Phytochemicals and Novel Nanotherapeutic Approaches in the Management of Rheumatic Diseases

Over 100 types of arthritis have been recognized in which the dominating forms are osteoarthritis and rheumatoid arthritis. Joint stiffness, pain, swelling, lowered range of motion of joints affected, redness around joints are the main complications of almost all types of arthritis. Medications like non-steroidal anti-inflammatory drugs (NSAIDs), opioids, corticosteroids, and immunosuppressants are only used to control the symptoms of the disease but are not able to alleviate them properly. However, with the incorporation of disease-modifying antirheumatic drugs (DMARDs) as well as tumor necrosis factor inhibitors (TNFi) in treatment, there are now promising therapeutic options to select from for the management of rheumatoid diseases. Nanotherapeutic approach has enabled us to deliver the disease-modifying agents directly to the inflammation site, thus eschewing off-target and unwanted systemic effects. Therefore, it provides an opportunity to reconsider the therapeutic compounds that were considered too toxic to be administrated via oral or parenteral route.

Current Approaches for the Management of Multiple Sclerosis – A Review

Multiple sclerosis (MS) is an autoimmune, neuroinflammatory disease which interfere with the central nervous system and damage the myelin sheath and axons. It is mediated by auto-reactive lymphocytes that cross the blood brain barrier cause inflammation, demyelination and axonal loss disturb the communications between the neurons. The exact cause of the MS is not known but it is reported that it may be due to the genetic, environmental factors, viral infections (Epstein Barr virus). There are various approaches for the management of Multiple sclerosis like disease modifying agents are mainly used. Some of the monoclonal antibodies (Ocrelizumab) are approved recently for the management of MS. Due to various unwanted side effects with conventional medicines people are eager to use cost effective medicines with no or less side effects; therefore herbal medicines are best choice for them, they works by different pharmacological actions like reduce oxidative stress, anti-inflammatory, antioxidant effects and others. Mainly used herbal plants like Ginkgobiloba, Salvia officinalis, Nigella sativa.

A Septuagenarian With Progressive Hemiparesis

A 78-year-old man with no pertinent medical history sought care for an 18-month history of progressive right lower extremity weakness, gait impairment, and falls. On neurologic examination, he had a hemiparetic gait. He had normal higher cognitive function and cranial nerve function. Motor examination showed decreased bulk over the right hand with no fasciculations, mild spasticity over the right leg, and right hemiparesis with an upper motor neuron pattern. Deep tendon reflexes were brisk throughout his limbs, and he had an extensor plantar reflex on the right side. He had impaired vibratory sense at the toes, with otherwise normal sensory and coordination examinations. Magnetic resonance imaging (MRI) of the brain showed ovoid periventricular and punctate subcortical and deep white matter T2 hyperintense foci. Some of these had corresponding T1 hypointensity. MRI of the cervical spine showed 1 eccentrically located T2 hyperintense lesion over the right lateral aspect of C2. Cerebrospinal fluid analysis showed no pleocytosis, an increased protein concentration of 66 mg/dL, and 4 unique oligoclonal bands. A diagnosis of primary progressive multiple sclerosis, very late onset, was made. With any diagnosis of late-onset multiple sclerosis, a decision about whether multiple sclerosis disease-modifying agents are indicated should be carefully considered. Our older patient had a progressive disease course, and neuroimaging studies did not reveal evidence of active disease. Based on this, a decision was made to monitor him clinically and radiologically. Management of spasticity with regular daily stretching exercises was discussed with him. A first clinical manifestation of multiple sclerosis can occur at a later-than-typical age. Most studies consider an onset at age 50 years or older to be late-onset multiple sclerosis, whereas first symptoms occurring at age 60 years or older are commonly referred to as very late–onset MS.

The Role of Polyphenols in the Treatment of Alzheimer's Disease: Narrative Review

Many epidemiological studies have suggested that consuming a diet rich in polyphenols can help prevent Alzheimer's disease (AD). Based on well-known in vitro and in vivo models of cerebral Aβ amyloidosis, we examined the data on the effects of various natural polyphenols on the aggregation of amyloid-protein (Aβ). These polyphenols effectively prevent oligomerization and fibril formation of Aβ through differential binding patterns, lowering Aβ oligomer-induced synaptic and neuronal toxicity, according to in vitro investigations. Furthermore, in a transgenic mouse model fed orally with such polyphenolic compounds, soluble Aβ oligomers as well as insoluble Aβ deposits in the brain were significantly reduced. Natural polyphenols exhibit anti-amyloidogenic effects on Aβ, in addition to well-known anti-oxidative and anti-inflammatory activities, according to an updated assessment of the literature, implying their potential as therapeutic and/or preventive agents for AD treatment. To prove polyphenols' efficacy as disease-modifying agents, well-designed clinical trials or preventive treatments using various polyphenols are required.

