Potential of Nano-Engineered Stem Cells in the Treatment of Multiple Sclerosis: A Comprehensive Review.

Multiple sclerosis (MS) is a chronic and degrading autoimmune disorder mainly targeting the central nervous system, leading to progressive neurodegeneration, demyelination, and axonal damage. Current treatment options for MS are limited in efficacy, generally linked to adverse side effects, and do not offer a cure. Stem cell therapies have emerged as a promising therapeutic strategy for MS, potentially promoting remyelination, exerting immunomodulatory effects and protecting against neurodegeneration. Therefore, this review article focussed on the potential of nano-engineering in stem cells as a therapeutic approach for MS, focusing on the synergistic effects of combining stem cell biology with nanotechnology to stimulate the proliferation of oligodendrocytes (OLs) from neural stem cells and OL precursor cells, by manipulating neural signalling pathways-PDGF, BMP, Wnt, Notch and their essential genes such as Sox, bHLH, Nkx. Here we discuss the pathophysiology of MS, the use of various types of stem cells in MS treatment and their mechanisms of action. In the context of nanotechnology, we present an overview of its applications in the medical and research field and discuss different methods and materials used to nano-engineer stem cells, including surface modification, biomaterials and scaffolds, and nanoparticle-based delivery systems. We further elaborate on nano-engineered stem cell techniques, such as nano script, nano-exosome hybrid, nano-topography and their potentials in MS. The article also highlights enhanced homing, engraftment, and survival of nano-engineered stem cells, targeted and controlled release of therapeutic agents, and immunomodulatory and tissue repair effects with their challenges and limitations. This visual illustration depicts the process of utilizing nano-engineering in stem cells and exosomes for the purpose of delivering more accurate and improved treatments for Multiple Sclerosis (MS). This approach targets specifically the creation of oligodendrocytes, the breakdown of which is the primary pathological factor in MS.

Advances and challenges in thyroid cancer: The interplay of genetic modulators, targeted therapies, and AI-driven approaches.

Thyroid cancer continues to exhibit a rising incidence globally, predominantly affecting women. Despite stable mortality rates, the unique characteristics of thyroid carcinoma warrant a distinct approach. Differentiated thyroid cancer, comprising most cases, is effectively managed through standard treatments such as thyroidectomy and radioiodine therapy. However, rarer variants, including anaplastic thyroid carcinoma, necessitate specialized interventions, often employing targeted therapies. Although these drugs focus on symptom management, they are not curative. This review delves into the fundamental modulators of thyroid cancers, encompassing genetic, epigenetic, and non-coding RNA factors while exploring their intricate interplay and influence. Epigenetic modifications directly affect the expression of causal genes, while long non-coding RNAs impact the function and expression of micro-RNAs, culminating in tumorigenesis. Additionally, this article provides a concise overview of the advantages and disadvantages associated with pharmacological and non-pharmacological therapeutic interventions in thyroid cancer. Furthermore, with technological advancements, integrating modern software and computing into healthcare and medical practices has become increasingly prevalent. Artificial intelligence and machine learning techniques hold the potential to predict treatment outcomes, analyze data, and develop personalized therapeutic approaches catering to patient specificity. In thyroid cancer, cutting-edge machine learning and deep learning technologies analyze factors such as ultrasonography results for tumor textures and biopsy samples from fine needle aspirations, paving the way for a more accurate and effective therapeutic landscape in the near future.

Targeting calcium homeostasis and impaired inter-organelle crosstalk as a potential therapeutic approach in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremors, rigidity, and bradykinesia. Current therapeutic strategies for PD are limited and mainly involve symptomatic relief, with no available treatment for the underlying causes of the disease. Therefore, there is a need for new therapeutic approaches that target the underlying pathophysiological mechanisms of PD. Calcium homeostasis is an essential process for maintaining proper cellular function and survival, including neuronal cells. Calcium dysregulation is also observed in various organelles, including the endoplasmic reticulum (ER), mitochondria, and lysosomes, resulting in organelle dysfunction and impaired inter-organelle communication. The ER, as the primary calcium reservoir, is responsible for folding proteins and maintaining calcium homeostasis, and its dysregulation can lead to protein misfolding and neurodegeneration. The crosstalk between ER and mitochondrial calcium signaling is disrupted in PD, leading to neuronal dysfunction and death. In addition, a lethal network of calcium cytotoxicity utilizes mitochondria, ER and lysosome to destroy neurons. This review article focused on the complex role of calcium dysregulation and its role in aggravating functioning of organelles in PD so as to provide new insight into therapeutic strategies for treating this disease. Targeting dysfunctional organelles, such as the ER and mitochondria and lysosomes and whole network of calcium dyshomeostasis can restore proper calcium homeostasis and improve neuronal function. Additionally targeting calcium dyshomeostasis that arises from miscommunication between several organelles can be targeted so that therapeutic effects of calcium are realised in whole cellular territory.

