023-00557-7 -
Journal of Translational Medicine Oct 2023Colorectal cancer (CRC) is the third most deadly and fourth most diagnosed cancer worldwide. Despite the progress in early diagnosis and advanced therapeutic options,...
BACKGROUND
Colorectal cancer (CRC) is the third most deadly and fourth most diagnosed cancer worldwide. Despite the progress in early diagnosis and advanced therapeutic options, CRC shows a poor prognosis with a 5 year survival rate of ~ 45%. PRDM2/RIZ, a member of PR/SET domain family (PRDM), expresses two main molecular variants, the PR-plus isoform (RIZ1) and the PR-minus (RIZ2). The imbalance in their expression levels in favor of RIZ2 is observed in many cancer types. The full length RIZ1 has been extensively investigated in several cancers where it acts as a tumor suppressor, whereas few studies have explored the RIZ2 oncogenic properties. PRDM2 is often target of frameshift mutations and aberrant DNA methylation in CRC. However, little is known about its role in CRC.
METHODS
We combined in-silico investigation of The Cancer Genome Atlas (TCGA) CRC datasets, cellular and molecular assays, transcriptome sequencing and functional annotation analysis to assess the role of RIZ2 in human CRC.
RESULTS
Our in-silico analysis on TCGA datasets confirmed that PRDM2 gene is frequently mutated and transcriptionally deregulated in CRC and revealed that a RIZ2 increase is highly correlated with a significant RIZ1 downregulation. Then, we assayed several CRC cell lines by qRT-PCR analysis for the main PRDM2 transcripts and selected DLD1 cell line, which showed the lowest RIZ2 levels. Therefore, we overexpressed RIZ2 in these cells to mimic TCGA datasets analysis results and consequently to assess the PRDM2/RIZ2 role in CRC. Data from RNA-seq disclosed that RIZ2 overexpression induced profound changes in CRC cell transcriptome via EGF pathway deregulation, suggesting that RIZ2 is involved in the EGF autocrine regulation of DLD1 cell behavior. Noteworthy, the forced RIZ2 expression increased cell viability, growth, colony formation, migration and organoid formation. These effects could be mediated by the release of high EGF levels by RIZ2 overexpressing DLD1 cells.
CONCLUSIONS
Our findings add novel insights on the putative RIZ2 tumor-promoting functions in CRC, although additional efforts are warranted to define the underlying molecular mechanism.
Topics: Humans; Cell Line, Tumor; Colorectal Neoplasms; Epidermal Growth Factor; ErbB Receptors; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Tumor Cells, Cultured
PubMed: 37853459
DOI: 10.1186/s12967-023-04621-6 -
Seizure Dec 2023We investigated the value of automated enlarged perivascular spaces (ePVS) quantification to distinguish chronic traumatic brain injury (TBI) patients with...
BACKGROUND
We investigated the value of automated enlarged perivascular spaces (ePVS) quantification to distinguish chronic traumatic brain injury (TBI) patients with post-traumatic epilepsy (PTE) from chronic TBI patients without PTE (PTE) in a feasibility study.
METHODS
Patients with and without PTE were recruited and underwent an MRI post-TBI. Multimodal auto identification of ePVS algorithm was applied to T1-weighted MRIs to segment ePVS. The total number of ePVS was calculated and corrected for white matter volume, and an asymmetry index (AI) derived.
RESULTS
PTE was diagnosed in 7 out of the 99 participants (male=69) after a median time of less than one year since injury (range 10-22). Brain lesions were observed in all 7 PTE cases (unilateral=4, 57%; bilateral=3, 43%) as compared to 40 PTE cases (total 44%; unilateral=17, 42%; bilateral=23, 58%). There was a significant difference between PTE (M=1.21e, IQR [8.89e]) and PTE cases (M=2.79e, IQR [6.25e]) in total corrected numbers of ePVS in patients with unilateral lesions (p=0.024). No differences in AI, trauma severity and lesion volume were seen between groups.
