Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway:a potential therapeutic approach for neurodegenerative diseases

The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain axis.The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine systems.Conversely,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host interactions.This reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological diseases.The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological diseases.This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological diseases.Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders.This can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage forms.These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

Small heat shock protein B8:from cell functions to its involvement in diseases and potential therapeutic applications

Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and migration.HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy.In line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and aggregation.In cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under investigation.Moreover,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar hemorrhage.Of note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other diseases.This is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial homeostasis.This review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its modulation.Drug-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.

Genetic factors that predict response and failure of biologic therapy in inflammatory bowel disease

Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.

New perspectives and prospects for the next generation of combination therapy in inflammatory bowel disease

This article comments on the letter by Lowell et al,which addresses the next generation of combination therapy for inflammatory bowel disease(IBD).As the understanding of the pathogenesis of IBD continues to improve,treatment strategies are evolving rapidly.The letter examines the current status and future directions of combination therapy for IBD,focusing on approaches that combine biologics with immunomodulators and the emerging dual-biologic therapy(DBT).The traditional combination of biologics and immunomodulators has demonstra-ted preliminary efficacy by enhancing the effects of biologics through immunomo-dulation.However,concerns regarding long-term safety warrant careful evalua-tion.Recent trials,including DUET-Crohn's disease and DUET-ulcerative colitis,have shown promising potential for the broader adoption of DBT.Nevertheless,comprehensive data on efficacy and safety,as well as the effective integration of supportive treatments,remain essential to establish new paradigms for the next generation of IBD care.

Periodontal disease:A silent factor in the development and progression of diabetic retinopathy

The global increase in the prevalence of type 2 diabetes mellitus(T2DM)and its complications presents significant challenges to public health.Recently,periodontal disease(PD)was recognized as a factor that is likely to influence the progression of T2DM and its complications due to its potential to exacerbate systemic inflammation and oxidative stress.In this editorial,we comment on the article published by Thazhe Poyil et al in the very recent issue of the World Journal of Diabetes in 2024,which investigated the correlation between PD and diabetic retinopathy(DR)in T2DM patients,with emphasis on the association between periodontal swollen surface area,glycated hemoglobin(HbA1c),interleukin-6(IL-6),and lipoprotein(a).The findings by Thazhe Poyil et al are significant as they demonstrate a strong link between PD and DR in T2DM patients.This correlation highlights the importance of addressing periodontal health in diabetes management to potentially reduce the risk and severity of DR,a complication of diabetes.The integration of periodontal evaluation and treatment into diabetes care protocols may lead to improved glycemic control and better overall outcomes for T2DM patients.A few studies have established an interconnection between PD and diabetic complication,specifically DR,in T2DM patients,which we aim to highlight in this editorial.Emphasis was placed on the different mechanisms that suggest a bidirectional relationship between PD and T2DM,where the presence of periodontal inflammation negatively influenced glycemic control and contributed to the development and progression of DR through shared inflammatory and vascular mechanisms.This article highlights the importance of collaboration amongst diabetes specialists,ophthalmologists,periodontists,and public health professionals to advance the prevention,early detection,and treatment of PD and DR.This will improve the health and quality of life of T2DM patients.Moreover,the editorial highlights the need for further research on the specific molecular and immunological mechanisms that underlie the link between periodontitis and DR,with identification of common inflammatory biomarkers and signaling pathways.This is expected to facilitate effective direction of therapeutic objectives,thereby improving the management of diabetes and its complications through integrated care that incorporates oral health.

Interleukin-mediated therapies in liver diseases and comorbidity effects

Cytokines like interleukins(ILs)play important roles in inflammation and innate immune.Yang and Zhang carried out an interesting study related to ILs and hepatic diseases.They described the role of ILs in the pathogenesis and resolution of hepatic disorders.The authors summarized alcohol-related liver disease and virus-induced hepatitis,as far as clinical studies a fortiori carried out on ILmediated treatments pertaining to these dysfunctions.This editorial contributes to the review by Yang and Zhang titled,"Interleukins in liver disease treatment",and focuses on therapies mediated by ILs in comorbid liver diseases.The documentary search was conducted on recent pertinent literature,primarily using the Google Scholar and PubMed databases.

