scholarly journals An Analysis of the Multifaceted Roles of Heme in the Pathogenesis of Cancer and Related Diseases

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4142
Author(s):  
Tianyuan Wang ◽  
Adnin Ashrafi ◽  
Pouya Modareszadeh ◽  
Alexander R. Deese ◽  
Maria Del Carmen Chacon Castro ◽  
...  
Keyword(s):  
Soluble Guanylate Cyclase ◽  
P53 Protein ◽  
Epidemiological Data ◽  
Cellular Proteins ◽  
Neurological Deficits ◽  
Oxygen Utilization ◽  
Prosthetic Group ◽  
Disease Pathogenesis ◽  
Common Diseases ◽  
Depth Analysis

Heme is an essential prosthetic group in proteins and enzymes involved in oxygen utilization and metabolism. Heme also plays versatile and fascinating roles in regulating fundamental biological processes, ranging from aerobic respiration to drug metabolism. Increasing experimental and epidemiological data have shown that altered heme homeostasis accelerates the development and progression of common diseases, including various cancers, diabetes, vascular diseases, and Alzheimer’s disease. The effects of heme on the pathogenesis of these diseases may be mediated via its action on various cellular signaling and regulatory proteins, as well as its function in cellular bioenergetics, specifically, oxidative phosphorylation (OXPHOS). Elevated heme levels in cancer cells intensify OXPHOS, leading to higher ATP generation and fueling tumorigenic functions. In contrast, lowered heme levels in neurons may reduce OXPHOS, leading to defects in bioenergetics and causing neurological deficits. Further, heme has been shown to modulate the activities of diverse cellular proteins influencing disease pathogenesis. These include BTB and CNC homology 1 (BACH1), tumor suppressor P53 protein, progesterone receptor membrane component 1 protein (PGRMC1), cystathionine-β-synthase (CBS), soluble guanylate cyclase (sGC), and nitric oxide synthases (NOS). This review provides an in-depth analysis of heme function in influencing diverse molecular and cellular processes germane to disease pathogenesis and the modes by which heme modulates the activities of cellular proteins involved in the development of cancer and other common diseases.

scholarly journals Assessment of the Sexual Violence Situation in a Regional Hospital in Guatemala: The Need for a Multidisciplinary Clinic

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S105-S105
Author(s):  
Blanca Soto ◽  
Miriam Canet ◽  
Diego Erdmenger
Keyword(s):  
Sexual Violence ◽  
Physical Violence ◽  
Negative Impact ◽  
Epidemiological Data ◽  
Depth Analysis ◽  
Significant Negative Impact ◽  
Comprehensive Health ◽  
History Of ◽  
Hepatitis B Testing

Abstract Background Sexual violence is a global health problem, in terms of age and sex, showing a significant negative impact on health. Incidence in Guatemala is among the highest of the region reaching an average of 23 cases reported daily nationally per statistics from the Ministry of Health in 2015. Methods Retrospective analysis of the database of all sexual violence cases reported from a secondary -level national hospital in Guatemala from January 2005 to September 2015 (period A) and in-depth analysis on demographic and epidemiological data along with information of the follow-up of cases between January 2012 and September 2015 (period B) was performed. Results Period A: 500 cases; female (96%; 481/500). Assault occurred between 16–20 years (34%; 163/481) 11–15 years (22.25%; 107/481), and 21–30 years (22.04%; 106/481). From all reported male cases, 73.68% (14/19) occurred under 15 years. Period B: 154/217 (70.96%) cases included; female (95.45%; 147/154), mean age: 17.87 years. Assault occurred in public spaces (57.14%; 88/154) and victim’s home (29.87%; 46/154). Almost 13% of victims reported history of previous assault, 5.84% by the same aggressor. More than one aggressor participated in 36.37% of assaults. Physical violence was associated in 57.79% of cases. Most victims (92.76%; 141/152) consulted within 72 hours of the assault. HIV, VDRL, and Hepatitis B testing performed in 100, 52, and 33.77%, respectively, were negative. Follow-up visits at 3, 6, and 12 months after the aggression were attended by 20.78% (30/154), 1.95% (3/154), and 1.95% (3/154) of victims, respectively. Psychology support was completed only in 18.18% (28/154). Emergency contraception was provided when indicated; pregnancy as result of the aggression was reported in nine cases (5.84%). Conclusion The study shows that young women were the most vulnerable group for sexual violence. There is a lack of multidisciplinary approach and follow-up. Interventions on infectious diseases screening have to be optimized to reduce the risk of ETS transmission. This evidence supports the need for a specialized clinic to ensure access to comprehensive health services for victims. Disclosures All authors: No reported disclosures.

