Epigenetic modifications in Parkinson's disease: A critical review.

Parkinson's Disease (PD) is a progressive neurodegenerative disorder expected to increase by over 50% by 2030 due to increasing life expectancy. The disease's hallmarks include slow movement, tremors, and postural instability. Impaired protein processing is a major factor in the pathophysiology of PD, leading to the buildup of aberrant protein aggregates, particularly misfolded α-synuclein, also known as Lewy bodies. These Lewy bodies lead to inflammation and further death of dopaminergic neurons, leading to imbalances in excitatory and inhibitory neurotransmitters, causing excessive uncontrollable movements called dyskinesias. It was previously suggested that a complex interplay involving hereditary and environmental variables causes the specific death of neurons in PD; however, the exact mechanism of the association involving the two primary modifiers is yet unknown. An increasing amount of research points to the involvement of epigenetics in the onset and course of several neurological conditions, such as PD. DNA methylation, post-modifications of histones, and non-coding RNAs are the primary examples of epigenetic alterations, that is defined as alterations to the expression of genes and functioning without modifications in DNA sequence. Epigenetic modifications play a significant role in the development of PD, with genes such as Parkin, PTEN-induced kinase 1 (PINK1), DJ1, Leucine-Rich Repeat Kinase 2 (LRRK2), and alpha-synuclein associated with the disease. The aberrant epigenetic changes implicated in the pathophysiology of PD and their impact on the design of novel therapeutic approaches are the primary focus of this review.

Effect of Aerobic Exercise and Time-Restricted Feeding on Metabolic Markers and Circadian Rhythm in Mice Fed with the High-Fat Diet.

SCOPE: Diet and exercise are significant players in obesity and metabolic diseases. Time-restricted feeding (tRF) has been shown to improve metabolic responses by regulating circadian clocks but whether it acts synergically with exercise remains unknown. It is hypothesized that forced exercise alone or combined with tRF alleviates obesity and its metabolic complications. METHODS AND RESULTS: Male C57bl6 mice are fed with high-fat or a control diet for 12 weeks either ad libitum or tRF for 10 h during their active period. High-fat diet (HFD)-fed mice are divided into exercise (treadmill for 1 h at 12 m min-1 alternate days for 9 weeks and 16 m min-1 daily for the following 3 weeks) and non-exercise groups. tRF and tRF-Ex significantly decreased body weight, food intake, and plasma lipids, and improved glucose tolerance. However, exercise reduced only body weight and plasma lipids. tRF and tRF-Ex significantly downregulated Fasn, Hmgcr, and Srebp1c, while exercise only Hmgcr. HFD feeding disrupted clock genes, but exercise, tRF, and tRF-Ex coordinated the circadian clock genes Bmal1, Per2, and Rev-Erbα in the liver, adipose tissue, and skeletal muscles. CONCLUSION: HFD feeding disrupted clock genes in the peripheral organs while exercise, tRF, and their combination restored clock genes and improved metabolic consequences induced by high-fat diet feeding.

Nutrient Combinations Sensed by L-Cell Receptors Potentiate GLP-1 Secretion.

Obesity is a risk factor for cardiometabolic diseases. Nutrients stimulate GLP-1 release; however, GLP-1 has a short half-life (<2 min), and only <10-15% reaches the systemic circulation. Human L-cells are localized in the distal ileum and colon, while most nutrients are absorbed in the proximal intestine. We hypothesized that combinations of amino acids and fatty acids potentiate GLP-1 release via different L-cell receptors. GLP-1 secretion was studied in the mouse enteroendocrine STC-1 cells. Cells were pre-incubated with buffer for 1 h and treated with nutrients: alpha-linolenic acid (αLA), phenylalanine (Phe), tryptophan (Trp), and their combinations αLA+Phe and αLA+Trp with dipeptidyl peptidase-4 (DPP4) inhibitor. After 1 h GLP-1 in supernatants was measured and cell lysates taken for qPCR. αLA (12.5 µM) significantly stimulated GLP-1 secretion compared with the control. Phe (6.25-25 mM) and Trp (2.5-10 mM) showed a clear dose response for GLP-1 secretion. The combination of αLA (6.25 µM) and either Phe (12.5 mM) or Trp (5 mM) significantly increased GLP-1 secretion compared with αLA, Phe, or Trp individually. The combination of αLA and Trp upregulated GPR120 expression and potentiated GLP-1 secretion. These nutrient combinations could be used in sustained-delivery formulations to the colon to prolong GLP-1 release for diminishing appetite and preventing obesity.