Overview of emerging therapies for demyelinating diseases

This paper provides an overview of autoimmune disorders of the central nervous system,specifically those caused by demyelination.We explore new research regarding potential therapeutic interventions,particularly those aimed at inducing remyelination.Remyelination is a detailed process,involving many cell types–oligodendrocyte precursor cells(OPCs),astrocytes,and microglia–and both the innate and adaptive immune systems.Our discussion of this process includes the differentiation potential of neural stem cells,the function of adult OPCs,and the impact of molecular mediators on myelin repair.Emerging therapies are also explored,with mechanisms of action including the induction of OPC differentiation,the transplantation of mesenchymal stem cells,and the use of molecular mediators.Further,we discuss current medical advancements in relation to many myelin-related disorders,including multiple sclerosis,optic neuritis,neuromyelitis optica spectrum disorder,myelin oligodendrocyte glycoprotein antibodyassociated disease,transverse myelitis,and acute disseminated encephalomyelitis.Beyond these emerging systemic therapies,we also introduce the dimethyl fumarate/silk fibroin nerve conduit and its potential role in the treatment of peripheral nerve injuries.Despite these aforementioned scientific advancements,this paper maintains the need for ongoing research to deepen our understanding of demyelinating diseases and advance therapeutic strategies that enhance affected patients’quality of life.

Periodontal and inflammatory bowel diseases: Is there evidence of complex pathogenic interactions?

Periodontal disease and inflammatory bowel disease(IBD) are both chronic inflammatory diseases. Their pathogenesis is mediated by a complex interplay between a dysbiotic microbiota and the host immuneinflammatory response, and both are influenced by genetic and environmental factors. This review aimed to provide an overview of the evidence dealing with a possible pathogenic interaction between periodontal disease and IBD. There seems to be an increased prevalence of periodontal disease in patients with IBD when compared to healthy controls, probably due to changes in the oral microbiota and a higher inflammatory response. Moreover, the induction of periodontitis seems to result in gut dysbiosis and altered gut epithelial cell barrier function, which might contribute to the pathogenesis of IBD. Considering the complexity of both periodontal disease and IBD, it is very challenging to understand the possible pathways involved in their coexistence. In conclusion, this review points to a complex pathogenic interaction between periodontal disease and IBD, in which one disease might alter the composition of the microbiota and increase the inflammatory response related to the other. However, we still need more data derived from human studies to confirm results from murine models. Thus, mechanistic studies are definitely warranted to clarify this possible bidirectional association.

Periodontal treatment and microbiome-targeted therapy in management of periodontitis-related nonalcoholic fatty liver disease with oral and gut dysbiosis

A growing body of evidence from multiple areas proposes that periodontal disease,accompanied by oral inflammation and pathological changes in the microbiome,induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease(NAFLD).A subgroup of NAFLD patients have a severely progressive form,namely nonalcoholic steatohepatitis(NASH),which is characterized by histological findings that include inflammatory cell infiltration and fibrosis.NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma.The oral microbiota may serve as an endogenous reservoir for gut microbiota,and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis.Gut dysbiosis increases the production of potential hepatotoxins,including lipopolysaccharide,ethanol,and other volatile organic compounds such as acetone,phenol and cyclopentane.Moreover,gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall,leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation.In particular,many animal studies support that oral administration of Porphyromonas gingivalis,a typical periodontopathic bacterium,induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis.NAFLD,also known as the hepatic phenotype of metabolic syndrome,is strongly associated with metabolic complications,such as obesity and diabetes.Periodontal disease also has a bidirectional relationship with metabolic syndrome,and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively.In this review,we will describe the link between periodontal disease and NAFLD with a focus on basic,epidemiological,and clinical studies,and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome.In conclusion,it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease,gut microbiota,and metabolic syndrome.Thus,the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics,prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease.

The Clinical Effects of Allantoin Powder for Gargle on Periodontal Diseases and Aphthous Ulcer

A newly developed mouthrinse, Allantoin Powder for Gargle, was clinically investigated. The compound of this agent is mainly allantoin, which is believed easy to penetrate into gingival sulcus and periodontal pockets as well as other places (such as tongue, soft palate, etc.) where it is inconvenient to use medication, 219 patients with various diseases of oral cavity were investigated in the double blind randomlized placebo controlled study. It was observed that apparent efficient rates of the experimental mouthrinse on periodontitis and marginal gingivitis were 81.25% and 56.86% respectively; and the efficient rate of it on aphthous ulcer was 68.57%. The data show that this agent has effective as an adjuctive on the treatments of periodontal diseases and aphthous ulcer.

