Exploring regulatory mechanisms on miRNAs and their implications in inflammation-related diseases.

This comprehensive exploration delves into the pivotal role of microRNAs (miRNAs) within the intricate tapestry of cellular regulation. As potent orchestrators of gene expression, miRNAs exhibit diverse functions in cellular processes, extending their influence from the nucleus to the cytoplasm. The complex journey of miRNA biogenesis, involving transcription, processing, and integration into the RNA-induced silencing complex, showcases their versatility. In the cytoplasm, mature miRNAs finely tune cellular functions by modulating target mRNA expression, while their reach extends into the nucleus, influencing transcriptional regulation and epigenetic modifications. Dysregulation of miRNAs becomes apparent in various pathologies, such as cancer, autoimmune diseases, and inflammatory conditions. The adaptability of miRNAs to environmental signals, interactions with transcription factors, and involvement in intricate regulatory networks underscore their significance. DNA methylation and histone modifications adds depth to understanding the dynamic regulation of miRNAs. Mechanisms like competition with RNA-binding proteins, sponging, and the control of miRNA levels through degradation and editing contribute to this complex regulation process. In this review, we mainly focus on how dysregulation of miRNA expression can be related with skin-related autoimmune and autoinflammatory diseases, arthritis, cardiovascular diseases, inflammatory bowel disease, autoimmune and autoinflammatory diseases, and neurodegenerative disorders. We also emphasize the multifaceted roles of miRNAs, urging continued research to unravel their complexities. The mechanisms governing miRNA functions promise advancements in therapeutic interventions and enhanced insights into cellular dynamics in health and disease.

Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions.

Advancing age is associated with several age-related diseases (ARDs), with musculoskeletal conditions impacting millions of elderly people worldwide. With orthopedic conditions contributing towards considerable number of patients, a deeper understanding of bone aging is the need of the hour. One of the underlying factors of bone aging is cellular senescence and its associated senescence associated secretory phenotype (SASP). SASP comprises of pro-inflammatory markers, cytokines and chemokines that arrest cell growth and development. The accumulation of SASP over several years leads to chronic low-grade inflammation with advancing age, also known as inflammaging. The pathways and molecular mechanisms focused on bone senescence and inflammaging are currently limited but are increasingly being explored. Most of the genes, pathways and mechanisms involved in senescence and inflammaging coincide with those associated with cancer and other ARDs like osteoarthritis (OA). Thus, exploring these pathways using techniques like sequencing, identifying these factors and combatting them with the most suitable approach are crucial for healthy aging and the early detection of ARDs. Several approaches can be used to aid regeneration and reduce senescence in the bone. These may be pharmacological, non-pharmacological and lifestyle interventions. With increasing evidence towards the intricate relationship between aging, senescence, inflammation and ARDs, these approaches may also be used as anti-aging strategies for the aging bone marrow (BM).

Cuproptosis and Cu: a new paradigm in cellular death and their role in non-cancerous diseases.

Cuproptosis, a newly characterized form of regulated cell death driven by copper accumulation, has emerged as a significant mechanism underlying various non-cancerous diseases. This review delves into the complex interplay between copper metabolism and the pathogenesis of conditions such as Wilson's disease (WD), neurodegenerative disorders, and cardiovascular pathologies. We examine the molecular mechanisms by which copper dysregulation induces cuproptosis, highlighting the pivotal roles of key copper transporters and enzymes. Additionally, we evaluate the therapeutic potential of copper chelation strategies, which have shown promise in experimental models by mitigating copper-induced cellular damage and restoring physiological homeostasis. Through a comprehensive synthesis of recent advancements and current knowledge, this review underscores the necessity of further research to translate these findings into clinical applications. The ultimate goal is to harness the therapeutic potential of targeting cuproptosis, thereby improving disease management and patient outcomes in non-cancerous conditions associated with copper dysregulation.

A novel treatment approach using vitamin B12-conjugated sericin for mitigating nanodiamond-induced toxicity in darkling beetles.

