scholarly journals Search for a molecular mechanism of action of the potentized homeopathic drugs in living organisms

2021 ◽  
Vol 11 (40) ◽  
pp. 147-147
Author(s):  
Anisur Rahman Khuda-Bukhsh
Keyword(s):  
Mechanism Of Action ◽  
Molecular Mechanisms ◽  
Arsenic Removal ◽  
Recovery Process ◽  
Human Beings ◽  
Mice Model ◽  
Electron Microscopic ◽  
Sod Activity ◽  
Cells In Culture ◽  
Homeopathic Drugs

The mechanism of action of the potentized homeopathic drugs, particularly those diluted beyond Avogadro’s limit, is still a debatable issue and various hypotheses in this regard have been advocated by many. In our studies since 1980, we found that certain ultra-highly diluted homeopathic remedies could produce ameliorative effects in various model test organisms like bacteria, fungus, mice and human beings, while the succussed alcohol (placebo) could not. These drugs could antagonize/ameliorate several types of experimentally induced tumors/cancers in mice as evident from electron microscopic studies and certain specific cancer biomarkers. They also demonstrated significant effect on cell viability and apoptotic effect (mostly mitochondria mediated) on cancer cells in culture (also in experimental mice), as revealed from various assays like AnnexinV-FITC, TUNEL, DNA fragmentation, DAPI, COMET, HOECHST 33258, Rhodamine 123 etc while the succussed alcohol (“vehicle”) failed to show such effect. Expression of some key signal proteins and mRNA expressions like Bcl2 family proteins, Cytochrome c, Apaf 1, PARP, Caspase family, p53 and p38 etc in experimental mice model could be modulated by potentized homeopathic drugs. Under arsenic stress, the bacterium Escherichia coli, and the fungus Saccharomyces cerevisiae, and macrophage cells in culture responded favorably to the treatment of potentized homeopathic drug, Arsenicum Album 30C and homeopathically prepared Glucose 30C, as evident from modulation of several parameters like ROS accumulation, SOD activity, lipid peroxidation and expression level of certain relevant genes (Ars B, pts-G genes using real-time PCR) denoting detoxification, mainly via arsenic removal mechanism and suitable enzymatic modulation. Ultra-highly diluted potentized drugs (at potency 30C or above) could demonstrate protective changes simultaneously in multiple parameters (most of them under genetic control) of study, and their action continued for sometime even after the drugs were withdrawn; this indicates the ability of the drugs to trigger “gene action” involving up-regulation or down-regulation of a cascade of downstream genes, getting the recovery process into motion. The convincing evidences that support a “gene regulatory hypothesis” to explain the molecular mechanisms of action of the potentized drugs will be discussed in the light of some of our recent experimental findings on fungus, bacteria and bacteriophages.

scholarly journals Structure-based mechanism of action of a viral poly(ADP-ribose) polymerase 1-interacting protein facilitating virus replication

IUCrJ ◽  
2018 ◽  
Vol 5 (6) ◽  
pp. 866-879 ◽  
Author(s):  
Woo-Chang Chung ◽  
Junsoo Kim ◽  
Byung Chul Kim ◽  
Hye-Ri Kang ◽  
JongHyeon Son ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Molecular Mechanisms ◽  
Lytic Replication ◽  
Transcription Activator ◽  
Interacting Protein ◽  
Murine Gammaherpesvirus ◽  
Unit Structure ◽  
Parp 1

