Slow Disease Progression Research Articles (Page 1)

Introduction: Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative disorders, causing progressive cognitive and motor decline. High rates of new diagnoses, coupled with increasing evidence linking gastrointestinal (GI) dysfunction to neurodegeneration, highlight the significance of understanding the gut-brain axis (GBA). Changes in gut microbiota composition are associated with amyloid-beta accumulation in AD and α-synuclein aggregation in PD, suggesting that gut dysbiosis and inflammation may worsen disease pathology. Methods: A systematic literature review was conducted using peer-reviewed primary research articles published between 2014 and 2025. Articles were selected based on their relevance to GI inflammation, gut microbiota dysbiosis, and neurodegenerative diseases. Studies involving human participants and relevant animal models were prioritized. Databases searched included PubMed, Google Scholar, ScienceDirect, JSTOR, and SpringerLink. Results: Gut dysbiosis was consistently associated with increased intestinal permeability, systemic inflammation, and neuroinflammatory responses in AD and PD. Specific microbial imbalances correlated with accelerated disease progression and cognitive decline. Animal studies demonstrated that fecal microbiota transplantation from diseased individuals worsened motor and mental symptoms, while interventions targeting gut health, such as probiotics and dietary modifications, reduced neuroinflammation and improved outcomes. Discussion: Findings support the GBA’s critical role in mediating neurodegeneration through immune activation and inflammatory pathways. Dysbiosis-induced changes in microbial metabolite production, including short-chain fatty acids (SCFAs) and tryptophan derivatives, further contribute to neuroinflammatory processes. Despite promising preclinical results, challenges remain in translating gut-targeted therapies to clinical use due to variability in individual microbiomes and limited longitudinal human data. Conclusion: This review emphasizes the gut microbiota as a modifiable factor in the pathogenesis of AD and PD. Targeting GI inflammation and restoring microbial balance may offer novel therapeutic strategies for slowing disease progression. Future research should focus on validating gut-derived biomarkers, personalizing microbiome-based treatments, and conducting longitudinal clinical trials to optimize gut-brain interventions in neurodegenerative diseases.

Introduction: Following infarction, heart often undergoes pathological remodeling and dysregulation of sodium and calcium homeostasis, predisposing patients to heart failure and arrhythmias. While current pharmacological therapies can slow disease progression, they are not aimed to directly address deficits in both cardiac contraction and action potential conduction. Previously, we have demonstrated that AAV-mediated gene therapy with the prokaryotic voltage-gated sodium channel (BacNav) can restore cardiac electrical and mechanical function in a setting of pressure-overload heart failure. Hypothesis: We hypothesized that AAV-BacNav gene therapy could rescue contractile and electrical dysfunction in a clinically relevant setting of chronic post-myocardial infarction. Method: 8-to-10-week-old male rats underwent a 45-min left anterior descending artery ligation followed by reperfusion. Two weeks after the ischemia/reperfusion surgery, we delivered a total of 1E12 viral genomes of either myo2A-cTnT-BacNav-HA-mScarlet (BacNav group) or myo2A-cTnT-mScarlet (mock group) via direct injection around the scar area in the left ventricle (a total of 200uL, split into 6-8 sites) (n=3 for BacNav group, n=5 for mock group). Cardiac contractile and electrical function was non-invasively monitored over the following four weeks using echocardiography and electrocardiography, respectively, followed by ex vivo epicardial voltage mapping in Langendorff-perfused hearts. Results: At 2 weeks post-surgery, all rats exhibited left ventricular ejection fraction (LVEF) reduction (BacNav: 46.45+/-3.81%; mock: 50.92+/-2.50%). The LVEF continued to deteriorate in the mock group during the following 4 weeks, while in the BacNav group it significantly improved (BacNav: 54.71+/-3.26%; mock: 42.66+/-3.34%). While both groups exhibited rare incidences of spontaneous arrhythmias in ECG, the BacNav group had reduced cardiac axis deviation (BacNav: 37.53-69.18°; mock: -152.14-135.54°). Ex vivo epicardial voltage mapping to test for arrhythmia vulnerability revealed spontaneous reentry in 100% of mock group hearts, compared to only 33.3% in the BacNav group. Conclusion: AAV-BacNav therapy significantly improved both contractile and electrical function in a rat model of ischemia-reperfusion heart failure, providing foundation for the future translational studies.