The escalating use of nanodiamonds (NDs) has raised concerns about their ecotoxicological impact, prompting exploration of therapeutic interventions. This paper pioneers the examination of Vitamin B12-conjugated sericin (VB12-SER) as a potential therapeutic approach against ND-induced toxicity in darkling beetles (Blaps polychresta). The study analyzes mortality rates and organ-specific effects, covering the testis, ovary, and midgut, before and after treatments. Following exposure to 10 mg NDs/g body weight, within a subgroup of individuals termed ND2 with a mortality rate below 50%, two therapeutic treatments were administered, including pure sericin (SER) at 10 mg/mL and VB12-SER at 10.12 mg/mL. Consequently, five experimental groups (control, SER, ND2, ND2+SER, ND2+SER+VB12) were considered. Kaplan-Meier survival analysis was performed to assess the lifespan distribution of the insects in these groups over a 30-d period. Analyses revealed increased mortality and significant abnormalities induced by NDs within the examined organs, including cell death, DNA damage, enzyme dysregulation, antioxidant imbalances, protein depletion, lipid peroxidation, and morphological deformities. In contrast, the proposed treatments, especially (ND2+SER+VB12), demonstrated remarkable recovery, highlighting VB12-conjugated SER's potential in mitigating ND-triggered adverse effects. Molecular docking simulations affirmed binding stability and favorable interactions of the VB12-SER complex with target proteins. This research enhances understanding of NDs' effects on B. polychresta, proposing it as an effective bioindicator, and introduces VB12-conjugated SER as a promising therapeutic strategy in nanotoxicological studies.

'We can be a family again, but different than before'. A single-case study on therapeutic interventions that initiated a recovery process in a family after the disclosure of sibling sexual behavior.

Disclosures of sibling sexual behavior (SSB) usually affect all family members but there remains, however, a paucity in studies on therapeutical family interventions and how they can initiate changes in families. This study was designed to explore relational impacts of SSB disclosures, goals for therapy and interventions that helped a family initiate the recovery process after a SSB disclosure. A single case study design was used to analyze a family's long-term therapy process. Data on this N = 1 study comprised 18 interviews with involved therapists, five interviews with involved family members, therapy files, and notes on family sessions. Data was analyzed using a thematic approach. Relational traumas were experienced in broken relationships, relationships under pressure and damaged trust between family members. Therapy goals were to (1) recreate family's safety, (2) help the family process the SSB consequences and (3) restore trust and search for relationship healing. Appropriate interventions to target the goals included individual-centered psycho trauma treatment as well as interventions for the parents, the involved siblings, and the uninvolved siblings, followed by sessions between the involved siblings and with the whole family. Therapy outcomes were found in reduced individual trauma symptoms, a recreated sense of family safety, the start of relational trauma processing, and newfound forms of sibling/family relationships. This study provides a unique and comprehensive insight into a family's healing process after SSB disclosures from the perspectives of both professionals and family members. The effective interventions identified in this study may provide tools for therapists working with these families. This study may also offer greater insights into both the abusive and mutual types of SSB.

Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects.

Sleep is crucial for wellness, and emerging research reveals a profound connection to gut microbiota. This review explores the bidirectional relationship between gut microbiota and sleep, exploring the mechanisms involved and the therapeutic opportunities it presents. The gut-brain axis serves as a conduit for the crosstalk between gut microbiota and the central nervous system, with dysbiosis in the microbiota impairing sleep quality and vice versa. Diet, circadian rhythms, and immune modulation all play a part. Specific gut bacteria, like Lactobacillus and Bifidobacterium, enhance sleep through serotonin and gamma-aminobutyric acid production, exemplifying direct microbiome influence. Conversely, sleep deprivation reduces beneficial bacteria, exacerbating dysbiosis. Probiotics, prebiotics, postbiotics, and fecal transplants show therapeutic potential, backed by animal and human research, yet require further study on safety and long-term effects. Unraveling this intricate link paves the way for tailored sleep therapies, utilizing microbiome manipulation to improve sleep and health. Accelerated research is essential to fully tap into this promising field for sleep disorder management.

Endothelial Cell Dysfunction: Onset, Progression, and Consequences.

