Contribution of dopaminergic polymorphisms to levodopa treatment response and drug concentration in Chinese patients with Parkinson's disease.

Background: Levodopa is the mainstay of treatments for Parkinson's disease (PD), but large heterogeneity exists in patient response. Pharmacogenetic studies highlighted that genetic factors may play a relevant influence in this drug response variability.

Objective: To explore the relationship between dopaminergic polymorphisms, levodopa treatment response, and drug concentration in Chinese patients with PD.

Targeted Gut Microbiota Modulation Enhances Levodopa Bioavailability and Motor Recovery in MPTP Parkinson's Disease Models.

Emerging evidence highlights the gut microbiota as a pivotal determinant of pharmacological efficacy. While ()-derived tyrosine decarboxylases () are known to decarboxylate levodopa (L-dopa), compromising systemic bioavailability, the causal mechanisms underlying microbiota-mediated pharmacodynamic variability remain unresolved. In our study, we employed antibiotic-induced microbiota depletion and fecal microbiota transplantation (FMT) to interrogate microbiota-L-dopa interactions in MPTP-induced Parkinson's disease (PD) mice.

Pharmacomicrobiomics: a new field contributing to optimizing drug therapy in Parkinson's disease.

Gut microbiota, which act as a determinant of pharmacokinetics, have long been overlooked. In recent years, a growing body of evidence indicates that the gut microbiota influence drug metabolism and efficacy. Conversely, drugs also exert a substantial influence on the function and composition of the gut microbiota.

Association between Fecal Bile Acids and Levodopa Response in Patients with Parkinson's Disease.

Levodopa is the mainstay of treatments for Parkinson's disease (PD), but large heterogeneity exists in patient response. Increasing evidence implicates bile acids (BAs) involved in the pathogenesis of PD. Furthermore, BAs have also participated in drug bioavailability.

Effect of strain Shirota supplementation on clinical responses and gut microbiome in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor issues and a range of non-motor symptoms. Microbial therapy may be a useful approach for the treatment of PD. However, comprehensive analyses of the impact of probiotic supplementation on motor and non-motor symptoms are still lacking and the mechanisms whereby the treatment works remain unclear.

Sodium butyrate ameliorates gut dysfunction and motor deficits in a mouse model of Parkinson's disease by regulating gut microbiota.

Background: A growing body of evidence showed that gut microbiota dysbiosis might be associated with the pathogenesis of Parkinson's disease (PD). Microbiota-targeted interventions could play a protective role in PD by regulating the gut microbiota-gut-brain axis. Sodium butyrate (NaB) could improve gut microbiota dysbiosis in PD and other neuropsychiatric disorders.

Association Between Microbial Tyrosine Decarboxylase Gene and Levodopa Responsiveness in Patients With Parkinson Disease.

Background And Objectives: Interindividual variability in levodopa efficacy is a challenge for the personalized treatment of Parkinson disease (PD). Gut microbiota might represent a new approach for personalized medicine. Recently, a novel microbial levodopa metabolism pathway was identified, which is mediated by tyrosine decarboxylase mainly encoded by tyrosine decarboxylase gene () in .

Parkinson's Disease Is Associated with Impaired Gut-Blood Barrier for Short-Chain Fatty Acids.

Background: Short-chain fatty acids (SCFAs) produced by gut microbiota are reduced in feces but paradoxically increased in plasma of patients with Parkinson's disease (PD), which may stem from intestinal wall leakage. Gut function should be taken into consideration when conducting microbial-metabolite research.

Objective: The objective was to investigate synchronous changes of SCFAs in feces and plasma of patients with PD, taking constipation as a confounder to better disentangle the SCFA metabolism exclusively associated with PD.

Plasma branched-chain and aromatic amino acids correlate with the gut microbiota and severity of Parkinson's disease.

Disturbances of circulating amino acids have been demonstrated in patients with Parkinson's disease (PD). However, there have been no consistent results for branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), and related factors have not been explored. We aimed to explore plasma BCAA and AAA profiles in PD patients, and identify their correlations with clinical characteristics and the gut microbiota.

Effect of Acute Levodopa Up-Titration on Blood Pressure in Patients With Early Stage Parkinson's Disease: Results of a Levodopa Challenge Test.

Levodopa up-titration is the primary therapeutic strategy as the Parkinson's disease (PD) progresses. However, the effects of levodopa up-titration on blood pressure (BP) are inconclusive. This study aimed to investigate the effect of acute levodopa up-titration simulated by levodopa challenge test (LCT) on BP in patients with early stage PD.

Sodium butyrate attenuates rotenone-induced toxicity by activation of autophagy through epigenetically regulating PGC-1α expression in PC12 cells.