Degenerative retinal diseases, such as diabetic retinopathy, age-related macular degeneration (AMD), and retinitis pigmentosa, cause irreversible vision loss by destroying vital retinal cells and represent major global health concerns. Traditional therapies have limited success in fully restoring vision due to the complex retinal structure and blood-retinal barriers (BRBs), though they may help alleviate symptoms or slow disease progression in some cases. Nanochemistry and peptide-based systems represent breakthrough approaches by leveraging nanoscale precision and biological specificity. This review examines the chemical design and synthesis of nanoparticles (NPs), nanoscaffolds, and peptide conjugates used in retinal neural regeneration. It also explores their biomedical applications, especially in targeted drug delivery, tissue engineering, and cellular repair. Biodegradable polymeric NPs, liposomes, and hybrid nanostructures are designed to cross barriers, release drugs in a controlled manner, and enhance biocompatibility. PEGylation improves stability and reduces immune responses in the ocular environment, while peptide functionalization enables specific cellular targeting and minimizes inflammatory reactions. Peptide-functionalized platforms, such as RGD-modified NPs and self-assembling hydrogels, provide receptor-mediated targeting and extracellular matrix (ECM) mimicry to support retinal regeneration for improved stem cell differentiation and neuroprotection. We discuss drug/gene delivery mechanisms, cellular interactions, and immune modulation, as well as neuroprotection, stem cell therapy, and diagnostic applications. Preclinical studies have demonstrated promising efficacy in animal models; however, concerns regarding scalability, long-term safety, and non-invasive delivery persist. Next-generation technologies, such as stimuli-responsive NPs, computationally designed peptides, and patient-specific delivery systems, are on the horizon to address unmet clinical needs. By marrying nanochemistry's precision with peptides' bioactivity, these technologies have the potential to transform retinal disease treatment, enabling the restoration of vision and an improvement in quality of life for millions of people worldwide.

Chronic kidney disease (CKD) is an irreversible and progressive kidney disease with a significant global health impact. Sarcopenia is an age-related syndrome characterized by the progressive loss of skeletal muscle mass and strength, and it exhibits a high prevalence, particularly among the elderly. There is a growing body of evidence indicating a strong bidirectional association between CKD and Sarcopenia. The prevalence of sarcopenia is significantly higher in CKD patients and increases as kidney function deteriorates. This review examines the potential relationship between CKD and sarcopenia, discusses their pathophysiological mechanisms, including chronic inflammation, oxidative stress, uremic toxin accumulation, metabolic acidosis, and hormonal disorders, and explores their clinical implications. Additionally, this review aims to elucidate potential pathogenic mechanisms and propose preventive and therapeutic strategies for CKD and sarcopenia, thereby guiding the optimization of clinical management and slowing disease progression.

Background: Patients with hereditary transthyretin amyloidosis (ATTRv) are often referred for cardiac evaluation, resulting in a primary focus on transthyretin amyloid cardiomyopathy (ATTR-CM). However, many with variants linked to ATTR-CM also experience polyneuropathy (ATTRv-PN). Neurological assessment is often overlooked, missing key opportunities to slow disease progression and maximize quality of life. This program aimed to improve workflows and strengthen multidisciplinary coordination for patients with ATTRv-PN. Research Question: Can implementing structured workflow processes improve early PN screening, care coordination, and patient-centered management for individuals with ATTRv-PN? Methods: Cardiologists and neurologists from three amyloidosis centers participated in focus groups and completed baseline surveys (N=34) from February to December 2023. Teams engaged in audit-feedback sessions, completed pre- and post-activity surveys, reviewed performance data, and developed action plans. Clinic champions participating in the program completed follow-up surveys (N=6). Each site conducted baseline (N=151) and follow-up (N=150) chart audits. Chi-square tests were used for statistical comparisons. Results: Chart audits performed before and after the audit-feedback sessions showed PN screening to support ATTRv diagnosis increased from 10% at baseline to 57% at follow-up (P <0.001). PN screening at any time during care rose from 38% to 76% (P <0.001). Baseline provider surveys revealed 13% of institutions had protocols for neurological workup, 33% had diagnostic protocols, and 40% lacked ATTRv protocols altogether. Documentation of ATTRv management strategies improved from 31% to 86% (P <0.001). Shared decision-making documentation also increased, including discussions on goals of ATTRv care (56% to 79%, P <0.001) and patient barriers (46% to 71%, P <0.001). After the program, 83% of providers reported improved collaboration between cardiology and neurology, and 100% noted more consistent evaluation for ATTRv-PN symptoms. Strategies linked to these improvements included use of a PN screening questionnaire for new referrals, neurology referrals for all patients with ATTRv, and baseline screening for presymptomatic patients. Conclusion: Practical structured workflow strategies can be implemented by amyloidosis centers to enhance early PN screening, patient-centered care, and multidisciplinary collaboration, ultimately improving care for patients with ATTRv-PN.