Endothelial cell dysfunction is a complex process involving various causes, early and late events, and subsequent consequences. This review provides an overview of each aspect and outlines therapeutic interventions targeting these stages. Causes of endothelial dysfunction encompass a spectrum of risk factors including hypertension, diabetes, smoking, obesity, inflammation, oxidative stress, and genetic predispositions. Early events such as endothelial activation, inflammatory response, and dysregulated vasomotor tone precede late events like oxidative stress, endothelial apoptosis, and microvascular rarefaction. The consequences include endothelial remodelling, neovascularization, organ dysfunction, and clinical manifestations, highlighting the diverse impacts across multiple systems. While depicted linearly, the progression of endothelial dysfunction is dynamic, influenced by various factors such as the underlying cause and affected vascular bed. Understanding these dynamics is crucial for tailoring therapeutic interventions, ranging from lifestyle modifications to targeted therapies, to address the underlying causes and effects effectively. Here we provide comprehensive understanding of endothelial cell dysfunction that is essential for developing strategies to mitigate the impact of this dysregulation on health and cardiovascular diseases progression.

Flatfoot Deformity; Exercise to Therapeutic Interventions: A Systematic Review.

Background: Deviation of the foot from the normal posture affects the function of the foot and lower limb and causes lower limb injuries in normal people and athletes. Flat feet or flatfoot deformity are usually associated with pain in the foot area and a decrease in the normal function of the foot, which can negatively affect the sports ability of athletes. Therefore, we aimed to investigate the abnormality of flat feet from training, exercise to therapeutic interventions. Methods: Articles were identified by searching five databases: PubMed, Scopus, Google Scholar, Science Direct, and Gate & Pasteur from 2000 to 2022. The keywords were selected specifically and correctly and all the researches and articles related to the title of the article were searched and found. This research was also searched in Persian databases that this database, included: Irandoc, Mag Iran and Noormagz. Results: Finally, 30 studies met the criteria for entering this study, selected and used to conduct this study. Conclusion: By using the results obtained in the research, which include corrective exercises and therapeutic interventions, especially the use of orthoses and various medical insoles, it is possible to help in the treatment and improvement of this anomaly.

Shedding light on subiculum's role in human brain disorders.

Subiculum is a pivotal output component of the hippocampal formation, a structure often overlooked in neuroscientific research. Here, this review aims to explore the role of the subiculum in various brain disorders, shedding light on its significance within the functional-neuroanatomical perspective on neurological diseases. The subiculum's involvement in multiple brain disorders was thoroughly examined. In Alzheimer's disease, subiculum alterations precede cognitive decline, while in epilepsy, the subiculum plays a critical role in seizure initiation. Stress involves the subiculum's impact on the hypothalamic-pituitary-adrenocortical axis. Moreover, the subiculum exhibits structural and functional changes in anxiety, schizophrenia, and Parkinson's disease, contributing to cognitive deficits. Bipolar disorder is linked to subiculum structural abnormalities, while autism spectrum disorder reveals an alteration of inward deformation in the subiculum. Lastly, frontotemporal dementia shows volumetric differences in the subiculum, emphasizing its contribution to the disorder's complexity. Taken together, this review consolidates existing knowledge on the subiculum's role in brain disorders, and may facilitate future research, diagnostic strategies, and therapeutic interventions for various neurological conditions.

Resurgence of respiratory syncytial virus infection during COVID-19 pandemic in Pune, India.

INTRODUCTION: Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infection in children worldwide. Understanding its prevalence, variations, and characteristics is vital, particularly in the context of the COVID-19 pandemic. OBJECTIVE: The study aimed to investigate the RSV positivity rate, subtype prevalence, age and gender distribution, symptomatology, and co-infection rates during pre-pandemic and pandemic periods. METHODS: We analyzed data from 15,381 patients tested for RSV between 2017 and 2023. RESULTS: Our analysis revealed a 7.2% average RSV positivity rate in the pre-pandemic period, with significant fluctuations during the pandemic (1.5% in 2020 to 32.0% in 2021). We observed variations in RSVA and RSVB detection rates. The 0-4 years' age group was consistently the most affected, with a slight male predominance. Fever and cough were common symptoms. Therapeutic interventions, particularly antiviral usage and ventilation requirements, decreased during the pandemic. We also identified variations in co-infection rates with other respiratory viruses. CONCLUSION: Our study offers critical insights into the impact of the COVID-19 pandemic on RSV prevalence, subtype distribution, patient characteristics, and clinical management. These findings underscore the need for ongoing surveillance and adaptive public health responses.