Arsenic Exposure and Amyloid Precursor Protein Processing: A Focus on Alzheimer's Disease.

BACKGROUND: Arsenic is present in above permissible safe limits in groundwater, soil, and food, in various areas of the world. This is increasing exposure to humankind and affecting health in various ways. Alternation in cognition is one among them. Epidemiological research has reflected the impact of arsenic exposure on children in the form of diminished cognition. AIMS: Considering this fact, the present study reviewed the impact of arsenic on amyloid precursor protein, which is known to cause one of the commonest cognitive disorders such as Alzheimer's disease. METHODS: The present study reviews the arsenic role in the generation of amyloid-beta from its precursor that leads to Alzheimer's disease through the published article from Pubmed and Scopus. DESCRIPTION: According to the findings, regular, long-term exposure to arsenic beginning in infancy changes numerous arsenic level-regulating regions in the rat brain, which are related to cognitive impairments. Arsenic also affects the BBB clearance route by increasing RAGE expression. Arsenic triggers the proamyloidogenic pathway by increasing APP expression and subsequently, its processing by ß-secretase and presenilin. Arsenic also affects mitochondrial dynamics, DNA repair pathway and epigenetic changes. The mechanism behind all these changes is explained in the present review article. CONCLUSION: A raised level of arsenic exposure affects the amyloid precursor protein, a factor for the early precipitation of Alzheimer's disease.

Fetal Humeral Diaphyseal Length in the Second Trimester - A Radiographic Observational Study among Indian Population.

Objectives: The present study was performed to provide a normal reference range for humerus diaphysis length at the second trimester of pregnancy in an Indian population. Materials and Methods: This cross-sectional study was performed on 25 radiographs of aborted normal human fetuses of gestational age (GA) between 13th and 28th weeks. The radiographs were used to measure the maximum length of the humerus using a vernier calliper. Data were collected, tabulated, and statistically analyzed. Results: The mean diaphyseal length of humerus at the fourth lunar month was 22.18 ± 6.59 mm, and at the seventh lunar month, it was 41.39 ± 10.08 mm. Simple linear regression analysis shows a strongly significant linear relationship of humerus length with GA, biparietal diameter, head circumference, and abdomen circumference. Conclusion: We have provided a normal reference range for humerus diaphysis length at the second trimester of pregnancy in an Indian population.

Monoamine Oxidase: A Potential Link in Papez circuit to Generalized Anxiety Disorders.

Anxiety is a common mental illness that affects a large number of people around the world, and its treatment is often based on the use of pharmacological substances such as benzodiazepines, serotonin, and 5-hydroxytyrosine (MAO) neurotransmitters. MAO neurotransmitters levels are deciding factors in the biological effects. This review summarizes the current understanding of the MAO system and its role in the modulation of anxiety-related brain circuits and behavior. The MAO-A polymorphisms have been implicated in the susceptibility to generalized anxiety disorder (GAD) in several investigations. The 5-HT system is involved in a wide range of physiological and behavioral processes, involving anxiety, aggressiveness, stress reactions, and other elements of emotional intensity. Among these, 5-HT, NA, and DA are the traditional 5-HT neurons that govern a range of biological activities, including sleep, alertness, eating, thermoregulation, pains, emotion, and memory, as anticipated considering their broad projection distribution in distinct brain locations. The DNMTs (DNA methyltransferase) protein family, which increasingly leads a prominent role in epigenetics, is connected with lower transcriptional activity and activates DNA methylation. In this paper, we provide an overview of the current state of the art in the elucidation of the brain's complex functions in the regulation of anxiety.