Poly(ADP-ribose) polymerase 1 (PARP-1), an enzyme that modifies nuclear proteins by poly(ADP-ribosyl)ation, regulates various cellular activities and restricts the lytic replication of oncogenic gammaherpesviruses by inhibiting the function of replication and transcription activator (RTA), a key switch molecule of the viral life cycle. A viral PARP-1-interacting protein (vPIP) encoded by murine gammaherpesvirus 68 (MHV-68) orf49 facilitates lytic replication by disrupting interactions between PARP-1 and RTA. Here, the structure of MHV-68 vPIP was determined at 2.2 Å resolution. The structure consists of 12 α-helices with characteristic N-terminal β-strands (Nβ) and forms a V-shaped-twist dimer in the asymmetric unit. Structure-based mutagenesis revealed that Nβ and the α1 helix (residues 2–26) are essential for the nuclear localization and function of vPIP; three residues were then identified (Phe5, Ser12 and Thr16) that were critical for the function of vPIP and its interaction with PARP-1. A recombinant MHV-68 harboring mutations of these three residues showed severely attenuated viral replication both in vitro and in vivo. Moreover, ORF49 of Kaposi's sarcoma-associated herpesvirus also directly interacted with PARP-1, indicating a conserved mechanism of action of vPIPs. The results elucidate the novel molecular mechanisms by which oncogenic gammaherpesviruses overcome repression by PARP-1 using vPIPs.

scholarly journals Biochemistry and Molecular Biology of Mechanisms of Action of Fibrates – An Overview

2019 ◽  
pp. 1-12 ◽  
Author(s):  
A.S. V. Prasad
Keyword(s):  
Mechanism Of Action ◽  
Molecular Mechanisms ◽  
Organic Anion ◽  
Density Lipoprotein ◽  
The United States ◽  
Mechanisms Of Action ◽  
Lipid Lowering ◽  
Intervention Trial ◽  
Ligand Interaction ◽  
Cholesterol Acyl Transferase

Fibrates are a class of medication that mainly lowers the blood triglyceride levels. They reduce the LDL and increase the levels of HDL C, in the blood. Clofibrate, the first member to be discovered  in 1962 , and introduced in USA in 1967, is withdrawn in 2002, due to unexplained hepatomegaly, hepato-toxicity and possible risk of hepatic cancer. Other fibrates are introduced in the late 1970s and early 1980s, such as gemfibrozil in the United States and bezafibrate and ciprofibrate in Europe. Their lipid lowering effects are found to decrease CVS risk , progression of atherosclerosis and metabolic syndrome,  macrovascular and microvascular diabetic complications  like stroke, myocardial infarction, peripheral vascular disease  and  diabetic  retinopathy .Various clinical trials like VA-HIT trial (Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial) ,  FIELD trail.  (the Fenofibrate Intervention and Event Lowering in Diabetes) Helsinki Heart Study,   ACCORD -Lipid trial  (The lipid component of the Action to Control Cardiovascular Risk in Diabetes trial ) and  BIP (Bezafibrate Infarction Prevention Study)  trial and angiography trials, like LOCAT (Lopid Coronary Angiography Trial)  and BECLAIT (Bezafibrate Coronary Atherosclerosis Intervention Trial) demonstrated the  beneficial effects of gemfibrozil and fenofibrate.  Their mechanism of action remained obscure for three decades, ie till 1990s, when their mode of action was found. The Mechanism of action of fibrates include limitation of substrate availability for triglyceride synthesis in the liver, promotion of the action of lipoprotein lipase, (LPL)  modulation of low density lipoprotein receptor/ligand interaction and stimulation of reverse cholesterol transport The biochemical and molecular mechanisms involving  the various  enzymes like LCAT (Lecithin-cholesterol acyl transferase)  and CYP7A1 etc.  (cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) ) ,  transporters like ABC , CETP (ATP-binding cassette transporter, Cholesterol ester binding protein) and NTCP, OATP (Na+-dependent taurocholate transporter / organic anion transporters) . These are the.) and nuclear factors like LXR, PPAR alfa etc. (liver orphan receptor α , and peroxisome proliferative nuclear factor) , in relation to the mechanisms  of action of fibrates are discussed . Areas of current interests in literature are briefed.

