Heterogeneous Determinants of Quality of Life in Different Phenotypes of Parkinson’s Disease

Objectives

Health-related quality of life (HRQoL) is considered a very important outcome indicator in patients with Parkinson’s disease (PD). A broad list of motor and non-motor features have been shown to affect HRQoL in PD, however, there is a dearth of information about the complexity of interrelationships between determinants of HRQoL in different PD phenotypes. We aimed to find independent determinates and the best structural model for HRQoL, also to investigate the heterogeneity in HRQoL between PD patients with different phenotypes regarding onset-age, progression rate and dominant symptom.

Methods

A broad spectrum of demographic, motor and non-motor characteristics were collected in 157 idiopathic PD patients, namely comorbidity profile, nutritional status, UPDRS (total items), psychiatric symptoms (depression, anxiety), fatigue and psychosocial functioning through physical examination, validated questionnaires and scales. Structural equation model (SEM) and multivariate regressions were applied to find determinants of Parkinson’s disease summary index (PDSI) and different domains of HRQoL (PDQ-39).

Results

Female sex, anxiety, depression and UPDRS-part II scores were the significant independent determinants of PDSI. A structural model consisting of global motor, global non-motor and co-morbidity indicator as three main components was able to predict 89% of the variance in HRQoL. In older-onset and slow-progression phenotypes, the motor domain showed smaller contribution on HRQoL and the majority of its effects were mediated through non-motor features. Comorbidity component was a significant determinant of HRQoL only among older-onset and non-tremor-dominant PD patients. Fatigue was not a significant indicator of non-motor component to affect HRQoL in rapid-progression PD.

Conclusions

Our findings showed outstanding heterogeneities in the pattern and determinants of HRQoL among PD phenotypes. These factors should be considered during the assessments and developing personalized interventions to improve HRQOL in PD patients with different phenotypes or prominent feature.     

miRNAs; a novel strategy for the treatment of COVID-19

Coronavirus disease 2019 (COVID-19) is the seventh member of the bat severe acute respiratory syndrome family. COVID-19 can fuse their envelopes with the host cell membranes and deliver their genetic material. COVID-19 attacks the respiratory system and stimulates the host inflammatory responses, enhances the recruitment of immune cells, and promotes angiotensin-converting enzyme 2 activities. Patients with confirmed COVID-19 may have experienced fever, dry cough, headache, dyspnea, acute kidney injury, acute respiratory distress syndrome, and acute heart injury. Several strategies such as oxygen therapy, ventilation, antibiotic or antiviral therapy, and renal replacement therapy are commonly used to decrease COVID-19-associated mortality. However, these approaches may not be good treatment options. Therefore, the search for an alternative-novel therapy is urgently important to prevent the disease progression. Recently, microRNAs (miRNAs) have emerged as a promising strategy for COVID-19. The design of oligonucleotide against the genetic material of COVID-19 might suppress virus RNA translation. Several previous studies have shown that host miRNAs play an antiviral role and improve the treatment of patients with COVID-19. miRNAs by binding to the 3′-untranslated region (UTR) or 5′-UTR of viral RNA play an important role in COVID-19-host interplay and viral replication. miRNAs interact with multiple pathways and reduce inflammatory biomarkers, thrombi formation, and tissue damage to accelerate the patient outcome. The information in this review provides a summary of the current clinical application of miRNAs for the treatments of patients with COVID-19.     

Experimental Analysis of E2BB (LTIIb) Signal Peptide in Secretory Production of Reteplase in Escherichia coli

International Journal of Peptide Research and Therapeutics - Recombinant reteplase is the truncated form of tissue plasminogen activator. Signal peptides play a pivotal role in the secretion of...     

Cloning,Expression and One-Step Purification of a Novel IP-10-(anti-HER2 scFv) Fusion Protein in Escherichia coli

International Journal of Peptide Research and Therapeutics - Breast cancer is the most common cancer in women, worldwide. The correlation between breast cancer malignancy and human epidermal growth...     

