Peymnie＇s disease （PD） is most simply referred to as a fibrotic wound-healing disorder of the tunica albuginea. It is both a physically and psychologically devastating disorder that causes penile deformity, curvatu...Peymnie＇s disease （PD） is most simply referred to as a fibrotic wound-healing disorder of the tunica albuginea. It is both a physically and psychologically devastating disorder that causes penile deformity, curvature, hinging, narrowing and shortening, which may compromise sexual function. Although a variety of non-surgical treatments have been suggested, none to date offer a reliable and effective correction of the penile deformity. As a result, surgery remains the gold standard treatment option, offering the most rapid and reliable treatment which will be the focus of this article. We review the preoperative evaluation, surgical algorithm, graft materials and postoperative management of PD. Outcomes for tunical shortening, tunical lengthening and penile prosthesis placement for penile straightening are reviewed. Tunica albuginea plication is the preferred method of straightening for men with adequate rigidity and less severe disease defined as curvature less than 70° without narrowing/hinging. Men who have more severe, complex deformity, but maintain strong preoperative erectile function should be considered candidates for straightening with plaque incision or partial excision and grafting. Finally, for those men who have inadequate rigidity and PD, penile prosthesis placement with straightening is the best approach to address both problems.展开更多
The surgical techniques used by Austoni and Egydio in the treatment of Peyronie＇s disease are based on geometric principles. The aim of this paper is to report our multicentric experience and technical changes to Aus...The surgical techniques used by Austoni and Egydio in the treatment of Peyronie＇s disease are based on geometric principles. The aim of this paper is to report our multicentric experience and technical changes to Austoni＇s original technique, focusing on several tips and tricks to make this technique easy to perform, even by less experienced practitioners. We performed operations in three different Italian institutions. We implanted a small soft Virilis I~ axial prostheses （Ф 7 Fr.）, using a bovine pericardium collagen matrix patch （Hydrix） to cover the defect in the tunica albuginea. Sixty patients with a mean age of 58 years （range 44-76 years） underwent surgery between September 2005 and January 2010. After surgery, mean lengthening of the shaft was 2 cm （range 1.2-2.3 cm） with complete correction of penile recurvatum. Thirty-nine patients resumed sexual activity 60 days later, 14 after 90 days and 7 after 120 days. The international index of erectile function （IIEF） score was 15.5 before surgery and it improved to 23 at 12 and 24 months after surgery. Furthermore, the visual analogue scale （VAS） showed good results in terms of the recovery of natural sexual intercourse （over 80% of couples） and of the original length and girth of the penis. The soft implant we used takes advantage of erection that occurs spontaneously, using the residual erection of the spared cavernous tissue. The method is easy to learn and reproducible, and the use of pericardium speeds up the operation, while also covering large defects of the tunica albuginea that result from complex recurvatum.展开更多
The pathophysiology of LaPeyronie＇s disease （PD） is considered to be multifactorial, involving genetic predisposition, trauma, inflammation and altered wound healing. However, these factors have not yet been valida...The pathophysiology of LaPeyronie＇s disease （PD） is considered to be multifactorial, involving genetic predisposition, trauma, inflammation and altered wound healing. However, these factors have not yet been validated using animal models. In this study, we have presented a new model obtained by tunica albuginea allograft. A total of 40, 16-week-old male rats were used. Of these, 8 rats served as controls and underwent a 10 × 2-mm-wide tunical excisionwith subsequent autografting, whereas the remaining 32 underwent the same excision with grafting of the defect with another rat＇s tunica. Morphological and functional testing was performed at 1, 3, 7 and 12 weeks after grafting. Intracavernous pressure, the degree of penile curvature and elastic fiber length were evaluated for comparison between the allograft and control groups. The tissues were obtained for histological examination. The penile curvature was significantly greater in the allografted rats as compared with the control rats. The erectile function was maintained in all rats, except in those assessed at 12 weeks. The elastin fiber length was decreased in the allografted tunica as compared to control. SMAD2 expression was detected in the inner part of the allograff, and both collagen-Ⅱ- and osteocalcin-positive cells were also noted. Tunica albuginea （TA） allograft in rats is an excellent model of PD. The persistence of curvature beyond 12 weeks and the presence of ossification in the inner layer of the TA were similar to those observed in men with PD. Validation studies using this animal model would aid understanding of the PD pathophysiology for effective therapeutic interventions.展开更多
Aim： To determine retrospectively the safety and efficacy of extracorporeal shock wave therapy （ESWT） in patients with Peyronie＇s disease. Methods： Fifty-three patients with stable Peyronie＇s disease underwent E...Aim： To determine retrospectively the safety and efficacy of extracorporeal shock wave therapy （ESWT） in patients with Peyronie＇s disease. Methods： Fifty-three patients with stable Peyronie＇s disease underwent ESWT （group 1）. Fifteen patients matched with the baseline characteristic of the patients in group 1, who received no treatment, were used as the control （group 2）. The patients＇ erectile function （International Index of Erectile Function [IIEF-5] score）, pain severity （visual analog scale）, plaque size and degree of penile angulation were assessed before and after the treatment in group 1 and during the follow-up in group 2. Results： The mean follow-up time was 32 months （range： 6-64 months） in group 1 and 35 months （range： 9-48 months） in group 2. All the patients were available for the follow-up. Considering erectile function and plaque size, no significant changes （P 〉 0.05） were observed in group 1 before or after the ESWT. A total of 39 patients （74%） reported a significant effect in pain relief in group 1 after ESWT. However, regarding improvement in pain, IIEF-5 score and plaque size, no significant differences were observed between the two groups. In 21 patients （40%） of group 1, the deviation angle was decreased more than 10° with a mean reduction in all patients of 11° （range： 6-20°）. No serious complications were noted considering ESWT procedure. Conclusion： ESWT is a minimally invasive and safe alternative procedure for the treatment of Peyronie＇s disease. However, the effect of ESWT on penile pain, sexual function and plaque size remains questionable.展开更多
