Standardization on purification process of Manosilai (Red Orpiment)

Siddha system of medicine emphasis, before going to medicine preparation every raw drug must be purified. The concept of Shuddhi (purification) in Siddha is not only a process of purification / detoxification, but also a process to enhance the potency and efficacy of the drug. There is no scientific evidence what all the changes occur during the purification process are. The Purification method of the chosen drug had been selected from the Siddha literature “Aagathiyar vaithiya kaaviyam 1500”. The classic method of purification was said by the famous Siddhar Aagathiyar who is known for his excellence in various realm of Siddha medicine. For the purpose of study, 500gm of raw drug Manosilai was procured from renowned country drug shop in Chennai. The authentication for raw drug was obtained from siddha central research institute, Chennai- 06. Ulunthu was procured from Market and authenticated by, Botanist, Plant Anatomy Research centre, Chennai-5. Then the raw drug was divided into two equal quantities of 250gm. One of the part of the raw drug was taken and powdered well and kept as such labelled as un purified raw drug Manosilai. The other part of the raw drug Manosilai was subjected to purification procedure Manosilai is made into small pieces and make in to a bundle, The above bundle is boiled with goat’s urine by using thula appliances and then the bundle is take out and kept in black gram boiled water after that the bundle is opened and dried it. Then it was powdered and labelled as purified drug Manosilai the qualitative and quantitative analyses were done for both the samples of unpurified and purified raw drug Manosilai. The physico-chemical analysis of the purified Manosilai reveals state of better absorption in the intestine, higher stability, purity, and Water solubility. The chemical analysis shows the presence of physiologically important metals and minerals such as arsenic, copper, Calcium, Magnesium,, Carbonate and mercury. The results of ICPOES analysis indicates the presence of increased concentration of physiologically important minerals in purified Manosilai and also slightly lower limits of heavy metals such as Mercury, Lead, Arsenic and Cadmium After purification. The results of FTIR analysis show the presence of Sulfide, Alcohol, Amine, CH, and NH2 48 functional groups. The HR-SEM analysis consists of agglomerates of various shapes and sizes in reduction with increase in magnification from before to after purification. The agglomerates were found leaving pores in between which would permit the circulation of body fluid throughout the coating, when it is used as a medicine. The XRD analysis results depicts clearly that the crystalline phase is increased with increase in intensity, which indicates that purified Manosilai is attributed for better bioavailability and dissolution rate. Pesticide residue, Microbial load& aflatoxin level were quantitatively measured in the raw Manosilai the result indicated the absence of them. CONCLUSION: The following inferences are drawn based on qualitative and quantitative analysis of before and after purification of Manosilai with goat’s urine and .boiled black gram water. a. Before purification the total ash value is 4.088% w/w w After purification the total ash value reduced to 3.319 % w/w. It denotes the impurities are removed. b. Before purification the moisture content is 0.4481 % w/w. After purification the moisture content reduced to 0.2953 % w/w. It denotes that the shelf life is increased after purification. c. ICP-0ES results suggest Mercury, Arsenic and Cadmium level reduced after purification. d. Crystalline is increased which enriches better bioavailability and dissolution of the drug. Siddha system insists on Purification before using them in the pharmaceutical preparations. The present study of purification process of Manosilai the impurities is removed and the quality of the drug is improved. Therefore the purified drug when used in medicine preparation may increase the efficacy and potency of the medicine. The changes found in after purification of Manosilai indicates the necessity of purification. This purification process of Manosilai with Goat’s urine and Boiled Black Gram water can be set as one of the standard purification process of Manosilai. Therefore it can be concluded that after the purification of Manosilai, through the above purification Method, has more efficacy and safety

Do not forget to see the linear hyperdense sign on CT

No Abstract

Multifactorial Aspects Influencing Non-Alcoholic Fatty Liver Disease (Nafld)

