Current Insights into Carpal Tunnel Syndrome: Clinical Strategies for Prevention and Treatment.

BACKGROUND: Carpal tunnel syndrome (CTS) is a condition that is caused by medial nerve compression, resulting in symptoms such as numbness, tightness, or weakness in the hand. OBJECTIVES: The aim of the study was to find out the genetic modulation, mechanism, available treatment, and recommendation for carpal tunnel syndrome at its specific stage. METHODS: Almost 200 papers were searched for this review article, and 145 articles were selected. The literature was collected from different sources like Google scholar, PubMed, a directory of open-access journals, and science.gov by using keywords, such as treatment, risk factors, recommendation, and clinical features of carpal tunnel syndrome. RESULTS: The most efficient non-surgical treatment is methylprednisolone acetate, which reduces inflammation by acting on the glucocorticoid receptor in conjunction with immunofilling. It has also been used successfully as a second-line drug for the treatment of patients with mild or moderate conditions in order to provide relief. New non-pharmacological options include laser therapy in acupuncture, transcutaneous electric nerve stimulation (TENS), and sham therapy. Modern treatments like TENS, laser therapy, splints, and injections of methylprednisolone acetate have been demonstrated to be helpful in sporadic situations. For patients with mild and moderate problems, more research should be conducted that includes the combination of these surgical and non-surgical treatments. CONCLUSION: We propose a multifunctional panel construct and define standard data items for future research into carpal tunnel syndrome. A discussion on idiopathic carpal tunnel syndrome, risk factors, combination of therapies, using guidelines-based recommendations and treatment should be initiated.

Unravelling the Crosstalk between Estrogen deficiency and Gut-biota Dysbiosis in the development of Diabetes Mellitus.

Estrogens are classically considered essential hormonal signals, but they exert profound effects in a number of physiological and pathological states, including glucose homeostasis and insulin resistance. Estrogen deficiency after menopause in most women leads to increased androgenicity and changes in body composition, and it is recommended to manipulate the ß-cell function of the pancreas, insulin-induced glucose transport, and hepatic glucose output, hence, the increasing incidence of type 2 diabetes mellitus. Recently, studies have reported that gut biota alteration due to estrogen deficiency contributes to altered energy metabolism and, hence, accentuates the pathology of diabetes mellitus. Emerging research suggests estrogen deficiency via genetic disposition or failure of ovaries to function in old age modulates the insulin resistance and glucose secretion workload on pancreatic beta cells by decreasing the levels of good bacteria such as Akkermansia muciniphila, Bifidobacterium spp., Lactobacillus spp., Faecalibacterium prausnitzii, Roseburia spp., and Prevotella spp., and increasing the levels of bad bacteria's such as Bacteroides spp., Clostridium difficile, Escherichia coli, and Enterococcus spp. Alteration in these bacteria's concentrations in the gut further leads to the development of impaired glucose uptake by the muscles, increased gluconeogenesis in the liver, and increased lipolysis and inflammation in the adipose tissues. Thus, the present review paper aims to clarify the intricate interactions between estrogen deficiency, gut microbiota regulation, and the development of diabetes mellitus.

Therapeutic Viewpoint on Rat Models of Locomotion Abnormalities and Neurobiological Indicators in Parkinson's Disease.