Short-chain fatty acids (SCFAs) are considered the key molecular link between gut microbiota and pathogenesis of Parkinson's disease (PD). However, the role of SCFAs in PD pathogenesis is controversial. Autophagy is important for the degradation of α-synuclein, which is critical to the development of PD.

LncRNA HOXA-AS2 regulates microglial polarization via recruitment of PRC2 and epigenetic modification of PGC-1α expression.

Background: Microglia-mediated neuroinflammation plays an important role in Parkinson's disease (PD), and it exerts proinflammatory or anti-inflammatory effects depending on the M1/M2 polarization phenotype. Hence, promoting microglia toward the anti-inflammatory M2 phenotype is a potential therapeutic approach for PD. Long noncoding RNAs (lncRNAs) are crucial in the progression of neurodegenerative diseases, but little is known about their role in microglial polarization in PD.

Plasma Short-Chain Fatty Acids Differences in Multiple System Atrophy from Parkinson's Disease.

Background: Multiple system atrophy (MSA) and Parkinson's disease (PD) have overlapping symptoms, making diagnosis challenging. Short-chain fatty acids (SCFAs) are produced exclusively by gut microbiota and were reduced in feces of MSA patients. However, plasma SCFA concentrations in MSA patients have not been investigated.

Findings in Chinese Patients With Parkinson's Disease: A Content Analysis From the SML Study.

Social media listening (SML) is a new process for obtaining information from social media platforms to generate insights into users' experiences and has been used to analyze discussions about a multitude of diseases. To understand Parkinson's disease patients' unmet needs and optimize communication between doctors and patients, social media listening was performed to investigate concerns in Chinese patients. A comprehensive search of publicly available social media platforms with Chinese-language content posted between January 2005 and April 2019 in mainland China was performed using defined Parkinson's disease-related terms.

Increased interleukin-18 level contributes to the development and severity of ischemic stroke.

Although interleukin-18 (IL-18) has been implicated in the pathophysiology of stroke, research findings concerning IL-18 level in stroke have been inconsistent. Thus, we performed a cross-sectional study in patients with first-episode ischemic stroke and then extracted relevant data from databases to validate our results. A total of 252 patients and 259 healthy subjects were recruited, and serum IL-18 level was evaluated in a cross-sectional study.

Development of a high-throughput Alamar blue assay for the determination of influenza virus infectious dose, serum antivirus neutralization titer and virus ca/ts phenotype.

FluMist is an intranasal influenza live vaccine containing two Influenza A strains (currently H1N1 and H3N2) and one B strain (Yamagata or Victoria lineage). Characterization of the vaccine requires determination of the median tissue culture infectious dose (TCID(50)) titer, serum antivirus neutralization titer and vaccine cold adapted/temperature sensitive (ca/ts) phenotype. Visual cytopathic effect (CPE) readings are used widely in viral assays, but these are subjective and labor intensive.

Functions of the C-terminal domain of varicella-zoster virus glycoprotein E in viral replication in vitro and skin and T-cell tropism in vivo.

Varicella-zoster virus (VZV) glycoprotein E (gE) is essential for VZV replication. To further analyze the functions of gE in VZV replication, a full deletion and point mutations were made in the 62-amino-acid (aa) C-terminal domain. Targeted mutations were introduced in YAGL (aa 582 to 585), which mediates gE endocytosis, AYRV (aa 568 to 571), which targets gE to the trans-Golgi network (TGN), and SSTT, an "acid cluster" comprising a phosphorylation motif (aa 588 to 601).

Development of an efficient fluorescence-based microneutralization assay using recombinant human cytomegalovirus strains expressing green fluorescent protein.

MedImmune Vaccines has created four, live, attenuated human cytomegalovirus (HCMV) vaccine candidates, each derived from defined portions of the parental strains, Towne and Toledo. To determine each candidate's ability to induce HCMV specific immunity, a fluorescence-based microneutralization assay was developed using recombinants of Toledo and Towne which express enhanced green fluorescent protein (EGFP). Replication of the EGFP recombinants in cell culture was the same as the respective parental strains.

Varicella-zoster virus infection facilitates VZV glycoprotein E trafficking to the membrane surface of melanoma cells.

Varicella-zoster virus glycoprotein E (gE) is the most abundant VZV glycoprotein on the surface of virus-infected cells. VZV gE has targeting sequences for the trans-Golgi network (TGN) and is transported from the ER to the TGN in infected and gE-transfected cells. In this study, VZV gE expressing melanoma cell lines were generated.

The requirement of varicella zoster virus glycoprotein E (gE) for viral replication and effects of glycoprotein I on gE in melanoma cells.

The glycoprotein E (gE) of varicella zoster virus (VZV), encoded by ORF68, is the most abundant viral glycoprotein. In the current experiments, we demonstrated that ORF68 deletion was incompatible with recovery of infectious virus from VZV cosmids. Replacing ORF68 at a nonnative AvrII site in the genome restored infectivity.