CONCLUSION
This study has shown that automated quantification of ePVS is feasible and provided initial evidence that individuals with PTE with unilateral lesions may have fewer ePVS compared to TBI patients without epilepsy. Further studies with larger sample sizes should be conducted to determine the value of ePVS quantification as a PTE-biomarker.
Topics: Humans; Male; Epilepsy, Post-Traumatic; Feasibility Studies; Brain Injuries, Traumatic; Magnetic Resonance Imaging; White Matter; Nervous System Malformations
PubMed: 37847935
DOI: 10.1016/j.seizure.2023.10.006 -
Current Diabetes Reviews 2024Prediabetes is a reversible condition before the onset of Type 2 Diabetes Mellitus. Untreated condition of prediabetes will develop into diabetes and its complications....
BACKGROUND
Prediabetes is a reversible condition before the onset of Type 2 Diabetes Mellitus. Untreated condition of prediabetes will develop into diabetes and its complications. The prevalence of prediabetes has been emerging worldwide and has a considerable socioeconomic impact. The current study reviews the roles of early detection, educational models, life modification, and prophylaxis of individuals with prediabetes in preventing the progression of prediabetes into Type 2 Diabetes Mellitus and complications in the future.
METHODS
This study included published articles from several electronic databases. The obtained articles were limited to March 2023. Articles that were not open access and not in Indonesian or English were excluded. The protocol for this study used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020.
RESULTS
Of 39627 articles, 39601 were excluded due to duplication and did not meet the eligibility criteria. At the final, there were 26 articles that were eligible for systematic review.
CONCLUSION
Prevention of the development of prediabetes into diabetes is essential. A comprehensive understanding and training on intensive lifestyle modification protocols from local and national experts in diabetes prevention through digital-based education models and linguistically and culturally approach can be considered. Intensive lifestyle modification and pharmacological approaches may improve the outcome. Regular monitoring of glycemic control is also important for early diagnosis of diabetes, especially in patients with special conditions.
Topics: Humans; Prediabetic State; Diabetes Mellitus, Type 2; Patient Education as Topic; Models, Educational; Early Diagnosis; Disease Progression
PubMed: 37818560
DOI: 10.2174/0115733998275518231006074504 -
Heliyon Sep 2023Hepatitis C is still a serious liver case of health. Up to now the development of anti-Hepatitis C Virus (HCV) drugs is challenging, especially the development of...
Hepatitis C is still a serious liver case of health. Up to now the development of anti-Hepatitis C Virus (HCV) drugs is challenging, especially the development of natural material compounds as anti-HCV. In the present study, we evaluated the probability of α-mangostin, piperine, and β-sitosterol as anti-HCV with the in silico and in vitro approaches. Molecular docking was performed between nonstructural protein 5B (NS5B, PDB ID 3FQL) with α-mangostin, piperine, and β-sitosterol by Autodock Tools® and BIOVIA Discovery Studio®. Subsequently, molecular dynamics simulations were conducted for 200 ns, evaluating the dynamic interaction between the ligands and the viral protein NS5B. Furthermore, compound characterization at the hepatocarcinoma cell line was employed. α-Mangostin with NS5B complex demonstrated the most negative binding free energy value based on MM-PBSA calculation with a value of -9.13 kcal/mol. In vitro test showed that IC of α -mangostin was 2.70 ± 0.92 μM, IC of piperine was 52.18 ± 3.21 μM, IC of β-sitosterol was >100 μM. α-Mangostin can serve as a valuable lead compound for further development of the anti-HCV.
PubMed: 37809693
DOI: 10.1016/j.heliyon.2023.e20141 -
Journal of Feline Medicine and Surgery Oct 2023The present study aimed to determine the inheritance pattern and genetic cause of congenital radial hemimelia (RH) in cats.
OBJECTIVES
The present study aimed to determine the inheritance pattern and genetic cause of congenital radial hemimelia (RH) in cats.
