Experimental Type 2 diabetes and lipotoxicity-associated neuroinflammation involve mitochondrial DNA-mediated cGAS/STING axis: implication of Type-1 interferon response in cognitive impairment.

Type-1 IFN (interferon)-associated innate immune response is increasingly getting attention in neurodegenerative and metabolic diseases like type 2 diabetes (T2DM). However, its significance in T2DM/lipotoxicity-induced neuroglia changes and cognitive impairment is missing. The present study aims to evaluate the involvement of cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon gene), IRF3 (interferon regulatory factor-3), TBK (TANK binding kinase)-mediated Type-1 IFN response in the diabetic brain, and lipotoxicity (palmitate-bovine serum albumin conjugate/PA-BSA)-induced changes in cells (neuro2a and BV2).

S1PR2 inhibition mitigates cognitive deficit in diabetic mice by modulating microglial activation via Akt-p53-TIGAR pathway.

Cognitive deficit is one of the challenging complications of type 2 diabetes. Sphingosine 1- phosphate receptors (S1PRs) have been implicated in various neurodegenerative and metabolic disorders. The association of S1PRs and cognition in type 2 diabetes remains elusive.

Sphingosine 1 phosphate lyase inhibition rescues cognition in diabetic mice by promoting anti-inflammatory microglia.

Sphingosine-1-phosphate (S1P) is emerging as a crucial sphingolipid modulating neuroinflammation and cognition. S1P levels in the brain have been found to be decreased in cognitive impairment. S1P lyase (S1PL) is the key enzyme in metabolizing S1P and has been implicated in neuroinflammation.

Necrostatin-1S mitigates type-2 diabetes-associated cognitive decrement and lipotoxicity-induced neuro-microglia changes through p-RIPK-RIPK3-p-MLKL axis.

Type-2 diabetes mellitus (T2DM) is associated with neuroinflammation and cognitive decrement. Necroptosis programmed necrosis is emerging as the major contributing factor to central changes. It is best characterized by the upregulation of p-RIPK(Receptor Interacting Kinase), p-RIPK3, and the phosphorylated-MLKL (mixed-lineage kinase domain-like protein).

Piceatannol promotes neuroprotection by inducing mitophagy and mitobiogenesis in the experimental diabetic peripheral neuropathy and hyperglycemia-induced neurotoxicity.

Piceatannol (PCN), a SIRT1 activator, regulates multiple oxidative stress mechanism and has anti-inflammatory potential in various inflammatory conditions. However, its role in Diabetic insulted peripheral neuropathy (DN) remains unknown. Oxidative stress and mitochondrial dysfunction are major contributing factors to DN.

Proteostasis in Parkinson's disease: Recent development and possible implication in diagnosis and therapeutics.

The protein dyshomeostasis is identified as the hallmark of many age-related neurodegenerative disorders including Parkinson's disease (PD). The diseased brain shows the deposition of Lewy bodies composed of α-synuclein protein aggregates. Functional proteostasis is characterized by the well-coordinated signaling network constituting unfolded protein response (UPR), the ubiquitin-proteasome system (UPS), and the autophagy-lysosome pathway (ALP).

Neuroprotective Effect of Phloretin in Rotenone-Induced Mice Model of Parkinson's Disease: Modulating mTOR-NRF2-p62 Mediated Autophagy-Oxidative Stress Crosstalk.

Background: Parkinson's disease (PD) is an age-related progressive multifactorial, neurodegenerative disease. The autophagy and Keap1-Nrf2 axis system are both implicated in the oxidative-stress response, metabolic stress, and innate immunity, and their dysregulation is associated with pathogenic processes in PD. Phloretin (PLT) is a phenolic compound reported possessing anti-inflammatory and antioxidant activities.

Fingolimod Alleviates Cognitive Deficit in Type 2 Diabetes by Promoting Microglial M2 Polarization via the pSTAT3-jmjd3 Axis.

