A systematic review of salivary biomarkers in Parkinson's disease

The search fo r reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis,to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies.Despite the need for non-invasively accessible biomarke rs,the majo rity of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers,which require invasive collection procedures.Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers.In the present study,after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease,we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients.A comprehensive literature search on PubMed and SCOPUS led to the discovery of 289articles.After screening and exclusion,34 relevant articles were derived fo r systematic review.Alpha-synuclein,the histopathological hallmark of Parkinson's disease,has been the most investigated Parkinson's disease biomarker in saliva,with oligomeric alphasynuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls,while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein,and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's disease.Beyond alpha-synuclein,other biomarkers to rgeting diffe rent molecular pathways have been explored in the saliva of Parkinson's disease patients:total tau,phosphorylated tau,amyloid-β1-42(pathological protein aggregation biomarkers);DJ-1,heme-oxygenase-l,metabolites(alte red energy homeostasis biomarkers);MAPLC-3beta(aberrant proteostasis biomarker);cortisol,tumor necrosis factor-alpha(inflammation biomarkers);DNA methylation,miRNA(DNA/RNA defects biomarkers);acetylcholinesterase activity(synaptic and neuronal network dysfunction biomarkers);Raman spectra,proteome,and caffeine.Despite a few studies investigating biomarkers to rgeting molecular pathways different from alpha-synuclein in Parkinson's disease,these results should be replicated and observed in studies on larger cohorts,considering the potential role of these biomarkers in determining the molecular variance among Parkinson's disease subtypes.Although the need fo r standardization in sample collection and processing,salivary-based biomarkers studies have reported encouraging results,calling for large-scale longitudinal studies and multicentric assessments,given the great molecular potentials and the non-invasive accessibility of saliva.

Relationship among Parkinson’s disease, constipation, microbes, and microbiological therapy

This comprehensive review elucidates the complex interplay between gut microbiota and constipation in Parkinson’s disease(PD),a prevalent non-motor symptom contributing significantly to patients’morbidity.A marked alteration in the gut microbiota,predominantly an increase in the abundance of Proteobacteria and Bacteroidetes,is observed in PD-related constipation.Conventional treatments,although safe,have failed to effectively alleviate symptoms,thereby necessitating the development of novel therapeutic strategies.Microbiological interventions such as prebiotics,probiotics,and fecal microbiota transplantation(FMT)hold therapeutic potential.While prebiotics improve bowel movements,probiotics are effective in enhancing stool consistency and alleviating abdominal discomfort.FMT shows potential for significantly alleviating constipation symptoms by restoring gut microbiota balance in patients with PD.Despite promising developments,the causal relationship between changes in gut microbiota and PD-related constipation remains elusive,highlighting the need for further research in this expanding field.

Constipation and colonoscopy

Constipation is a significant sociomedical problem,which can be caused by various reasons.In the diagnostic approach to patients with constipation,the following data are usually sufficient:History,complete physical examination(including rectal examination),and additional diagnostic tests.A colonoscopy is not a necessary diagnostic method for all patients with constipation.However,if patients have alarm symptoms/signs,that suggest an organic reason for constipation,a colonoscopy is necessary.The most important alarm symptoms/signs are age>50 years,gastrointestinal bleeding,new-onset constipation,a palpable mass in the abdomen and rectum,weight loss,anemia,inflammatory bowel disease,and family history positive for colorectal cancer.Most endoscopists do not like to deal with patients with constipation.There are two reasons for this,namely the difficulty of endoscopy and the adequacy of preparation.Both are adversely affected by constipation.To improve the quality of colonoscopy in these patients,good examination techniques and often more extensive preparation are necessary.Good colonoscopy technique implies adequate psychological preparation of the patient,careful insertion of the endoscope with minimal insufflation,and early detection and resolution of loops.Bowel preparation for colonoscopy often requires prolonged preparation and sometimes the addition of other laxatives.