Aim： To discuss important points on medical history, preoperative evaluation, real expectations, and selection of the appropriate surgical procedure to improve patient satisfaction after surgical procedures for Peyro...Aim： To discuss important points on medical history, preoperative evaluation, real expectations, and selection of the appropriate surgical procedure to improve patient satisfaction after surgical procedures for Peyronie＇s disease. Methods： Recent advances in approaches to Peyronie＇s disease are discussed based on the literature and personal experiences. Issues concerning surgical indication, patient selection, surgical techniques, and grafting are discussed. Lengthening procedures on the convex side of the penile curvature by means of grafting offer the best possible gain from a reconstruction standpoint. Penile rectification and rigidity are required to achieve a completely functional penis. Most patients experience associated erectile dysfunction （ED）, and penile straightening alone may not be enough to restore complete function. Twenty-five patients were submitted to total penile reconstruction on length and girth with concomitant penile prosthesis implant. The maximum length restoration was possible and limited by the length of the dissected neurovascular bundle. The mean age was 55.4 years （32-69 years） and the mean angle of curvature 74.2± 22.4° （0-100°）. Pericardial grafting was used to cover the defect. The mean follow-up time was 11.2 ± 5.9 months （3-22 months）. Results： Mean functional penile length gain was 3.40 ＋ 0.73 cm （2-5 cm）. Penile prosthesis maintained the penis straight. No infections occurred. Sexual intercourse was restored in all patients and all reported recovered self-esteem. Conclusion： Improving patient satisfaction with the surgical treatment includes proper preoperative evaluation on stable disease, penile shortening, vascular and erectile status, patient decision and selection as well as extensive discussion on surgical technique for restoring functional penis （length and rigidity）. Length and girth restoration is very important for self-esteem and patient satisfaction.展开更多
The present paper provides a review of the available non-surgical treatments for Peyronie＇s disease （PD）. A review of published literature on oral, intralesional, external energy and iontophoresis therapies for PD ...The present paper provides a review of the available non-surgical treatments for Peyronie＇s disease （PD）. A review of published literature on oral, intralesional, external energy and iontophoresis therapies for PD was performed, and the published results of available treatment options reviewed. The authors＇ recommendations for appropriate non-surgical management of PD are provided. Although there are many published reports that show the efficacy of non-surgical therapies for PD, there is a lack of large scale, multicenter controlled clinical trials, which makes treatment recommendations difficult. Careful review of the literature does suggest that there are treatment options that make scientific sense and appear to stabilize the disease process, reduce deformity, and improve function. Offering no treatment at all will encourage our patients to pursue alternative treatments, which might do harm, and misses the opportunity to do some good. Clearly further work is necessary to develop safe and effective non-surgical treatments for PD.展开更多
We evaluated penile prosthesis implantation with tunica albuginea-relaxing incisions without grafting in the treatment of Peyronie＇s disease associated with erectile dysfunction. Between April 2005 and June 2011, 62 ...We evaluated penile prosthesis implantation with tunica albuginea-relaxing incisions without grafting in the treatment of Peyronie＇s disease associated with erectile dysfunction. Between April 2005 and June 2011, 62 patients underwent surgery due to severe Peyronie＇s disease associated with erectile dysfunction. Malleable and inflatable penile prostheses were inserted in 49 and 13 cases, respectively. Penile prostheses were inserted into the corpora cavernosa using the standard ventral approach. After lifting the neurovascular bundle, the tunica albuginea was incised and opened at the plaque region to correct the deformities and to lengthen the penis. Subsequently, the wide neurovascular bundle was replaced, and all incisions of the tunica albuginea were covered to prevent corporal grafting. In the median follow-up of 35 months （range 14-82 months）, the penis was completely straightened in 59 （95%） patients. Numbness of the glans, which the patients found initially upsetting, decreased or disappeared spontaneously 3-6 months later. Penile prosthesis implantation with tunica albuginea incisions is a viable alternative in the treatment of Peyronie＇s disease because the extensive dissection of the neurovascular bundle allows a good approach to the plaque and provides excellent covering of the incised tunica albuginea without additional grafting.展开更多
This retrospective cohort study from a single clinical practice enrolled patients with evidence of calcified Peyronie＇s disease （PD） plaques detected on penile ultrasound at the time of initial presentation. The pr...This retrospective cohort study from a single clinical practice enrolled patients with evidence of calcified Peyronie＇s disease （PD） plaques detected on penile ultrasound at the time of initial presentation. The primary objective was to describe the effect of pentoxifylline （PTX） treatment on subtunical calcifications in men with PD. A PD-specific questionnaire was administered and sonographic evaluations were performed at baseline and follow-up visits. Descriptive statistics and X2 analysis were used to characterize the effect of PTX on calcified tunical plaques. In all, 71 men （mean age： 51.9 years） with PD and sonographic evidence of calcification were identified. Of them, 62 of these men were treated with PTX for a mean duration of I year, and nine with vitamin E or no treatment. Improvement or stabilization in calcium burden at follow-up was noted in 57 （91.9%） of men treated with PTX versus four （44,4%） of those not treated with PTX （P〈0.001）. PTX users were much less likely to have a subjective worsening of their clinical condition （25.0% versus 78.3%, P=0.002）. Treatment with PTX appeared to stabilize or reduce calcium content in PD plaques. A randomized controlled trial is warranted to further explore this effect.展开更多