INFANTILE CIRRHOSIS

PEDIATRICS ◽  
1961 ◽  
Vol 28 (1) ◽  
pp. 107-127
Author(s):  
Hans F. Smetana ◽  
G. Gordon Hadley ◽  
Satyavati M. Sirsat
Keyword(s):  
Portal Hypertension ◽  
Liver Disease ◽  
Viral Hepatitis ◽  
Secretory Granules ◽  
Liver Cells ◽  
Common Source ◽  
Infantile Cirrhosis ◽  
Human Beings ◽  
Electron Microscopic ◽  
Mallory Bodies

Infantile cirrhosis is a very serious, often fatal, liver disease, largely limited to India or to descendants of Indians residing in the region of southern Asia. It occurs most frequently in children between 1 and 3 years of age and affects both sexes with about equal frequency; familial instances are not uncommon. The clinical picture is characterized by irritability, gastrointestinal upsets, jaundice, anemia and retarded development. In a number of cases there is a history of fever in some stages of the disease. Children with advanced cases develop hepatosplenomegaly, a sharp and hard anterior edge of the liver, and evidence of effects of progressive portal hypertension. The basic pathogenetic process leading to this liver disease is characterized histopathologically by evidence of profound injury to individual liver cells, resulting in severe degenerative changes and dissociation of the cytoplasmic contents; marked swelling; partial hyalinization of the cytoplasm (Mallory bodies); "bird's eye" nuclei, indicating difficulty in protein synthesis; and satellitosis about Mallory bodies—probably an attempt to remove the necrobiotic liver cells. In certain cases there is massive progressive degeneration and necrosis of liver cells, causing hepatic insufficiency without formation of regenerative pseudolobules and without development of portal hypertension. This course is interpreted as the result of a severe, diffuse injury of hepatic cells, which are unable to regenerate. This condition can perhaps be compared with the experimental massive acute necrosis due to thiamin deficiency in animals and with the diffuse hepatic necrosis seen in "florid cirrhosis" in human beings. In the majority of cases, however, there is development of a portal type of cirrhosis with formation of unilobular, regenerative islets, followed by rising portal hypertension with its usual consequences; not infrequently the regenerated elements are again destroyed by the persisting injurious process. Evidence of a causal relationship between viral hepatitis and infantile cirrhosis cannot be considered established; neither epidemiologic features nor histopathologic findings are thought to be compatible with the effects of viral hepatitis. The familial occurrence appears to be related to environmental factors rather than to a common source of infection from a silent carrier or to heredity. The nonspecific inflammatory infiltrates (satellites) accompanying this process are interpreted as a scavenger reaction secondary to the injury, degeneration, and necrosis of liver cells. Regeneration of liver cells can take place only if there are viable hepatic elements. The resulting cirrhosis of the liver is characterized by regenerated pseudolobules developing from such surviving liver cells, embedded in and surrounded by the collapsed pre-existent parenchymal stromal elements, including the surviving tissues from the portal canals. The role of the supporting tissue is considered to be entirely passive and incidental to the primary process of cell destruction. The necrobiotic changes of individual liver cells, with formation of Mallory bodies, the progressive destruction of the hepatic parenchyma, and the development of a portal type of cirrhosis are quite indicative of a nutritional cause, despite the absence of fatty metamorphosis. The histologic changes are unlike those described in persistent viral hepatitis or in the developing stages of posthepatitic (coarse, nodular) cirrhosis. The obliterative vascular changes of advanced infantile cirrhosis are interpreted as secondary phenomena accompanying the complete reorganization of the liver parenchyma. Electron microscopic studies of liver tissue from cases of histologically established infantile cirrhosis demonstrate profound disorganization of ultramicroscopic structures of liver cells, with reduction in number, distortion and partial obliteration of mitochondria, secretory granules and microsomes; deformity and distention of the channels of the intracytoplasmic reticulum; and alteration of nuclei and nuclear components. The "alcoholic hyalin" of the Mallory body appears to be the result of condensation and fusion of damaged, distorted and obliterated mitochondria.