Dysregulated autophagy: A key player in the pathophysiology of type 2 diabetes and its complications.

Autophagy is essential in regulating the turnover of macromolecules via removing damaged organelles, misfolded proteins in various tissues, including liver, skeletal muscles, and adipose tissue to maintain the cellular homeostasis. In these tissues, a specific type of autophagy maintains the accumulation of lipid droplets which is directly related to obesity and the development of insulin resistance. It appears to play a protective role in a normal physiological environment by eliminating the invading pathogens, protein aggregates, and damaged organelles and generating energy and new building blocks by recycling the cellular components. Ageing is also a crucial modulator of autophagy process. During stress conditions involving nutrient deficiency, lipids excess, hypoxia etc., autophagy serves as a pro-survival mechanism by recycling the free amino acids to maintain the synthesis of proteins. The dysregulated autophagy has been found in several ageing associated diseases including type 2 diabetes (T2DM), cancer, and neurodegenerative disorders. So, targeting autophagy can be a promising therapeutic strategy against the progression to diabetes related complications. Our article provides a comprehensive outline of understanding of the autophagy process, including its types, mechanisms, regulation, and role in the pathophysiology of T2DM and related complications. We also explored the significance of autophagy in the homeostasis of ß-cells, insulin resistance (IR), clearance of protein aggregates such as islet amyloid polypeptide, and various insulin-sensitive tissues. This will further pave the way for developing novel therapeutic strategies for diabetes-related complications.

Targeting mitochondrial bioenergetics as a promising therapeutic strategy in metabolic and neurodegenerative diseases.

Mitochondria are the organelles that generate energy for the cells and act as biosynthetic and bioenergetic factories, vital for normal cell functioning and human health. Mitochondrial bioenergetics is considered an important measure to assess the pathogenesis of various diseases. Dysfunctional mitochondria affect or cause several conditions involving the most energy-intensive organs, including the brain, muscles, heart, and liver. This dysfunction may be attributed to an alteration in mitochondrial enzymes, increased oxidative stress, impairment of electron transport chain and oxidative phosphorylation, or mutations in mitochondrial DNA that leads to the pathophysiology of various pathological conditions, including neurological and metabolic disorders. The drugs or compounds targeting mitochondria are considered more effective and safer for treating these diseases. In this review, we make an effort to concise the available literature on mitochondrial bioenergetics in various conditions and the therapeutic potential of various drugs/compounds targeting mitochondrial bioenergetics in metabolic and neurodegenerative diseases.

Metabolic syndrome and risk of major coronary events among the urban diabetic patients: North Indian Diabetes and Cardiovascular Disease Study-NIDCVD-2.

OBJECTIVE: The present study aimed at estimating the prevalence of metabolic syndrome (MetS) and prospectively, evaluating cardiovascular events among Asian Indians type 2 diabetic subjects. METHODS: The sample comprised 1522 type 2 diabetic mellitus (T2DM) subjects aged 25-91years, who participated in the North Indian Diabetes and Cardiovascular Disease Study (NIDCVD). The participants were screened for hypertension, dyslipidemia, obesity and cardiovascular events. Anthropometric, clinical and biochemical measurements were done in all subjects. The prevalence of MetS was estimated in all the subjects according to the harmonized criteria of 2009. RESULTS: The prevalence of MetS among urban Indian diabetic subjects was 71.9% and was significantly higher in females (86%) as compared to males (57.9%). To determine the independent predictors of the MetS in diabetic sample, binary logistic regression analyses were performed using demographic and biochemical parameters. Significant differences in the indices of generalized and abdominal obesity and lipids (total cholesterol, high density lipoprotein) were observed (p<0.01) in male:female and MetS and non-MetS comparisons. Regression analysis for prediction of CAD showed that family history, age, body mass index (BMI), SBP, physical inactivity and hypertension independently and significantly predicted the disease outcome. Binary logistic regression analysis revealed that MetS may be an independent risk/predictor of CAD (odd ratio (OR)=3.44, CI 1.31-9.01, p=0.012) along with higher age groups, BMI and hypertension in Indian population. CONCLUSION: The study demonstrated that the high prevalence of MetS and its different components were positively associated with a higher risk of CAD in north Indian diabetic subjects. Nevertheless, MetS is a major health problem in India, comprehensive population studies are warranted for estimation of incidence and prevalence, and education should be provided on its prevention and control to reduce the diabetes-related morbidity and mortality.