Differential Analysis of A-to-I mRNA Edited Sites in Parkinson’s Disease

Parkinson’s disease (PD) is a widespread neuronal degenerative disorder with unexplored etiology. It is associated with various pathological events. In particular, the prefrontal cortex Brodmann area 9 (BA9) region is affected in PD. This frontal lobe brain region plays an important role in cognitive, motor, and memory-related functions. BA9 develops Lewy bodies in PD patients and shows essential changes in transcriptome and proteome, connected with mitochondria related pathways, protein folding pathways, and metallothioneins. Recently, altered adenosine to inosine mRNA editing patterns have been detected in various neurological pathologies. In this article, we present an investigation of differences in A-to-I RNA editing levels and specificity of mRNA editing sites in brain tissues of healthy and PD patients based on RNA sequencing data. Overall, decreased editing levels in the brains of PD patients were observed, potential editing sites with altered editing during PD were identified, and the role of different adenosine deaminases in this process was analyzed.

Reliability of Sit to Stand Test in Fall Identification in Knee Osteoarthritis- A Literature Review

Osteoarthritis is the second most prevalent degenerative illness as well as the most frequent joint condition in India. It is one of the most common degenerative disorder of the articular cartilage and surface of weightbearing joints causing disability in elderly patients. Gait, stair-climbing, unipedal stance, and the sitting-to-standing (STS) task have all been shown to be altered in research. Most of the research article had proved that sit to stand test, we can use to physiotherapy department to identify the risk of fall in knee OA patients. Most of the patients had severe knee pain and reduced lower limb muscle strength so, during the test patient may take a long time to complete the test and there is a loss of balance. Due to pain and reduced endurance and loss of balance, the patient may not be capable of completing the test. So, the test is reliable to determine the risk of a fall in knee OA patient.

EFFECTIVENESS OF SAHACHARADI TAILAM FOURTEEN TIMES AVARTHI WITH PRE-MEDICATION IN QUALITY OF LIFE OF PARKINSON’S DISEASE AS AN ADD ON TO MODERN MEDICINE

Parkinsons disease (PD) is an idiopathic degenerative disorder that affects mainly old age. Community-based prevalence studies from India have documented crude prevalence rates of PD from 7 to 328 per 100,000 in the overall population. The current management in PD is effective in alleviating signs and symptoms but the quality of life is not preserved. This study was undertaken to the clinical evaluation of Sahacharadi Tailam fourteen times Avarthi with premedication in improving the quality of life in Parkinson's patients. Since Kapha and Vata plays an important role in Samprapthi of Parkinson's disease, Kapha Vatha Hara Chikitsa should be effective. All types of Sneha Dravya are used in Vatha Vyadhi Chikitsa and Taila is more effective when Vatha is associated with Kapha. Most of the drugs in Sahachaadi Tailam have Vata Kapha Hara properties. The study design was an interventional study pre and post evaluation with a sample size of ten patients. Parkinson's disease of age group 40-70 years of both sex attending the OPD and IPD of Department of Kayachikitsa, Govt. Ayurveda College, Thiruvananthapuram was selected for the study. The patient selected for the study was subjected to Deepana – Pachana with Gandharvahastadi Kashayam 48 ml at7 am & 7 pm one hour before food and vaiswanarachoorna 6 gm with Kasayam internally and Udvarthana with Kolakulathadi Choorna externally for 1-7 days, Snehapana with Rasnadasamoola Gritham starting with 25ml with increasing dosage for 3-7 days, abhyanga and Ushma Sveda with Balatailam and Virechana with Gandharveranda Tailam 30-45ml and Samsarjanakrama as a preparatory phase for the administration of study drug. Then patients received Sahacharadi Tailam fourteen times Avarthi for two months. Follow up was done 15 days after the intervention. On statistical analysis, there was a significant reduction in symptoms like tremor rigidity and pain before treatment, after Shodhana, after interven- tion & after follow up assessments. Keywords: PD, Sahacharadi Tailam fourteen times Avarthi, Deepana- Pachana, Udvarthana, Snehapana, Abyanga, Ushma Sveda, Virechana, Samsarjana Krama, Kaphavatahara and Vata Vyadhi.