Molecule which changed the view on skin treatment

2021 ◽  
pp. 44-55
Author(s):  
L.Ya. Fedorich
Keyword(s):  
Retinoic Acid ◽  
Nuclear Receptors ◽  
Mechanism Of Action ◽  
Molecular Mechanisms ◽  
Local Treatment ◽  
Mechanisms Of Action ◽  
Clinical Effects ◽  
Topical Retinoids ◽  
Acne Therapy ◽  
Universal Mechanism

Objective — to study the modern classification, mechanisms of action and clinical effects of vitamin A derivatives, to analyze retinoid for local treatment of various dermatoses with a universal mechanism of action at the epidermis and dermis levels. Materials and methods. A review of the literature and an analysis of the results of international clinical trials of drugs based on the natural retinoid of the first generation — tretinoin (retinoic acid) is presented. The works of dozens of authors since 1980s to the present day are analyzed. Most sources provide detailed information on the results of topical retinoids in acne therapy, which are the base of clinical guidelines. Long-term (6 months or more) studies of retinoic acid-based preparations carried out in recent decades have discovered the unique clinical effects of tretinoin in the treatment of skin photoaging, actinic keratosis, etc. They are achieved due to the effect of tretinoid on the nuclear receptors of keratinocytes and fibroblasts. Results and discussion. The molecular mechanisms of action of retinoic acid, realizing the cellular and tissue effects of the most studied retinoid, are systematized and grouped in a single review. It has been proven that a unique feature of tretinin is its ability to activate directly all subtypes of RARs- and, indirectly, RARs-nuclear receptors of skin cells. A new modern drug for external use is presented — AltrenoТМ lotion containing micronized 0.05 % tretinoin in combination with sodium hyaluronate, soluble collagen and glycerin. This combination exhibits the expected clinical efficacy in acne therapy and prevents side effects such as dryness, redness and exfoliation. AltrenoТМ is approved for use in children of 9 years of age and older. Conclusions. Tretinoin (retinoic acid) is a modern powerful retinoid with a universal mechanism of action, recommended for the treatment of acne.

scholarly journals Dietary Supplementation with Sea Bass (Lateolabrax maculatus) Ameliorates Ulcerative Colitis and Inflammation in Macrophages through Inhibiting Toll-Like Receptor 4-Linked Pathways

2019 ◽  
Vol 20 (12) ◽  
pp. 2907 ◽  
Author(s):  
Jiali Chen ◽  
Muthukumaran Jayachandran ◽  
Wenxia Zhang ◽  
Lingyuqing Chen ◽  
Bin Du ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Intestinal Inflammation ◽  
In Vitro Study ◽  
Sea Bass ◽  
Mice Model ◽  
Food Material ◽  
Lateolabrax Maculatus ◽  
Associated Conditions ◽  
Anti Inflammatory

Sea bass (Lateolabrax maculatus) is a kind of food material commonly consumed in daily life. In traditional Chinese medicinal books, it has been indicated that sea bass can be applied for managing many inflammation-associated conditions. However, the studies on the pharmacological mechanisms of inflammation of sea bass remain scarce. Hence, this study aims to investigate the molecular mechanisms of the anti-inflammatory activity of sea bass. Anti-inflammatory activities of sea bass were assessed using dextran sulfate sodium (DSS)-induced colitis in a mice model and lipopolysaccharide (LPS)-activated macrophages model. Low body weight and short colon length were observed in DSS-fed mice that were significantly recovered upon sea bass treatments. Moreover, the colon histopathology score showed that sea bass-treated mice had decreased crypt damage, focal inflammation infiltration and the extent of inflammation, suggesting that treatment with sea bass could attenuate intestinal inflammation. In addition, the in-vitro study conjointly indicated that sea bass could suppress the inflammatory mediators in LPS-activated macrophage by inhibiting the TLR4-linked pathway. The present findings demonstrated that sea bass has an inhibitory effect on TLR4 signaling; thus, it could be a promising candidate for treating inflammation-associated conditions. A further justification for the clinical application of sea bass in treating inflammation-associated conditions is necessary.