Impact of periodontal treatment on inflammatory oxidative stress in chronic kidney disease subjects: An interventional clinical trial.

PURPOSE: To evaluate the role of improvement in inflammatory oxidative stress by periodontal therapy (NSPT) in chronic kidney disease (CKD) subjects. METHODS: 50 stable subjects of CKD (stage III-IV) and having chronic periodontitis were enrolled for the present study. Group A (control group) subjects who did not receive NSPT and Group B (test group) subjects who received NSPT. Oral hygiene instructions were given to both groups, malondialdehyde (MDA) in gingival crevicular fluid (GCF) and serum, albumin creatinine ratio (ACR), urine protein creatinine ratio (UPCR), pocket depth (PD), clinical attachment loss (CAL), plaque index (PI), gingival index (GI), Interleukin 1-beta (IL-1ß), high sensitivity C-reactive protein (hs-CRP) in serum were assessed at baseline and 6 months. RESULTS: There was a significant difference observed in PD, CAL, PI, GI and MDA-GCF, hs-CRP, IL-1ß in serum following NSPT in the test group compared to the control group at 6 months follow up. Within the limitations of the study, the results revealed that NSPT can be used as an effective method to reduce inflammatory oxidative stress in CKD subjects and improve renal health. Further well-designed longitudinal trials with larger sample size and longer follow ups are needed. CLINICAL SIGNIFICANCE: The non-surgical periodontal intervention showed statistically significant improvement on oxidative and inflammatory stress markers in gingival crevicular fluid and serum in subjects suffering from chronic kidney disease which suggests that periodontal treatment may be beneficial for these subjects.

Chimeric Antigen Receptor T-cell Therapy in Cancer: A Critical Review.

Targeted cancer therapy acts on targeted molecules, is less toxic to normal cells, and acts more specifically on cancer cells. The two primary strategies for preventing malignancy growth are the blocking of T-cell repression signals or forwarding of T-cell to tumor target with both T and tumor-specific antibodies. The CAR comprises three domains, the extracellular antigen recognition domain and the intracellular T-cell signaling domain, which participate in activating T-cells. The two most common adverse effects of CAR T-cell treatment are cytokine release syndrome (CRS) and cell-associated neurotoxicity syndrome (CANS). The adaptability of intracellular signaling domains inside CARs allows the cell to counterbalance the downregulation of costimulatory molecules produced by tumor cells, either indirectly or directly. The major disadvantage of CAR-T cell therapy is off-target toxicity. Treatment with CARs expressing CD3, CD123, Lewis Y, CLL-1, CD44v6, FLT3, and folate receptors showed promising results in preclinical models of acute myeloid leukemia (AML). A recent study has revealed that B7-H3 CART cells exhibit significant anticancer efficacy in a variety of solid tumor preclinical models, including PDAC, ovarian cancer, neuroblastoma, and various pediatric malignancies. The notion of SUPRA CAR, with its unique capacity to alter targets without the need to re-engineer, is a recent innovation in CAR. Given the importance of NK cells in tumor development and metastatic defence, NK cell-based immunotherapies, including adoptive transfer of NK cells, have garnered a lot of interest. With the advancement of improved cellular manufacturing methods, novel cellular engineering strategies, precision genome editing technologies, and combination therapy approaches, we firmly believe that CAR-T cells will soon become an off-the-shelf, cost-effective, and potentially curative therapy for oncogenesis.

Prevalence of Palm-Print Patterns and their Association with ABO Blood Group and Gender, among Medical Students of North India.

