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.

Genetic screening of liver cancer:State of the art

Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver cancer.This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer.We discuss the genetic underpinnings of liver cancer,emphasizing the critical role of risk-associated genetic variants,somatic mutations,and epigenetic alterations.We also explore the intricate interplay between environmental factors and genetics,highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy,and advancements in high-throughput sequencing technologies.By synthesizing the latest research findings,we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer,shedding light on their potential to revolutionize early detection,risk assessment,and targeted therapies in the fight against this devastating disease.

Clinical issues and challenges in imaging of gastrointestinal diseases:A minireview and our experience

Imaging techniques play a crucial role in the modern era of medicine,particularly in gastroenterology.Nowadays,various non-invasive and invasive imaging modalities are being routinely employed to evaluate different gastrointestinal(GI)diseases.However,many instrumental as well as clinical issues are arising in the area of modern GI imaging.This minireview article aims to briefly overview the clinical issues and challenges encountered in imaging GI diseases while highlighting our experience in the field.We also summarize the advances in clinically available diagnostic methods for evaluating different diseases of the GI tract and demonstrate our experience in the area.In conclusion,almost all imaging techniques used in imaging GI diseases can also raise many challenges that necessitate careful consideration and profound expertise in this field.

Rhabdomyolysis-related acute kidney injury in patients with COVID- 19

BACKGROUND Viral and bacterial infections may be complicated by rhabdomyolysis,which has a spectrum of clinical presentations ranging from asymptomatic laboratory abnor-malities to life-threatening conditions such as renal failure.Direct viral injury as well as inflammatory responses may cause rhabdomyolysis in the course of coronavirus disease 2019(COVID-19).When presented with acute kidney injury(AKI),rhabdomyolysis may be related to higher morbidity and mortality.AIM To compare rhabdomyolysis-related AKI with other AKIs during COVID-19.METHODS A total of 115 patients with COVID-19 who had AKI were evaluated retrospec-tively.Fifteen patients had a definite diagnosis of rhabdomyolysis(i.e.,creatine kinase levels increased to>5 times the upper normal range with a concomitant increase in transaminases and lactate dehydrogenase).These patients were aged 61.0±19.1 years and their baseline creatinine levels were 0.87±0.13 mg/dL.Patients were treated according to national COVID-19 treatment guidelines.They were compared with patients with COVID-19 who had AKI due to other reasons.RESULTS For patients with rhabdomyolysis,creatinine reached 2.47±1.17 mg/dL during follow-up in hospital.Of these patients,13.3%had AKI upon hospital admission,and 86.4%developed AKI during hospital follow-up.Their peak C-reactive protein reached as high as 253.2±80.6 mg/L and was higher than in patients with AKI due to other reasons(P<0.01).Peak ferritin and procalcitonin levels were also higher for patients with rhabdomyolysis(P=0.02 and P=0.002,respective-ly).The mortality of patients with rhabdomyolysis was calculated as 73.3%,which was higher than in other patients with AKI(18.1%)(P=0.001).CONCLUSION Rhabdomyolysis was present in 13.0%of the patients who had AKI during COVID-19 infection.Rhabdomyolysis-related AKI is more proinflammatory and has a more mortal clinical course.

Crosstalk among canonical Wnt and Hippo pathway members in skeletal muscle and at the neuromuscular junction

Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.

First report of the histopathological effect of electrocautery using on the urethral taste rosea during glans penis injury by incision in rabbits

Objective:Currently,electrocautery devices have frequently been used in penile surgical procedures.We hypothesized that electrocautery using during penile surgical procedures may harm the taste rosea and the dorsal nerve of the penis or clitoris.Methods:Eighteen young age male New Zealand rabbits were studied:five in the control(Group I,n=5),five in the penile surgery without using electrocautery(sham group,Group II,n=5),eight in the monopolar cautery(study group,Group III,n=8)groups under general anesthesia.The animals were followed for 3 weeks and sacrificed.Penile tissue—pudendal nerve root complexes and dorsal root ganglion of sacral 3 level were examined using stereological methods.The results were compared statistically.Results:The live and degenerated taste bud-like structures and degenerated neuron densities of pudendal ganglia(mean±standard deviation,n/mm^(3))were estimated as 198±24/mm^(3),4±1/mm^(3),and 5±1/mm^(3) in Group I;8±3/mm^(3),174±21/mm^(3),and 24±7/mm^(3) in Group II;and 21±5/mm^(3),137±14/mm^(3),and 95±12/mm^(3) in Group III,respectively.Neurodegeneration of taste buds and pudendal ganglia was significantly different between groups.Conclusion:Intact spinal cord and normal parasympathetic and thoracolumbar sympathetic networks are crucial for human sexual function.The present study indicates that the glans penis injury by using electrocautery may lead to pudendal ganglia degeneration.Iatrogenic damage to taste rosea and retrograde degeneration of the pudendal nerve may be the cause of sexual dysfunction responsible mechanism.

