Genome-wide Identification and Characterization of Hsp70 gene family in Pearl millet (Pennisetumglaucum)

Heat shock proteins (Hsps) are a class of molecular chaperons which are crucial for protein folding, assembly, and translocation in many normal cellular processes. They stabilize proteins and membranes, and can assist in protein refolding under stress conditions in plants. Pearl millet (Pennisetum glaucum) is highly abiotic stress tolerant, but its Hsps have not been characterized. In the present study, PgHsp70 genes were retrieved and gene information analyzed in order to characterize their structure, localization and functions. Genome-wide screening using the tools of bioinformatics identified 18 PgHsp70 genes in the pearl millet genome which have been categorized into four subfamilies depending on their cellular localization such as endoplasmic reticulum, mitochondria, chloroplast and cytoplasm. Number of introns ranged from 0-11 in PgHsp70 family genes and the genes are located across 1 to 7 chromosomes. Phylogenetic analysis of Hsp70s revealed that they are closely related to Sorghum Hsp70s. Promoter analysis showed the presence of cisacting elements such as GCN4, HSE, LTR, MBS, ABRE, MYB, and TC Aassociated with abiotic stress conditions indicating the involvement of these genes in the abiotic stress. Under vapour pressure deficit (VPD) conditions, leaf and root tissues of VPD-sensitive ICMR 1152 line, showed mild expression and in the presence of high VPD, VPD-insensitive ICMR1122 PgHsp70 genes showed high expression in leaf and root tissues in comparison with VPD-sensitive line. Gene PgcHsp70-1 displayed high transcript level under high VPD conditions. These results expand our horizon of understanding of the structure and function of Hsp70s, especially under abiotic stress conditions which can further be validated and employed in breeding programs and genetic engineering

Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: a systematic review and individual-participant data meta-analysis

Background: Adequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid dysfunction and hypertensive disorders of pregnancy, the methods and definitions of abnormalities in thyroid function tests were heterogeneous, and the results were conflicting. We aimed to examine the association between abnormalities in thyroid function tests and risk of gestational hypertension and pre-eclampsia. Methods: In this systematic review and meta-analysis of individual-participant data, we searched MEDLINE (Ovid), Embase, Scopus, and the Cochrane Database of Systematic Reviews from date of inception to Dec 27, 2019, for prospective cohort studies with data on maternal concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase (TPO) antibodies, individually or in combination, as well as on gestational hypertension, pre-eclampsia, or both. We issued open invitations to study authors to participate in the Consortium on Thyroid and Pregnancy and to share the individual-participant data. We excluded participants who had pre-existing thyroid disease or multifetal pregnancy, or were taking medications that affect thyroid function. The primary outcomes were documented gestational hypertension and pre-eclampsia. Individual-participant data were analysed using logistic mixed-effects regression models adjusting for maternal age, BMI, smoking, parity, ethnicity, and gestational age at blood sampling. The study protocol was registered with PROSPERO, CRD42019128585. Findings: We identified 1539 published studies, of which 33 cohorts met the inclusion criteria and 19 cohorts were included after the authors agreed to participate. Our study population comprised 46 528 pregnant women, of whom 39 826 (85·6%) women had sufficient data (TSH and FT4 concentrations and TPO antibody status) to be classified according to their thyroid function status. Of these women, 1275 (3·2%) had subclinical hypothyroidism, 933 (2·3%) had isolated hypothyroxinaemia, 619 (1·6%) had subclinical hyperthyroidism, and 337 (0·8%) had overt hyperthyroidism. Compared with euthyroidism, subclinical hypothyroidism was associated with a higher risk of pre-eclampsia (2·1% vs 3·6%; OR 1·53 [95% CI 1·09–2·15]). Subclinical hyperthyroidism, isolated hypothyroxinaemia, or TPO antibody positivity were not associated with gestational hypertension or pre-eclampsia. In continuous analyses, both a higher and a lower TSH concentration were associated with a higher risk of pre-eclampsia (p=0·0001). FT4 concentrations were not associated with the outcomes measured. Interpretation: Compared with euthyroidism, subclinical hypothyroidism during pregnancy was associated with a higher risk of pre-eclampsia. There was a U-shaped association of TSH with pre-eclampsia. These results quantify the risks of gestational hypertension or pre-eclampsia in women with thyroid function test abnormalities, adding to the total body of evidence on the risk of adverse maternal and fetal outcomes of thyroid dysfunction during pregnancy. These findings have potential implications for defining the optimal treatment target in women treated with levothyroxine during pregnancy, which needs to be assessed in future interventional studies