Effects of subarachnoid hemorrhage on cerebral blood volume, blood flow, and oxygen utilization in humans

1977 ◽  
Vol 46 (4) ◽  
pp. 446-453 ◽  
Author(s):  
Robert L. Grubb ◽  
Marcus E. Raichle ◽  
John O. Eichling ◽  
Mokhtar H. Gado
Keyword(s):  
Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Blood Volume ◽  
Cerebral Vasospasm ◽  
Cerebral Blood Volume ◽  
Neurological Deficits ◽  
Regional Cerebral Blood ◽  
Oxygen Utilization ◽  
Ruptured Intracranial Aneurysm ◽  
Regional Cerebral Blood Volume

✓ Forty-five studies of regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and regional cerebral oxygen utilization (rCMRO2) were performed in 30 patients undergoing diagnostic cerebral angiography for evaluation of a subarachnoid hemorrhage due to a ruptured intracranial aneurysm. Tracer methods employing radioactive oxygen-15 were used to measure rCBV, rCBF, and rCMRO2. The patient studies were divided into groups based on their neurological status and the presence or absence of cerebral vasospasm. Subarachnoid hemorrhage, with and without vasospasm, produced significant decreases in CBF and CMRO2. In general, patients with more severe neurological deficits, and patients with more severe degrees of vasospasm, had a more marked depression of CBF and CMRO2. The most striking finding was a significant (p < 0.001) increase in CBV (to 58% above normal) in patients with severe neurological deficits associated with severe cerebral vasospasm. This large increase suggests that cerebral vasospasm consists of constriction of the large, radiographically visible extraparenchymal vessels accompanied by a massive dilation of intraparenchymal vessels.

scholarly journals The Neglect and Fast Spread of Some Arboviruses: A Note for Healthcare Providers in Nigeria

Diseases ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 99
Author(s):  
Olatunji Kolawole ◽  
Adebimpe Seriki ◽  
Ahmad Irekeola ◽  
Jeremiah Ogah
Keyword(s):  
Rift Valley Fever ◽  
Healthcare Providers ◽  
Epidemiological Data ◽  
Valley Fever ◽  
Health Burden ◽  
Depth Analysis ◽  
Health Practitioners ◽  
Missed Diagnosis ◽  
Significant Health ◽  
Diagnosis Of Diseases

Arboviruses are distributed worldwide and constitute significant health burden globally. Outbreaks of arboviruses have been reported in Africa and beyond. In Nigeria, like in many other countries, arbovirus infections are more often than not neglected. As the early clinical features of arbovirus infections are generally nonspecific, most healthcare providers mistake them for other diseases. Outbreaks have been reported in Africa and beyond. The consequence of missed diagnosis of diseases cannot be overstated. In this review, some epidemiological data, classical syndromes, and risk factors for five human arboviruses (yellow fever YF, dengue DENV, chikungunya CHIKV, Rift Valley fever RVF, and West Nile virus WNV) found in Nigeria are presented. Health practitioners should ensure in-depth analysis rather than a superficial diagnosis of diseases before declaring a course of treatment.

scholarly journals NARCISSISM IN PAULA HAWKINS' NOVEL THE GIRL ON THE TRAIN

2021 ◽  
Vol 5 (1) ◽  
pp. 170-178
Author(s):  
Riska Rahayu Roisiah ◽  
Pramudana Ihsan ◽  
Wijayadi Wijayadi
Keyword(s):  
Mental Disorder ◽  
Interpersonal Relationships ◽  
Common Mental Disorder ◽  
Psychoanalytic Theory ◽  
The Novel ◽  
Main Character ◽  
Social Conscience ◽  
Self Confidence ◽  
Common Diseases ◽  
Depth Analysis