Influence of periodontitis and nonsurgical periodontal intervention on atherosclerosis diseases

Objective: Periodontitis and atherosclerosis diseases are chronic inflammatory disorders which are highly prevalent in populations. Nonsurgical periodontal intervention belongs to the initial therapy strategy to periodontal diseases. Periodontal pathogen can enter into blood stream through the ulceration epithelial resulting in bacteraemia when periodontitis is severe. The objective is to investigate the relationship between periodontitis and atherosclerosis diseases, and the influence of nonsurgical periodontal intervention on atheroma and atherosclerosis diseases. Methods: This study reviewed and analyzed the papers which published in the world associated with periodontitis or periodontal intervention on atherosclerosis diseases. Results: Periodontitis and periodontal infectious are important risk factors for atherosclerotic diseases. Much evidence has proved the durative severe periodontitis can result in bacteraemia and systemic inflammation, elevated C-response protein in serum, gingival microcirculation changed, periodontal microorganism reproduced, and endothelial dys-function and endocarditis. Nonsurgical periodontal intervention can remove the pathogenesis bacteria and calculus to recover periodontal health. Effective periodontal therapy can reduce bacteraemia and stop the hurt to vessels. Nonsurgical periodontal therapy may interfere periodontal bacteria, inhibit inflammation response and C-response protein, improving gingival microcirculation and vessel epithelial function to prevent atherosclerosis. Conclusion: Nonsurgical periodontal intervention can improve or decrease the rate of atherosclerotic disease by interfere the severe periodontitis. The detailed mechanism of periodontal intervention on atheroma and atherosclerotic disease is still need to be explored.

<i>Helicobacter Pylori</i>and Periodontal diseases: An update and proposal of a multidisciplinary clinical protocol

Helicobacter Pylori has been closely linked to chronic gastritis, peptic ulcers and increased risk of gastric carcinoma. Oral cavity, in particular dental plaque in periodontal pockets, may be a possible reservoir harboring H. Pylori, and may therefore be involved in the gastric reinfection by the bacterium, even after triple therapy regimen. This report is an update of scientific data showing the potential localization of H. Pylori in the oral cavity of periodontitis patients. A multidisciplinary clinical protocol combining full-mouth disinfection and triple therapy is also suggested. This protocol could permit to enhance oral H. Pylori eradication.

The Impact of Age and Gender on Severity and Types of Periodontal Diseases among Patients from Two Regions in Saudi Arabia

Background: Periodontitis is the predominant disease in the oral cavity and there are alterations in the periodontal tissues associated with the aging and gender of the patient. Objective: The present study was designed to assess the impact of age and gender of the patient on severity and types of periodontal diseases among patients from two regions in Saudi Arabia. Materials and Methods: The current study was done on 600 Saudi patients from Aseer and Tabuk regions in Saudi Arabia (50% males and 50% females) and divided into three equal groups (n = 200) according to the patients age: children and young patients (1 - 24 years old), adults patients (25 - 64 years old) and seniors patients (more than 65 years old). Plaque index (PLI), gingival index (GI), periodontal pocket depth (PPD) and clinical attachment loss (CAL) were recorded from all participants. The data were collected and analyzed with SPSS to determine the mean and standard deviation (±SD) and the values of significance (P ≤ 0.005). Results: The results of the present study revealed that 340 patients (56.7%) were affected with gingivitis dental biofilm induced and 260 patients were affected by periodontitis. Gingivitis dental biofilm-induced is especially detected in children and young patients (33.3%), adult patients (16.7%) and seniors patients (6.7%) whereas periodontitis cases were seen among the adult and seniors patients (16.7%) and (26.6%) respectively. Furthermore, the present study displayed the higher severity and prevalence of gingivitis dental biofilm-induced and periodontitis among females more than males in group II and group III maybe due to hormonal changes. The present study saw that there are statistically significant differences in clinical findings in the comparison between groups of this study (P ≤ 0.005). Conclusion: We conclude that there is a relation between severity and types of periodontal diseases and the ages and genders of Saudi patients in Aseer and Tabuk regions, Saudi Arabia.

