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3.
Nutrients ; 13(4)2021 Apr 02.
Article in English | MEDLINE | ID: mdl-33918317

ABSTRACT

Diet and nutrition are fundamental in maintaining the general health of populations, including women's health. Health status can be affected by nutrient deficiency and vice versa. Gene-nutrient interactions are important contributors to health management and disease prevention. Nutrition can alter gene expression, as well as the susceptibility to diseases, including cancer, through several mechanisms. Gynecological diseases in general are diseases involving the female reproductive system and include benign and malignant tumors, infections, and endocrine diseases. Benign diseases such as uterine fibroids and endometriosis are common, with a negative impact on women's quality of life, while malignant tumors are among the most common cause of death in the recent years. In this comprehensive review article, a bibliographic search was performed for retrieving information about nutrients and how their deficiencies can be associated with gynecological diseases, namely polycystic ovary syndrome, infertility, uterine fibroids, endometriosis, dysmenorrhea, and infections, as well as cervical, endometrial, and ovarian cancers. Moreover, we discussed the potential beneficial impact of promising natural compounds and dietary supplements on alleviating these significant diseases.


Subject(s)
Deficiency Diseases/therapy , Genital Diseases, Female/therapy , Nutrition Therapy/trends , Deficiency Diseases/complications , Deficiency Diseases/physiopathology , Female , Genital Diseases, Female/etiology , Genital Diseases, Female/physiopathology , Humans , Nutritional Status
5.
Nutrients ; 13(1)2021 Jan 13.
Article in English | MEDLINE | ID: mdl-33450823

ABSTRACT

Micronutrient deficiencies are relatively common, in particular iron and cobalamin deficiency, and may potentially lead to life-threatening clinical consequences when not promptly recognized and treated, especially in elderly patients. The stomach plays an important role in the homeostasis of some important hematopoietic micronutrients like iron and cobalamin, and probably in others equally important such as ascorbic acid, calcium, and magnesium. A key role is played by the corpus oxyntic mucosa composed of parietal cells whose main function is gastric acid secretion and intrinsic factor production. Gastric acid secretion is necessary for the digestion and absorption of cobalamin and the absorption of iron, calcium, and probably magnesium, and is also essential for the absorption, secretion, and activation of ascorbic acid. Several pathological conditions such as Helicobacter pylori-related gastritis, corpus atrophic gastritis, as well as antisecretory drugs, and gastric surgery may interfere with the normal functioning of gastric oxyntic mucosa and micronutrients homeostasis. Investigation of the stomach by gastroscopy plus biopsies should always be considered in the management of patients with micronutrient deficiencies. The current review focuses on the physiological and pathophysiological aspects of gastric acid secretion and the role of the stomach in iron, cobalamin, calcium, and magnesium deficiency and ascorbate homeostasis.


Subject(s)
Deficiency Diseases/etiology , Deficiency Diseases/therapy , Micronutrients/deficiency , Achlorhydria/etiology , Achlorhydria/metabolism , Animals , Biomarkers , Bone Density , Calcium/metabolism , Deficiency Diseases/diagnosis , Digestive System Surgical Procedures/adverse effects , Disease Management , Disease Susceptibility , Dysbiosis , Gastric Acid/metabolism , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Hemorrhage/complications , Humans , Stomach Diseases/complications , Vitamin B 12/metabolism , Vitamin B 12 Deficiency
6.
Clin Nutr ESPEN ; 41: 423-428, 2021 02.
Article in English | MEDLINE | ID: mdl-33487301