The long-term outcomes of 157 patients affected by Peyronie＇s disease （PD） who underwent penile straightening with Egydio＇s technique between January 2004 and December 2008 are reported. Only patients with PD who ...The long-term outcomes of 157 patients affected by Peyronie＇s disease （PD） who underwent penile straightening with Egydio＇s technique between January 2004 and December 2008 are reported. Only patients with PD who were stable for at least 6-12 months prior to surgery were enrolled in this study. Preoperative assessment included a dynamic echo colour Doppler ultrasound scan to evaluate the degree of penile deformity and the peak systolic velocity in the cavernosal arteries and an assessment of erectile function with the administration of the International Index of Erectile Function 5 （IIEF-5） questionnaire. Stretched penile length was recorded pre- and postoperatively. Surgical complications, cosmesis and sexual function, patient satisfaction and postoperative erectile function were assessed postoperatively at 3 months, I year and 2 years, respectively. After a median follow-up period of 20 months （range： 12-24 months）, we found that mild residual curvature （12%） and glans hypoesthesia （3%） were the only causes of partial dissatisfaction. No rejection of the graft was observed. All patients recovered their ability to penetrate with no difficulty. In addition, an intraoperative average increase of 2.5 cm （range： 1.7-4.1 cm） in stretched penile length was recorded, with all patients engaging in penetrative sexual intercourse. In conclusion, this procedure represents a safe and reproducible technique for the correction of penile curvature resulting from PD and yields excellent cosmetic and functional results.展开更多
Many different materials are available for grafting during surgery for Peyronie＇s disease （PD）. To study the outcomes associated with the use of a lyophilized bovine pericardium graft （Peri-Guard） to repair tunic...Many different materials are available for grafting during surgery for Peyronie＇s disease （PD）. To study the outcomes associated with the use of a lyophilized bovine pericardium graft （Peri-Guard） to repair tunical defects in patients with PD, descriptive study of 43 patients with disabling penile curvature was performed. Curvature was measured before and after the intervention using a standardized procedure. Surgical technique was plaque excision and grafting of the tunical defect carried out by a single surgeon. A lyophilized bovine pericardium patch was used for grafting. We measured the change in penile curvature and length, the ability to perform successful sexual intercourse without further pharmacological or surgical treatment, and the satisfaction with treatment. Follow-up data were available for a total of 41 patients. Median age was 50 years （IQR 48-52）; mean follow-up time was 14 ± 6 months. Complete penile straightening was achieved in 33 patients （80.5%） and five patients （12.2%） had curvature under 20. Three months after surgery and stretching therapy, mean （s.d.） flaccid penile length increased from 11.2 ± 2.8 cm to 12.1 ± 2.9 cm （P = 0.062）. Seventy-five percentage of patients reported being able to achieve successful intercourse without further treatment. Eighty-five percentage of patients reported to be satisfied with the treatment. There was no evidence of tissue rejection or infection, and only four patients suffered an adverse event. Plaque excision and grafting of the tunical defect with lyophilized bovine pericardium seems to be a safe and effective treatment for patients with PD.展开更多
Peyronie’s disease(PD)is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages.In this study,we aimed to compare four injectable induct...Peyronie’s disease(PD)is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages.In this study,we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD:transforming growth factor-β1(TGF-β1),fibrin,sodium tetradecyl sulfate(STS)combined with TGF-β1,and polidocanol(POL)combined with TGF-β1.The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature.The STS+TGF-β1 combination resulted in both histological and morphological alterations,but with a high incidence of localized necrosis that led to animal death.The POL+TGF-β1 combination produced pathological changes and curvature comparable to STS+TGF-β1 and led to fewer complications.In conclusion,fibrin,STS+TGF-β1,and POL+TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats.The POL+TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.展开更多
Peyronie’s disease(PD)is a connective tissue disorder characterized by abnormal collagen deposition in the tunica albuginea,leading to penile curvature,pain,and erectile dysfunction.This study aimed to evaluate the o...Peyronie’s disease(PD)is a connective tissue disorder characterized by abnormal collagen deposition in the tunica albuginea,leading to penile curvature,pain,and erectile dysfunction.This study aimed to evaluate the outcomes of a combined treatment protocol incorporating collagenase clostridium histolyticum(CCH),vacuum erection device,and tadalafil.A retrospective analysis was conducted on 99 male patients with PD treated at the Department of Urology,Hamad Medical Corporation(Doha,Qatar)between January 2018 and January 2020.Patients received 4–8 CCH injections alongside vacuum therapy and daily tadalafil(5 mg).The baseline mean penile curvature of 49.0°improved by an average of 21.4%post-treatment.Erectile function scores also increased significantly,with a mean improvement of 2.3 points on the International Index of Erectile Function.Minor complications were observed in 15 patients,while 13 were dissatisfied with treatment,with six opting for surgery.The modified protocol demonstrated significant improvements in penile curvature and erectile function with minimal complications,offering a safe,cost-effective alternative to traditional intensive treatments.展开更多
Peyronie’s disease(PD)presents a multifaceted challenge in contemporary urological practice,marked by penile deformity,pain,and the potential for erectile dysfunction.We meticulously explored the existing literature ...Peyronie’s disease(PD)presents a multifaceted challenge in contemporary urological practice,marked by penile deformity,pain,and the potential for erectile dysfunction.We meticulously explored the existing literature of intralesional/topical interventions,aiming to provide clinicians with a nuanced understanding of available options for comprehensive PD management.To conduct this review,we performed a systematic search using the PubMed,Scopus,and ScienceDirect databases,including the keywords of combination of the“Peyronie’s disease/plastic induration of the penis(PIP)and intralesional/topical treatments”.The study selection was based on adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,resulting in the inclusion of 16 articles.We delve into the effectiveness and safety profiles of collagenase Clostridium histolyticum(CCH),interferon,platelet-rich plasma(PRP),hyaluronic acid,botulinum toxin,stem cell,extracorporeal shock wave therapy(ESWT),and traction therapy,assessing their impact on penile curvature,length improvement,and patient-reported symptoms and outcomes.The best options evaluated are intralesional injections of CCH and penile traction devices,alone or in combination.Despite PD remains a challenge for urologists,the objective of this review is to contribute to the evolving landscape of PD management,fostering informed decision-making,and personalized care for individuals grappling with this challenging condition.展开更多