BACKGROUND: Locomotion problems in Parkinson's syndrome are still a research and treatment difficulty. With the recent introduction of brain stimulation or neuromodulation equipment that is sufficient to monitor activity in the brain using electrodes placed on the scalp, new locomotion investigations in patients having the capacity to move freely have sprung up. OBJECTIVE: This study aimed to find rat models and locomotion-connected neuronal indicators and use them all over a closed-loop system to enhance the future and present treatment options available for Parkinson's disease. METHODS: Various publications on locomotor abnormalities, Parkinson's disease, animal models, and other topics have been searched using several search engines, such as Google Scholar, Web of Science, Research Gate, and PubMed. RESULTS: Based on the literature, we can conclude that animal models are used for further investigating the locomotion connectivity deficiencies of many biological measuring devices and attempting to address unanswered concerns from clinical and non-clinical research. However, translational validity is required for rat models to contribute to the improvement of upcoming neurostimulation-based medicines. This review discusses the most successful methods for modelling Parkinson's locomotion in rats. CONCLUSION: This review article has examined how scientific clinical experiments lead to localised central nervous system injuries in rats, as well as how the associated motor deficits and connection oscillations reflect this. This evolutionary process of therapeutic interventions may help to improve locomotion- based treatment and management of Parkinson's syndrome in the upcoming years.

Transcutaneous vagus nerve stimulation ameliorates cardiac abnormalities in chronically stressed rats.

Chronically stressed patients often have low vagal tone and increased levels of proinflammatory cytokines, which increase their risk for developing cardiac dysfunction. Transcutaneous vagus nerve stimulation (taVNS) is a way to activate the parasympathetic system, which has the ability to reduce inflammation and antagonize excessive sympathetic responses. However, the effectiveness of taVNS in treating cardiac dysfunction caused by chronic unpredictable stress (CUS) has not been studied. To investigate this, we first validated a rat model of CUS, in which the rats were exposed to random stressors daily for 8 weeks. Post CUS, the rats were treated with taVNS (1.0 ms, 6 V, 6 Hz, for 40 min × 2 weeks, alternatively) and their cardiac function and cholinergic flow were evaluated. Furthermore, serum cardiac troponin I (cTnI), cardiac caspase-3, inducible nitric oxide synthase (iNOS), and transforming growth factor (TGF)-ß1 expression in rats were also assessed. The chronically stressed rats showed depressed behavior with increased levels of serum corticosterone and proinflammatory cytokines. Electrocardiogram (ECG) and heart rate variability (HRV) studies revealed elevated heart rate, diminished vagal tone, and altered sinus rhythm in CUS rats. Furthermore, the CUS rats demonstrated cardiac hypertrophy and fibrosis with increased caspase-3, iNOS, and TGF-ß expression in their myocardium and increased levels of serum cTnI. Interestingly, alternate taVNS therapy for 2 weeks, post CUS, helped alleviate these cardiac abnormalities. These suggest that taVNS could be a useful adjunctive and non-pharmacological approach for managing CUS induced cardiac dysfunction.

The pandemic's unseen wounds: COVID-19's profound effects on mental health.

Objective: This review aims to explore the impact of the COVID-19 pandemic on mental health, with a focus on the physiological and psychological consequences, including comorbidities. The goal is to understand the direct and indirect populations affected by mental distress and identify potential interventions. Methodology: A comprehensive literature search was conducted using various databases, including Google Scholar, ResearchGate, ScienceDirect, PubMed, PLoS One, and Web of Science. The search utilized relevant keywords to investigate the direct and indirect impacts of COVID-19 on mental health. The selected articles were critically evaluated and analyzed to identify key findings and insights. Main findings: Mental health, being an intrinsic component of overall well-being, plays a vital role in physiological functioning. The COVID-19 pandemic, caused by the emergence of the novel SARS-CoV-2 virus, has had a devastating global impact. Beyond the respiratory symptoms, individuals recovering from COVID-19 commonly experience additional ailments, such as arrhythmia, depression, anxiety, and fatigue. Healthcare professionals on the frontlines face an elevated risk of mental illness. However, it is crucial to recognize that the general population also grapples with comparable levels of mental distress. Conclusion: The COVID-19 pandemic has underscored the significance of addressing mental health concerns. Various strategies can help mitigate the impact, including counselling, fostering open lines of communication, providing mental support, ensuring comprehensive patient care, and administering appropriate medications. In severe cases, treatment may involve the supplementation of essential vitamins and antidepressant therapy. By understanding the direct and indirect impacts of COVID-19 on mental health, healthcare providers and policymakers can develop targeted interventions to support individuals and communities affected by the pandemic. Continued research and collaborative efforts are essential to address this pervasive issue effectively.