ABSTRACT

INTRODUCTION: The nutritional diagnosis and early nutritional management of COVID-19 patients must be integrated into the overall therapeutic strategy. The aim of our study is to assess the nutritional status of patients with COVID-19 after a stay in intensive care, to describe the prevalence of undernutrition, to determine the factors influencing undernutrition and to describe the nutritional management. TOOLS AND METHODS: This is a descriptive observational study of adult patients admitted to the endocrinology service for additional care after a stay in intensive care during the period from April 17, 2020 to May 26, 2020. The assessment tool used was the Mini Nutritional Assessment (MNA). RESULTS: Our study included 41 patients; the average age of the patients was 55 years, 51.2% had a severe or critical form of COVID-19, 75.6% stayed in intensive care, 12.2% had a loss of autonomy. The average BMI was 25.2 kg/m2 (17-42 kg/m2), 42.5% were overweight, 61% had weight loss, 26.2% had weight loss greater than 10%, 14.6% of our patients were undernourished, 65.9% were at risk of undernutrition, 19.5% had hypoalbuminemia, 17.1% had hypoprotidemia, 19.5% hypocalcemia, 34.1% anemia, 12.2% hypomagnesemia and 51.2% had a deficiency in vitamin D. A positive correlation was found between poor nutritional status and a longer stay in intensive care (>5 days) (p = 0.011) and lymphopenia (p = 0,02). CONCLUSION: Despite a personalized diet, 14.6% of patients presented undernutrition. Particular attention should be paid to patients with a long stay in intensive care.


Subject(s)
COVID-19 , Critical Care , Intensive Care Units , Length of Stay , Malnutrition/etiology , Nutritional Status , Adult , Aged , Body Mass Index , COVID-19/therapy , Deficiency Diseases/diagnosis , Deficiency Diseases/epidemiology , Deficiency Diseases/etiology , Deficiency Diseases/therapy , Diet , Female , Humans , Lymphopenia/etiology , Male , Malnutrition/diagnosis , Malnutrition/epidemiology , Malnutrition/therapy , Middle Aged , Nutrients/deficiency , Nutrition Assessment , Overweight/epidemiology , Pandemics , Patient Discharge , Prevalence , SARS-CoV-2 , Weight Loss
8.
Dermatol Clin ; 39(1): 101-115, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33228854

ABSTRACT

"Currently, an estimated 70.8 million individuals worldwide are forcibly displaced due to war, violence, and persecution. Barriers to providing dermatologic care include the large number of affected people, their movement within and across international borders, security issues, and limited access to dermatology expertise and formularies. Screening protocols for skin diseases and sexually transmitted infections differ worldwide, raising the need for shared guidelines to assess migrants' health. This article reviews the literature of skin and sexually transmitted infections in migrants and displaced persons, highlighting the impact of social determinants on skin health and challenges faced in providing care."


Subject(s)
Deficiency Diseases , Environmental Exposure , Refugees , Skin Diseases , Transients and Migrants , Violence , Coinfection/diagnosis , Coinfection/therapy , Culturally Competent Care , Deficiency Diseases/diagnosis , Deficiency Diseases/therapy , Drugs, Essential , Gender-Based Violence , HIV Infections/diagnosis , HIV Infections/therapy , Health Services Accessibility , Humans , Malnutrition/diagnosis , Malnutrition/therapy , Neglected Diseases , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/therapy , Skin Diseases/diagnosis , Skin Diseases/therapy , Skin Diseases, Infectious/diagnosis , Skin Diseases, Infectious/therapy , Torture , Tuberculosis/diagnosis , Tuberculosis/therapy , Vaccine-Preventable Diseases/diagnosis , Vaccine-Preventable Diseases/therapy
9.
Khirurgiia (Mosk) ; (10): 95-103, 2020.
Article in Russian | MEDLINE | ID: mdl-33047592

ABSTRACT

The article presents an algorithm for perioperative nutritional support of surgical patients operated on as planned. Today, planned surgical care is provided in accordance with the canons of the accelerated rehabilitation Program (ARP). The relevance of the problem of nutritional insufficiency, which is an important component of ARP, is due to the dependence of the results of surgical treatment on the initial nutritional status of the patient. Methods of screening for nutritional deficiency and options for correcting protein-energy disorders are described. The predominant method is the enteral delivery of nutrients and energy. Oral supplemental nutrition by sipping is a convenient way to correct nutritional disorders at all stages of the perioperative period.