Introduction: The Palmprint, a dermatoglyphic marker, is defi¬ned as the print of a palm, which is mainly composed of the palmar flexion creases and ridges. The palm print patterns and blood groups are unique, stable and remain unchanged throughout the life. Hence, the present study was undertaken to investigate association between Palm print patterns and ABO and Rh blood groups in both the genders of the North Indian population. Material and Method: The sample for the cross- sectional study was consist of palmprints from 300 (Male: female 1:1,150 each) medical students of North India. The palmprints of both the hands of the subjects were recorded by the ink and roller method. Result: The distribution of palmprint patterns of both hands showed a high frequency of Category 5, moderate of category 4, small of category 6 & 3 and none of category 1 &2. The study also show gender discrimination as category 5 was more common in males while Category 4 was more common in females (P-value for Right hand is.012 and for Left hand is <.001). Positive correlation was found between palm print patterns and blood group but was not statistically significant. Conclusion: The findings of present study revealed statistically significant sexual dimorphism in the study population. Palm print patterns also showed a positive correlation with ABO blood groups.

Localization of mandibular foramen - a comparison between dry bones and orthopantomogram.

An inferior alveolar nerve block is a usual practice by a dental practitioner. Panoramic radiography is a widely used technique in dentistry to get a clear and comprehensive view before planning any treatment. The study aimed to compare the morphometric localization of mandibular foramen (MF) on dry bones and orthopantomogram. The study was designed in two phases: a morphometric study on dry human mandibles (phase I) and orthopantomograms of the same dry human mandibles (phase II). The study materials were 200 dry north Indian human mandibles belonging to unknown sex obtained from the Department of Anatomy. Descriptive statistics, including range, mean±standard deviation, paired t-test to compare dry bones and orthopantomogram, Pearson's correlation coefficient, and measurement error, were used. T-test was applied separately to compare the right and left sides of dry bones. The distance of mandibular foramen from the posterior border and lower border is shorter on the right side than on the left. Its distance from the anterior border and the mandibular notch was greater on the right side. On panoramic radiographs, the distance of MF from nearby anatomical landmarks on the mandible was highly unreliable except for the mandibular notch. Our findings demonstrate a statistically significant difference between distances on dry bone and OPG but no statistically significant difference between MF-notch on both sides and MF-AB on the right side. As a result, a surgeon can rely upon a mandibular notch to locate mandibular foramen during clinical procedures. Magnification is an inbuilt property of OPG; for precise localization of MF, it is advisable to proceed with advanced three-dimensional techniques to protect viable anatomical structures.

Ethanol exposure induces cerebellar neuronal loss in rats

Ethanol exposure causes cerebellar dysfunction and cerebellar ataxia. Cerebellar Purkinje cells damage has not been explained as a constant finding in studies addressing the alcoholic brain or in experimental studies. The present study aimed to find out the changes of cerebellar Purkinje cells in adult rats. Adult rats were divided into control (C) and ethanol treated (E) groups eight animal each. The rats in group E were exposed to ethanol 1g/kg bodyweight for three months. Moderate ethanol intake produces significant reduction in the count of Purkinje cells in the anterior lobe of cerebellum with irregular shrunken outline losing their characteristic pyriform shape. Eosinophilic swelling seen adjacent to Purkinje cell bodies. Purkinje cells were observed without a prominent nucleolus or well defined nuclear membrane. Pyknosis of Purkinje cells was also observed

No disponible

An unusual 'w' shaped thyroid gland with absence of isthmus - a case report.

Thyroid gland is one of the largest endocrine glands located in the neck opposite C5-T1 vertebrae. It consists of 2 lobes connected to each other by an isthmus. It depicts a number of congenital anomalies. One such variant was seen in a 55-year-old male cadaver whereby the gland was 'W' shaped in toto with each lobe consisting of medial & lateral limbs. The medial limbs of the 2 lobes united with each other in the midline in the form of an inverted '^' and thus the gland was 'W' shaped. The isthmus as such was absent. It is an extremely rare condition which should be known to the surgeons operating in this area. Its ontogeny, phylogeny & clinical/surgical implications are discussed in detail.

