Toxic Metal -Mediated Neurodegradation: A Focus on Glutathione and GST Gene Variants.

Increasing pieces of evidence have supported those chemicals from industrial, agricultural wastes and organoleptic activities play important role in the development of neurological disorders. The frequency of neurological disorders is increased to a much extent in recent years with the advancements in science and technology. Google Scholar, PubMed, and Scopus databases were selected to search the relevant information by using keywords including "Heavy metals", "Neurotoxicity", "Glutathione", "Glutathione AND Neurodegenerative disorders" etc. Heavy metals are particularly recognized as a major resource of toxicities during the stage of early pregnancy where a fetus gets exposed to them from maternal activities and circulation. As infants have a weak immune system and cannot respond to the specific challenge as faced by the body during mercury, zinc, iron, and cadmium exposure. Daily diet and drinking habits in addition to industrial activities also form a major field of study under investigation. This study aims to investigate the role of these metals in the accumulation of pollutants in the brain, liver, and kidneys hence leading to serious consequences. Moreover, their prevalence in teenagers that are under the age of ten years is being observed that leads them to learn, writing, and intellectual abilities. Males are more affected due to their hormonal differences. The role of the GST gene in the development of cognitive conditions and its phenotypes has been discussed thoroughly in this review. The mutations of GST lead to the accumulation of peroxides and superoxides which exacerbate oxidative damage to cells. Binding of toxic metals to GSH genes and the role of glutathione transferase genes is was demonstrated in this review.

Increasing Efficacy of Covid-19 Vaccines by Lifestyle Interventions.

COVID-19 caused a serious threat to the world population as it spread worldwide rapidly. Existing medicines and vaccines could not cure and control this deadly disease. In this regard, several vaccines have been proposed and designed to control this infection's spread effectively. Along with these vaccines, the general population should adopt specific lifestyle interventions to strengthen their immune system and combat deadly viruses. We used Google Scholar and PubMed databases to find the related information using key terms such as 'COVID-19', 'COVID-19 AND Vaccine efficacy', 'Lifestyle intervention AND COVID-19', and "Lifestyle intervention AND Vaccines," etc. Only articles that discussed the interactions between lifestyle intervention and the efficacy of COVID-19 vaccines were selected for this study. Several previous clinical trials and scientific observations with influenza, polio, and other viral vaccines have demonstrated that vaccine response varies across individuals for antibody titer, independent of vaccine antigenicity. This different vaccine response observed among individuals is attributed to several factors such as dietary and nutritional habits, physical activity, stress and sleep deprivation, deficiency of micronutrients (minerals, vitamins), gut microbiota composition, immunosenescence, smoking, and drinking habits. Although there is not much information about COVID-19 vaccine efficacy and lifestyle interventions, experience with other vaccines can undoubtedly be used to suggest lifestyle interventions to improve COVID-19 vaccine efficacy. These lifestyle interventions may boost antibody responses against COVID-19 vaccines, leading to higher protection from the disease, especially among elderly and immunocompromised people. In conclusion, the present review attempts to understand the role of various nutritional and psychological factors that lead to poor vaccine response and suggests specific nutritional and psychological interventions that can enhance vaccine efficacy and improve immune response against COVID-19 vaccines.

A Review on Metabolic Paradoxes and their Impact on Metabolism.

The current review paper portrays the important link of different nutrients like trace elements, proteins, fatty acids, vitamins, and amino acids with the immune system as well as information related to metabolic paradoxes. Optimum working of the metabolic system is essential because it gives various types of supplements to the human body and aid in chemical pathways. Here related data have been retrieved from two databases i.e., PubMed and Google scholar to grasp detailed knowledge about micronutrients and nutrients as well as their association in the metabolic system. Like protein play important role in the normal development of different immune components, amino acids including alanine, Arginine, and glutamic acid properly control the movement of neutrophils, macrophages, and cytokines. While fatty acids act as an anti-inflammatory agent because they possess the ability to inhibit the expression of the MHC class. Apart from these, many essential molecules like uric acid, proteins, calcium, lanolin are also obtained as end products after catabolic and anabolic reactions, and it was found that the uric acid paradox has a cancer inhibitory role. Additionally, TGF and IL-6 paradoxes have a role in the development of tumors, the onset of diabetes, and low-grade inflammatory disorders respectively. However, the entire functioning of metabolic processes depends upon daily diet because humans get the important nutrient from the diet which further vital role in the immune system. Moreover, it was also observed that calcium paradox is related to heart disorders because high calcium accumulation leads to cardiac disorders. Thus, the complete knowledge about these essential components as well as metabolic paradoxes is very important due to their antagonistic role to plan better and improved therapeutic strategies for various diseases.