Subject(s)
Elective Surgical Procedures , Malnutrition/therapy , Nutritional Support/methods , Perioperative Care/methods , Administration, Oral , Deficiency Diseases/diagnosis , Deficiency Diseases/therapy , Dietary Supplements , Enhanced Recovery After Surgery , Enteral Nutrition/methods , Humans , Malnutrition/diagnosis , Mass Screening , Nutritional Status , Perioperative Period
10.
Nutrients ; 12(7)2020 Jul 06.
Article in English | MEDLINE | ID: mdl-32640531

ABSTRACT

In order to develop evidence-based recommendations and expert consensus for nutrition management of patients undergoing bariatric surgery and postoperative follow-up, we conducted a systematic literature search using PRISMA methodology plus critical appraisal following the SIGN and AGREE-II procedures. The results were discussed among all members of the GARIN group, and all members answered a Likert scale questionnaire to assess the degree of support for every recommendation. Patients undergoing bariatric surgery should be screened preoperatively for some micronutrient deficiencies and treated accordingly. A VLCD (Very Low-Calorie Diet) should be used for 4-8 weeks prior to surgery. Postoperatively, a liquid diet should be maintained for a month, followed by a semi-solid diet also for one month. Protein requirements (1-1.5 g/kg) should be estimated using adjusted weight. Systematic use of specific multivitamin supplements is encouraged. Calcium citrate and vitamin D supplements should be used at higher doses than are currently recommended. The use of proton-pump inhibitors should be individualised, and vitamin B12 and iron should be supplemented in case of deficit. All patients, especially pregnant women, teenagers, and elderly patients require a multidisciplinary approach and specialised follow-up. These recommendations and suggestions regarding nutrition management when undergoing bariatric surgery and postoperative follow-up have direct clinical applicability.


Subject(s)
Bariatric Surgery , Deficiency Diseases , Obesity, Morbid/therapy , Postoperative Complications , Deficiency Diseases/prevention & control , Deficiency Diseases/therapy , Evidence-Based Medicine , Humans , Postoperative Complications/prevention & control , Postoperative Complications/therapy , Treatment Outcome
11.
Prensa méd. argent ; 106(1): 1-5, 20200000. fig
Article in Spanish | LILACS, BINACIS | ID: biblio-1369670

ABSTRACT

El escorbuto es una enfermedad ocasionada por el déficit de vitamina C. La vitamina C, también llamada ácido ascórbico, actúa como cofactor de la propil-lisil hidroxilasa, enzima que interviene en la biosíntesis de colágeno; por ello es de vital importancia en la integridad estructural de piel, mucosas, anexos, vasos sanguíneos, huesos y dientes. Las manifestaciones clínicas incluyen síntomas constitucionales severos como debilidad y fatiga. Los hallazgos cutáneos iniciales son pápulas hiperqueratósicas foliculares y púrpura palpable perifolicular. Con el tiempo aparecen áreas extensas de equimosis, edema en miembros inferiores, hemorragias en astillas en uñas y alopecia difusa. Por lo general se describe esta enfermedad como asociada a tiempos pasados y extremadamente infrecuente en países desarrollados. Sin embargo, actualmente se ha detectado un aumento en el número de casos, asociados con malnutrición severa. Desórdenes psiquiátricos como la anorexia nerviosa, alcoholismo y deficiencias nutricionales por dietas excesivas y mal balanceadas o escasez de recursos económicos constituyen los principales factores de riesgo hoy en día. El tratamiento consiste en la corrección del déficit mediante la mediante suplementación con vitamina C vía oral. Presentamos una mujer de 24 años con escorbuto asociado a anorexia nerviosa y a dieta pobre en vegetales y fruta.