Nanozymes: Potential Therapies for Reactive Oxygen Species Overproduction and Inflammation in Ischemic Stroke and Traumatic Brain Injury.

Nanozymes, which can selectively scavenge reactive oxygen species (ROS), have recently emerged as promising candidates for treating ischemic stroke and traumatic brain injury (TBI) in preclinical models. ROS overproduction during the early phase of these diseases leads to oxidative brain damage, which has been a major cause of mortality worldwide. However, the clinical application of ROS-scavenging enzymes is limited by their short in vivo half-life and inability to cross the blood-brain barrier. Nanozymes, which mimic the catalytic function of natural enzymes, have several advantages, including cost-effectiveness, high stability, and easy storage. These advantages render them superior to natural enzymes for disease diagnosis and therapeutic interventions. This review highlights recent advancements in nanozyme applications for ischemic stroke and TBI, emphasizing their potential to mitigate the detrimental effect of ROS overproduction, oxidative brain damage, inflammation, and blood-brain barrier compromise. Therefore, nanozymes represent a promising treatment modality for ROS overproduction conditions in future medical practices.

Beyond lecanemab: Examining Phase III potential in Alzheimer's therapeutics.

This review focuses on the development of therapeutic interventions for Alzheimer's dementia. While established treatments targeted acetylcholine and NMDA receptors, there is a growing demand for innovative therapies as the aging population increases. The paper highlights the US Food and Drug Administration's approval of aducanumab (Aduhelm) and lecanemab (Leqembi), emphasizing the developmental status of new treatments. Specifically, it covers seven principal drugs in Phase III trials, detailing their mechanisms of action, clinical trial specifics in the United States and Japan, and the current status of regulatory applications. The review focuses on amyloid removal (donanemab), tau protein mitigation (E2814), drug repositioning (Semaglutide, GV1001), and disease-modifying small molecules (fosgonimeton, hydralazine, masitinib). However, Gantenerumab and Solanezumab, unsuccessful in Phase III, are not covered. While the future approval status remains uncertain, we hope these drugs will offer beneficial therapeutic effects for potential dementia patients.

Is Antibiotic Prophylaxis Needed for the Extraction of Premolars for Orthodontic Purposes?

Introduction Antibiotic prophylaxis for tooth extractions is a common practice in dentistry to prevent postoperative infections. However, the routine use of antibiotics has been questioned due to concerns about bacterial resistance and potential side effects. This study aimed to evaluate the necessity of postoperative antibiotics in patients undergoing orthodontic tooth extraction. Materials and methods This prospective study involved 100 patients requiring orthodontic tooth extraction, divided into two groups. The patients were recruited from Saveetha Dental College and Hospital, Chennai, India, after obtaining approval from the Institutional Human Ethics Committee, Saveetha Dental College (approval number: IHEC/SDC/OMFS-2103/23/293). Group 1 (n = 50) received antibiotics (amoxicillin 500 mg, three times a day for three days) after extraction, while Group 2 (n = 50) did not receive antibiotics. Postoperative infection was assessed on postoperative days (POD) 3 and 7. Data analysis was conducted using IBM SPSS Statistics for Windows, version 26.0 (released 2019, IBM Corp., Armonk, NY). Categorical variables were presented as frequencies and percentages, and differences between groups were assessed using chi-square or Fisher's exact tests. A p-value of <0.05 was considered statistically significant. Results The incidence of postoperative infection was recorded in both groups. In group 1 at POD 3 and POD 7, there were two patients and one patient with infection, respectively. In group 2 at POD 3 and POD 7, there were four patients and two patients with infection, respectively. Conclusion The findings of this study suggest that the routine administration of antibiotics for the non-traumatic extraction of teeth in healthy patients might not be necessary. The absence of postoperative infections in patients who did not receive antibiotics indicates that antibiotics may be avoidable in many cases of orthodontic tooth extraction. These results emphasize the importance of reconsidering the widespread use of antibiotics to combat the growing concern of bacterial resistance. Antibiotics should be prescribed judiciously, only for patients with specific medical conditions who are prone to infection. One of the limitations of this study is the limited sample size; hence, studies with larger and heterogeneous groups should be done to validate the same.

