Surgery for Peyronie＇s disease

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.

Corporoplasty with small soft axial prostheses （VIRILIS ） and bovine pericardial graft （HYDRIX） in Peyronie＇s disease

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.

Extracorporeal shockwave therapy for Peyronie＇s disease： an alternative treatment？

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.

Surgical treatment of Peyronie＇s disease： choosing the best approach to improve patient satisfaction

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.

Non-surgical therapy of Peyronie＇s disease

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.

Tunica albuginea allograft： a new model of LaPeyronie＇s disease with penile curvature and subtunical ossification

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.

Penile prosthesis implantation and tunica albuginea incision without grafting in the treatment of Peyronie＇s disease with erectile dysfunction

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.

Pentoxifylline treatment and penile calcifications in men Nith Peyronie＇s disease

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.

Long-term results of the surgical treatment of Peyronie＇s disease with Egydio＇s technique： a European multicentre study

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.

OJU Peyronie’s Disease in an Elderly Ghanaian Gentleman—A Case-Report and Literature Review

Background: Peyronie’s disease is characterized by fibrous plaque formation in the tunica albuginea, leading to penile curvature and sexual dysfunction. Surgical correction is often required in cases of severe deformity or significant functional impairment. Aim: To present the case of a patient with severe Peyronie’s disease who underwent surgical correction using an autologous fascia lata graft. Case Presentation: We report the case of a 77-year-old Black-African gentleman with Peyronie’s disease, presenting with a self-reported penile curvature of 70 degrees and significant sexual frustration. He was managed surgically with plaque excision followed by a tunica albuginea patch using a subcutaneously harvested autologous fascia lata graft, all performed in a single surgical session. Conclusion: This case highlights the importance of individualized surgical planning and patient-specific considerations in achieving optimal outcomes in the management of Peyronie’s disease, particularly in cases requiring grafting for severe curvature.

The role of exosomes in adult neurogenesis:implications for neurodegenerative diseases

Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.

Mitophagy in neurodegenerative disease pathogenesis

Mitochondria are critical cellular energy resources and are central to the life of the neuron.Mitophagy selectively clears damaged or dysfunctional mitochondria through autophagic machinery to maintain mitochondrial quality control and homeostasis.Mature neurons are postmitotic and consume substantial energy,thus require highly efficient mitophagy pathways to turn over damaged or dysfunctional mitochondria.Recent evidence indicates that mitophagy is pivotal to the pathogenesis of neurological diseases.However,more work is needed to study mitophagy pathway components as potential therapeutic targets.In this review,we briefly discuss the characteristics of nonselective autophagy and selective autophagy,including ERphagy,aggrephagy,and mitophagy.We then introduce the mechanisms of Parkin-dependent and Parkin-independent mitophagy pathways under physiological conditions.Next,we summarize the diverse repertoire of mitochondrial membrane receptors and phospholipids that mediate mitophagy.Importantly,we review the critical role of mitophagy in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.Last,we discuss recent studies considering mitophagy as a potential therapeutic target for treating neurodegenerative diseases.Together,our review may provide novel views to better understand the roles of mitophagy in neurodegenerative disease pathogenesis.

Targeting tau in Alzheimer's disease:from mechanisms to clinical therapy

Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older adults.Primary features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neurofibrillary tangles,fo rmed by tau protein,in the cells.While there are amyloid-β-ta rgeting therapies for the treatment of Alzheimer’s disease,these therapies are costly and exhibit potential negative side effects.Mounting evidence suggests significant involvement of tau protein in Alzheimer’s disease-related neurodegeneration.As an important microtubule-associated protein,tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal growth.In fact,clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-βin the brain.Various therapeutic strategies targeting tau protein have begun to emerge,and are considered possible methods to prevent and treat Alzheimer’s disease.Specifically,abnormalities in post-translational modifications of the tau protein,including aberrant phosphorylation,ubiquitination,small ubiquitin-like modifier(SUMO)ylation,acetylation,and truncation,contribute to its microtubule dissociation,misfolding,and subcellular missorting.This causes mitochondrial damage,synaptic impairments,gliosis,and neuroinflammation,eventually leading to neurodegeneration and cognitive deficits.This review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer’s disease and discusses tau-targeted treatment of Alzheimer’s disease.