Nonalcoholic fatty liver disease (NAFLD) is a growing public health concern, with a prevalence of up to 25% worldwide. While once considered a benign condition, NAFLD is now recognized as a major cause of chronic liver disease, liver failure, and hepatocellular carcinoma. The pathogenesis of NAFLD is multifactorial and involves a complex interplay between genetic, environmental, and metabolic factors. In this review, we provide an overview of the multifactorial aspects of NAFLD, including genetic predisposition, insulin resistance, dyslipidemia, gut microbiota, dietary factors, and physical inactivity. We also discuss the role of inflammation, oxidative stress, and hepatic steatosis in the progression of NAFLD to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Finally, we review the current and emerging therapies for NAFLD and NASH, including lifestyle modifications, pharmacological interventions, and surgical approaches. The multifactorial nature of NAFLD requires a comprehensive approach to diagnosis, treatment, and prevention, with a focus on addressing the underlying metabolic and environmental factors that contribute to its development and progression

TSH Receptor Gene and Autoimmune Thyroid Diseases

The primary regulators of thyroid activity are the thyroid-stimulating hormone (TSH) and its receptor (TSH-R). Studies have shown that genetic variants in the TSHR gene can increase susceptibility to autoimmune thyroid diseases (AITD). The TSHR gene is located on chromosome 14q31 and encodes a membrane-bound receptor that interacts with TSH to regulate thyroid hormone synthesis and secretion. AITD including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are the most common thyroid disorders, affecting millions of people worldwide. In AITD, autoantibodies can bind to and activate the TSHR, leading to increased thyroid hormone production and secretion in GD, or thyroid destruction and hypothyroidism in HT. In addition to its role in thyroid hormone synthesis and secretion, some studies also revealed that the TSHR has also been implicated in a variety of other physiological processes, including bone metabolism, reproduction, and immune regulation. Genetic variation in the TSHR region may affect the expression, post-translational processing, and/or protein structure, which in turn may cause or worsen the autoimmune response. The TSHR gene and its products are widely used in diagnostic testing for AITD. Understanding the molecular mechanisms underlying the interaction between the TSHR and autoantibodies is critical for developing new diagnostic and therapeutic strategies for AITD

Crystallization and preliminary X-ray analysis of shikimate dehydrogenase fromEscherichia coli

Shikimate dehydrogenase from Escherichia coli has been crystallized by the vapour-diffusion method using ammonium sulfate as a precipitant. Mass spectrometry confirmed the purity of the enzyme and dynamic light scattering was used to find the appropriate additives to yield a monodisperse enzyme solution. The crystals are monoclinic, space group C2, with unit-cell parameters a = 110.0, b = 139.8, c = 102.6 Å, [beta] = 122.2° (at 100 K). Native crystals diffract to 2.3 Å in-house on a rotating-anode X-ray source. The asymmetric unit is likely to contain four molecules, related by 222 symmetry, corresponding to a packing density of 2.86 Å3 Da-1

Genetic Aspects of Implantation Failure

Implantation failure refers to the inability of a fertilized egg, or embryo, to successfully implant itself in the endometrial lining of the uterus, leading to pregnancy loss. The repeated failure of good quality embryo implantation is referred to as recurrent implantation failure (RIF). This can occur for a variety of reasons, including chromosomal abnormalities in the embryo, problems with the endometrium, or issues with the immune system. Factors such as advanced maternal age, obesity, smoking, and certain medical conditions can also increase the risk of implantation failure. While treatment such as in vitro fertilization (IVF) can help to improve the chances of successful implantation, there is currently no definite way to prevent or treat implantation failure.  Patients and healthcare professionals have substantial diagnostic and treatment hurdles as a result of many etiological factors and lack of knowledge about RIF. A number of studies have indicated a correlation between irregular hormone levels, disruptions in angiogenic and immunomodulatory factors, specific genetic polymorphisms, and the prevalence of RIF. Nonetheless, the precise and intricate underlying pathophysiology of RIF remains elusive.  However, many studies are ongoing in this field to understand the underlying causes and to find new ways to help couples achieve pregnancy. This review article extensively explores diverse molecular and genetic facets aimed at enhancing the diagnosis and management of implantation failure

Novel Role of Phosphorylation-Dependent Interaction between FtsZ and FipA in Mycobacterial Cell Division