Sphingosine receptors (S1PRs) are implicated in the progression of neurodegenerative diseases and metabolic disorders like obesity and type 2 diabetes (T2D). The link between S1PRs and cognition in type 2 diabetes, as well as the mechanisms that underpin it, are yet unknown. Neuroinflammation is the common pathology shared among T2D and cognitive impairment.

Neuroepigenetic alterations in the prefrontal cortex of type 2 diabetic mice through DNA hypermethylation.

Background: DNA methylation changes have known to downregulate several regulatory proteins epigenetically during various neurodegenerative disorders. Our study aims to understand the effect of this global DNA methylation on the cerebral complications of type 2 diabetes mice, and its notable effect on maintaining the synaptic fidelity. METHODS AND RESULTS: Chronic high fat diet and streptozotocin-induced diabetic mice were studied for the neurobehavioral and neuroanatomic parameters pertaining to prefrontal cortex, subsequently elucidating the associated changes in DNA methylation within these diabetic brains.

Neuroepigenetic Changes in DNA Methylation Affecting Diabetes-Induced Cognitive Impairment.

Chronic diabetic conditions have been associated with certain cerebral complications, that include neurobehavioral dysfunctional patterns and morphological alterations of neurons, especially the hippocampus. Neuroanatomical studies done by the authors have shown decreased total dendritic length, intersections, dendritic length per branch order and nodes in the CA1 hippocampal region of the diabetic brain as compared to its normal control group, indicating reduced dendritic arborization of the hippocampal CA1 neurons. Epigenetic alterations in the brain are well known to affect age-associated disorders, however its association with the evolving diabetes-induced damage in the brain is still not fully understood.

Activation of SIRT1 by silibinin improved mitochondrial health and alleviated the oxidative damage in experimental diabetic neuropathy and high glucose-mediated neurotoxicity.

Background: Silibinin (SBN), a sirtuin 1 (SIRT1) activator, has been evaluated for its anti-inflammatory activity in many inflammatory diseases. However, its role in diabetes-induced peripheral neuropathy (DPN) remains unknown. The SIRT1 activation convalesces nerve functions by improving mitochondrial biogenesis and mitophagy.

Nanotechnological Advances for Nose to Brain Delivery of Therapeutics to Improve the Parkinson Therapy.

Blood-Brain Barrier (BBB) acts as a highly impermeable barrier, presenting an impediment to the crossing of most classical drugs targeted for neurodegenerative diseases including Parkinson's disease (PD). About the nature of drugs and other potential molecules, they impose unavoidable doserestricted limitations eventually leading to the failure of therapy. However, many advancements in formulation technology and modification of delivery approaches have been successful in delivering the drug to the brain in the therapeutic window.

Glia: A major player in glutamate-GABA dysregulation-mediated neurodegeneration.

The imbalance between glutamate and γ-aminobutyric acid (GABA) results in the loss of synaptic strength leading to neurodegeneration. The dogma on the field considered neurons as the main players in this excitation-inhibition (E/I) balance. However, current strategies focusing only on neurons have failed to completely understand this condition, bringing up the importance of glia as an alternative modulator for neuroinflammation as glia alter the activity of neurons and is a source of both neurotrophic and neurotoxic factors.

Metabolic Regulation of Glia and Their Neuroinflammatory Role in Alzheimer's Disease.

Alzheimer's disease (AD) is an aging-related neurodegenerative disorder. It is characterized clinically by progressive memory loss and impaired cognitive function. Its progression occurs from neuronal synapse loss to amyloid pathology and Tau deposit which eventually leads to the compromised neuronal function.

Role of MicroRNAs, Aptamers in Neuroinflammation and Neurodegenerative Disorders.