METHODS
Clinical and genetic analyses were conducted on a Siamese cat family (n = 18), including two siblings with RH. Radiographs were obtained for the affected kittens and echocardiograms of an affected kitten and sire. Whole genome sequencing was completed on the two cases and the parents. Genomic data were compared with the 99 Lives Cat Genome data set of 420 additional domestic cats with whole genome and whole exome sequencing data. Variants were considered as homozygous in the two cases of the siblings with RH and heterozygous in the parents. Candidate variants were genotyped by Sanger sequencing in the extended pedigree.
RESULTS
Radiographs of the female kitten revealed bilateral absence of the radii and bowing of the humeri, while the male kitten showed a dysplastic right radius. Echocardiography suggested the female kitten had restrictive cardiomyopathy with a positive left atrial-to-aortic root ratio (LA:Ao = 1.83 cm), whereas hypertrophic cardiomyopathy was more likely in the sire, showing diastolic dysfunction using tissue Doppler imaging (59.06 cm/s). Twenty-two DNA variants were unique and homozygous in the affected kittens and heterozygous in the parents. Seven variants clustered in one chromosomal region, including two frameshift variants in () and five variants in , ( ), including a missense and an in-frame deletion.
CONCLUSIONS AND RELEVANCE
The present study suggested an autosomal recessive mode of inheritance with variable expression for RH in the Siamese cat family. Candidate variants for the phenotype were identified, implicating their roles in bone development. These genes should be considered as potentially causal for other cats with RH. Siamese cat breeders should consider genetically testing their cats for these variants to prevent further dissemination of the suspected variants within the breed.
Topics: Female; Male; Cats; Animals; Ectromelia; Cardiomyopathies; Risk Factors; Cardiomyopathy, Hypertrophic; Humerus; Cat Diseases
PubMed: 37791865
DOI: 10.1177/1098612X231193557 -
Microorganisms Sep 2023Guanylate-binding proteins (GBPs) are highly expressed interferon-stimulated genes (ISGs) that play significant roles in protecting against invading pathogens. Although...
Guanylate-binding proteins (GBPs) are highly expressed interferon-stimulated genes (ISGs) that play significant roles in protecting against invading pathogens. Although their functions in response to RNA viruses have been extensively investigated, there is limited information available regarding their role in DNA viruses, particularly poxviruses. Ectromelia virus (ECTV), a member of the orthopoxvirus genus, is a large double-stranded DNA virus closely related to the monkeypox virus and variola virus. It has been intensively studied as a highly effective model virus. According to the study, GBP2 overexpression suppresses ECTV replication in a dose-dependent manner, while GBP2 knockdown promotes ECTV infection. Additionally, it was discovered that GBP2 primarily functions through its N-terminal GTPase activity, and the inhibitory effect of GBP2 was disrupted in the GTP-binding-impaired mutant GBP2. This study is the first to demonstrate the inhibitory effect of GBP2 on ECTV, and it offers insights into innovative antiviral strategies.
PubMed: 37764102
DOI: 10.3390/microorganisms11092258 -
Animals : An Open Access Journal From... Sep 2023is a relevant zoonotic infectious agent causing swine erysipelas (SE) in wild boar. In Portugal, there is no information on its occurrence. For this reason, this study...
is a relevant zoonotic infectious agent causing swine erysipelas (SE) in wild boar. In Portugal, there is no information on its occurrence. For this reason, this study aims to perform a first serosurvey of SE in hunted wild boars in Portugal. During the 2019/2020 hunting season, 111 sera from hunted wild boar were collected and analysed serologically in the laboratory with a commercial ELISA kit. No animals were eviscerated and examined after the hunt. The hunters took it all for private consumption. The results identified 18 animals that were exposed to SE, corresponding to a seroprevalence of 16.2% (95% CI: 19.9-24.4%). No statistical significance was observed on the effect of gender and age on seropositivity. However, wild boar hunted in Pinhel County, had five times more likely to be seropositivity (-value < 0.05; OD = 5.4). Apart from its potential debilitating capacity and chronicity in the wild boar population, SE is also a very serious occupational zoonosis. Thus, the result of this first serosurvey in Portugal should raise awareness and alert competent national veterinary authorities and those involved in the hunting sector, especially hunters who directly handle these carcasses. Further studies should be conducted to better understand the role of wild boar as a reservoir and spillover of this disease to other animals and humans.