Background Qing-Re-Xiao-Zheng-Yi-Qi formula (QRXZYQF), based on the "Shen-Luo-Zheng-Jia" principles of traditional Chinese medicine, has been reported to reduce 24-hour urinary total protein in diabetic kidney disease (DKD) patients, slow disease progression, and improve podocyte injury. This study aims to explore the mechanisms of QRXZYQF in improving podocyte injury. Methods Diabetes was induced in male C57BL/6J mice by intraperitoneal injection of streptozotocin (STZ). After 12 weeks of QRXZYQF, blood glucose, blood urea nitrogen, serum creatinine, microalbumin, and the urinary albumin-to-creatinine ratio (UACR) were monitored. Renal pathological changes were evaluated using hematoxylin and eosin (H&E), Masson, and periodic acid–Schiff (PAS) staining. RNA sequencing (RNA-Seq) was performed to identify differences in renal mRNA expression and enrichment pathways. The involvement of autophagy–lysosomal and NOD-like receptor pathways was examined by western blotting and immunofluorescence in renal tissues and cultured podocytes. Results Following 12 weeks of QRXZYQF, renal function improved and ECM accumulation and glomerulosclerosis were markedly reduced. Subsequently, RNA-Seq analysis showed that the autophagy–lysosomal and NOD-like receptor signaling pathways were the potential pathways involved in the mechanism of QRXZYQF. Moreover, QRXZYQF reduced the levels of NLRP3, apoptosis-associated speck-like protein (ASC), as well as Caspase-1 in vitro. Furthermore, we performed interventions using the lysosomal membrane-permeabilizing agent (L-leucyl-L-leucine-O-methylester) and found that QRXZYQF inhibits NLRP3 overexpression by protecting lysosomal membranes and preventing the leakage of Cathepsin B (CB) into the cytoplasm. Conclusions QRXZYQF inhibits NLRP3-mediated podocyte pyroptosis by stabilizing lysosomal membranes, providing insights into its protective mechanism and potential therapeutic targets for DKD.

DNA damage activates the DNA damage response (DDR) machinery. However, aging impairs DDR in neurons, thereby increasing susceptibility to neurodegenerative diseases, such as Huntington’s disease (HD). The mutant huntingtin (mHTT) protein interferes with DNA repair, leading to DNA lesions and a feedback loop of cellular stress that accelerates neurodegeneration. Although the individual roles of FBXW7, ATM, and checkpoint kinase (CHK) are well-known in DDR, their combined roles in HD remain unclear. In this study, we investigated the FBXW7-mediated CHK2 pathway in HD, in which mHTT levels increase, whereas wild-type (WT) HTT levels decrease. HD cells containing mHTT or expanded polyQ-HTT were more prone to DNA damage than cells containing wtHTT or normal-length polyQ, demonstrating the increased vulnerability of HD neurons. Downregulating the expression of FBXW7 reduces susceptibility to DNA damage and promotes cellular stability. Additionally, FBXW7 specifically prevented CHK2 degradation, but not CHK1 degradation. This suggests a selective role in DDR regulation. Thus, the FBXW7-CHK2 pathway may alleviate DNA damage in HD by supporting DDR and inducing cell cycle arrest. The intricate relationship between DDR and HTT is fundamental to the pathophysiology of HD. Elucidating these mechanisms could facilitate the development of new therapeutic strategies that enhance DNA repair or correct DDR dysfunction, thereby slowing disease progression or delaying symptom onset. Understanding this pathway may provide insights into the targeting of DNA repair defects in HD and related neurodegenerative disorders.