Exploring the microRNAs and aptamers for their therapeutic role as biological drugs has expanded the horizon of its applicability against various human diseases, explicitly targeting the genetic materials. RNA-based therapeutics are widely being explored for the treatment and diagnosis of multiple diseases, including neurodegenerative disorders (NDD). Latter includes microRNA, aptamers, ribozymes, and small interfering RNAs (siRNAs), which control the gene expression mainly at the transcriptional strata.

Diabetic Complications: An Update on Pathobiology and Therapeutic Strategies.

Despite the advent of novel therapies which manage and control diabetes well, the increased risk of morbidity and mortality in diabetic subjects is associated with the devastating secondary complications it produces. Long-standing diabetes majorly drives cellular and molecular alterations, which eventually damage both small and large blood vessels. The complications are prevalent both in type I and type II diabetic subjects.

Knowledge, attitude, and implementation of nicotine replacement therapy by dental and medical interns in Davangere city: A cross-sectional survey.

Background: One of the prime causes of illness and premature death is smoking. Almost 50% of smokers attempt to quit the habit; however, at most, 2%-3% achieve success. The rationale is that innumerable withdrawal attempts are unplanned, and the most effective cessation aids are unacquainted.

Modified coronally advanced flap design in management of isolated gingival recession: Saddle flap technique.

Saddle flap technique, a modified coronally advanced flap approach for isolated gingival recession management was introduced and assessed in terms of clinical efficacy and patient satisfaction. A total of 10 systemically healthy subjects with isolated gingival recession defect (Miller Class I and II) were enrolled in the study. The primary endpoint measure was patient satisfaction in terms of esthetics and percentage root coverage.

DRESS syndrome: Addressing the drug hypersensitivity syndrome on combination of Sodium Valproate and Olanzapine.

A case of an adolescent with symptoms of Mania, who developed Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) syndrome on exposure to combination of oral Olanzapine and Sodium Valproate is presented. We have attempted to highlight the atypical presentation of DRESS syndrome in this patient as well as management difficulties in patient who develops DRESS syndrome with the conventional psychotropic medication. Hence, it is necessary for mental health professionals to be vigilant about this life threatening drug reaction associated with high morbidity and mortality, thus ensuring prompt diagnosis and management.

Autism Behavioural Interventional Research in low-resource settings: Overcoming prevailing challenges - an Asian perspective.

Acceleration of Autism interventional research is evident in high-income countries (HIC), however, remains limited in low-resource settings. Though studies have established efficacy of behavioural interventions for Autism spectrum disorder, conducting behavioural interventional research in low resource setting poses unique challenges in economic, ethical and cultural facets. This brief communication discusses the prevailing challenges in low resource setting in designing and testing the efficacy of behaviour interventional model that is generalizable to primary care settings.

Galactosylated albumin nanoparticles of simvastatin.

The present study was an attempt to develop galactosylated albumin nanoparticles of Simvastatin for treatment of hypercholesterolemia. By developing the galactosylated nanoparticulated delivery, the required action of the drug at the target site at the liver can be provided. The advantage of targeting helps to reduce the systemic side effects that may occur due to the distribution of the drug to the other organs and thus helps in maintaining the required concentration of drug at the desired site.

Shilajit attenuates behavioral symptoms of chronic fatigue syndrome by modulating the hypothalamic-pituitary-adrenal axis and mitochondrial bioenergetics in rats.

Ethnopharmacological Relevance: Shilajit has been used as a rejuvenator for ages in Indian ancient traditional medicine and has been validated for a number of pharmacological activities.

Aim Of The Study: The effect of processed shilajit which was standardized to dibenzo-α-pyrones (DBPs;0.43% w/w), DBP-chromoproteins (DCPs; 20.

Intravenous leiomyomatosis.

Leiomyomas are benign tumors arising from smooth muscle of the uterus. Intravenous leiomyomatosis is characterized by intraluminal growth of benign smooth muscle into either venous or lymphatic vessels outside the limits of myoma. It commonly extends into the pelvic veins and manifests as worm-like protrusions of tumor emanating from veins at the parametrial margins of hysterectomy specimen.