A rare presentation of the double inferior vena cava with an anomalous retrocaval right ureter: embryogenesis and clinical implications.

On dissection of the abdomen of an adult male cadaver, in addition to the normal inferior vena cava on the right side, an unusual venous channel which connected the left renal vein with the left common iliac vein was found; (probably the left inferior vena cava). The left testicular and the left suprarenal veins were opening into the left renal vein as usual. Other than this, a retrocaval ureter was found on the right side. The works of previous authors have highlighted the incidence of a venacaval duplication and its surgical implications, but here, we are presenting a unique case of a double inferior vena cava with an anomalous retrocaval ureter. A conglomeration of such vascular malformations is of immense surgical importance, and it is indicative of a grossly defective angiogenesis. Keeping in mind the clinical relevance of the variations which were observed, an attempt was made to explain them in the light of the embryogenic development.

Vitamin D status and its seasonal variability in healthy young adults in an Asian Indian urban population.

OBJECTIVE: To assess the vitamin D status and its seasonal variability in healthy young adults in Chandigarh, a city in northern India. METHODS: The history was elicited and examination was performed pertaining to metabolic bone disease in 329 young adults (18 to 25 years of age) at the end of summer and 237 subjects from the same cohort at the end of winter. The calcium profile, 25-hydroxyvitamin D [25(OH)D], and intact parathyroid hormone were measured during both the seasons. RESULTS: Among the young adults in this study cohort, 25(OH)D sufficiency (≥ 30 ng/mL) was found in 72.5% in summer and in 50.7% in winter. A significantly higher number of men were 25(OH)D sufficient in comparison with women in summer (P = .001). The mean (standard deviation) serum 25(OH)D levels were significantly higher at the end of summer-52.9 (33.7) ng/mL-in comparison with that at the end of winter-31.8 (21.1) ng/mL; P<.001. The intact parathyroid hormone levels were significantly lower in the 25(OH)D-sufficient group (P = .001) and began to increase at 25(OH)D levels below 25 ng/mL. The serum 25(OH)D levels correlated positively with the duration of exposure to sunlight during summer (r = 0.111; P = .05) and also the calcium intake during summer (r = 0.129; P = .03). CONCLUSION: Vitamin D sufficiency may be a reality with a combination of young skin, optimal and effective exposure to sunlight, and adequate calcium intake.

Diabetes and periodontitis.

The main aim of this review is to update the reader with practical knowledge concerning the relationship between diabetes mellitus and periodontal diseases. Exclusive data is available on the association between these two chronic diseases till date. Articles published on this relationship often provide the knowledge of definitions of diabetes mellitus and periodontal diseases, prevalence, extent, severity of periodontal disease, complications of diabetes along with the possible underlying mechanisms. The authors reviewed human epidemiological studies, cross-sectional observations and longitudinal cohort, case control that evaluated variables exclusively over the past 30 years and the predominant findings from the "certain" articles are summarized in this review. This review clarifies certain queries such as 1) Do periodontal diseases have an effect on the metabolic control of diabetes? 2) Does diabetes act as a risk factor of periodontitis? 3) What are the possible underlying mechanisms relating the connection between these two chronic diseases? 4) What is the effect of periodontal intervention on metabolic control of diabetes? After a thorough survey of literature, it was observed that diabetes acts as a risk factor in development of periodontitis as periodontitis is significantly aggravated in patients suffering from diabetes having long term hyperglycemia. Different mechanisms underlying the association between the accelerated periodontal disease and diabetes are emerging but still more work is required. Major efforts are required to elucidate the impact of periodontal diseases on diabetes. At the same time, patients are needed to be made aware of regular periodontal maintenance schedule and oral hygiene.