Scurvy is a disease caused by a deficit of vitamin C. Vitamin C, also called ascorbic acid, acts as a cofactor for propyl-lysyl hydroxylase, an enzyme that is involved in collagen biosynthesis, vitally important in the structural integrity of skin, mucous membranes, annexes, blood vessels, bones and teeth. Clinical manifestations include severe constitutional symptoms such as weakness and fatigue. The initial cutaneous findings are follicular hyperkeratotic papules and perifollicular palpable purpura. Over time, large areas of ecchymosis, edema of the lower limbs, splinter hemorrhages in nails and diffuse alopecia appear. Usually this disease is described as associated with past times and extremely uncommon in developed countries. However, the number of cases have been increasing, especially those associated with severe malnutrition. Psychiatric disorders such as anorexia nervosa, alcoholism and nutritional deficiencies due to excessive and poorly balanced diets or shortage of economic resources are the main risk factors nowadays. Correcting the deficit with oral vitamin C supplementation is the treatment of the disease. We present a 24-year-old woman with scurvy associated with anorexia nervosa and a diet low in vegetables and fruit.


Subject(s)
Humans , Female , Adult , Purpura , Ascorbic Acid/therapeutic use , Ascorbic Acid Deficiency/therapy , Scurvy/diagnosis , Deficiency Diseases/therapy , Malnutrition/complications , Early Diagnosis
12.
Curr Gastroenterol Rep ; 22(1): 5, 2020 Jan 29.
Article in English | MEDLINE | ID: mdl-31997099

ABSTRACT

PURPOSE OF REVIEW: Inflammatory bowel disease (IBD) is often diagnosed during adolescence and can have a deep impact on the physical, hormonal, developmental, and psychosocial changes associated with this life period. The purpose of this review is to address the particular manifestations of IBD (such as growth and pubertal delay), health maintenance issues, and treatment considerations in the adolescent. RECENT FINDINGS: The need for a multidisciplinary approach to recognize and address growth and pubertal delay, bone health, as well as the psychosocial impact of IBD on the adolescent has been increasingly recognized as an integral part of IBD care in this population. Vaccinations schedule, preventive health measures, and promoting compliance with care are particularly important during adolescence. Replacing nutrients deficits is also crucial: in particular, vitamin D has been shown to play a role in the gut immune system, and adequate vitamin D levels might promote IBD remission. Iron replacement should be done by intravenous route since oral iron is poorly absorbed in chronic inflammatory states. Finally, recent data have shed light on the increased risk of particular types of lymphoma in adolescent on thiopurines, whereas biologic therapies, in particular, anti-TNF, now are positioned as a preferred and effective steroid-sparing agents in moderate to severe IBD. Management of adolescents with IBD is not without significant challenges. An early implementation of steroid-sparing therapies, a multidisciplinary treatment approach, and a dynamic physician-patient relationship are essential to achieve remission, prevent disease-related complications but also optimize developmental, physical, and psychosocial health, and encourage compliance and transition to adult care.


Subject(s)
Deficiency Diseases/therapy , Inflammatory Bowel Diseases/therapy , Adolescent , Adolescent Health , Deficiency Diseases/etiology , Humans , Inflammatory Bowel Diseases/complications
13.
Curr Opin Gastroenterol ; 36(2): 110-117, 2020 03.
Article in English | MEDLINE | ID: mdl-31895229

ABSTRACT

PURPOSE OF REVIEW: Trace elements are vital components involved in major body functions. Cases of trace elements deficiencies are increasingly encountered in clinical practice, although often underrecognized. This review gives a thorough insight into the newest findings on clinical situations associated with trace elements deficiencies in children and adults, their recognition and management. RECENT FINDINGS: Trace elements deficiencies are frequently found in various conditions, most commonly in burns, bariatric surgery, intestinal failure, renal replacement therapy, oncology, critical illness and cardiac surgery. The main trace elements involved are selenium, zinc, copper and iron. Trace elements deficiencies are associated with increased risk of morbidity and mortality. Recognition of clinical signs of trace elements deficiencies can be challenging. Although trace elements supplementation is indisputable in many circumstances, it is still debatable in other situations such as sepsis and cardiac surgery. SUMMARY: Recent findings on trace elements deficiencies could have important implications on health outcomes. Trace elements delivery is a core component of nutritional care. Front-line clinicians should be aware of at-risk clinical situations to provide correct and timely intervention. Future research should be directed towards investigating the potential benefits of antioxidant trace elements supplementation in children in whom studies are scarce, especially in critical conditions such as burns, sepsis and cardiac surgery.