Olfactory dysfunction and its related molecular mechanisms in Parkinson’s disease

Changes in olfactory function are considered to be early biomarkers of Parkinson’s disease.Olfactory dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients with early-stage Parkinson’s disease,and can often predate the diagnosis by years.Therefore,olfactory dysfunction should be considered a reliable marker of the disease.However,the mechanisms responsible for olfactory dysfunction are currently unknown.In this article,we clearly explain the pathology and medical definition of olfactory function as a biomarker for early-stage Parkinson’s disease.On the basis of the findings of clinical olfactory function tests and animal model experiments as well as neurotransmitter expression levels,we further characterize the relationship between olfactory dysfunction and neurodegenerative diseases as well as the molecular mechanisms underlying olfactory dysfunction in the pathology of early-stage Parkinson’s disease.The findings highlighted in this review suggest that olfactory dysfunction is an important biomarker for preclinical-stage Parkinson’s disease.Therefore,therapeutic drugs targeting non-motor symptoms such as olfactory dysfunction in the early stage of Parkinson’s disease may prevent or delay dopaminergic neurodegeneration and reduce motor symptoms,highlighting the potential of identifying effective targets for treating Parkinson’s disease by inhibiting the deterioration of olfactory dysfunction.

Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.

Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease

Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease.Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae Semen on Alzheimer’s disease remains unelucidated.In the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated.Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy.In addition,Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo model.Moreover,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent.Most importantly,Citri Reticulatae Semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease mice.As revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.

Antisense therapy:a potential breakthrough in the treatment of neurodegenerative diseases

Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and this means a heavy burden for patients and the health system worldwide.Therefore,it is necessary to find new therapeutic approaches,and antisense therapies offer this possibility,having the great advantage of not modifying cellular genome and potentially being safer.Many preclinical and clinical studies aim to test the safety and effectiveness of antisense therapies in the treatment of neurodegenerative diseases.The objective of this review is to summarize the recent advances in the development of these new technologies to treat the most common neurodegenerative diseases,with a focus on those antisense therapies that have already received the approval of the U.S.Food and Drug Administration.

Predicting short-term major postoperative complications in intestinal resection for Crohn’s disease:A machine learning-based study

BACKGROUND Due to the complexity and numerous comorbidities associated with Crohn’s disease(CD),the incidence of postoperative complications is high,significantly impacting the recovery and prognosis of patients.Consequently,additional stu-dies are required to precisely predict short-term major complications following intestinal resection(IR),aiding surgical decision-making and optimizing patient care.AIM To construct novel models based on machine learning(ML)to predict short-term major postoperative complications in patients with CD following IR.METHODS A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022.The study participants were randomly allocated to either a training cohort or a validation cohort.The logistic regression and random forest(RF)were applied to construct models in the training cohort,with model discrimination evaluated using the area under the curves(AUC).The validation cohort assessed the performance of the constructed models.RESULTS Out of the 259 patients encompassed in the study,5.0%encountered major postoperative complications(Clavien-Dindo≥III)within 30 d following IR for CD.The AUC for the logistic model was 0.916,significantly lower than the AUC of 0.965 for the RF model.The logistic model incorporated a preoperative CD activity index(CDAI)of≥220,a diminished preoperative serum albumin level,conversion to laparotomy surgery,and an extended operation time.A nomogram for the logistic model was plotted.Except for the surgical approach,the other three variables ranked among the top four important variables in the novel ML model.CONCLUSION Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complic-ations in patients with CD,with the RF model showing more superiority.A preoperative CDAI of≥220,a di-minished preoperative serum albumin level,and an extended operation time might be the most crucial variables.The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

Neural stem cells promote neuroplasticity: a promising therapeutic strategy for the treatment of Alzheimer’s disease

Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s disease.Hence,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be alleviated.Due to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to plasticity.These events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian brain.Consequently,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative diseases.In this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.