Peyronie's disease(PD)is a challenging condition that significantly impacts male sexual health,often leading to penile curvature,pain,and erectile dysfunction.Treatment options range from conservative pharmacologi...Peyronie's disease(PD)is a challenging condition that significantly impacts male sexual health,often leading to penile curvature,pain,and erectile dysfunction.Treatment options range from conservative pharmacologic approaches to more invasive surgical interventions,with collagenase clostridium histolyticum(CCH)being the only U.S.Food and Drug Administration(FDA)-approved intralesional therapy.However,optimizing treatment strategies to enhance efficacy while minimizing patient burden remains an area of ongoing investigation.^(1,2)展开更多
This well-documented uncontrolled study tracks improvement in the International Index of Erectile Function(IIEF)scores and penile curvature in 99 men with Peyronie's disease.^(1) It was conducted over the course o...This well-documented uncontrolled study tracks improvement in the International Index of Erectile Function(IIEF)scores and penile curvature in 99 men with Peyronie's disease.^(1) It was conducted over the course of two years and identified statistically significant improvement in penile curvature and erectile function with a tolerable complication rate in response to a tri-modal protocol of intralesional clostridium collagenase histolyticum(CCH),tadalafil,and vacuum treatment.Despite lack of controls,it does serve to confirm the safety,efficacy,and clinical utility of their nonsurgical approach and supports the growing body of literature on combined therapy for this difficult disorder.Based on results in multiple"real world"studies following the Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies(IMPRESS)Trial,^(2) it is encouraging to see that both chronic-and acute-phase patients were included.展开更多
Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as ...Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as deep brain stimulation and transcranial magnetic stimulation,show limitations such as invasiveness,restricted cortical targeting,and irreversible tissue effects.In this context,low-intensity transcranial ultrasound has emerged as a promising noninvasive alternative that can penetrate deep into the brain and modulate neuroplasticity.This review comprehensively assesses the therapeutic mechanisms,efficacy,and translational potential of low-intensity transcranial ultrasound in treating neurodegenerative diseases,with emphasis on its role in promoting neuronal regeneration,modulating neuroinflammation,and enhancing functional recovery.We summarize the findings of previous studies and systematically illustrate the potential of low-intensity transcranial ultrasound in regulating cell death mechanisms,enhancing neural repair and regeneration,and alleviating symptoms associated with neurodegenerative diseases.Preclinical findings indicate that low-intensity transcranial ultrasound can enhance the release of neurotrophic factors(e.g.,brain-derived neurotrophic factor),promote autophagy to clear protein aggregates,modulate microglial activation,and temporarily open the blood-brain barrier to facilitate targeted drug delivery.Existing clinical trial data show that low-intensity transcranial ultrasound can reduce amyloid-βplaques,improve motor and cognitive deficits,and promote remyelination in various disease models.Early clinical trials suggest that low-intensity transcranial ultrasound may enhance cognitive scores in Alzheimer’s disease and alleviate motor symptoms in Parkinson’s disease,all while demonstrating a favorable safety profile.Past studies support the notion that by integrating safety,precision,and reversibility,low-intensity transcranial ultrasound can transform the treatment landscape for neurodegenerative disease.However,more advancements are necessary for future clinical application of low-intensity transcranial ultrasound,including optimizing parameters such as frequency,intensity,and duty cycle;considering individual anatomical differences;and confirming long-term efficacy.We believe establishing standardized protocols,conducting larger trials,and investigating the underlying mechanisms to clarify dose-response relationships and refine personalized application strategies are essential in this regard.Future research should focus on translating preclinical findings into clinical practice,addressing technical challenges,and exploring combination therapies with pharmacological or gene interventions.展开更多
Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined ex...Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.展开更多
Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
Chemical exchange saturation transfer magnetic resonance imaging is an advanced imaging technique that enables the detection of compounds at low concentrations with high sensitivity and spatial resolution and has been...Chemical exchange saturation transfer magnetic resonance imaging is an advanced imaging technique that enables the detection of compounds at low concentrations with high sensitivity and spatial resolution and has been extensively studied for diagnosing malignancy and stroke.In recent years,the emerging exploration of chemical exchange saturation transfer magnetic resonance imaging for detecting pathological changes in neurodegenerative diseases has opened up new possibilities for early detection and repetitive scans without ionizing radiation.This review serves as an overview of chemical exchange saturation transfer magnetic resonance imaging with detailed information on contrast mechanisms and processing methods and summarizes recent developments in both clinical and preclinical studies of chemical exchange saturation transfer magnetic resonance imaging for Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,and Huntington’s disease.A comprehensive literature search was conducted using databases such as PubMed and Google Scholar,focusing on peer-reviewed articles from the past 15 years relevant to clinical and preclinical applications.The findings suggest that chemical exchange saturation transfer magnetic resonance imaging has the potential to detect molecular changes and altered metabolism,which may aid in early diagnosis and assessment of the severity of neurodegenerative diseases.Although promising results have been observed in selected clinical and preclinical trials,further validations are needed to evaluate their clinical value.When combined with other imaging modalities and advanced analytical methods,chemical exchange saturation transfer magnetic resonance imaging shows potential as an in vivo biomarker,enhancing the understanding of neuropathological mechanisms in neurodegenerative diseases.展开更多
Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol chan...Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol changes that occur in the brain during Alzheimer’s disease remains unclear.In this study,we compared brain tissues extracted from 32-week-old male wild-type mice and 5×FAD transgenic Alzheimer’s disease model mice,which carry mutations in the amyloid precursor protein(APP)and presenilin 1(PS1)genes.Using untargeted lipidomics and sterolomics techniques,we investigated the metabolic profiles of lipids,with a focus on sterols specifically,in three brain regions:cerebellum,hippocampus,and olfactory bulb.Our results revealed significant alterations in various lipids,particularly in the hippocampus and olfactory bulb,suggesting changes in energy levels in these regions.Further pathway analysis indicated notable disruptions in key metabolic processes,particularly those related to fatty acids and cell membrane components.Additionally,we observed decreased expression of 15 genes involved in lipid and sterol regulation.Collectively,these findings provide new insights into how imbalances in lipid and sterol metabolism may contribute to the progression of Alzheimer’s disease,highlighting potential metabolic pathways involved in the development of this debilitating disease.展开更多
文摘Peymnie＇s disease （PD） is most simply referred to as a fibrotic wound-healing disorder of the tunica albuginea. It is both a physically and psychologically devastating disorder that causes penile deformity, curvature, hinging, narrowing and shortening, which may compromise sexual function. Although a variety of non-surgical treatments have been suggested, none to date offer a reliable and effective correction of the penile deformity. As a result, surgery remains the gold standard treatment option, offering the most rapid and reliable treatment which will be the focus of this article. We review the preoperative evaluation, surgical algorithm, graft materials and postoperative management of PD. Outcomes for tunical shortening, tunical lengthening and penile prosthesis placement for penile straightening are reviewed. Tunica albuginea plication is the preferred method of straightening for men with adequate rigidity and less severe disease defined as curvature less than 70° without narrowing/hinging. Men who have more severe, complex deformity, but maintain strong preoperative erectile function should be considered candidates for straightening with plaque incision or partial excision and grafting. Finally, for those men who have inadequate rigidity and PD, penile prosthesis placement with straightening is the best approach to address both problems.
文摘The surgical techniques used by Austoni and Egydio in the treatment of Peyronie＇s disease are based on geometric principles. The aim of this paper is to report our multicentric experience and technical changes to Austoni＇s original technique, focusing on several tips and tricks to make this technique easy to perform, even by less experienced practitioners. We performed operations in three different Italian institutions. We implanted a small soft Virilis I~ axial prostheses （Ф 7 Fr.）, using a bovine pericardium collagen matrix patch （Hydrix） to cover the defect in the tunica albuginea. Sixty patients with a mean age of 58 years （range 44-76 years） underwent surgery between September 2005 and January 2010. After surgery, mean lengthening of the shaft was 2 cm （range 1.2-2.3 cm） with complete correction of penile recurvatum. Thirty-nine patients resumed sexual activity 60 days later, 14 after 90 days and 7 after 120 days. The international index of erectile function （IIEF） score was 15.5 before surgery and it improved to 23 at 12 and 24 months after surgery. Furthermore, the visual analogue scale （VAS） showed good results in terms of the recovery of natural sexual intercourse （over 80% of couples） and of the original length and girth of the penis. The soft implant we used takes advantage of erection that occurs spontaneously, using the residual erection of the spared cavernous tissue. The method is easy to learn and reproducible, and the use of pericardium speeds up the operation, while also covering large defects of the tunica albuginea that result from complex recurvatum.
文摘The pathophysiology of LaPeyronie＇s disease （PD） is considered to be multifactorial, involving genetic predisposition, trauma, inflammation and altered wound healing. However, these factors have not yet been validated using animal models. In this study, we have presented a new model obtained by tunica albuginea allograft. A total of 40, 16-week-old male rats were used. Of these, 8 rats served as controls and underwent a 10 × 2-mm-wide tunical excisionwith subsequent autografting, whereas the remaining 32 underwent the same excision with grafting of the defect with another rat＇s tunica. Morphological and functional testing was performed at 1, 3, 7 and 12 weeks after grafting. Intracavernous pressure, the degree of penile curvature and elastic fiber length were evaluated for comparison between the allograft and control groups. The tissues were obtained for histological examination. The penile curvature was significantly greater in the allografted rats as compared with the control rats. The erectile function was maintained in all rats, except in those assessed at 12 weeks. The elastin fiber length was decreased in the allografted tunica as compared to control. SMAD2 expression was detected in the inner part of the allograff, and both collagen-Ⅱ- and osteocalcin-positive cells were also noted. Tunica albuginea （TA） allograft in rats is an excellent model of PD. The persistence of curvature beyond 12 weeks and the presence of ossification in the inner layer of the TA were similar to those observed in men with PD. Validation studies using this animal model would aid understanding of the PD pathophysiology for effective therapeutic interventions.
文摘Aim： To determine retrospectively the safety and efficacy of extracorporeal shock wave therapy （ESWT） in patients with Peyronie＇s disease. Methods： Fifty-three patients with stable Peyronie＇s disease underwent ESWT （group 1）. Fifteen patients matched with the baseline characteristic of the patients in group 1, who received no treatment, were used as the control （group 2）. The patients＇ erectile function （International Index of Erectile Function [IIEF-5] score）, pain severity （visual analog scale）, plaque size and degree of penile angulation were assessed before and after the treatment in group 1 and during the follow-up in group 2. Results： The mean follow-up time was 32 months （range： 6-64 months） in group 1 and 35 months （range： 9-48 months） in group 2. All the patients were available for the follow-up. Considering erectile function and plaque size, no significant changes （P 〉 0.05） were observed in group 1 before or after the ESWT. A total of 39 patients （74%） reported a significant effect in pain relief in group 1 after ESWT. However, regarding improvement in pain, IIEF-5 score and plaque size, no significant differences were observed between the two groups. In 21 patients （40%） of group 1, the deviation angle was decreased more than 10° with a mean reduction in all patients of 11° （range： 6-20°）. No serious complications were noted considering ESWT procedure. Conclusion： ESWT is a minimally invasive and safe alternative procedure for the treatment of Peyronie＇s disease. However, the effect of ESWT on penile pain, sexual function and plaque size remains questionable.