Preventive effect of kiwi berry(Actinidia arguta)on loperamide-induced constipation

Constipation is a common intestinal disease.Kiwi berries can effectively prevent constipation.However,studies have yet to be done to determine how kiwi berries prevent constipation.For two weeks,mice in this study were continually orally gavaged with kiwi berry,loperamide,or a combination of the 2.This study found that the kiwi group's feces had more water than the constipated mice.In addition,kiwi berries can speed up gastrointestinal transit(GI),shorten the time it takes to pass the first dark stool,and dramatically enhance body weight gain.In the interstitial cells of Caj al(ICC)cells and colon tissues,alterations in the protein expression of vasoactive intestinal peptide(VIP),cyclic adenosine monophosphate(cAMP),protein kinase A(PKA),and aquapcrin-3(AQP3)were found.At 3,6,and 12 h of ICC cells and mouse colon,the kiwi group's VIP,cAMP,PKA,and AQP3 protein expression levels were lower than those of the constipated mice.The kiwi berry can decrease the Firmicutes to Bacteroidetes ratio and boost the diversity and quantity of gut microbiota.By influencing the gut microbiota and VIP-cAMP-PKA-AQP3 signaling pathway,kiwi berries prevent constipation.

Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.

Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway

BACKGROUND Constipation,a highly prevalent functional gastrointestinal disorder,induces a significant burden on the quality of patients'life and is associated with substantial healthcare expenditures.Therefore,identifying efficient therapeutic modalities for constipation is of paramount importance.Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms.Consequently,we postulate that hydrogen therapy,an emerging and promising intervention,can serve as a safe and efficacious treatment for constipation.AIM To determine whether hydrogen-rich water(HRW)alleviates constipation and its potential mechanism.METHODS Constipation models were established by orally loperamide to Sprague-Dawley rats.Rats freely consumed HRW,and were recorded their 24 h total stool weight,fecal water content,and charcoal propulsion rate.Fecal samples were subjected to 16S rDNA gene sequencing.Serum non-targeted metabolomic analysis,malondialdehyde,and superoxide dismutase levels were determined.Colonic tissues were stained with hematoxylin and eosin,Alcian blue-periodic acid-Schiff,reactive oxygen species(ROS)immunofluorescence,and immunohistochemistry for cell growth factor receptor kit(c-kit),PGP 9.5,sirtuin1(SIRT1),nuclear factor-erythroid-2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1,Nrf2 and HO-1.A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor,EX527,into constipated rats.NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression.RESULTS HRW alleviated constipation symptoms by improving the total amount of stool over 24 h,fecal water content,charcoal propulsion rate,thickness of the intestinal mucus layer,c-kit expression,and the number of intestinal neurons.HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism.HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway.This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats.The serum metabolites,β-leucine(β-Leu)and traumatic acid,were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1.CONCLUSION HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway,modulating gut microbiota and serum metabolites.β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.

Effects of psychological nursing in Parkinson's related depression patients undergoing functional magnetic resonance imaging:A randomized controlled trial

BACKGROUND Patients with Parkinson’s disease(PD)often experience depression,and some may require magnetic resonance imaging(MRI)for diagnosis,which can lead to MRI failure due to claustrophobia.AIM To explore the value of psychological interventions in successfully completing functional MRI scans of the brain for PD-related depression.METHODS Ninety-six patients with PD were randomly divided into two groups.The control group(47 patients)received general care,and the experimental group(49 patients)received general care combined with psychological care.The Unified Parkinson's Disease Assessment Scale(UPDRS),Hamilton Depression Scale(HAMD),and Geriatric Depression Scale(GDS)-15 scores,heart rate,systolic blood pressure,and MRI-Anxiety Questionnaire(MRI-AQ)scores before and after the scan were recorded.The completion rate of magnetic resonance(MR)scanning,scanning duration,and image quality scores were recorded.RESULTS Before scanning,no statistically significant difference was observed between the two groups in terms of heart rate,systolic blood pressure,and UPDRS,HAMD,GDS-15,and MRI-AQ scores.After scanning,systolic blood pressure,MRI-AQ score,and scan time in the experimental group were significantly lower than those in the control group,whereas the scan completion rate and image quality score were significantly higher than those in the control group.CONCLUSION Psychological nursing interventions are helpful in alleviating PD-related depression and assessing MR depression scores and may be helpful in the successful completion of functional MRI scans of the patient's brain.

NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation

Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

Exploration of the complex origins of primary constipation

Constipation is a common gastrointestinal disorder characterized by infrequentbowel movements and difficulty in passing stools.It can significantly affect anindividual's quality of life and overall well-being.Understanding the causes ofconstipation is important for its effective management and treatment.In thispaper,we have reviewed the primary causes of constipation or functional constipation.Primary constipation is a bowel disorder associated with colonic oranorectal sensorimotor or neuromuscular dysfunction.As per the literature,it ismultifactorial and involves factors such as decreased interstitial cells of Cajal,altered colonic motility,enteric nervous system dysfunction,intestinal flora disturbances,and psychological influences.Clinical symptoms include difficulty indefecation,decreased frequency of defecation,or a feeling of incomplete evacuation.A comprehensive evaluation and management of constipation require aninterdisciplinary approach incorporating dietary modifications,lifestyle changes,pharmacotherapy,and psychological interventions.Further research is imperativeto explain the intricate mechanisms underlying constipation and develop targetedtherapies for improved patient outcomes.

Exploring the Mechanism of Action of Gastrodin in Parkinson's Disease Based on Network Pharmacology

[Objectives]To explore the mechanism of action of gastrodin in the treatment of Parkinson's disease(PD)by employing network pharmacology technology,and to provide a scientific theoretical basis for the rational clinical application of gastrodin.[Methods]The target of gastrodin was identified through a search of the SwissTargetPrediction database.The keyword"Parkinson Disease"was employed to identify the pertinent targets of PD in the GeneCards and OMIM databases.The relationship between gastrodin and PD was elucidated,and a Veen map was constructed to identify the genes that were common to both.A total of 52 common drug targets associated with PD as identified in the Wayne chart were imported into the String database(https://string-db.org/)for protein-protein interaction prediction.Subsequently,Cytoscape 3.9.1 software was employed to construct a"drug-target"network.The potential targets of gastrodin in the treatment of PD were then imported into the DAVID database,where GO analysis and KEGG enrichment results were obtained.[Results]A total of 22 core targets and 53 related pathways of gastrodin were identified as potentially beneficial for the treatment of PD.[Conclusions]Gastrodin may be a potential therapeutic agent for the treatment of PD by modulating the biological process of apoptosis,affecting the relevant pathways such as the IL-17 signaling pathway and the TNF signaling pathway,and acting on GAPDH,EGFR,CASP3,MMP9 and other targets.

Microbiota treatment of functional constipation:Current status and future prospects

Functional constipation(FC)is a common disorder that is characterized by diffi-cult stool passage,infrequent bowel movement,or both.FC is highly prevalent,recurs often,accompanies severe diseases,and affects quality of life;therefore,safe and effective therapy with long-term benefits is urgently needed.Microbiota treatment has potential value for FC treatment.Microbiota treatments include modulators such as probiotics,prebiotics,synbiotics,postbiotics,and fecal micro-biota transplantation(FMT).Some probiotics and prebiotics have been adopted,and the efficacy of other microbiota modulators is being explored.FMT is con-sidered an emerging field because of its curative effects;nevertheless,substantial work must be performed before clinical implementation.

Preservation of superior rectal artery in laparoscopic colectomy:The best choice for slow transit constipation?

Laparoscopic colectomy with ileorectal anastomosis may be beneficial for patients with slow transit constipation who do not respond to conservative treatment,particularly if the superior rectal artery(SRA)is preserved.Several important concerns have been addressed in this commentary.It is important to first go over the definition of surgical procedure as it is used in this text.Second,the current study lacked a control group that had SRA preservation.Thirdly,it would be best to use a prospective,randomized controlled study.Lastly,a description of the mesenteric defect’s state following a laparoscopic colectomy is necessary.