scholarly journals Molecular Mechanism ofN,N-Dimethylformamide Degradation inMethylobacteriumsp. Strain DM1

2019 ◽  
Vol 85 (12) ◽  
Author(s):  
Xinyu Lu ◽  
Weiwei Wang ◽  
Lige Zhang ◽  
Haiyang Hu ◽  
Ping Xu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Gene Clusters ◽  
Sole Source ◽  
Human Beings ◽  
Sequencing Data ◽  
Carbon And Nitrogen ◽  
Redundant Genes ◽  
Evolutionary Advantage ◽  
Redundant Gene ◽  
Phenotype Identification

ABSTRACTN,N-Dimethylformamide (DMF) is one of the most common xenobiotic chemicals, and it can be easily emitted into the environment, where it causes harm to human beings. Herein, an efficient DMF-degrading strain, DM1, was isolated and identified asMethylobacteriumsp. This strain can use DMF as the sole source of carbon and nitrogen. Whole-genome sequencing of strain DM1 revealed that it has a 5.66-Mbp chromosome and a 200-kbp megaplasmid. The plasmid pLVM1 specifically harbors the genes essential for the initial steps of DMF degradation, and the chromosome carries the genes facilitating subsequent methylotrophic metabolism. Through analysis of the transcriptome sequencing data, the complete mineralization pathway and redundant gene clusters of DMF degradation were elucidated. The dimethylformamidase (DMFase) gene was heterologously expressed, and DMFase was purified and characterized. Plasmid pLVM1 is catabolically crucial for DMF utilization, as evidenced by the phenotype identification of the plasmid-free strain. This study systematically elucidates the molecular mechanisms of DMF degradation byMethylobacterium.IMPORTANCEDMF is a hazardous pollutant that has been used in the chemical industry, pharmaceutical manufacturing, and agriculture. Biodegradation as a method for removing DMF has received increasing attention. Here, we identified an efficient DMF degrader,Methylobacteriumsp. strain DM1, and characterized the complete DMF mineralization pathway and enzymatic properties of DMFase in this strain. This study provides insights into the molecular mechanisms and evolutionary advantage of DMF degradation facilitated by plasmid pLVM1 and redundant genes in strain DM1, suggesting the emergence of new ecotypes ofMethylobacterium.

scholarly journals Silicon Promotes Adventitious Shoot Regeneration and Enhances Salinity Tolerance ofAjuga multifloraBunge by Altering Activity of Antioxidant Enzyme

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Iyyakkannu Sivanesan ◽  
Byoung Ryong Jeong
Keyword(s):  
Salinity Tolerance ◽  
Shoot Regeneration ◽  
Microscopic Analysis ◽  
Adventitious Shoot ◽  
Induction Medium ◽  
Shoot Induction ◽  
Electron Microscopic ◽  
Sod Activity ◽  
Scanning Electron Microscopic Analysis ◽  
Shoot Induction Medium

We investigated the effect of Si concentration on shoot regeneration and salinity tolerance ofAjuga multiflora. Addition of Si to the shoot induction medium significantly increased the frequency of shoot induction. The average number of shoots regenerated per explant decreased on the medium containing NaCl alone, while there was less decrease when the shoot induction medium was supplemented with both NaCl and Si. The shoot induction percentage increased linearly with increasing concentration of Si in the NaCl containing medium. Addition of Si to the shoot induction medium significantly increased SOD, POD, APX, and CAT activity in regenerated shoot buds as compared with the control. The inclusion of Si to the NaCl containing medium significantly increased the SOD activity in leaves and roots, while it decreased POD, APX, and CAT activity in both organs. Scanning electron microscopic analysis showed that there are no distinct differences in the structure of stomata between the control and Si-treated plants. However, NaCl treatment significantly affected the structure and number of stomata as compared to the control. Wavelength dispersive X-ray analysis confirmed the high Si deposition in trichomes of plants grown in the Si containing medium but not in plants grown in the medium without Si.

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