文摘Aim： To discuss important points on medical history, preoperative evaluation, real expectations, and selection of the appropriate surgical procedure to improve patient satisfaction after surgical procedures for Peyronie＇s disease. Methods： Recent advances in approaches to Peyronie＇s disease are discussed based on the literature and personal experiences. Issues concerning surgical indication, patient selection, surgical techniques, and grafting are discussed. Lengthening procedures on the convex side of the penile curvature by means of grafting offer the best possible gain from a reconstruction standpoint. Penile rectification and rigidity are required to achieve a completely functional penis. Most patients experience associated erectile dysfunction （ED）, and penile straightening alone may not be enough to restore complete function. Twenty-five patients were submitted to total penile reconstruction on length and girth with concomitant penile prosthesis implant. The maximum length restoration was possible and limited by the length of the dissected neurovascular bundle. The mean age was 55.4 years （32-69 years） and the mean angle of curvature 74.2± 22.4° （0-100°）. Pericardial grafting was used to cover the defect. The mean follow-up time was 11.2 ± 5.9 months （3-22 months）. Results： Mean functional penile length gain was 3.40 ＋ 0.73 cm （2-5 cm）. Penile prosthesis maintained the penis straight. No infections occurred. Sexual intercourse was restored in all patients and all reported recovered self-esteem. Conclusion： Improving patient satisfaction with the surgical treatment includes proper preoperative evaluation on stable disease, penile shortening, vascular and erectile status, patient decision and selection as well as extensive discussion on surgical technique for restoring functional penis （length and rigidity）. Length and girth restoration is very important for self-esteem and patient satisfaction.
文摘The present paper provides a review of the available non-surgical treatments for Peyronie＇s disease （PD）. A review of published literature on oral, intralesional, external energy and iontophoresis therapies for PD was performed, and the published results of available treatment options reviewed. The authors＇ recommendations for appropriate non-surgical management of PD are provided. Although there are many published reports that show the efficacy of non-surgical therapies for PD, there is a lack of large scale, multicenter controlled clinical trials, which makes treatment recommendations difficult. Careful review of the literature does suggest that there are treatment options that make scientific sense and appear to stabilize the disease process, reduce deformity, and improve function. Offering no treatment at all will encourage our patients to pursue alternative treatments, which might do harm, and misses the opportunity to do some good. Clearly further work is necessary to develop safe and effective non-surgical treatments for PD.
文摘We evaluated penile prosthesis implantation with tunica albuginea-relaxing incisions without grafting in the treatment of Peyronie＇s disease associated with erectile dysfunction. Between April 2005 and June 2011, 62 patients underwent surgery due to severe Peyronie＇s disease associated with erectile dysfunction. Malleable and inflatable penile prostheses were inserted in 49 and 13 cases, respectively. Penile prostheses were inserted into the corpora cavernosa using the standard ventral approach. After lifting the neurovascular bundle, the tunica albuginea was incised and opened at the plaque region to correct the deformities and to lengthen the penis. Subsequently, the wide neurovascular bundle was replaced, and all incisions of the tunica albuginea were covered to prevent corporal grafting. In the median follow-up of 35 months （range 14-82 months）, the penis was completely straightened in 59 （95%） patients. Numbness of the glans, which the patients found initially upsetting, decreased or disappeared spontaneously 3-6 months later. Penile prosthesis implantation with tunica albuginea incisions is a viable alternative in the treatment of Peyronie＇s disease because the extensive dissection of the neurovascular bundle allows a good approach to the plaque and provides excellent covering of the incised tunica albuginea without additional grafting.
文摘This retrospective cohort study from a single clinical practice enrolled patients with evidence of calcified Peyronie＇s disease （PD） plaques detected on penile ultrasound at the time of initial presentation. The primary objective was to describe the effect of pentoxifylline （PTX） treatment on subtunical calcifications in men with PD. A PD-specific questionnaire was administered and sonographic evaluations were performed at baseline and follow-up visits. Descriptive statistics and X2 analysis were used to characterize the effect of PTX on calcified tunical plaques. In all, 71 men （mean age： 51.9 years） with PD and sonographic evidence of calcification were identified. Of them, 62 of these men were treated with PTX for a mean duration of I year, and nine with vitamin E or no treatment. Improvement or stabilization in calcium burden at follow-up was noted in 57 （91.9%） of men treated with PTX versus four （44,4%） of those not treated with PTX （P〈0.001）. PTX users were much less likely to have a subjective worsening of their clinical condition （25.0% versus 78.3%, P=0.002）. Treatment with PTX appeared to stabilize or reduce calcium content in PD plaques. A randomized controlled trial is warranted to further explore this effect.