Lifestyle Genetics-Based Reports in the Treatment of Obesity.

Obesity becomes a chronic disease due to the increasing number of mortality and morbidity cases around the world. In most regions, chronic illnesses, such as obesity, are important sources of morbidity and mortality. Due to a lack of effective strategies for prevention and management, the adverse effects of obesity and related diseases on health continue to be a serious problem. Relevant information was searched from Google Scholar, Scopus, and PubMed using such different terms as "Obesity", "Obesity Management", "Obesity AND Physical activity", "Obesity AND Genetics", "Obesity AND Diet", and "Obesity AND Nutrigenomics". Obesity is characterized by a complex interaction of hereditary and lifestyle factors, which includes food. Diet is an environmental element that plays an important and considerable role in the management of health and reduces the risk of obesity and its comorbidities. Changes in lifestyle patterns not only help burn extra calories but also prevent the development of obesity via its modulating effect on genetic factors. Different people respond differently to an obesogenic environment. The notion of nutrigenetics emerged as a result of various genetic variations that may explain this heterogeneity. Nutritional genomics, also known as nutrigenetics, is the study that investigates and analyses gene variations linked to varied responses to certain foods; moreover, it links this variation to diseases, such as obesity. As a result, tailored nutrition advice based on a person's genetic profile may improve the outcomes of a specific dietary strategy and offer a novel dietary strategy to improve life quality and preventing obesity. This study concluded that physical activity and dietary interventions play an effective role in the management of obesity. Moreover, understanding of the function of the most prominent obesity-related genes, as well as the interaction between nutrition and gene expression, will help researchers design personalized treatment strategies for humans.

Oral Aphthous: Pathophysiology, Clinical Aspects and Medical Treatment.

Oral aphthosis is a painful inflammatory process of the oral mucosa. Oral aphthous can appear alone or secondary to numerous distinct disease processes. If recurrence occurs frequently, it is called recurrent aphthous stomatitis. The pathophysiology of oral aphthous ulcers remains unclear but various bacteria are part of its microbiology. Three morphological types hold great importance in literature because these types help manage the illness properly. Google Scholar and PubMed databases were used to retrieve the relevant data and information. Different keywords including "Aphthous", "Aphthosis", "Canker sores", "Aphthous stomatitis", "Aphthous ulcer causes", "Aphthous ulcer AND Microbiota" and "Aphthous ulcer AND treatment". The causes for oral aphthous ulcerations are widespread and ranges from localized trauma to rare syndromes, underlying intestinal disease, or even malignant disease processes. A detailed history and thorough examination of systems can assist the physician or dermatologist in defining whether it is related to a systemic disease process or truly idiopathic. Management of oral aphthous ulcers is challenging. For oral aphthous or recurrent aphthous ulcers from an underlying disease, topical medications are preferred due to their minimum side effects. Systemic medications are necessary if the disease progresses. Within the limitation of research and literature provided, it is safe to say that topical corticosteroids are the first line of treatment. Herein, the author discusses the pathophysiology, types, causes, diagnosis, and appropriate treatment ladder of oral aphthous stomatitis as described in the literature.

Association of rheumatoid arthritis with Mdm2 SNP309 and genetic evidence for an allele-specific interaction between MDM2 and p53 P72R variants: a case control study.