Chronic stress predisposes to the aggravation of inflammation in autoimmune diseases with focus on rheumatoid arthritis and psoriasis.

The global incidence of autoimmune diseases is on the rise, and many healthcare professionals believe that chronic stress plays a prominent role in both the aggravation and remission of these conditions. It is believed that prolonged exposure to stress is associated with neuroimmune axis malfunction, which eventually dysregulates multiple immunological factors as well as deregulates autoimmune responses that play a central role in various autoimmune diseases, including rheumatoid arthritis and psoriasis. Herein, we performed validation of an 8-week long rat model of chronic unpredictable stress (CUS) which consisted of exposing groups of rats to random stressors daily for 8 weeks. Additionally, we developed a novel rat model combining 8-week long random stressor-induced CUS with CIA-triggered arthritis and IMQ-triggered psoriasis and have successfully used both these models to assess the role of chronic stress in the aggravation of arthritis and psoriasis, respectively. Notably, the 8-week CUS protocol extensively aggravated and prolonged both arthritis and psoriasis condition in the rat model by upregulating the release of different pro-inflammatory cytokines, dysregulation of immune cell responses and oxidative stress system, which were all related to severe inflammation. Further, CUS aggravated macroscopic features and the increase in destruction of joint tissue and epidermal thickness induced by CIA and IMQ, respectively, in rats. In conclusion, this study suggests that exposure to an 8-week long CUS paradigm aggravates the distinctive characteristics of rheumatoid arthritis and psoriasis in rats via amplifying the inflammatory circuits and immune cell responses linked to these autoimmune diseases.

Investigation of Pancreatic-beta cells Role in the Biological Process of Ageing.

BACKGROUND: Cellular senescence is associated with the formation and progression of a range of illnesses, including ageing and metabolic disorders such as diabetes mellitus and pancreatic beta cell dysfunction. Ageing and reduced glucose tolerance are interconnected. Often, Diabetes is becoming more common, which is concerning since it raises the risk of a variety of age-dependent disorders such as cardiovascular disease, cancer, Parkinson's disease, stroke, and Alzheimer's disease. OBJECTIVES: The objectives of this study are to find out the most recent research on how ageing affects the functions of pancreatic beta cells, beta cell mass, beta cell senescence, mitochondrial dysfunction, and hormonal imbalance. METHODS: Various research and review manuscripts are gathered from various records such as Google Scholar, PubMed, Mendeley, Scopus, Science Open, the Directory of Open Access Journals, and the Education Resources Information Centre, using different terms like "Diabetes, cellular senescence, beta cells, ageing, insulin, glucose". RESULTS: In this review, we research novel targets in order to discover new strategies to treat diabetes. Abnormal glucose homeostasis and type 2 diabetes mellitus in the elderly may aid in the development of novel medicines to delay or prevent diabetes onset, improve quality of life, and, finally, increase life duration. CONCLUSION: Aging accelerates beta cell senescence by generating premature cell senescence, which is mostly mediated by high glucose levels. Despite higher plasma glucose levels, hepatic gluconeogenesis accelerates and adipose tissue lipolysis rises, resulting in an increase in free fatty acid levels in the blood and worsening insulin resistance throughout the body.

Butein ameliorates chronic stress induced atherosclerosis via targeting anti-inflammatory, anti-fibrotic and BDNF pathways.