Effects of phenolic monomers on growth of Acidothermus cellulolyticus

Previous studies on biological pretreatment of switchgrass by solid-state fermentation with Acidothermus cellulolyticus 11B have shown that inhibitory compounds prevent growth on untreated switchgrass. A. cellulolyticus was grown in liquid medium containing cellobiose with phenolic monomers added to determine if the phenolic compounds are one possible source of inhibition. Cinnamic acid derivatives (trans-p-coumaric, trans-ferulic, and hydrocinnamic acids), hydroxybenzoic acids (p-hydroxybenzoic, syringic, and vanillic acids), benzaldehydes (vanillin and p-hydroxybenzaldehyde), and condensed tannin monomers (catechin and epicatechin) were tested at levels up to 20 mM. All compounds exhibited a dose-response relationship and strongly inhibited growth at 20 mM. trans-p-Coumaric acid was found to be the strongest inhibitor of A. cellulolyticus growth, with a specific growth rate of 0.004 h(-1) at 1 mM (0.18 h(-1) without phenolic monomer). GC-MS and HPLC methods were used to confirm the presence of these phenolic compounds in switchgrass and measure the amounts extracted using different conditions. The amounts of phenolic compounds measured were found to be higher than the threshold for growth inhibition. Leaching with water at 55°C was inefficient at removing bound phenolics, whereas NaOH treatment improved efficiency. Phenolic compounds spiked into alkaline pretreated switchgrass were also found to inhibit growth of A. cellulolyticus in solid-state fermentation. However, addition of insoluble polyvinylpolypyrrolidone (PVPP) to switchgrass improved growth of A. cellulolyticus in liquid cultures, providing a possible approach for alleviating microbial inhibition due to phenolic compounds in lignocellulose.     

Investigation of deregulated genes of Notch signaling pathway in human T cell acute lymphoblastic leukemia cell lines and clinical samples

In diagnostic research challenges, quantitative real-time PCR (QPCR) has been widely utilized in gene expression analysis because of its sensitivity, accuracy, reproducibility, and most importantly, quantitativeness. Real-time PCR base kits are wildly applicable in cancer signaling pathways, especially in cancer investigations. T-cell acute lymphoblastic leukemia (T-ALL) is a type of leukemia that is more common in older children and teenagers. Deregulation of the Notch signaling pathway promotes proliferation and inhibits apoptosis of the lymphoblastic T cells. The aim of this study was to investigate the effect of Notch signaling activation on the expression of target genes using real-time QPCR and further use this method in clinical examination after validation. Two T-ALL cell lines, Jurkat and Molt-4, were used as models for activation of the Notch signaling via over-expression of the Notch1 intracellular domain. Expression analysis was performed for six downstream target genes (NCSTN, APH1, PSEN1, ADAM17, NOTCH1 and C-MYC) which play critical roles in the Notch signaling pathway. The results showed significant difference in the expression of target genes in the deregulated Notch signaling pathway. These results were also verified in 12 clinical samples bearing over-expression of the Notch signaling pathway. Identification of such downstream Notch target genes, which have not been studied inclusively, provides insights into the mechanisms of the Notch function in T cell leukemia, and may help identify novel diagnoses and therapeutic targets in acute lymphoblastic leukemia.     

Identification of a novel missense mutation of PEX7 gene in an Iranian patient with rhizomelic chondrodysplasia punctata type 1

Deficiency in the PTS2 protein import pathway due to mutations in PEX7 gene results in the rhizomelic chondrodysplasia punctata (RCDP) type 1. In the present study, we have reported a novel missense mutation, W75R, in the PEX7 gene in an Iranian patient with the RCDP type 1. The inability of PEX7 protein to transport PTS2 containing proteins including peroxisomal 3-ketoacyl-CoA thiolase and PTS2-EGFP protein to the surface of the peroxisomes showed that the W75R mutation in PEX7 gene severely impaired the function of PEX7 protein and was responsible for RCDP type 1 in this patient.     

Prenatal liver stromal cells: Favorable feeder cells for long-term culture of hepatic progenitor cells

Clinical and pharmaceutical applications of primary hepatocytes (PHs) are limited due to inadequate number of donated livers and potential challenges in successful maintenance of PHs in culture. Freshly isolated hepatocytes lose their specific features and rapidly de-differentiate in culture. Bipotent hepatoblasts, as liver precursor cells that can differentiate into both hepatocytes and cholangiocytes (Alb- and Ck19-positive cells, respectively), could be used as an alternative and reliable cell source to produce enough PHs for drug discovery or possible clinical applications. In this study, growth factor-free coculture systems of prenatal or postnatal murine liver stromal cells (pre-LSCs or post-LSCs, respectively) were used as feeder cells to support freshly isolated mice hepatoblasts. DLK1-positive hepatoblasts were isolated from mouse fetuses (E14.5) and cocultured with feeder cells under adherent conditions. The hepatoblasts' bipotent features, proliferation rate, and colony formation capacity were assessed on day 5 and 7 post-seeding. Immunofluorescence staining showed that the hepatoblasts remained double positive for Alb and Ck19 on both Pre- and Post-LSCs, after 5 and 7 days of coculture. Moreover, application of pre-LSCs as feeder cells significantly increased the number of DLK1-positive cells and their proliferation rate (ie, increased the number of Ki-67 positive cells) on day 7, compared to Post-LSCs group. Finally, to address our ultimate goal, which was an extension of hepatoblasts ex vivo maintenance, 3D spheres of isolated hepatoblasts were, cultured in conditioned medium (CM) derived from pre-LSCs until day 30. It was observed that the CM derived from Pre-LSCs could successfully prolong the maintenance of hepatic progenitor cells (HPCs) in 3D suspension culture.