PubMed: 37760336
DOI: 10.3390/ani13182936 -
Marine Drugs Sep 2023Peptic ulcer disease is generated by the activation of NF-kappaB activity. A recent clinical study reported a significant increase in NF-kappaB2 gene expression in 79...
Peptic ulcer disease is generated by the activation of NF-kappaB activity. A recent clinical study reported a significant increase in NF-kappaB2 gene expression in 79 samples of peptic ulcer patients compared to the control group. Moreover, the deacetylated chitin could alter the translocation of NF-kappaB p65 to the nucleus. Considering this, our work aims to explore the effect of chitin extracted from the shell of blue swimming crabs ( Linn.) towards NF-kappaB p65 levels in ethanol-induced gastric ulcerative Wistar rats. The shells are found abundantly as the waste of seafood processing in the northern part of West Java, Indonesia. In this study, chitin extraction was carried out using the microwave-assisted extraction method by employing choline chloride (CHClNO) and DL-malic acid (C₄H₆O₅) as the solvents. The inhibitory activity assay of chitin on the expression of NF-kappaB p65 was performed by using Western blot. The extraction yielded a good quality of chitin with a deacetylation degree of 30.8026%, molecular weight of 3.35 × 10 Da, and a negligible heavy metals level. Moreover, chitin extract at doses of 150, 300, and 600 mg/kg BW significantly reduced the percentage of gastric ulcer index compared to the negative control group. Meanwhile, chitin extract at doses of 300 and 600 mg/kg BW significantly inhibited NF-kappaB expression compared to the negative control group. Histopathological examination demonstrated a decrease in the number of necrotic cells and fat degeneration in the gastric mucosa and an increase in normal cells. Taken together, chitin extract obtained from the shells of blue swimming crabs may be able to prevent gastric ulcers induced by ethanol via the inhibition of NF-kappaB p65; however, further studies are needed to verify its anti-ulcerative properties.
PubMed: 37755101
DOI: 10.3390/md21090488 -
Scientific Reports Sep 2023In Brazil, data on the management of triple negative breast cancer (TNBC) as well as the burden of the disease in terms of health care resources utilization (HCRU) are...
In Brazil, data on the management of triple negative breast cancer (TNBC) as well as the burden of the disease in terms of health care resources utilization (HCRU) are scarce. To characterize the treatment patterns and HCRU associated with the management of Brazilian TNBC patients from the perspective of the private healthcare setting. Patients with at least one claim related to ICD-10 C50 from January 2012 until December 2017, and at least one claim for breast cancer treatment were assessed from a private claims database and classified as early and locally advanced, or metastatic. All patients with hormone and/or targeted therapy were excluded. Three thousand and four patients were identified, of which 82.8% were diagnosed in early and locally advanced stages. For early and locally advanced TNBC patients, 75.3% were treated in an adjuvant setting, mainly with anthracycline regimes. For mTNBC patients, bevacizumab regimens were the main treatment prescribed. More than 48% of mTNBC patients were switched to a second line of treatment. HCRU was higher for mTNBC patients when compared to early and locally advanced patients, with higher costs for metastatic disease management. The treatment setting has little influence on the HCRU pattern or the cost of disease management. The highest burden of disease was observed for metastatic management.
Topics: Humans; Triple Negative Breast Neoplasms; Brazil; Patient Acceptance of Health Care; Adjuvants, Immunologic; Adjuvants, Pharmaceutic
PubMed: 37737435
DOI: 10.1038/s41598-023-43131-9