Chronic stress is a major risk factor for various diseases, including cardiovascular diseases (CVDs). Chronic stress enhances the release of pro-inflammatory cytokines like IL-1ß, IL-6, and TNF-α, making individuals susceptible to atherosclerosis which is dominant cause for CVDs. In present study, we validated a mouse model of chronic unpredictable stress (CUS), and assessed the characteristic features of atherosclerosis in thoracic aortas of CUS mice. The CUS procedure consisted of exposing groups of mice to random stressors daily for 10-weeks. The stress response was verified by presence of depressive-like behaviors and increased serum corticosterone in mice which was determined by battery of behavioural tests (SPT, EPMT, NSFT) and ELISA, respectively. Atherosclerosis parameters in CUS mice were evaluated by lipid indices estimation followed by histological assessment of plaque deposition and fibrosis in thoracic aorta. Further, we assessed the efficacy of a polyphenol, i.e. Butein in conferring protection against chronic stress-induced atherosclerosis and the possible mechanism of action. Butein (20 mg/kg x 28 days, alternatively, i.p.) was administered to CUS mice after 6-weeks of CUS exposure till the end of the protocol. Butein treatment decreased peripheral IL-1ß and enhanced peripheral as well as central BDNF levels. Histological assessment revealed decreased macrophage expression and reduced fibrosis in thoracic aorta of Butein treated mice. Further, treatment with Butein lowered lipid indices in CUS mice. Our findings thus, suggest that 10-weeks of CUS induce characteristic features of atherosclerosis in mice and Butein can offer protection in CUS-induced atherosclerosis through multiple mechanisms including anti-inflammatory, antifibrotic and anti-adipogenic actions.

The Role of Medicinal Plants in the Diabetic Wound Healing Process.

AIMS: The aim of this study is to determine the relationship between diabetes and delayed wound healing from the literature. Research literature from 2010-2020 was searched and it was found that various medicinal plants and their phytoconstituents are effective in treating wounds associated with diabetes. Potential medicinal plants that are used to treat wounds and can be used to treat diabetes have been determined. METHODS: Research and review articles from 2010-2020 have been researched on a variety of topics such as PubMed, Scopus, Mendeley, Google Scholar, Indian traditional medicine system, Ayurvedic treatment programme using different words such as "diabetes", "treatment of diabetes", "plants in the treatment of diabetes", "wound healing", "wound healing plants". CONCLUSION: Other herbs are also traditionally used to treat wounds. In this study, the main focus is on medicinal plants that are used specifically to treat wounds in diabetic conditions. Although quite a few medicinal flora for wound restoration may be observed in the literature, there is a need for the isolation and characterization of the bioactive compounds responsible for the wound restoration properties. Also, cytotoxicity research needs to be conducted on promising agents or bioactive fractions or extracts.

Protein Uncoupling as an Innovative Practice in Diabetes Mellitus Treatment: A Metabolic Disorder.

BACKGROUND: Uncoupling proteins (UCPs) are unpaired electron carriers that uncouple oxygen intake by the electron transport chain from ATP production in the inner membrane of the mitochondria. The physiological activities of UCPs have been hotly contested, and the involvement of UCPs in the pathogenesis and progression of diabetes mellitus is among the greatest concerns. UCPs are hypothesised to be triggered by superoxide and then reduce mitochondrial free radical production, potentially protecting diabetes mellitus patients who are experiencing oxidative stress. OBJECTIVES: The objectives of the study are to find out the newest ways to treat diabetes mellitus through protein uncoupling. METHODS: Research and review papers are collected from different databases like google scholar, PubMed, Mendeley, Scopus, Science Open, Directory of open access journals, and Education Resources Information Center, using different keywords such as "uncoupling proteins in diabetes mellitus treatment", "UCP 1", "UCP 2", and 'UCP 3". RESULTS: UCP1, UCP2, and UCP 3 are potential targets as uncoupling proteins for the treatment of diabetes mellitus for new drugs. New drugs treat the disease by reducing oxidative stress through thermogenesis and energy expenditure. CONCLUSION: UCP1, UCP2, and UCP3 have a role in fatty acid metabolism, negative control of insulin production, and insulin sensitivity by beta-cells. Polymorphisms in the UCP 1, 2, and 3 genes significantly reduce the risk of developing diabetes mellitus. Protein uncoupling indirectly targets the GPCR and islet of Langerhans. This review summarises the advances in understanding the role of UCP1, UCP2, and UCP3 in diabetes mellitus.