Subject(s)
Deficiency Diseases/etiology , Trace Elements/deficiency , Deficiency Diseases/diagnosis , Deficiency Diseases/therapy , Humans , Trace Elements/administration & dosage
14.
Nutr Clin Pract ; 35(4): 724-728, 2020 Aug.
Article in English | MEDLINE | ID: mdl-31270844

ABSTRACT

BACKGROUND: Copper (Cu) is an essential trace element, with deficiency causing anemia, neutropenia, and other abnormalities. Cu is mainly absorbed in the small intestine. Patients with intestinal failure or jejunostomy have increased Cu losses and require additional Cu supplementation in parenteral nutrition (PN). The American Society for Clinical Nutrition standards for trace element recommendations in PN, including Cu, were created in 1988, and the American Society for Parenteral and Enteral Nutrition currently follows the same recommendations. METHODS: Patients admitted to the neonatal intensive care unit for surgical intervention resulting in an ostomy (ileal or jejunal) were included in this retrospective study. Patients received PN support with Cu dosed individually, rather than in a multi-trace element package. Cu and ostomy output were analyzed daily. Serum Cu was obtained 2 months postsurgical intervention. RESULTS: Out of the 7 patients enrolled, 71% had low serum Cu. Weekly mean Cu intake for all 7 patients ranged from 5.3 to 154.8 µg/kg/day from enteral and parenteral sources, with individual mean weekly Cu intake ranging from 18.9 to 74.4 µg/kg/day from surgical intervention to 2 months post-surgery. Patients' weekly ostomy outputs ranged from 0 mL/kg/day to 77.2 mL/kg/day, with individual mean weekly output ranging from 3.7 to 41.6 mL/kg/day. CONCLUSION: Providing 20 µg/kg/day of Cu in PN to neonates with ostomies is insufficient to prevent Cu deficiency. Further studies are warranted to determine an optimal dosage of parenteral Cu to prevent Cu deficiency.


Subject(s)
Copper/administration & dosage , Deficiency Diseases/therapy , Ileostomy/adverse effects , Jejunostomy/adverse effects , Parenteral Nutrition/methods , Postoperative Complications/therapy , Trace Elements/administration & dosage , Copper/blood , Copper/deficiency , Deficiency Diseases/etiology , Dietary Supplements , Female , Humans , Infant, Newborn , Intensive Care Units, Neonatal , Intensive Care, Neonatal/methods , Male , Nutrition Policy , Nutritional Requirements , Postoperative Complications/etiology , Retrospective Studies , Trace Elements/blood , Trace Elements/deficiency , Treatment Outcome
15.
Behav Brain Res ; 379: 112357, 2020 02 03.
Article in English | MEDLINE | ID: mdl-31733310

ABSTRACT

Iron is the most common micronutrient deficiency in the world and it is most prevalent in young children, exposing their developing brain to inadequate iron levels. The damage related to neuroanatomical parameters is not reversed after iron treatment. However, evidence suggest that tactile stimulation (TS) may offer great therapeutic efficacy in cases of nutritional disorders postnatally, since the brain is remarkably responsive to its interaction with the environment. Recently, we shown that neonatal iron deficient rats achieved some remedial effect by exposing them to TS treatment early in life, reinforcing the fact that the TS approach is a positive enriching experience, therefore, here we ask whether exposure to TS treatment, could also be employed to prevent fine structural changes in the fibers from optic nerve of rats maintained on an iron-deficient diet during brain development. To elucidate the protective effect of tactile stimulation, our methods resulted in 10,859 analyzed fibers, divided into small and large fibers. We found that iron deficiency led to a decreased axon, fiber and myelin size of small fibers, however, TS completely reversed the iron-decifiency-induced alteration on those fiber measurements. Large fibers were disproportionately affected by iron deficiency and there was no remediating effect due to tactile stimulation treatment. The present study adds new information regarding different alterations between small and large fibers due to diet and TS, which suggest a size-based selectivity. These results emphasize the concept that compromised brain development can be mitigated at an early age by environmental factors, such as tactile stimulation.