Revisiting the Role of GSK3, A Modulator of Innate Immunity, in Idiopathic Inclusion Body Myositis

Idiopathic or sporadic inclusion body myositis (IBM) is the leading age-related (onset > 50 years of age) autoimmune muscular pathology, resulting in significant debilitation in affected individuals. Once viewed as primarily a degenerative disorder, it is now evident that much like several other neuro-muscular degenerative disorders, IBM has a major autoinflammatory component resulting in chronic inflammation-induced muscle destruction. Thus, IBM is now considered primarily an inflammatory pathology. To date, there is no effective treatment for sporadic inclusion body myositis, and little is understood about the pathology at the molecular level, which would offer the best hopes of at least slowing down the degenerative process. Among the previously examined potential molecular players in IBM is glycogen synthase kinase (GSK)-3, whose role in promoting TAU phosphorylation and inclusion bodies in Alzheimer’s disease is well known. This review looks to re-examine the role of GSK3 in IBM, not strictly as a promoter of TAU and Abeta inclusions, but as a novel player in the innate immune system, discussing some of the recent roles discovered for this well-studied kinase in inflammatory-mediated pathology.

An Observational Study to Assess Samprapti Ghataka in Cervical Spondylosis with Special Reference to Radiological Findings

The western lifestyle, characterized by convenience food, television and PC’s taking its all on children as well as adults and is producing increased number of overweight, passive youngsters with lifestyle diseases. Spondylosis is degenerative inter vertebral disc with secondary proliferative osteoarthritis. Disc spaces collapse and associated ligament thickening and bony proliferation result in nerve root compression and narrowing of spinal canal. Cervical spondylosis which is a degenerative disorder in which structural and also functional derangements take place. It is an age related and also work-related disability usually found in the 30-60 years of age group. According to Ayurveda it is one among the Vataja Nanatmaja Vikara. There is no exact clinical entity mentioned in classics like cervical spondylosis, but it can be compared to Greevastambha, Apabahuka, Vishwachi Manyastamba, Manyagraha, Shirograham, Greevahundanam, Greevasandhigatavata. Cervical Spondylosis also known as cervical osteoarthritis or neck arthritis, is a common age-related condition that affects the joints and discs in our neck.

Limonin Inhibits IL-1β-Induced Inflammation and Catabolism in Chondrocytes and Ameliorates Osteoarthritis by Activating Nrf2

Osteoarthritis (OA), a degenerative disorder, is considered to be one of the most common forms of arthritis. Limonin (Lim) is extracted from lemons and other citrus fruits. Limonin has been reported to have anti-inflammatory effects, while inflammation is a major cause of OA; thus, we propose that limonin may have a therapeutic effect on OA. In this study, the therapeutic effect of limonin on OA was assessed in chondrocytes in vitro in IL-1β induced OA and in the destabilization of the medial meniscus (DMM) mice in vivo. The Nrf2/HO-1/NF-κB signaling pathway was evaluated to illustrate the working mechanism of limonin on OA in chondrocytes. In this study, it was found that limonin can reduce the level of IL-1β induced proinflammatory cytokines such as INOS, COX-2, PGE2, NO, TNF-α, and IL-6. Limonin can also diminish the biosynthesis of IL-1β-stimulated chondrogenic catabolic enzymes such as MMP13 and ADAMTS5 in chondrocytes. The research on the mechanism study demonstrated that limonin exerts its protective effect on OA through the Nrf2/HO-1/NF-κB signaling pathway. Taken together, the present study shows that limonin may activate the Nrf2/HO-1/NF-κB pathway to alleviate OA, making it a candidate therapeutic agent for OA.