文摘The long-term outcomes of 157 patients affected by Peyronie＇s disease （PD） who underwent penile straightening with Egydio＇s technique between January 2004 and December 2008 are reported. Only patients with PD who were stable for at least 6-12 months prior to surgery were enrolled in this study. Preoperative assessment included a dynamic echo colour Doppler ultrasound scan to evaluate the degree of penile deformity and the peak systolic velocity in the cavernosal arteries and an assessment of erectile function with the administration of the International Index of Erectile Function 5 （IIEF-5） questionnaire. Stretched penile length was recorded pre- and postoperatively. Surgical complications, cosmesis and sexual function, patient satisfaction and postoperative erectile function were assessed postoperatively at 3 months, I year and 2 years, respectively. After a median follow-up period of 20 months （range： 12-24 months）, we found that mild residual curvature （12%） and glans hypoesthesia （3%） were the only causes of partial dissatisfaction. No rejection of the graft was observed. All patients recovered their ability to penetrate with no difficulty. In addition, an intraoperative average increase of 2.5 cm （range： 1.7-4.1 cm） in stretched penile length was recorded, with all patients engaging in penetrative sexual intercourse. In conclusion, this procedure represents a safe and reproducible technique for the correction of penile curvature resulting from PD and yields excellent cosmetic and functional results.
文摘Many different materials are available for grafting during surgery for Peyronie＇s disease （PD）. To study the outcomes associated with the use of a lyophilized bovine pericardium graft （Peri-Guard） to repair tunical defects in patients with PD, descriptive study of 43 patients with disabling penile curvature was performed. Curvature was measured before and after the intervention using a standardized procedure. Surgical technique was plaque excision and grafting of the tunical defect carried out by a single surgeon. A lyophilized bovine pericardium patch was used for grafting. We measured the change in penile curvature and length, the ability to perform successful sexual intercourse without further pharmacological or surgical treatment, and the satisfaction with treatment. Follow-up data were available for a total of 41 patients. Median age was 50 years （IQR 48-52）; mean follow-up time was 14 ± 6 months. Complete penile straightening was achieved in 33 patients （80.5%） and five patients （12.2%） had curvature under 20. Three months after surgery and stretching therapy, mean （s.d.） flaccid penile length increased from 11.2 ± 2.8 cm to 12.1 ± 2.9 cm （P = 0.062）. Seventy-five percentage of patients reported being able to achieve successful intercourse without further treatment. Eighty-five percentage of patients reported to be satisfied with the treatment. There was no evidence of tissue rejection or infection, and only four patients suffered an adverse event. Plaque excision and grafting of the tunical defect with lyophilized bovine pericardium seems to be a safe and effective treatment for patients with PD.
基金supported by the National Natural Science Foundation of China(grant No.81971380 and No.82301822).
文摘Peyronie’s disease(PD)is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages.In this study,we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD:transforming growth factor-β1(TGF-β1),fibrin,sodium tetradecyl sulfate(STS)combined with TGF-β1,and polidocanol(POL)combined with TGF-β1.The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature.The STS+TGF-β1 combination resulted in both histological and morphological alterations,but with a high incidence of localized necrosis that led to animal death.The POL+TGF-β1 combination produced pathological changes and curvature comparable to STS+TGF-β1 and led to fewer complications.In conclusion,fibrin,STS+TGF-β1,and POL+TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats.The POL+TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.
文摘Peyronie’s disease(PD)is a connective tissue disorder characterized by abnormal collagen deposition in the tunica albuginea,leading to penile curvature,pain,and erectile dysfunction.This study aimed to evaluate the outcomes of a combined treatment protocol incorporating collagenase clostridium histolyticum(CCH),vacuum erection device,and tadalafil.A retrospective analysis was conducted on 99 male patients with PD treated at the Department of Urology,Hamad Medical Corporation(Doha,Qatar)between January 2018 and January 2020.Patients received 4–8 CCH injections alongside vacuum therapy and daily tadalafil(5 mg).The baseline mean penile curvature of 49.0°improved by an average of 21.4%post-treatment.Erectile function scores also increased significantly,with a mean improvement of 2.3 points on the International Index of Erectile Function.Minor complications were observed in 15 patients,while 13 were dissatisfied with treatment,with six opting for surgery.The modified protocol demonstrated significant improvements in penile curvature and erectile function with minimal complications,offering a safe,cost-effective alternative to traditional intensive treatments.
文摘Peyronie’s disease(PD)presents a multifaceted challenge in contemporary urological practice,marked by penile deformity,pain,and the potential for erectile dysfunction.We meticulously explored the existing literature of intralesional/topical interventions,aiming to provide clinicians with a nuanced understanding of available options for comprehensive PD management.To conduct this review,we performed a systematic search using the PubMed,Scopus,and ScienceDirect databases,including the keywords of combination of the“Peyronie’s disease/plastic induration of the penis(PIP)and intralesional/topical treatments”.The study selection was based on adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,resulting in the inclusion of 16 articles.We delve into the effectiveness and safety profiles of collagenase Clostridium histolyticum(CCH),interferon,platelet-rich plasma(PRP),hyaluronic acid,botulinum toxin,stem cell,extracorporeal shock wave therapy(ESWT),and traction therapy,assessing their impact on penile curvature,length improvement,and patient-reported symptoms and outcomes.The best options evaluated are intralesional injections of CCH and penile traction devices,alone or in combination.Despite PD remains a challenge for urologists,the objective of this review is to contribute to the evolving landscape of PD management,fostering informed decision-making,and personalized care for individuals grappling with this challenging condition.
文摘Peyronie's disease(PD)is a challenging condition that significantly impacts male sexual health,often leading to penile curvature,pain,and erectile dysfunction.Treatment options range from conservative pharmacologic approaches to more invasive surgical interventions,with collagenase clostridium histolyticum(CCH)being the only U.S.Food and Drug Administration(FDA)-approved intralesional therapy.However,optimizing treatment strategies to enhance efficacy while minimizing patient burden remains an area of ongoing investigation.^(1,2)
文摘This well-documented uncontrolled study tracks improvement in the International Index of Erectile Function(IIEF)scores and penile curvature in 99 men with Peyronie's disease.^(1) It was conducted over the course of two years and identified statistically significant improvement in penile curvature and erectile function with a tolerable complication rate in response to a tri-modal protocol of intralesional clostridium collagenase histolyticum(CCH),tadalafil,and vacuum treatment.Despite lack of controls,it does serve to confirm the safety,efficacy,and clinical utility of their nonsurgical approach and supports the growing body of literature on combined therapy for this difficult disorder.Based on results in multiple"real world"studies following the Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies(IMPRESS)Trial,^(2) it is encouraging to see that both chronic-and acute-phase patients were included.