Dysfunction of synaptic endocytic trafficking in Parkinson's disease

Parkinson's disease is characterized by the selective degeneration of dopamine neurons in the nigrostriatal pathway and dopamine deficiency in the striatum.The precise reasons behind the specific degeneration of these dopamine neurons remain largely elusive.Genetic investigations have identified over 20 causative PARK genes and 90 genomic risk loci associated with both familial and sporadic Parkinson's disease.Notably,several of these genes are linked to the synaptic vesicle recycling process,particularly the clathrinmediated endocytosis pathway.This suggests that impaired synaptic vesicle recycling might represent an early feature of Parkinson's disease,followed by axonal degeneration and the eventual loss of dopamine cell bodies in the midbrain via a"dying back"mechanism.Recently,several new animal and cellular models with Parkinson's disease-linked mutations affecting the endocytic pathway have been created and extensively characterized.These models faithfully recapitulate certain Parkinson's disease-like features at the animal,circuit,and cellular levels,and exhibit defects in synaptic membrane trafficking,further supporting the findings from human genetics and clinical studies.In this review,we will first summarize the cellular and molecular findings from the models of two Parkinson's disease-linked clathrin uncoating proteins:auxilin(DNAJC6/PARK19)and synaptojanin 1(SYNJ1/PARK20).The mouse models carrying these two PARK gene mutations phenocopy each other with specific dopamine terminal pathology and display a potent synergistic effect.Subsequently,we will delve into the involvement of several clathrin-mediated endocytosis-related proteins(GAK,endophilin A1,SAC2/INPP5 F,synaptotagmin-11),identified as Parkinson's disease risk factors through genome-wide association studies,in Parkinson's disease pathogenesis.We will also explore the direct or indirect roles of some common Parkinson's disease-linked proteins(alpha-synuclein(PARK1/4),Parkin(PARK2),and LRRK2(PARK8))in synaptic endocytic trafficking.Additionally,we will discuss the emerging novel functions of these endocytic proteins in downstream membrane traffic pathways,particularly autophagy.Given that synaptic dysfunction is considered as an early event in Parkinson's disease,a deeper understanding of the cellular mechanisms underlying synaptic vesicle endocytic trafficking may unveil novel to rgets for early diagnosis and the development of interventional therapies for Parkinson's disease.Future research should aim to elucidate why generalized synaptic endocytic dysfunction leads to the selective degeneration of nigrostriatal dopamine neurons in Parkinson's disease.

Assessment of the triglyceride glucose index in adult patients with chronic diarrhea and constipation

BACKGROUND Accumulating evidence suggests that the gut microbiome is involved in the pathogenesis of insulin resistance(IR).However,the link between two of the most prevalent bowel disorders,chronic diarrhea and constipation,and the triglyceride glucose(TyG)index,a marker of IR,has not yet been investigated.AIM To investigate the potential association between TyG and the incidence of chronic diarrhea and constipation.METHODS This cross-sectional study enrolled 2400 participants from the National Health and Nutrition Examination Survey database from 2009-2010.TyG was used as an exposure variable,with chronic diarrhea and constipation as determined by the Bristol Stool Form Scale used as the outcome variables.A demographic investigation based on TyG quartile subgroups was performed.The application of multivariate logistic regression models and weighted generalized additive models revealed potential correlations between TyG,chronic diarrhea,and constipation.Subgroup analyses were performed to examine the stability of any potential associations.RESULTS In the chosen sample,chronic diarrhea had a prevalence of 8.00%,while chronic constipation had a prevalence of 8.04%.In multiple logistic regression,a more prominent positive association was found between TyG and chronic diarrhea,particularly in model 1(OR=1.45;95%CI:1.17-1.79,P=0.0007)and model 2(OR=1.40;95%CI:1.12-1.76,P=0.0033).No definite association was observed between the TyG levels and chronic constipation.The weighted generalized additive model findings suggested a more substantial positive association with chronic diarrhea when TyG was less than 9.63(OR=1.89;95%CI:1.05-3.41,P=0.0344),and another positive association with chronic constipation when it was greater than 8.2(OR=1.74;95%CI:1.02-2.95,P=0.0415).The results of the subgroup analyses further strengthen the extrapolation of these results to a wide range of populations.CONCLUSION Higher TyG levels were positively associated with abnormal bowel health.