OBJECTIVE: This study examines two common, functional, single nucleotide polymorphisms (SNP) in the genes coding the human homolog of murine-double-minute-2 (MDM2) and p53 in patients with rheumatoid arthritis (RA) based on the hypothesis that p53 may be an important negative regulator of the pro-inflammatory transcription factor nuclear factor kappa b (NFKappaB). METHODS: Genomic DNA was obtained from 221 patients with RA who fulfilled at least 4 ACR criteria and from 521 healthy controls. Mdm2 SNP309 and p53 P72R were genotyped by polymerase chain reaction and restriction enzyme analysis. RESULTS: In RA patients the frequencies of the mdm2 SNP309 G allele and both G-containing genotypes were significantly reduced (G allele: OR: 0.75, 95% CI: 0.59-0.95, p=0.016; genotype TG: OR: 0.71, 95% CI: 0.50-1.00; genotype GG: OR. 0.58, 95% CI: 0.34-0.99; both: p=0.049). Concerning p53 P72R, no differences in allele or genotype frequencies were detected. A combined analysis of both polymorphisms revealed a significant interaction between them (p=0.046). In individuals carrying >1 p53 72R allele, MDM2 had a protective effect, whereas in individuals homozygous for p53 72P, MDM2 had the opposite effect. CONCLUSION: The function of MDM2 depends on the p53 P72R genotype, resulting in either an increased or reduced risk for RA. We suggest that in most cases MDM2 stabilizes the conformation of p53, whereas in p53 PP-positive subjects MDM2 supports the degradation of p53.

A subchronic 90-day oral rat toxicity study and in vitro genotoxicity studies with a conjugated linoleic acid product.

Conjugated linoleic acid (CLA) is the term given to a group of positional and geometric isomers of the essential fatty acid linoleic acid. CLA is found naturally in foods such as dairy and meat products. CLA is reported to have a number of beneficial effects including anticarcinogenic activity. However, safety data are limited. Clarinol G80 is a commercial preparation containing equal amounts of the 9cis,11trans and 10trans,12cis CLA isomers in the form of glycerides. In order to support the safety-in-use of Clarinol G80 as an ingredient in food, the preparation was tested in two in vitro mutagenicity assays, an Ames test and an in vitro cytogenetics assay, and a 90-day repeat-dose oral toxicity rat study. Clarinol G80 was non-mutagenic in both in vitro assays. In the 90-day study, Clarinol G80 produced hepatocellular hypertrophy in female rats at the highest dose level (15% w/w). This effect was an adaptive effect in response to feeding high levels of Clarinol G80 in the diet and was reversible upon withdrawal of test material. An increase in plasma insulin levels was also observed female rats fed 15% w/w Clarinol G80 but there was no effect on plasma glucose levels. A No Observed Adverse Effect Level of 2433 mg/kg bw/day for male and 2728 mg/kg bw/day female rats was identified in the study.

Two-dimensional electrophoretic analysis of nuclear proteins from human tumors.

During the last decade several strategies have been developed to identify proteins which could serve as markers in tumor biology. One avenue of great promise to detect such proteins seems to be the separation of prefractionated organelles from tumor cells by high resolution two-dimensional electrophoresis. Using detergent-lysed nuclei from several human tumor cell lines, especially from brain tumors, and two-dimensional electrophoresis, we analyzed the nuclear protein pattern obtained after sequential salt extraction of tumor cell nuclei. In addition to proteins occurring in all tumor cell lines, the pattern of different tumor cell lines exhibits considerable differences when proteins were visualized by silver staining, thus emphasizing the specificity of nuclear proteins with respect to the cell type. Even quantitative variations of the nuclear phosphoproteins 23/4 were detectable, indicating a potential correlation between their synthesis/phosphorylation and the proliferation behavior of tumor cells. The data indicate that nuclear proteins with their distinct heterogeneity and tissue specificity may represent a powerful source in determining tumor-specific proteins. The extent of chromosomal protein heterogeneity may be additionally increased by their covalent modification by nuclear kinases; therefore, tumor-specific nuclear proteins may occur as quantitative and qualitative variations.

CT guided percutaneous fine-needle biopsy of the pancreas.

147 CT guided fine-needle biopsies of the pancreas were carried out on 141 patients (45 malignant tumours, 79 chronic pancreatitis and pancreas without lesions, respectively). In 23 pseudocysts a malignant lesion could be excluded. By analysing the remaining 124 biopsies (non-cystic targets) an overall accuracy of 79%, a sensitivity of 71% and a specificity of 84% in differentiating between benign and malignant lesions were obtained. By excluding 12% of biopsies with no diagnostic material, an overall accuracy of 90% might be recorded. The comparison between the number of aspirates per examination and the cytological diagnoses would indicate that a minimum of four aspirates is required for satisfactory results.