Therapeutic Interventions for Diabetes Mellitus-Associated Complications.

BACKGROUND: Diabetes Mellitus (DM) is an alarming health concern, affecting approximately 537 million people worldwide. As a leading cause of morbidity and mortality, DM demands a comprehensive understanding of its diverse pathophysiological mechanisms and disease progression. METHODS: This traditional review has consolidated literature on the pathogenesis of hyperglycemia, its progression into complications, and advances in optimal treatment strategies. The literature in the last two decades has been reviewed using several keywords, including "diabetes," "diabetes-associated complications", "novel therapeutic interventions for diabetes-associated diseases", "phyto-extracts as antidiabetic drugs", etc. in prominent databases, such as PubMed, Scopus, Google Scholar, Web of Science, and ClinicalTrials.gov. RESULTS: We have discussed macrovascular and microvascular complications, such as atherosclerosis, cardiovascular disease, Peripheral Arterial Disease (PAD), stroke, diabetic nephropathy, retinopathy, and neuropathy, as well as various pharmacological and non-pharmacological interventions that are currently available for the management of DM. We have also focused on the potential of natural products in targeting molecular mechanisms involved in carbohydrate metabolism, insulin production, repair of pancreatic cells, and reduction of oxidative stress, thereby contributing to their antidiabetic activity. Additionally, novel therapeutic approaches, like genetic, stem cell, and immunomodulatory therapies, have been explored. We have also discussed the benefits and limitations of each intervention, emerging research and technologies, and precision medicine interventions. CONCLUSION: This review has emphasized the need for an improved understanding of these advancements, which is essential to enhance clinicians' ability to identify the most effective therapeutic interventions.

Advances on the Mechanisms and Therapeutic Strategies in Non-coding CGG Repeat Expansion Diseases.

Non-coding CGG repeat expansions within the 5' untranslated region are implicated in a range of neurological disorders, including fragile X-associated tremor/ataxia syndrome, oculopharyngeal myopathy with leukodystrophy, and oculopharyngodistal myopathy. This review outlined the general characteristics of diseases associated with non-coding CGG repeat expansions, detailing their clinical manifestations and neuroimaging patterns, which often overlap and indicate shared pathophysiological traits. We summarized the underlying molecular mechanisms of these disorders, providing new insights into the roles that DNA, RNA, and toxic proteins play. Understanding these mechanisms is crucial for the development of targeted therapeutic strategies. These strategies include a range of approaches, such as antisense oligonucleotides, RNA interference, genomic DNA editing, small molecule interventions, and other treatments aimed at correcting the dysregulated processes inherent in these disorders. A deeper understanding of the shared mechanisms among non-coding CGG repeat expansion disorders may hold the potential to catalyze the development of innovative therapies, ultimately offering relief to individuals grappling with these debilitating neurological conditions.

Intervenções terapêuticas não farmacológicas para o tratamento de úlceras no pé diabético: revisão integrativa / Intervenciones terapéuticas no farmacológicas para el tratamiento de las úlceras diabéticas: revisión integral de la literatura / Non-pharmacological therapeutic interventions for the treatment of diabetic foot ulcers: an integrative literature review