Role of the globus pallidus in motor and non-motor symptoms of Parkinson's disease

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.

Advances in Research of Chinese Medicine Tianma in the Treatment of Parkinson's Disease

In this study,a systematic review was conducted on the experimental study as well as the clinical application of Tianma(Gastrodia elata Blume),a traditional Chinese medicine,in the prevention and treatment of Parkinson's disease(PD).On this basis,a summary and outlook were made,so as to provide ideas and theoretical basis for the study,development and utilization of Tianma PD field.

Research Progress on Neuroprotective Effects of Salvianolic Acid B in an Animal Model of Parkinson's Disease

As an active ingredient extracted from Salvia miltiorrhiza,the neuroprotective effects of salvianolic acid B in Parkinson's disease include antioxidation,improvement of mitochondrial function,modulation of neuroinflammation,inhibition of apoptosis,promotion of neuronal differentiation and proliferation,and influence on intestinal flora.As an adjuvant drug,salbutamol B can be used in combination with conventional therapeutic drugs to enhance the efficacy and minimize the side effects,which provides a method and basis for the early diagnosis and treatment of Parkinson's disease in clinical practice.

Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease

An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.

CHCHD2 Thr61Ile mutation impairs F1F0-ATPase assembly in in vitro and in vivo models of Parkinson's disease

Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.

Effectiveness of traditional chinese medicine nursing intervention on constipation and anxiety in chemotherapy

Background:In a study conducted from March to September 2021,124 cancer patients undergoing chemotherapy at our hospital were divided into two groups.The control group received routine inpatient nursing care,while the observation group received Traditional Chinese Medicine(TCM)nursing interventions in addition to routine care.Data analysis was conducted to compare the incidence of clinical adverse reactions,constipation scores,and changes in anxiety levels between the two groups.The results showed that the observation group,receiving TCM nursing interventions,had lower incidence of clinical adverse reactions and lower constipation scores compared to the control group.Additionally,anxiety levels were found to decrease significantly in the observation group post-intervention.These findings suggest that incorporating TCM nursing interventions in the care of cancer patients undergoing chemotherapy may help in reducing the occurrence of adverse reactions,alleviating constipation,and managing anxiety levels.Further research is needed to explore the full potential of integrating TCM into conventional nursing care for cancer patients.Methods:Following interventions,both groups experienced varying degrees of clinical adverse reactions,with the observation group demonstrating a significantly lower total incidence(29.03%)compared to the control group.This disparity was statistically significant(P<0.05).Furthermore,improvements were observed in defecation time(0.53±0.18)points and defecation frequency(1.17±0.25)points post-intervention.These findings suggest that the intervention had a positive impact on reducing adverse reactions and improving defecation patterns.Results:In a recent study,researchers found that individuals in the observation group experienced lower levels of difficulty with defecation and had a more regular defecation form compared to those in the control group.The results showed a significant difference in defecation difficulty and form,with the observation group scoring lower in both aspects.Interestingly,there was no significant difference in anxiety levels between the two groups prior to the intervention.However,after the intervention,both groups experienced a decrease in anxiety levels,with the observation group showing a greater reduction compared to the control group.This suggests that the intervention had a positive impact on reducing anxiety levels,particularly in the observation group,where anxiety scores were significantly lower.These findings highlight the possible benefits of certain interventions in improving both physical and psychological well-being.Conclusion:TCM nursing interventions have shown to be beneficial in reducing anxiety and improving constipation symptoms in cancer patients.These methods not only enhance the quality of life for patients but also offer a promising approach in clinical cancer treatment.The efficacy of TCM nursing highlights its value and encourages further promotion and application in future cancer care strategies.TCM nursing helps cancer patients undergoing chemotherapy with constipation and anxiety.