Prevention of Cirrhosis Complications: Looking for Potential Disease Modifying Agents

The current therapeutic strategies for the management of patients with cirrhosis rely on the prevention or treatment of specific complications. The removal of the causative agents (i.e., viruses or alcohol) prevents decompensation in the vast majority of patients with compensated cirrhosis. In contrast, even when etiological treatment has been effective, a significant proportion of patients with decompensated cirrhosis remains at risk of further disease progression. Therefore, therapies targeting specific key points in the complex pathophysiological cascade of decompensated cirrhosis could represent a new approach for the management of these severely ill patients. Some of the interventions currently employed for treating or preventing specific complications of cirrhosis or used in other diseases (i.e., poorly absorbable oral antibiotics, statins, albumin) have been proposed as potential disease-modifying agents in cirrhosis (DMAC) since clinical studies have shown their capacity of improving survival. Additional multicenter, large randomized clinical trials are awaited to confirm these promising results. Finally, new drugs able to antagonize key pathophysiological mechanisms are under pre-clinical development or at the initial stages of clinical assessment.

The pharmacological treatment of epilepsy: recent advances and future perspectives

The pharmacological armamentarium against epilepsy has expanded considerably over the last three decades, and currently includes over 30 different antiseizure medications. Despite this large armamentarium, about one third of people with epilepsy fail to achieve sustained seizure freedom with currently available medications. This sobering fact, however, is mitigated by evidence that clinical outcomes for many people with epilepsy have improved over the years. In particular, physicians now have unprecedented opportunities to tailor treatment choices to the characteristics of the individual, in order to maximize efficacy and tolerability. The present article discusses advances in the drug treatment of epilepsy in the last 5 years, focusing in particular on comparative effectiveness trials of second-generation drugs, the introduction of new pharmaceutical formulations for emergency use, and the results achieved with the newest medications. The article also includes a discussion of potential future developments, including those derived from advances in information technology, the development of novel precision treatments, the introduction of disease modifying agents, and the discovery of biomarkers to facilitate conduction of clinical trials as well as routine clinical management.

GSK-3β, FYN, and DYRK1A: Master Regulators in Neurodegenerative Pathways

Protein kinases (PKs) have been recognized as central nervous system (CNS)-disease-relevant targets due to their master regulatory role in different signal transduction cascades in the neuroscience space. Among them, GSK-3β, FYN, and DYRK1A play a crucial role in the neurodegeneration context, and the deregulation of all three PKs has been linked to different CNS disorders with unmet medical needs, including Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal lobar degeneration (FTLD), and several neuromuscular disorders. The multifactorial nature of these diseases, along with the failure of many advanced CNS clinical trials, and the lengthy approval process of a novel CNS drug have strongly limited the CNS drug discovery. However, in the near-decade from 2010 to 2020, several computer-assisted drug design strategies have been combined with synthetic efforts to develop potent and selective GSK-3β, FYN, and DYRK1A inhibitors as disease-modifying agents. In this review, we described both structural and functional aspects of GSK-3β, FYN, and DYRK1A and their involvement and crosstalk in different CNS pathological signaling pathways. Moreover, we outlined attractive medicinal chemistry approaches including multi-target drug design strategies applied to overcome some limitations of known PKs inhibitors and discover improved modulators with suitable blood–brain barrier (BBB) permeability and drug-like properties.

Behavioral Variant Frontotemporal Dementia: Diagnosis and Treatment Interventions

Purpose of Review The diagnosis and treatment of behavioral variant frontotemporal dementia is challenging and often delayed because of overlapping symptoms with more common dementia syndromes or primary psychiatric illnesses. The purpose of this paper is to explore the relevant presentation, diagnostic workup, pathophysiology, and both pharmacologic and non-pharmacologic management. Recent Findings Behavioral variant frontotemporal dementia is a highly heritable disorder. The gradual accumulation of diseased protein culminates in the destruction of those brain circuits responsible for much of one’s emotional and social functioning. Summary Behavioral variant frontotemporal dementia is a progressive neurodegenerative disorder with a far-reaching impact on patients and caregivers. Patients often present with emotional blunting, lack of empathy, apathy, and behavioral disinhibition. Non-pharmacologic interventions and caregiver support are the cornerstone of treatment. The use of cholinesterase inhibitors and memantine is not supported by the evidence. While current pharmacologic therapies target only certain symptoms, there are disease modifying agents currently in or nearing the clinical research stage.

LncRNAs Associated with Neuronal Development and Oncogenesis Are Deregulated in SOD1-G93A Murine Model of Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease caused in 10% of cases by inherited mutations considered “familial”. An ever-increasing amount of evidence is showing a fundamental role for RNA metabolism in ALS pathogenesis, and long non-coding RNAs (lncRNAs) appear to play a role in ALS development. Here, we aim to investigate the expression of a panel of lncRNAs (linc-Enc1, linc–Brn1a, linc–Brn1b, linc-p21, Hottip, Tug1, Eldrr, and Fendrr) which could be implicated in early phases of ALS. Via Real-Time PCR, we assessed their expression in a murine familial model of ALS (SOD1-G93A mouse) in brain and spinal cord areas of SOD1-G93A mice in comparison with that of B6.SJL control mice, in asymptomatic (week 8) and late-stage disease (week 18). We highlighted a specific area and pathogenetic-stage deregulation in each lncRNA, with linc-p21 being deregulated in all analyzed tissues. Moreover, we analyzed the expression of their human homologues in SH-SY5Y-SOD1-WT and SH-SY5Y-SOD1-G93A, observing a profound alteration in their expression. Interestingly, the lncRNAs expression in our ALS models often resulted opposite to that observed for the lncRNAs in cancer. These evidences suggest that lncRNAs could be novel disease-modifying agents, biomarkers, or pathways affected by ALS neurodegeneration.