Introdução: As úlceras no pé diabético surgem da interação complexa entreneuropatia periférica e doença arterial periférica, comprometendo a cicatrização após traumas. Objetivo: Explorar a diversidade de intervenções terapêuticas não farmacológicas que têm sido estudadas e avaliadas quanto à sua eficácia e segurança no tratamento de úlceras no pé diabético. Metodologia: Pesquisa do tipo revisão integrativa da literatura. Para obtenção dos resultados foi realizado um levantamento nas plataformas PubMed e Biblioteca Virtual em Saúde. Para elaboração dos resultados foram selecionados 21 artigos. Resultados: As intervenções encontradas foram oxigenoterapia hiperbárica, terapia de feridas por pressão negativa, uso de matriz dérmica, plasma rico em plaquetas, plasma atmosférico frio, tratamentos com curativos especiais e uso de solas rígidas, entre outros. Mostraram uma variabilidade na taxa de cicatrização e no tempo de fechamento da ferida, bem como na melhoria da regeneração tecidual. Conclusão: As pesquisas mostram uma diversidade de intervenções terapêuticas não farmacológicas utilizadas no tratamento de úlceras no pé diabético, ressaltando a necessidade de abordagens individualizadas e mais estudos para determinar a eficácia e segurança de cada intervenção (AU).

Introduction:Diabetic foot ulcers arise from the complex interaction between peripheral neuropathy and peripheral arterial disease, compromising wound healing after traumas. Objective:To explore the diversity of non-pharmacological therapeutic interventions that have been studied and evaluated for their effectiveness and safety in the treatment of diabetic foot ulcers. Methodology: An integrative literature review was conducted. The search for results was performed on the PubMed and Virtual Health Library platforms. Twenty-one articles were selected for result elaboration.Results:The identified interventions included hyperbaric oxygen therapy, negative pressure wound therapy, use of dermal matrix, platelet-rich plasma, cold atmospheric plasma, treatments with special dressings, and the use of rigid soles, among others. They exhibited variability in the healing rate and wound closure time, as well as improvement in tissue regeneration.Conclusion:The research demonstrates a diversity of non-pharmacological therapeutic interventions used in the treatment of diabetic foot ulcers, emphasizing the need for individualized approaches and further studies to determine the effectiveness and safety of each intervention (AU).

Introducción: Las úlceras en el pie diabético surgen de la interacción compleja entre neuropatía periférica y enfermedad arterial periférica, comprometiendo la cicatrización después de traumas.Objetivo: Explorar la diversidad de intervenciones terapéuticas no farmacológicas que han sido estudiadas y evaluadas en cuanto a su eficacia y seguridad en el tratamiento de úlceras en el pie diabético.Metodología: Investigación del tipo revisión integrativa de la literatura. Para obtener los resultados se realizó un estudio en las plataformas PubMed y Biblioteca Virtual en Salud. Para la elaboración de los resultados se seleccionaron 21 artículos. Resultados: Las intervenciones encontradas fueron oxigenoterapia hiperbárica, terapia de heridas por presión negativa, uso de matriz dérmica, plasma rico en plaquetas, plasma atmosférico frío, tratamientos con curativos especiales y uso de suelas rígidas, entre otros. Mostraron una variabilidad en la tasa de cicatrización y en el tiempo de cierre de la herida, así como en la mejora de la regeneración tisular. Conclusión: Las investigaciones muestran una diversidad de intervenciones terapéuticas no farmacológicas utilizadas en el tratamiento de úlceras en el pie diabético, resaltando la necesidad de enfoques individualizados y más estudios para determinar la eficacia y seguridad de cada intervención (AU).

Evaluating the efficacy and safety of therapeutic interventions for corneal neuropathy: A systematic review.