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.

Harnessing autophagy: A potential breakthrough in digestive disease treatment

Autophagy,a conserved cellular degradation process,is crucial for various cellular processes such as immune responses,inflammation,metabolic and oxidative stress adaptation,cell proliferation,development,and tissue repair and remodeling.Dysregulation of autophagy is suspected in numerous diseases,including cancer,neurodegenerative diseases,digestive disorders,metabolic syndromes,and infectious and inflammatory diseases.If autophagy is disrupted,for example,this can have serious consequences and lead to chronic inflammation and tissue damage,as occurs in diseases such as Chron's disease and ulcerative colitis.On the other hand,the influence of autophagy on the development and progression of cancer is not clear.Autophagy can both suppress and promote the progression and metastasis of cancer at various stages.From inflammatory bowel diseases to gastrointestinal cancer,researchers are discovering the intricate role of autophagy in maintaining gut health and its potential as a therapeutic target.Researchers should carefully consider the nature and progression of diseases such as cancer when trying to determine whether inhibiting or stimulating autophagy is likely to be beneficial.Multidisciplinary approaches that combine cutting-edge research with clinical expertise are key to unlocking the full therapeutic potential of autophagy in digestive diseases.

Automated evaluation of parapapillary choroidal microvasculature in crowded optic discs:a controlled,optical coherence tomography angiography study

AIM:To compare superficial and deep vascular properties of optic discs between crowded discs and controls using optical coherence tomography angiography(OCT-A).METHODS:Thirty patients with crowded discs,and 47 control subjects were enrolled in the study.One eye of each individual was included and OCT-A scans of optic discs were obtained in a 4.5×4.5 mm^(2) rectangular area.Radial peripapillary capillary(RPC)density,peripapillary retinal nerve fiber layer(pRNFL)thickness,cup volume,rim area,disc area,cup-to-disc(c/d)area ratio,and vertical c/d ratio were obtained automatically using device software.Automated parapapillary choroidal microvasculature(PPCMv)density was calculated using MATLAB software.When the vertical c/d ratio of the optic disc was absent or small cup,it was considered as a crowded disc.RESULTS:The mean signal strength index of OCT-A images was similar between the crowded discs and control eyes(P=0.740).There was no difference in pRNFL between the two groups(P=0.102).There were no differences in RPC density in whole image(P=0.826)and peripapillary region(P=0.923),but inside disc RPC density was higher in crowded optic discs(P=0.003).The PPCMv density in the inner-hemisuperior region was also lower in crowded discs(P=0.026).The pRNFL thickness was positively correlated with peripapillary RPC density(r=0.498,P<0.001).The inside disc RPC density was negatively correlated with c/d area ratio(r=-0.341,P=0.002).CONCLUSION:The higher inside disc RPC density and lower inner-hemisuperior PPCMv density are found in eyes with crowded optic discs.