Narcissism is one of the most common diseases in psychology, but its concern is the least. Therefore, this research was focused on narcissism disorder of one of the main characters named Megan Hipwell in the novel The Girl on the Train by Paula Hawkin. The analysis was done by applying psychoanalytic theory, in narcissism, which is the most common mental disorder among the members of a society. The method of research was qualitative, which required an in-depth analysis of the literary works used by the writers of this research according to the selected theories. The analysis was aimed to find illustrations and evidence of the main character in the novel The Girl on the Train to illustrate narcissism disorder. In this research, it was found that the main character suffered from narcissistic disorder, such as big ego, over-self confidence, exploitation of Interpersonal relationships, arrogance, and deficient social conscience. The triggers were rationalization and projection.

Anti-NMDA receptor encephalitis

2021 ◽  
Vol 2 (3) ◽  
pp. 137-145
Author(s):  
Umida M. Azizova ◽  
Raisa Ts. Bembeeva ◽  
Anastasia A. Kozyreva ◽  
Nikolay N. Zavadenko
Keyword(s):  
Biological Fluids ◽  
Clinical Manifestations ◽  
Diagnostic Errors ◽  
Autoimmune Encephalitis ◽  
Diagnostic Algorithm ◽  
Epidemiological Data ◽  
Healthy Person ◽  
Favourable Outcome ◽  
Neurological Deficits ◽  
Nmdar Encephalitis

Autoimmune diseases of the central nervous system (CNS) are one of the most socially and economically significant problems of neurology. Despite the identification of new nosological forms of autoimmune encephalitis, the creation of diagnostic panels for the verification of autoantibodies in biological fluids, and the use of highly effective pathogenetic therapy, the number of diagnostic errors remains high, which poses a threat to the patient’s life and a high risk of developing severe complications. Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR encephalitis) is autoimmune encephalitis caused by the presence of antibodies (Ab) to the NR1 subunit of NMDA-receptors (NMDAR) characterized by the development of severe mental and neurological deficits in a previously healthy person. This article summarizes the recent literature on anti-NMDAR encephalitis. The literature search was carried out using the Scopus, Web of Science, Pubmed, CyberLeninka databases. The review presents the facts of the history of the study of the disease, epidemiological data, modern ideas about the pathogenetic mechanisms of the development of the disease, the spectrum of clinical manifestations and various forms of the course of the disease. The diagnostic criteria and research methods used to confirm the diagnosis are described, approaches to the treatment of anti-NMDAR encephalitis are outlined. Anti-NMDAR encephalitis is clinically manifested by a combination of mental disorders, epileptic seizures, speech and extrapyramidal disorders, and disturbances in the rhythm of sleep and wakefulness. The disease occurs at any age. The development of the disease can be associated with such immunological triggers as oncological process and herpetic encephalitis, or be idiopathic in nature. There are features of the course of the clinical picture depending on the age of the patient, paraneoplastic or postherpetic aetiology of the disease. The diagnostic algorithm, along with neuroimaging, determination of specific antibodies, electroencephalography, should also include the search for an oncological process. The recovery of patients can take from several months to years. In some cases, persistent neurological deficits develop. Predictors of a favourable outcome include early initiation and use of combination therapy, detection and removal of neoplasms, a low titer of anti-NMDAR antibodies, and age of patients over 12 years of age. In up to 25% of cases, a relapsing course of the disease is possible, and therefore requires long-term monitoring of these patients.

scholarly journals A Mutant of Human Papillomavirus Type 16 E6 Deficient in Binding α-Helix Partners Displays Reduced Oncogenic Potential In Vivo