Corneal neuropathy involves corneal nerve damage that disrupts ocular surface integrity, negatively impacting quality-of-life from pain and impaired vision. Any ocular or systemic condition that damages the trigeminal nerve can lead to corneal neuropathy. However, the condition currently does not have standardized diagnostic criteria or treatment protocols. The primary aim of this systematic review was to evaluate the efficacy and safety of interventions for treating corneal neuropathy. Randomized controlled trials (RCTs) that investigated corneal neuropathy treatments were eligible if the intervention(s) was compared to a placebo or active comparator. Comprehensive searches were conducted in Ovid MEDLINE, Ovid Embase and clinical trial registries from inception to July 2022. The Cochrane Risk-of-Bias 2 tool was used to assess study methodological quality. Certainty of the body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Overall, 20 RCTs were included. Evaluated interventions comprised regenerative therapies (n = 6 studies), dietary supplements (n = 4), anti-glycemic agents (n = 3), combination therapy (n = 3), supportive therapies (n = 2) and systemic pain pharmacotherapies (n = 2). Nine RCTs were judged at high risk of bias for most outcomes. Definitions for corneal neuropathy in the populations varied substantially across studies, consistent with lack of consensus on diagnostic criteria. A diverse range of outcomes were quantified, likely reflecting absence of an agreed core outcome set. There was insufficient evidence to draw definitive conclusions on the efficacy or safety of any intervention. There was low or very low certainty evidence for several neuroregenerative agents and dietary supplements for improving corneal nerve fiber length in corneal neuropathy due to dry eye disease and diabetes. Low or very low certainty evidence was found for neuroregenerative therapies and dietary supplements not altering corneal immune cell density. This review identifies a need to standardize the clinical definition of corneal neuropathy and define a minimum set of core outcome measures. Together, this will provide a foundation for improved phenotyping of clinical populations in studies, and improve the capacity to synthesize data to inform evidence-based care. Protocol registration: PROSPERO ID: CRD42022348475.

Treating Alzheimer's disease using nanoparticle-mediated drug delivery strategies/systems.

The administration of promising medications for the treatment of neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) is significantly hampered by the blood-brain barrier (BBB). Nanotechnology has recently come to light as a viable strategy for overcoming this obstacle and improving drug delivery to the brain. With a focus on current developments and prospects, this review article examines the use of nanoparticles to overcome the BBB constraints to improve drug therapy for AD The potential for several nanoparticle-based approaches, such as those utilizing lipid-based, polymeric, and inorganic nanoparticles, to enhance drug transport across the BBB are highlighted. To shed insight on their involvement in aiding effective drug transport to the brain, methods of nanoparticle-mediated drug delivery, such as surface modifications, functionalization, and particular targeting ligands, are also investigated. The article also discusses the most recent findings on innovative medication formulations encapsulated within nanoparticles and the therapeutic effects they have shown in both preclinical and clinical testing. This sector has difficulties and restrictions, such as the need for increased safety, scalability, and translation to clinical applications. However, the major emphasis of this review aims to provide insight and contribute to the knowledge of how nanotechnology can potentially revolutionize the worldwide treatment of NDDs, particularly AD, to enhance clinical outcomes.

Nesprin proteins: bridging nuclear envelope dynamics to muscular dysfunction.

This review presents a comprehensive exploration of the pivotal role played by the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, with a particular focus on Nesprin proteins, in cellular mechanics and the pathogenesis of muscular diseases. Distinguishing itself from prior works, the analysis delves deeply into the intricate interplay of the LINC complex, emphasizing its indispensable contribution to maintaining cellular structural integrity, especially in mechanically sensitive tissues such as cardiac and striated muscles. Additionally, the significant association between mutations in Nesprin proteins and the onset of Dilated Cardiomyopathy (DCM) and Emery-Dreifuss Muscular Dystrophy (EDMD) is highlighted, underscoring their pivotal role in disease pathogenesis. Through a comprehensive examination of DCM and EDMD cases, the review elucidates the disruptions in the LINC complex, nuclear morphology alterations, and muscular developmental disorders, thus emphasizing the essential function of an intact LINC complex in preserving muscle physiological functions. Moreover, the review provides novel insights into the implications of Nesprin mutations for cellular dynamics in the pathogenesis of muscular diseases, particularly in maintaining cardiac structural and functional integrity. Furthermore, advanced therapeutic strategies, including rectifying Nesprin gene mutations, controlling Nesprin protein expression, enhancing LINC complex functionality, and augmenting cardiac muscle cell function are proposed. By shedding light on the intricate molecular mechanisms underlying nuclear-cytoskeletal interactions, the review lays the groundwork for future research and therapeutic interventions aimed at addressing genetic muscle disorders.