Racial Differences Effects on Oral Health and Periodontal Diseases Extent, Staging and Grading among the Multi-Ethnic Expatriates in Aseer Region, Saudi Arabia

Background: Given the increase in the numbers of expatriates in Saudi Arabia and the shortage of information about expatriates’ oral health and periodontal disease severity and progression. Objectives: This study aimed to evaluate the effects of the racial differences on oral health and periodontal disease extent, staging, and grading among the multi-ethnic expatriates in the Aseer region, Saudi Arabia. Materials and Methods: This cross-sectional study was carried out on 300 expatriates in Aseer region, Saudi Arabia. They were divided into three equal racial different groups (n = 100), Arabs (AR), Asians (AS), and Africans (AF). The interviews of all participants were completed then the clinical examinations of periodontal diseases extent, staging, and grading parameters were performed. Statistical analysis was done by ANOVA test, Tukey’s test, and Chi-square test. The statistical significance level was determined at p < 0.05. Results: There were statistically significant differences in the comparison between the three ethnic/racial groups in clinical parameters except in GBI, PCR, FI, TFO, and BC, where there were no statistically significant differences in the comparison between the three ethnic/racial groups. There were differences associated with age, gender, smoking, and diabetes, without statistically significant differences among the three racial groups. Conclusion: We concluded that most participants in this study had a generalized severe grade 4 plaque-induced gingivitis and localized periodontitis stage III grade B.

Risks Factors of Caries and Periodontal Diseases in the Patients, after 5 Years Use a Partial Removable Denture

Objective: The goal of the removable partial denture is to restore impaired esthetics and masticatory function by replacing missing teeth. The aim of this study was to establish a possible correla-tion between removable partial denture in acrylic resin use after 5 years and dental diseases. Materials and Methods: Partially edentulous patients presenting for removable denture treatment at the Prosthodontics service of the Affiliated Hospital of Kinshasa University, Democratic Republic of Congo were assessed in this study. Patients were randomly assigned into 2 groups: Denture and non-denture group. Caries and periodontal diseases were compared between both groups. Statistical significance was set at p < 0.05. Results: The average age in the denture and non-denture-group was 53.15 (±SD 22.05) and 31.59 (±SD 11.98) years. Out of 160 teeth were decayed, both 110 teeth (68.75%) in the denture-group and 50 teeth (31.25%) in the non-denture group. The DMFT index calculated at start time of the study was 0.2 for both groups, after five years was 7.1 for the denture-group and 2.6 for the non-denture-group. The plaque index in the denture-group had an index of 1 and that of non-denture-group was 0.5. Conclusion: The relationship has been found between patients’ wearers a RPD and dental diseases.

Periodontal Diseases in Pregnant Women in Prenatal Consultation

Background: The relationship between pregnancy and periodontal health had well documented in the literature. Of many studies of periodontal diseases in the Democratic Republic of Congo, no study had evaluated these diseases in pregnant women during Prenatal Consultation (PC). This study aimed to describe the occurrence and clinical profile of periodontal diseases in pregnant women admitted to the PC at the General Military Hospital of BOBILA. Materials and Methods: It is a cross-sectional and analytical study of pregnant women admitted to the PC from August to December 31, 2018, at the General Reference Military Hospital of BOBILA/Kinshasa City. The data were collected through a survey combined with the stomatological interview. Sociodemographic data, clinical and periodontal indices included Oral Hygiene Index Simplified (OHI-S), Bleeding on Probing (BOP), and Periodontal Disease Index (PDI) were assessed. The statistical analyses were carried out using the SPSS version 20.0 software. The Chi-square tests, Student t-test were used to determine differences in the distribution of variables, and the odd Ratio with a confidence interval (IC) at 95% was used to estimate the degree of association. The results were significant at p < 0.05. Results: Of the 105 pregnant women received at the PC, 83 were included in this study. The age group between 20 - 29 was the most represented, with a predominance of stay-at-home mothers (75.9%) and married cases (73.4%), they had an average economic status (56.6%) and a secondary education level (63.8%). Gingival bleeding (44.6%) was the main complaint of the pregnant. Gestational age was a significant factor associated with gum bleeding (p < 0.005). Most of the pregnant had poor oral hygiene, localized gravidities (69.6%) during the third semester. Conclusion: A significant proportion of women had experienced periodontal diseases during the pregnancy period, mostly in the third trimester, and was associated with a gestational age of pregnant women.