Subject(s)
Axons/pathology , Deficiency Diseases/pathology , Deficiency Diseases/therapy , Handling, Psychological , Iron Deficiencies , Nerve Fibers, Myelinated/pathology , Optic Nerve/pathology , Touch/physiology , Animals , Animals, Newborn , Disease Models, Animal , Male , Physical Stimulation , Rats , Rats, Wistar
16.
Obes Surg ; 29(11): 3743-3748, 2019 11.
Article in English | MEDLINE | ID: mdl-31522331

ABSTRACT

BACKGROUND: Selenium is an essential element that plays a vital role in maintaining human health and its deficiency can lead to cardiovascular and hypothyroidism complications. In this context, the main concern is about morbidly obese patients who undergo a Roux-en-Y Gastric Bypass (RYGB). Although RYGB leads to 60-70% excess weight loss, micronutrient deficiencies are common after this procedure and can be problematic if not promptly detected. This review will therefore examine the evidence regarding selenium deficiency in RYGB patients, as well its nutritional treatment methods. METHODS: There were a total of 6 studies regarding RYGB and selenium deficiency, which were retrieved from PUBMED and SCOPUS electronic databases, ranging from 2006 to 2017. CONCLUSION: Selenium deficiency was observed before and after RYGB. Lifelong supplementation and regular patient monitoring after surgery are recommended.


Subject(s)
Deficiency Diseases , Gastric Bypass/adverse effects , Obesity, Morbid/surgery , Postoperative Complications , Selenium , Deficiency Diseases/etiology , Deficiency Diseases/therapy , Humans , Postoperative Complications/etiology , Postoperative Complications/therapy , Selenium/blood , Selenium/deficiency
17.
J Pak Med Assoc ; 69(5): 722-724, 2019 May.
Article in English | MEDLINE | ID: mdl-31105296

ABSTRACT

A 12-year-old boy who underwent gastric wedge resection was transferred to our hospital because of vomiting, growth failure, and weight loss in January, 2016. We tried to restore his general condition by maintaining additional nutritional supply through peripheral parenteral nutrition (PN). However, continuous vomiting, weight loss, and superior mesenteric artery syndrome persisted because of low treatment compliance. The findings of hyponatraemia and bicytopenia did not improve. Bone marrow biopsy was performed, and it revealed copper deficiency. PN with additional micronutrient agents, including copper, were administered. In particular, invasive diagnosis and treatment, and adequate education improved the treatment compliance of the child. His copper deficiency and bicytopenia improved, and his weight and dietary intake also increased. We confirmed that treatment compliance is important in paediatric patients with malnutrition. In chronic malnutrition, attention should also be paid to deficiency of micronutrients such as copper, which can lead to haematologic problems.


Subject(s)
Anemia/etiology , Child Nutrition Disorders/complications , Copper/deficiency , Deficiency Diseases/complications , Leukopenia/etiology , Anorexia , Child , Child Nutrition Disorders/therapy , Chronic Disease , Deficiency Diseases/therapy , Dietary Supplements , Enteral Nutrition , Gastrectomy , Humans , Ileostomy , Male , Parenteral Nutrition , Patient Compliance , Superior Mesenteric Artery Syndrome , Vomiting , Weight Loss
18.
Curr Opin Clin Nutr Metab Care ; 22(3): 223-229, 2019 05.
Article in English | MEDLINE | ID: mdl-30893089