An evaluation of ureteral diameter ratio and vesicoureteral reflux index in the treatment of primary vesicoureteral reflux

Objective:Vesicoureteral reflux(VUR)index is a simple,validated tool that reliably predicts significant improvement and spontaneous resolution of primary reflux in children.The aim of this study was to evaluate and compare the ureter diameter ratio(UDR)and VUR index(VURx)of patients treated with endoscopic injection(EI)and ureteroneocystostomy(UNC)methods in the pediatric age group due to primary VUR.Methods:Patients under the age of 18 years old who underwent EI and UNC with the diagnosis of primary VUR between January 2011 and September 2021 were determined as the participants.The UDR was assessed using voiding cystourethrography,and the VURx score was determined prior to treatment based on hospital records included in the study.Results:A total of 255 patients,60(23.5%)boys and 195(76.5%)girls,with a mean age of 76.5(range 13.0e204.0)months,were included in the study.EI was applied to 130(51.0%)patients and UNC was applied to 125(49.0%)patients due to primary VUR.The optimum cut-off for the distal UDR was obtained as 0.17 with sensitivity and specificity of 73.0%and 63.0%,respectively.The positive and negative predictive values were 66.0%and 70.0%,respectively.Conclusion:When the UDR and VURx score are evaluated together for the surgical treatment of primary VUR in the pediatric age group,it is thought that it may be useful in predicting the clinical course of the disease and evaluating surgical treatment options.

Multiple sclerosis drug repurposing for neuroregeneration

Multiple sclerosis(MS)is an autoimmune disorder of the central nervous system(CNS)and is primarily characterized by immune cell infiltration leading to relapses followed by remission phases and a disease course turning progressive over time with neurodegenerative processes taking over(Amin and Hersh,2023).Of note,beyond relapse-associated worsening early in disease progression independent of relapse activity may arise independently of relapse activity and can occur in all phenotypes.Autoimmune-mediated damage of myelin sheaths and the subsequent loss of mature oligodendrocytes are resulting in impaired axonal integrity,neurodegeneration and accounts for irreversible neuronal damage(Kuhlmann et al.,2023).The current landscape of available disease-modifying therapies comprises mainly immunomodulatory drugs that effectively diminish relapses and slow down progression at the onset form of the disease,namely relapsing MS(RMS).In this regard,a number of drugs have been approved as disease-modifying therapies for MS by US Food and Drug Administration and European Medicines Agencies(Box 1).

Novel insights into autophagy in gastrointestinal pathologies,mechanisms in metabolic dysfunction-associated fatty liver disease and acute liver failure

In this editorial,we comment on three articles published in a recent issue of World Journal of Gastroenterology.There is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and also novel insights into some liver conditions,such as metabolic dysfunction-associated fatty liver disease(MAFLD)and acute liver failure(ALF).Despite advancements,understanding autophagy's intricate mechanisms and implications in these diseases remains incomplete.Moreover,MAFLD's pathogenesis,encompassing hepatic steatosis and metabolic dysregulation,require further elucidation.Similarly,the mechanisms underlying ALF,a severe hepatic dysfunction,are poorly understood.Innovative studies exploring the interplay between autophagy and GI disorders,as well as defined mechanisms of MAFLD and ALF,are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.

Star power: harnessing the reactive astrocyte response to promote remyelination in multiple sclerosis

Astrocytes are indispensable for central nervous system development and homeostasis.In response to injury and disease,astrocytes are integral to the immunological-and the,albeit limited,repair response.In this review,we will examine some of the functions reactive astrocytes play in the context of multiple sclerosis and related animal models.We will consider the heterogeneity or plasticity of astrocytes and the mechanisms by which they promote or mitigate demyelination.Finally,we will discuss a set of biomedical strategies that can stimulate astrocytes in their promyelinating response.

Inhibition of tubulin detyrosination:a novel strategy to promote central nervous system regeneration

The adult mammalian central nervous system(CNS) coordinates essential functions such as sensation,movement,autonomic control,thought processes,and communication.Consequently,injuries or diseases of the CNS are often associated with devastating and permanent functional impairments because damaged axons normally fail to regenerate.An insufficient neuron-intrinsic growth capacity and an inhibitory environment at the injury site are the leading causes of this regenerative failure.

When to repair a retinal detachment?

Rhegmatogenous retinal detachment(RRD)is the most common retinal emergency,threatening visual acuity,with an incidence of 1/10000[1].The number of RRDs is increasing[2-3].I recently had to prepare two expert reports about the correct timing of RRD surgery.