2002 ◽  
Vol 76 (24) ◽  
pp. 13039-13048 ◽  
Author(s):  
Marie Nguyen ◽  
Shiyu Song ◽  
Amy Liem ◽  
Elliot Androphy ◽  
Yun Liu ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
P53 Protein ◽  
Human Papillomaviruses ◽  
Skin Tumors ◽  
Cellular Proteins ◽  
Viral Gene ◽  
Gene Encoding ◽  
Tumor Viruses ◽  
Α Helix

ABSTRACT Human papillomaviruses (HPVs) are small DNA tumor viruses that are the causative agent of warts and are associated with many anogenital cancers. The viral gene encoding the E6 protein has been found to be involved in HPV oncogenesis. E6 is known to inactivate the cellular tumor suppressor, p53. In addition, E6 has been shown to bind to a variety of other cellular proteins. The focus of this study was to determine what role the interactions of E6 with a subset of cellular proteins which contain a common α-helical domain in their E6 binding region (α-helix partners) play in E6-mediated phenotypes. We generated transgenic mice expressing a mutant of E6, E6I128T, which is defective for binding at least a subset of the α-helix partners, including E6AP, the ubiquitin ligase that mediates E6-dependent degradation of the p53 protein, to determine whether binding of α-helix partners plays a role in E6-mediated activities in vivo. Unlike mice expressing the wild-type E6 (strain K14E6WT), the mice expressing E6I128T lacked the ability to alter the radiation-induced block to DNA synthesis and promote the formation of benign skin tumors in conjunction with chemical carcinogens. Additionally, they displayed reduced levels of skin hyperplasia, spontaneous skin tumors, and tumor progression activity compared to those of the K14E6WT mice. From these results, we conclude that a domain in E6 that mediates α-helix partner binding is critical for E6-induced phenotypes in transgenic mice.

scholarly journals Carcinogenesis as Side Effects of Iron and Oxygen Utilization: From the Unveiled Truth toward Ultimate Bioengineering

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3320
Author(s):  
Shinya Toyokuni ◽  
Yingyi Kong ◽  
Zhen Cheng ◽  
Kotaro Sato ◽  
Shotaro Hayashi ◽  
...  
Keyword(s):  
Side Effects ◽  
Tumor Suppressor Genes ◽  
Epidemiological Data ◽  
Oxygen Utilization ◽  
Excess Iron ◽  
The Past ◽  
Non Thermal Plasma ◽  
Life On Earth ◽  
Electron Transfers ◽  
Great Advance

Evolution from the first life on earth to humans took ~3.8 billion years. During the time there have been countless struggles among the species. Mycobacterium tuberculosis was the last major uncontrollable species against the human public health worldwide. After the victory with antibiotics, cancer has become the leading cause of death since 1981 in Japan. Considering that life inevitably depends on ceaseless electron transfers through iron and oxygen, we believe that carcinogenesis is intrinsically unavoidable side effects of using iron and oxygen. Many animal models unequivocally revealed that excess iron is a risk for carcinogenesis. This is supported by a variety of human epidemiological data on cancer risk and prognosis. Cancer is basically a disease of the genome with persistently activated oncogenes and inactivated tumor suppressor genes through which iron addiction with ferroptosis-resistance is maintained. Engineering has made a great advance in the past 50 years. In particular, nanotechnology is distinct in that the size of the engineered molecules is similar to that of our biomolecules. While some nano-molecules are found carcinogenic, there are principles to avoid such carcinogenicity with a smart possibility to use nano-molecules to specifically kill cancer cells. Non-thermal plasma is another modality to fight against cancer.

scholarly journals The molecular basis of transient heme-protein interactions: analysis, concept and implementation

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Amelie Wißbrock ◽  
Ajay Abisheck Paul George ◽  
Hans Henning Brewitz ◽  
Toni Kühl ◽  
Diana Imhof
Keyword(s):  
Protein Interactions ◽  
Molecular Basis ◽  
Bacterial Infections ◽  
Specific Binding ◽  
Heme Protein ◽  
Future Research ◽  
Heme Binding ◽  
Prosthetic Group ◽  
Binding Behavior ◽  
Depth Analysis