Nano to rescue: repository of nanocarriers for targeted drug delivery to curb breast cancer.

Breast cancer is a heterogeneous disease with different intrinsic subtypes. The conventional treatment of surgical resection, chemotherapy, immunotherapy and radiotherapy has not shown significant improvement in the survival rate of breast cancer patients. The therapeutics used cause bystander toxicities deteriorating healthy tissues. The breakthroughs of nanotechnology have been a promising feat in selective targeting of tumor site thus increasing the therapeutic gain. By the application of nanoenabled carriers, nanomedicines ensure targeted delivery, stability, enhanced cellular uptake, biocompatibility and higher apoptotic efficacy. The present review focuses on breakthrough of nanoscale intervention in targeted drug delivery as novel class of therapeutics. Nanoenabled carriers like polymeric and metallic nanoparticles, dendrimers, quantum dots, liposomes, solid lipid nanoparticles, carbon nanotubes, drug-antibody conjugates and exosomes revolutionized the targeted therapeutic delivery approach. These nanoassemblies have shown additional effect of improving the solubility of drugs such as paclitaxel, reducing the dose and toxicity. The present review provides an insight on the different drug conjugates employed/investigated to curb breast cancer using nanocarrier mediated targeted drug delivery. However, identification of appropriate biomarkers to target, clearer insight of the biological processes, batch uniformity, reproducibility, nanomaterial toxicity and stabilities are the hurdles faced by nanodrugs. The potential of nano-therapeutics delivery necessitates the agglomerated efforts of research community to bridge the route of nanodrugs for scale-up, commercialization and clinical applications.

Genetic architecture of motor neuron diseases.

Motor neuron diseases (MNDs) are rare and frequently fatal neurological disorders in which motor neurons within the brainstem and spinal cord regions slowly die. MNDs are primarily caused by genetic mutations, and > 100 different mutant genes in humans have been discovered thus far. Given the fact that many more MND-related genes have yet to be discovered, the growing body of genetic evidence has offered new insights into the diverse cellular and molecular mechanisms involved in the aetiology and pathogenesis of MNDs. This search may aid in the selection of potential candidate genes for future investigation and, eventually, may open the door to novel interventions to slow down disease progression. In this review paper, we have summarized detailed existing research findings of different MNDs, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), spinal bulbar muscle atrophy (SBMA) and hereditary spastic paraplegia (HSP) in relation to their complex genetic architecture.

Interleukin-6 expression and its modulation by diacerein in a rat model of chronic stress induced cardiac dysfunction.

People with chronic stress have higher levels of pro-inflammatory cytokines, which enhance their susceptibility to cardiovascular diseases. Diacerein has ability to modulate pro-inflammatory cytokines such as IL-1ß and IL-6; however, its efficacy in chronic stress associated cardiovascular diseases is not yet assessed. In this study, we standardized a rat model of chronic unpredictable stress (CUS) demonstrating cardiovascular dysfunctions and further assessed the effect of IL-6 modulator, diacerein, on cardiovascular functions in CUS exposed rats. The CUS procedure consisted of exposing male albino Wistar rats to random stressors, everyday for 8 weeks. The binding affinity of diacerein with IL-6 was ascertained using Docking tools viz AutoDock and SwissDock. Moreover, diacerein was administered (50 mg/kg/day x 20 days P.O) post CUS exposure to rats and the serum IL-6 levels and heart functions of CUS rats were determined by ELISA and ECG-HRV analysis, respectively. 8 weeks of CUS exposure resulted in two-fold increase in serum corticosterone and IL-6 levels in rats. The ECG and HRV analysis of CUS rats showed altered sinus rhythm, elevated heart rate, systolic blood pressure and sympathetic tone. Molecular docking studies revealed diacerein high binding affinity towards IL-6 receptor. The post-treatment of diacerein in CUS rats prevented these cardiovascular dysfunctions. Our findings thus suggests that IL-6 may have a prominent role in chronic stress induced cardiovascular dysfunctions and diacerein, could be used as a preventive measure for such conditions.