Improving early diagnosis of multiple endocrine neoplasia type 1 by assessing the gastrointestinal symptoms,hypercalcemia,and elevated serum gastrin

Despite advancements in the field,early diagnosis of multiple endocrine neoplasia type 1(MEN1)remains unachievable.This letter to the editor highlighted the importance of carefully assessing gastrointestinal symptoms,hypercalcemia,and elevated serum gastrin levels,as suggested by Yuan et al in their paper.They focused on a patient with recurrent abdominal pain and diarrhea whose diagnostic path led to establishing a MEN1 diagnosis within a year.This emphasized the need for clinicians to consider MEN1 in patients with similar presentations,particularly when gastrointestinal symptoms persist or recur after discontinuation of proton pump inhibitors,especially knowing that early recognition and intervention are crucial for improving patient outcomes.

Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.

Levisticum officinale extract protects against CCl4-induced hepatotoxicity through anti-inflammatory,anti-fibrotic,and antioxidant properties in rats

Objective:To investigate the hepatoprotective effects of Levisticum officinale extract on CCl4-induced hepatotoxicity.Methods:Different doses of Levisticum officinale extract were given orally to rats for 10 days,then rats received a single dose of CCl4(2.5 mL/kg,50%v/v in liquid paraffin).Biochemical and histopathological assays were performed to assess the effects of the extract on liver function and architecture.Moreover,antioxidant and oxidative markers as well as inflammatory and fibrotic indicators were measured.Results:Pretreatment with Levisticum officinale extract significantly mitigated CCl4-induced damage to liver structure,improved serum levels of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,urea,total bilirubin,and total protein,enhanced glutathione content and superoxide dismutase and catalase activities in the liver,as well as decreased plasma and hepatic malondialdehyde levels.Immunohistochemical results demonstrated that the extract reduced Ki-67 andα-SMA expression and Masson’s trichrome staining revealed decreased liver collagen in rats treated with Levisticum officinale extract.Moreover,Levisticum officinale extract markedly decreased the gene expressions of TNF-α,IL-6,TGF-β1,MCP-1,and COX-2.Conclusions:Levisticum officinale extract exerts hepatoprotective effects on CCl4-induced hepatotoxicity through antioxidant,anti-inflammatory,and anti-fibrotic activities.

Interferon-gamma release assays as a tool for differential diagnosis of gastrointestinal tuberculosis

In this editorial,we comment on an article published in a recent issue of the World Journal of Clinical Cases.There is a pressing need for reliable tools for diagnosing tuberculosis(TB)of the gastrointestinal tract.Despite advancements in the diagnosis and treatment,TB remains a global health challenge.Ali et al demon-strated that TB may mimic gastrointestinal conditions,such as gastric outlet obstruction,causing a delay in the diagnosis.Furthermore,the latter complication is frequently observed during infections,including Helicobacter pylori,and rarely is related to TB,as in the presented case.In line with this,we think that laboratory tests based on interferon-gamma release assays can be a helpful tool for diagnosing latent TB paced in the gastrointestinal tract.Innovative strategies and approaches for diagnosing latent/active extra pulmonary TB are crucial for establishing the diagnosis early and enhancing treatment strategies to mitigate the global burden of TB.

Manipulating the Gut Microbiome to Alleviate Steatotic Liver Disease:Current Progress and Challenges

The prevalence of metabolic-dysfunction-associated steatotic liver disease(MASLD)is alarmingly high;it is estimated to affect up to a quarter of the global population,making it the most common liver disorder worldwide.MASLD is characterized by excessive hepatic fat accumulation and is commonly associated with comorbidities such as obesity,dyslipidemia,and insulin resistance;however,it can also manifest in lean individuals.Therefore,it is crucial to develop effective therapies for this complex condition.Currently,there are no approved medications for MASLD treatment,so there is a pressing need to investigate alternative approaches.Extensive research has characterized MASLD as a multifaceted disease,frequently linked to metabolic disorders that stem from dietary habits.Evidence suggests that changes in the gut microbiome play a fundamental role in the development and progression of MASLD from simple steatosis to steatohepatitis and even hepatocellular carcinoma(HCC).In this review,we critically examine the literature on the emerging field of gut-microbiota-based therapies for MASLD and metabolicdysfunction-associated steatohepatitis(MASH),including interventions such as fecal microbiota transplantation(FMT),probiotics,prebiotics,short-chain fatty acids,antibiotics,metabolic pathway targeting,and immune checkpoint kinase blockade.