ABSTRACT

PURPOSE OF REVIEW: Iron deficiency remains highly prevalent in women and young children in low-income and middle-income countries. To prevent the potentially life-long consequences of iron deficiency when occurring during early life, the WHO recommends iron supplementation of pregnant women and young children. However, increasing evidence of limited efficacy and risk of current iron intervention strategies are cause of concern. This review aims to highlight recent advances and challenges of established and novel intervention strategies for the prevention of iron deficiency during the first 1000 days in low-income and middle-income countries. RECENT FINDINGS: Recent meta-analyses and trials challenged the WHO's current recommendation to provide iron-folic acid rather than multiple micronutrient supplements during routine antenatal care. Furthermore, several studies explored optimal windows for iron supplementation, such as prior to conception. Studies are demonstrating that infectious and noninfectious inflammation is compromising the efficacy of iron interventions in vulnerable groups. Therefore, strategies addressing iron deficiency should focus on targeting infection and inflammation while simultaneously providing additional iron. Furthermore, both iron deficiency and iron supplementation may promote an unfavourable gut microbiota. Recent trials in infants indicate that the provision of a prebiotic together with iron may alleviate the adverse effects of iron on the gut microbiome and gut inflammation, and may even enhance iron absorption. SUMMARY: Recent studies highlight the need for and potential of novel intervention strategies that increase the efficacy and limit the potential harm of universal iron supplementation.


Subject(s)
Anemia, Iron-Deficiency , Deficiency Diseases , Iron , Anemia, Iron-Deficiency/prevention & control , Anemia, Iron-Deficiency/therapy , Child, Preschool , Deficiency Diseases/prevention & control , Deficiency Diseases/therapy , Developing Countries , Female , Humans , Infant , Infant, Newborn , Iron/blood , Iron/therapeutic use , Iron Deficiencies , Poverty , Pregnancy , Pregnancy Complications/prevention & control , Pregnancy Complications/therapy
19.
PLoS Comput Biol ; 14(11): e1006503, 2018 11.
Article in English | MEDLINE | ID: mdl-30388104

ABSTRACT

Multiscale modeling provides a very powerful means of studying complex biological systems. An important component of this strategy involves coarse-grained (CG) simplifications of regions of the system, which allow effective exploration of complex systems. Here we studied aspects of CG modeling of the human zinc transporter ZnT2. Zinc is an essential trace element with 10% of the proteins in the human proteome capable of zinc binding. Thus, zinc deficiency or impairment of zinc homeostasis disrupt key cellular functions. Mammalian zinc transport proceeds via two transporter families: ZnT and ZIP; however, little is known about the zinc permeation pathway through these transporters. As a step towards this end, we herein undertook comprehensive computational analyses employing multiscale techniques, focusing on the human zinc transporter ZnT2 and its bacterial homologue, YiiP. Energy calculations revealed a favorable pathway for zinc translocation via alternating access. We then identified key residues presumably involved in the passage of zinc ions through ZnT2 and YiiP, and functionally validated their role in zinc transport using site-directed mutagenesis of ZnT2 residues. Finally, we use a CG Monte Carlo simulation approach to sample the transition between the inward-facing and the outward-facing states. We present our structural models of the inward- and outward-facing conformations of ZnT2 as a blueprint prototype of the transporter conformations, including the putative permeation pathway and participating residues. The insights gained from this study may facilitate the delineation of the pathways of other zinc transporters, laying the foundations for the molecular basis underlying ion permeation. This may possibly facilitate the development of therapeutic interventions in pathological states associated with zinc deficiency and other disorders based on loss-of-function mutations in solute carriers.


Subject(s)
Cation Transport Proteins/metabolism , Models, Theoretical , Zinc/metabolism , Cation Transport Proteins/genetics , Computational Biology/methods , Deficiency Diseases/metabolism , Deficiency Diseases/therapy , Homeostasis , Humans , Monte Carlo Method , Mutagenesis, Site-Directed , Permeability , Zinc/deficiency
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