The multifactorial roles of microglia and macrophages in the maintenance and progression of glioblastoma.

The functional characteristics of glial cells, in particular microglia, have attained considerable importance in several diseases, including glioblastoma, the most hostile and malignant type of intracranial tumor. Microglia performs a highly significant role in the brain's inflammatory response mechanism. They exhibit anti-tumor properties via phagocytosis and the activation of a number of different cytotoxic substances. Some tumor-derived factors, however, transform these microglial cells into immunosuppressive and tumor-supportive, facilitating survival and progression of tumorigenic cells. Glioma-associated microglia and/or macrophages (GAMs) accounts for a large proportion of glioma infiltrating cells. Once within the tumor, GAMs exhibit a distinct phenotype of initiation that subsequently supports the growth and development of tumorigenic cells, angiogenesis and stimulates the infiltration of healthy brain regions. Interventions that suppress or prohibit the induction of GAMs at the tumor site or attenuate their immunological activities accommodating anti-tumor actions are likely to exert positive impact on glioblastoma treatment. In the present paper, we aim to summarize the most recent knowledge of microglia and its physiology, as well as include a very brief description of different molecular factors involved in microglia and glioblastoma interplay. We further address some of the major signaling pathways that regulate the baseline motility of glioblastoma progression. Finally, we discussed a number of therapeutic approaches regarding glioblastoma treatment.

Involvement of myocyte enhancer factor 2c in the pathogenesis of autism spectrum disorder.

Myocyte enhancer factor 2 (MEF2), a family of transcription factor of MADS (minichromosome maintenance 1, agamous, deficiens and serum response factor)-box family needed in the growth and differentiation of a variety of human cells, such as neural, immune, endothelial, and muscles. As per existing literature, MEF2 transcription factors have also been associated with synaptic plasticity, the developmental mechanisms governing memory and learning, and several neurologic conditions, like autism spectrum disorders (ASDs). Recent genomic findings have ascertained a link between MEF2 defects, particularly in the MEF2C isoform and the ASD. In this review, we summarized a concise overview of the general regulation, structure and functional roles of the MEF2C transcription factor. We further outlined the potential role of MEF2C as a risk factor for various neurodevelopmental disorders, such as ASD, MEF2C Haploinsufficiency Syndrome and Fragile X syndrome.

Potential of long non-coding RNAs as a therapeutic target and molecular markers in glioblastoma pathogenesis.

Glioblastoma (GB) is by far the most hostile type of malignant tumor that primarily affects the brain and spine, derived from star-shaped glial cells that are astrocytes and oligodendrocytes. Despite of significant efforts in recent years in glioblastoma research, the clinical efficacy of existing medical intervention is still limited and very few potential diagnostic markers are available. Long non-coding RNAs (lncRNAs) that lacks protein-coding capabilities were previously thought to be "junk sequences" in mammalian genomes are quite indispensible epigenetic regulators that can positively or negatively regulate gene expression and nuclear architecture, with significant roles in the initiation and development of tumors. Nevertheless, the precise mechanism of these distortedly expressed lncRNAs in glioblastoma pathogenesis is not yet fully understood. Since the advent of high-throughput sequencing technologies, more and more research have elucidated that lncRNAs are one of the most promising prognostic biomarkers and therapeutic targets for glioblastoma. In this paper, I briefly outlined the existing findings of lncRNAs. And also summarizes the profiles of different lncRNAs that have been broadly classified in glioblastoma research, with emphasis on both their prognostic and therapeutic values.