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

Pathological and therapeutic effects of extracellular vesicles in neurological and neurodegenerative diseases

Extracellular vesicles are released by all cell types and contain proteins,microRNAs,mRNAs,and other bioactive molecules.Extracellular vesicles play an important role in intercellular communication and in the modulation of the immune system and neuroinflammation.The cargo of extra cellular vesicles(e.g.,proteins and microRNAs)is altered in pathological situations.Extracellular vesicles contribute to the pathogenesis of many pathologies associated with sustained inflammation and neuroinflammation,including cance r,diabetes,hype rammonemia and hepatic encephalopathy,and other neurological and neurodegenerative diseases.Extracellular vesicles may cross the blood-brain barrier and transfer pathological signals from the periphery to the brain.This contributes to inducing neuroinflammation and cognitive and motor impairment in hyperammonemia and hepatic encephalopathy and in neurodegenerative diseases.The mechanisms involved are beginning to be unde rstood.For example,increased tumor necrosis factor a in extracellular vesicles from plasma of hype rammonemic rats induces neuroinflammation and motor impairment when injected into normal rats.Identifying the mechanisms by which extracellular vesicles contribute to the pathogenesis of these diseases will help to develop new treatments and diagnostic tools for their easy and early detection.In contrast,extra cellular vesicles from mesenchymal stem cells have therapeutic utility in many of the above pathologies,by reducing inflammation and neuroinflammation and improving cognitive and motor function.These extra cellular vesicles recapitulate the beneficial effects of mesenchymal stem cells and have advantages as therapeutic tools:they are less immunoge nic,may not diffe rentiate to malignant cells,cross the blood-brain barrier,and may reach more easily target organs.Extracellular vesicles from mesenchymal stem cells have beneficial effects in models of ischemic brain injury,Alzheimer's and Parkinson's diseases,hyperammonemia,and hepatic encephalopathy.Extracellular vesicles from mesenchymal stem cells modulate the immune system,promoting the shift from a pro-inflammato ry to an anti-inflammatory state.For example,extracellular vesicles from mesenchymal stem cells modulate the Th17/Treg balance,promoting the anti-inflammatory Treg.Extracellular vesicles from mesenchymal stem cells may also act directly in the brain to modulate microglia activation,promoting a shift from a pro-inflammatory to an anti-inflammatory state.This reduces neuroinflammation and improves cognitive and motor function.Two main components of extracellular vesicles from mesenchymal stem cells which contribute to these beneficial effects are transforming growth factor-βand miR-124.Identifying the mechanisms by which extracellular vesicles from mesenchymal stem cells induce the beneficial effects and the main molecules(e.g.,proteins and mRNAs)involved may help to improve their therapeutic utility.The aims of this review are to summarize the knowledge of the pathological effects of extracellular vesicles in different pathologies,the therapeutic potential of extra cellular vesicles from mesenchymal stem cells to recover cognitive and motor function and the molecular mechanisms for these beneficial effects on neurological function.

Cell reprogramming therapy for Parkinson’s disease

Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.

Meta-analysis of the association between chronic periodontitis and chronic kidney disease

BACKGROUND Many scholars have performed several clinical studies have investigated the association between chronic periodontitis(CP)and chronic kidney disease(CKD).However,there are still differences between these research results,and there is no unified conclusion.Therefore,a systematic review is required to understand this issue fully.AIM To explore the correlation between CP and CKD.METHODS Literature on the correlation between CP and CKD,as well as the clinical attachment level(CAL)and pocket probing depth(PPD)of CKD and non-CKD,were retrieved from PubMed,Embase,the Cochrane Library,and Web of Science repositories until January 2024.After the effective data were extracted,data processing and statistics were performed using Stata 12.0.RESULTS Of the 22 studies,13 were related to CP and CKD,and 9 reported CAL and PPD in patients with CKD and healthy controls.Meta-analysis of the correlation between CP and CKD revealed that CKD probability in people with CP was 1.54 times that of healthy individuals[relative risk=1.54,95%confidence interval(CI):1.40-1.70],and CP incidence in patients with CKD was 1.98 times that of healthy individuals[overall risk(OR)=1.98,95%CI:1.53-2.57].Meta-analysis of CAL and PPD evaluations between CKD patients and healthy individuals showed that CAL and PPD levels were higher in CKD patients[standard mean difference(SMD)of CAL=0.65,95%CI:0.29-1.01;SMD of PPD=0.33,95%CI:0.02-0.63].CONCLUSION A bidirectional association exists between CP and CKD.CKD risk is increased in CP patients and vice versa.Periodontal tissue or tooth loss risks increase over time in CKD patients.