Candida albicans Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis

Atherosclerosis is a chronic degenerative disorder characterized by lipid-dense plaques and low-grade inflammation affecting arterial walls. Foamy macrophages are important in the formation of atherosclerotic plaques and the induction of low-grade inflammation. The presence of lipid-laden macrophages has occurred in infections caused by opportunistic pathogens. Candida albicans is the major cause of candidiasis in immunocompromised patients, including those with diabetes mellitus. However, the role played by C. albicans in macrophage foaming and the associated inflammation is poorly understood. We investigated whether C. albicans induces foaming along with inflammation in macrophages and, if so, by which mechanism(s). We incubated THP-1 macrophages with heat-killed C. albicans (HKCA). HKCA-induced lipid accumulation in macrophages along with increased expression of inflammatory markers, including CD11b and CD11c or expression and secretion of IL-1β. HKCA also increased the expression of PPARγ, CD36, and FABP4 in macrophages. Mechanistically, we found that the foamy and inflammatory macrophage phenotype induced by HKCA requires FABP4 because disruption of FABP4 in macrophages either by chemical inhibitor BMS309404 or small interfering RNA (siRNA) abrogated foam cell formation and expression of inflammatory markers CD11b, CD11c, and IL-1β. Furthermore, HKCA-treated macrophages displayed high expression and secretion of MMP-9. Inhibition of FABP4 resulted in suppression of HCKA-induced MMP-9 production. Overall, our results demonstrate that C. albicans induces foam cell formation, inflammation, and MMP-9 expression in macrophages via the upregulation of FABP4, which may constitute a novel therapeutic target for treating C. albicans-induced atherosclerosis.

Rare single nucleotide variants in COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482

Background Keratoconus is a chronic degenerative disorder of the cornea characterized by thinning and cone-shaped protrusions. Although genetic factors play a key role in keratoconus development, the etiology is still under investigation. The occurrence of single-nucleotide polymorphisms (SNPs) associated with keratoconus in Russian patients is poorly studied. The purpose of this study was to validate whether three reported keratoconus-associated SNPs (rs1536482 near the COL5A1 gene, rs2721051 near the FOXO1 gene, rs1324183 near the MPDZ gene) are also actual for a Russian cohort of patients. Additionally, we investigated the COL5A1 promoter sequence for single-nucleotide variants (SNVs) in a subgroup of keratoconus patients with at least one rs1536482 minor allele (rs1536482+) to assess the role of these SNVs in keratoconus susceptibility associated with rs1536482. Methods This case-control study included 150 keratoconus patients and two control groups (main and additional, 205 and 474 participants, respectively). We performed PCR targeting regions flanking SNVs and the COL5A1 promoter, followed by Sanger sequencing of amplicons. The additional control group was genotyped using an SNP array. Results The minor allele frequency was significantly different between the keratoconus and control cohorts (main and combined) for rs1536482, rs2721051, and rs1324183 (p-value < 0.05). The rare variants rs1043208782 and rs569248712 were found in the COL5A1 promoter in two out of 94 rs1536482+ keratoconus patients. Conclusion rs1536482, rs2721051, and rs1324183 were associated with keratoconus in a Russian cohort. SNVs in the COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482.

Discourse Analysis in Tamil Speaking Individuals with Parkinson’s Disease

Background: Parkinson’s disease (PD) is a degenerative disorder of the central nervous system. Though PD is primarily a motor speech disorder during the initial stages, as the disease progresses, a gradual decline in linguistic aspects is observed as well. The effects of disease (PD) on cognition, word retrieval, syntax, and speech/voice processes may act together to manifest uniquely in spoken language tasks. There is a dearth of studies focusing on the discourse abilities in PD, especially in Indian context. Aim: The present study aims at investigating the micro and macrostructure discourse by using personal narrative task in Tamil speaking individuals with idiopathic PD and comparing it with the neuro-typical individuals Method: Two groups comprising 5 Tamil-speaking individuals with idiopathic PD in the age range of 60–85 years and 5 neuro-typical individuals were included in the study. To assess their discourse skills, participants were engaged in a personal narrative task. The analyses done were based on macro and micro structural aspects of discourse. The raw scores were subjected to suitable statistical analysis. Results: There was a statistical significance between the Parkinson & Normal group on Total number of words, No. of Different words, No. of content words, No. of Functional words, Free morphemes, Complex structure per utterances & Relevant piece per utterance in microstructural aspects. However there was no significant difference observed in the macrostructural aspects due to smaller sample size. Conclusion: It can be concluded that in addition to speech impairment, language structure is also affected in persons with PD. Intervening at the level of discourse is an important aspect as it enhances the quality of life. Keywords: Parkinson’s disease, Discourse, Tamil speaking, Micro analysis, Macro Analysis.