Abstract Deviant levels of available heme and related molecules can result from pathological situations such as impaired heme biosynthesis or increased hemolysis as a consequence of vascular trauma or bacterial infections. Heme-related biological processes are affected by these situations, and it is essential to fully understand the underlying mechanisms. While heme has long been known as an important prosthetic group of various proteins, its function as a regulatory and signaling molecule is poorly understood. Diseases such as porphyria are caused by impaired heme metabolism, and heme itself might be used as a drug in order to downregulate its own biosynthesis. In addition, heme-driven side effects and symptoms emerging from heme-related pathological conditions are not fully comprehended and thus impede adequate medical treatment. Several heme-regulated proteins have been identified in the past decades, however, the molecular basis of transient heme-protein interactions remains to be explored. Herein, we summarize the results of an in-depth analysis of heme binding to proteins, which revealed specific binding modes and affinities depending on the amino acid sequence. Evaluating the binding behavior of a plethora of heme-peptide complexes resulted in the implementation of a prediction tool (SeqD-HBM) for heme-binding motifs, which eventually led and will perspectively lead to the identification and verification of so far unknown heme-regulated proteins. This systematic approach resulted in a broader picture of the alternative functions of heme as a regulator of proteins. However, knowledge on heme regulation of proteins is still a bottomless barrel that leaves much scope for future research and development.

scholarly journals Utilizing three years of epidemiological data from medical missions in Cambodia to shape the mobile medical clinic formulary

2017 ◽  
Vol 4 (1) ◽  
pp. 13 ◽  
Author(s):  
Jeany Kim Jun ◽  
Junia S. Koo ◽  
Amy Y. Kang ◽  
Deborah B. Chien ◽  
Albert Shim ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intestinal Parasites ◽  
Epidemiological Data ◽  
Gastrointestinal Disorders ◽  
Channel Blockers ◽  
Medical Clinic ◽  
Converting Enzyme Inhibitors ◽  
Medical Clinics ◽  
Common Diseases ◽  
Common Diagnosis

Objective:  The purpose of this project was to gather epidemiological data on common diseases and medications dispensed during medical mission teams to Cambodia to shape the mobile medical clinic formulary.Methods:  Data for patients seen during week-long, mobile, medical clinics was collected in Cambodia during Septembers 2012 to 2014.  Patient’s gender, age, weight, blood pressure, glucose, pertinent laboratory values, diagnoses, and medications dispensed were collected.  Blood pressure and glucose were measured in patients 18 years and above.  Data collected onto paper intake forms were transferred onto spreadsheets without patient identifying information and analyzed for aggregate means, common diseases, and most dispensed medications.  This project received institutional review board approval.Results:  A total of 1,015 patients were seen over three years.  Women made up 61.4% and the mean age was 41.8 years.   The most common diagnosis was gastrointestinal disorders  (22.9%), which included gastroesophageal reflux disease and intestinal parasites.  Next, 20.1% of patients had hypertension (BP>140/90), 18.0% had presbyopia, 15.4% had back and joint pain, followed by 8.8% with headache, including migraines.  Approximately 8.4% of patients had hyperglycemia (RPG >140 mg/dl).  Top five medications dispensed were acetaminophen, omeprazole, multivitamin, ibuprofen and metformin.   For hypertension, amlodipine and lisinopril were dispensed.Conclusion:  Cambodia lacks systematic public health collection of epidemiological data for prevalence of diseases.  Hence, investigators collected and analyzed information from week-long mobile medical clinics over three years.  Proton-pump inhibitors and H. pylori lab tests are recommended for gastrointestinal disorders.  Acetaminophen and ibuprofen are recommended for pain.  Angiotensin-converting-enzyme inhibitors and dihydropyridine calcium channel blockers are recommended over diuretics since patients are already dehydrated.  Metformin is recommended for diabetes.  Vitamins and supplements are recommended for malnourished patients.  Hemoglobin machine and urine test strips are suggested.  This information should help future teams decide what medications and laboratory tests are most beneficial on medical teams in Cambodia. 

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