The bacterial divisome is a multiprotein complex. Specific protein-protein interactions specify whether cell division occurs optimally, or whether division is arrested. Little is known about these protein-protein interactions and their regulation in mycobacteria. We have investigated the interrelationship between the products of the Mycobacterium tuberculosis gene cluster Rv0014c-Rv0019c, namely PknA (encoded by Rv0014c) and FtsZ-interacting protein A, FipA (encoded by Rv0019c) and the products of the division cell wall (dcw) cluster, namely FtsZ and FtsQ. M. smegmatis strains depleted in components of the two gene clusters have been complemented with orthologs of the respective genes of M. tuberculosis. Here we identify FipA as an interacting partner of FtsZ and FtsQ and establish that PknA-dependent phosphorylation of FipA on T77 and FtsZ on T343 is required for cell division under oxidative stress. A fipA knockout strain of M. smegmatis is less capable of withstanding oxidative stress than the wild type and showed elongation of cells due to a defect in septum formation. Localization of FtsQ, FtsZ and FipA at mid-cell was also compromised. Growth and survival defects under oxidative stress could be functionally complemented by fipA of M. tuberculosis but not its T77A mutant. Merodiploid strains of M. smegmatis expressing the FtsZ(T343A) showed inhibition of FtsZ-FipA interaction and Z ring formation under oxidative stress. Knockdown of FipA led to elongation of M. tuberculosis cells grown in macrophages and reduced intramacrophage growth. These data reveal a novel role of phosphorylation-dependent protein-protein interactions involving FipA, in the sustenance of mycobacterial cell division under oxidative stress

Positive feedback and noise activate the stringent response regulator Rel in mycobacteria

Phenotypic heterogeneity in an isogenic, microbial population enables a subset of the population to persist under stress. In mycobacteria, stresses like nutrient and oxygen deprivation activate the stress response pathway involving the two-component system MprAB and the sigma factor, SigE. SigE in turn activates the expression of the stringent response regulator, rel. The enzyme polyphosphate kinase 1 (PPK1) regulates this pathway by synthesizing polyphosphate required for the activation of MprB. The precise manner in which only a subpopulation of bacterial cells develops persistence, remains unknown. Rel is required for mycobacterial persistence. Here we show that the distribution of rel expression levels in a growing population of mycobacteria is bimodal with two distinct peaks corresponding to low (L) and high (H) expression states, and further establish that a positive feedback loop involving the mprAB operon along with stochastic gene expression are responsible for the phenotypic heterogeneity. Combining single cell analysis by flow cytometry with theoretical modeling, we observe that during growth, noise-driven transitions take a subpopulation of cells from the L to the H state within a "window of opportunity" in time preceding the stationary phase. We find evidence of hysteresis in the expression of rel in response to changing concentrations of PPK1. Our results provide, for the first time, evidence that bistability and stochastic gene expression could be important for the development of "heterogeneity with an advantage" in mycobacteria.Comment: Accepted for publication in PLoS On

Evaluating Gene Expression Dynamics Using Pairwise RNA FISH Data

Recently, a novel approach has been developed to study gene expression in single cells with high time resolution using RNA Fluorescent In Situ Hybridization (FISH). The technique allows individual mRNAs to be counted with high accuracy in wild-type cells, but requires cells to be fixed; thus, each cell provides only a “snapshot” of gene expression. Here we show how and when RNA FISH data on pairs of genes can be used to reconstruct real-time dynamics from a collection of such snapshots. Using maximum-likelihood parameter estimation on synthetically generated, noisy FISH data, we show that dynamical programs of gene expression, such as cycles (e.g., the cell cycle) or switches between discrete states, can be accurately reconstructed. In the limit that mRNAs are produced in short-lived bursts, binary thresholding of the FISH data provides a robust way of reconstructing dynamics. In this regime, prior knowledge of the type of dynamics – cycle versus switch – is generally required and additional constraints, e.g., from triplet FISH measurements, may also be needed to fully constrain all parameters. As a demonstration, we apply the thresholding method to RNA FISH data obtained from single, unsynchronized cells of Saccharomyces cerevisiae. Our results support the existence of metabolic cycles and provide an estimate of global gene-expression noise. The approach to FISH data presented here can be applied in general to reconstruct dynamics from snapshots of pairs of correlated quantities including, for example, protein concentrations obtained from immunofluorescence assays