基金supported by STI2030-Major Project,No,2021ZD0204200(to LX).
文摘Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as deep brain stimulation and transcranial magnetic stimulation,show limitations such as invasiveness,restricted cortical targeting,and irreversible tissue effects.In this context,low-intensity transcranial ultrasound has emerged as a promising noninvasive alternative that can penetrate deep into the brain and modulate neuroplasticity.This review comprehensively assesses the therapeutic mechanisms,efficacy,and translational potential of low-intensity transcranial ultrasound in treating neurodegenerative diseases,with emphasis on its role in promoting neuronal regeneration,modulating neuroinflammation,and enhancing functional recovery.We summarize the findings of previous studies and systematically illustrate the potential of low-intensity transcranial ultrasound in regulating cell death mechanisms,enhancing neural repair and regeneration,and alleviating symptoms associated with neurodegenerative diseases.Preclinical findings indicate that low-intensity transcranial ultrasound can enhance the release of neurotrophic factors(e.g.,brain-derived neurotrophic factor),promote autophagy to clear protein aggregates,modulate microglial activation,and temporarily open the blood-brain barrier to facilitate targeted drug delivery.Existing clinical trial data show that low-intensity transcranial ultrasound can reduce amyloid-βplaques,improve motor and cognitive deficits,and promote remyelination in various disease models.Early clinical trials suggest that low-intensity transcranial ultrasound may enhance cognitive scores in Alzheimer’s disease and alleviate motor symptoms in Parkinson’s disease,all while demonstrating a favorable safety profile.Past studies support the notion that by integrating safety,precision,and reversibility,low-intensity transcranial ultrasound can transform the treatment landscape for neurodegenerative disease.However,more advancements are necessary for future clinical application of low-intensity transcranial ultrasound,including optimizing parameters such as frequency,intensity,and duty cycle;considering individual anatomical differences;and confirming long-term efficacy.We believe establishing standardized protocols,conducting larger trials,and investigating the underlying mechanisms to clarify dose-response relationships and refine personalized application strategies are essential in this regard.Future research should focus on translating preclinical findings into clinical practice,addressing technical challenges,and exploring combination therapies with pharmacological or gene interventions.
基金supported by the National Natural Science Foundation of China,No.81472235(to HF)the Shanghai Jiao Tong University Medical and Engineering Project,Nos.YG2021QN53(to HF),YG2017MS71(to HF)+1 种基金the International Cooperation Project of the National Natural Science Foundation of China,No.82020108017(to DC)the Innovation Group Project of the National Natural Science Foundation of China,No.81921002(to DC).
文摘Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.
基金supported by the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
基金supported by The University of Hong Kong,China(109000487,109001694,204610401,and 204610519)National Natural Science Foundation of China(82402225)(to JH).
文摘Chemical exchange saturation transfer magnetic resonance imaging is an advanced imaging technique that enables the detection of compounds at low concentrations with high sensitivity and spatial resolution and has been extensively studied for diagnosing malignancy and stroke.In recent years,the emerging exploration of chemical exchange saturation transfer magnetic resonance imaging for detecting pathological changes in neurodegenerative diseases has opened up new possibilities for early detection and repetitive scans without ionizing radiation.This review serves as an overview of chemical exchange saturation transfer magnetic resonance imaging with detailed information on contrast mechanisms and processing methods and summarizes recent developments in both clinical and preclinical studies of chemical exchange saturation transfer magnetic resonance imaging for Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,and Huntington’s disease.A comprehensive literature search was conducted using databases such as PubMed and Google Scholar,focusing on peer-reviewed articles from the past 15 years relevant to clinical and preclinical applications.The findings suggest that chemical exchange saturation transfer magnetic resonance imaging has the potential to detect molecular changes and altered metabolism,which may aid in early diagnosis and assessment of the severity of neurodegenerative diseases.Although promising results have been observed in selected clinical and preclinical trials,further validations are needed to evaluate their clinical value.When combined with other imaging modalities and advanced analytical methods,chemical exchange saturation transfer magnetic resonance imaging shows potential as an in vivo biomarker,enhancing the understanding of neuropathological mechanisms in neurodegenerative diseases.
基金supported by the National Natural Science Foundation of China,Nos.82200784,32271311Qizhen Foundation,No.226‐2023‐00008(all to LH).
文摘Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol changes that occur in the brain during Alzheimer’s disease remains unclear.In this study,we compared brain tissues extracted from 32-week-old male wild-type mice and 5×FAD transgenic Alzheimer’s disease model mice,which carry mutations in the amyloid precursor protein(APP)and presenilin 1(PS1)genes.Using untargeted lipidomics and sterolomics techniques,we investigated the metabolic profiles of lipids,with a focus on sterols specifically,in three brain regions:cerebellum,hippocampus,and olfactory bulb.Our results revealed significant alterations in various lipids,particularly in the hippocampus and olfactory bulb,suggesting changes in energy levels in these regions.Further pathway analysis indicated notable disruptions in key metabolic processes,particularly those related to fatty acids and cell membrane components.Additionally,we observed decreased expression of 15 genes involved in lipid and sterol regulation.Collectively,these findings provide new insights into how imbalances in lipid and sterol metabolism may contribute to the progression of Alzheimer’s disease,highlighting potential metabolic pathways involved in the development of this debilitating disease.