Effect of Origanum majorana tea on oxidative stress biomarkers in Parkinson's disease: a randomized placebo-controlled pilot study.

Molecular mechanisms by which mitochondrial dysfunction drives neuromuscular junction degeneration in amyotrophic lateral sclerosis.

Recent Advances in Primary Biliary Cholangitis Treatment.

Moderate-intensity exercise attenuates bone loss in hyperuricemic nephropathic mice.

The immunoregulatory function and therapeutic potential of tetrandrine in connective tissue disease-associated interstitial lung disease.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to progressive muscle weakness and paralysis. Approximately 10% of ALS cases are familial (FALS), with the VAPB gene's P56S pathogenic variant being notably prevalent in Brazilian families, contributing to the rare ALS8. This variant progresses more slowly than typical ALS, with distinct clinical features.To identify VAPB gene pathogenic variants in Brazilian FALS patients, particularly the P56S pathogenic variant associated with ALS8 and explore its clinical presentation and progression.Twelve FALS patients from 12 unrelated families in Rio de Janeiro were included in the study between 2023 and 2024. Clinical, laboratory, and electrophysiological data were reviewed. Collection of DNA samples happened via oral swabs, and VAPB gene sequencing was performed to identify pathogenic variants, specifically the P56S variant linked to ALS8.There were 3 cases of the P56S pathogenic variant, all presenting ALS8 with symptom onset in the lower limbs and slower disease progression. A family with 11 affected members across four generations showed an autosomal dominant inheritance pattern, with varying survival rates, highlighting its clinical variability.The present study underscores the importance of genetic screening for ALS subtypes, particularly ALS8, in Brazil. Identifying the P56S pathogenic variant enhances our understanding of ALS's genetic diversity and clinical presentation, offering a foundation for improved diagnostic practices and personalized care.

The potential role of misfolded wild-type SOD1 protein in sporadic amyotrophic lateral sclerosis (ALS): a review of the evidence.

A Gly-β-muricholic acid and FGF15 combination therapy synergistically reduces "humanized" bile acid pool toxicity in cholestasis mice.

Mesenchymal stem cells in clinical trials for multiple sclerosis: A systematic literature review and review of clinical trials.

The prospects and challenges of small molecule drugs in the treatment of Duchenne muscular dystrophy.

Metabolic reprogramming of glial cells: Fatty acid pathways as regulators of remyelination in multiple sclerosis.

Effects of Empagliflozin on Urine Biomarkers in EMPA-KIDNEY.

Treatment of neurodegenerative diseases aims to slow disease progression, alleviate symptoms, and improve life quality. Adipose-Derived Stem Cells (ADSCs) have emerged as a promising treatment for neurodegenerative diseases that can be easily obtained from adipose tissues. Their abundance, accessibility, and potential for multilinear differentiation make them an attractive candidate for regenerative medicine. ADSCs can release neurotrophic factors, modulate neuroinflammation, and potentially differentiate into neurons, giving hope for neuronal repair and replacement. Preclinical studies have shown the efficacy of several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and spinal cord injuries. ADSC has demonstrated the potential to improve functional results, promote neurogenesis, induce tissue integrity, and reduce neuron loss. Clinical trials are still underway, but evidence of the effectiveness of ADSC in neurodegeneration is still being developed. The first clinical studies focused on safety and feasibility and achieved promising results. Optimizing cell transmission, controlling tumor growth, standardizing treatment protocols and such challenges remain. Current research is aimed at addressing these obstacles and transforming ADSC therapy into a widespread clinical practice. This review focuses on the characteristics, problems, and future approaches of ADSC in the context of neurodegenerative diseases and therapeutic processes.