Risk factors for thyroid dysfunction in pregnancy: an individual participant data meta-analysis

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction

Effects of levothyroxine therapy on pregnancy outcomes in women with subclinical hypothyroidism

Background: Subclinical hypothyroidism (SCH) has been associated with increased risk of adverse pregnancy outcomes in some, but not all, studies. Uncertainty remains regarding the impact of levothyroxine (LT4) therapy on improving health outcomes in pregnant women with SCH. The objective of this study was to assess the potential benefits of LT4 therapy in pregnant women with SCH. Methods: The medical records were reviewed of pregnant women with SCH, defined as an elevated serum thyrotropin (TSH) of &amp;gt;2.5 mIU/L for the 1st trimester or &amp;gt;3 mIU/L for the 2nd and 3rd trimesters, but &amp;lt;= 10 mIU/L. Pregnant women were divided into two groups depending on whether they received LT4 (group A) or not (group B). Pregnancy loss and other pre-specified adverse outcomes were evaluated during follow-up. Results: There were 82 women in group A and 284 in group B. Group A had a higher body mass index (p = 0.04) and a higher serum TSH level (p &amp;lt; 0.0001) compared with group B. Group A had fewer pregnancies lost (n = 5 [ 6.1%] vs. n = 25 [ 8.8%]; p = 0.12), low birth weight (LBW) offspring (1.3% vs. 10%; p &amp;lt; 0.001), and no neonates with a five-minute Apgar score &amp;lt;= 7 (0% vs. 7%; p &amp;lt; 0.001) compared with group B. Other pregnancy-related adverse outcomes were similar between the two groups. Inferences remained unchanged after considering different models to adjust for potential predictors of outcome. Conclusions: LT4 therapy is associated with a decreased risk of LBW and a low Apgar score among women with SCH. This association awaits confirmation in randomized trials before the widespread use of LT4 therapy in pregnant women with SCH

Effects of levothyroxine therapy on pregnancy outcomes in women with subclinical hypothyroidism

Background: Subclinical hypothyroidism (SCH) has been associated with increased risk of adverse pregnancy outcomes in some, but not all, studies. Uncertainty remains regarding the impact of levothyroxine (LT4) therapy on improving health outcomes in pregnant women with SCH. The objective of this study was to assess the potential benefits of LT4 therapy in pregnant women with SCH. Methods: The medical records were reviewed of pregnant women with SCH, defined as an elevated serum thyrotropin (TSH) of &amp;gt;2.5 mIU/L for the 1st trimester or &amp;gt;3 mIU/L for the 2nd and 3rd trimesters, but &amp;lt;= 10 mIU/L. Pregnant women were divided into two groups depending on whether they received LT4 (group A) or not (group B). Pregnancy loss and other pre-specified adverse outcomes were evaluated during follow-up. Results: There were 82 women in group A and 284 in group B. Group A had a higher body mass index (p = 0.04) and a higher serum TSH level (p &amp;lt; 0.0001) compared with group B. Group A had fewer pregnancies lost (n = 5 [ 6.1%] vs. n = 25 [ 8.8%]; p = 0.12), low birth weight (LBW) offspring (1.3% vs. 10%; p &amp;lt; 0.001), and no neonates with a five-minute Apgar score &amp;lt;= 7 (0% vs. 7%; p &amp;lt; 0.001) compared with group B. Other pregnancy-related adverse outcomes were similar between the two groups. Inferences remained unchanged after considering different models to adjust for potential predictors of outcome. Conclusions: LT4 therapy is associated with a decreased risk of LBW and a low Apgar score among women with SCH. This association awaits confirmation in randomized trials before the widespread use of LT4 therapy in pregnant women with SCH

Лечение гормонами щитовидной железы беременных женщин с субклиническим гипотиреозом: национальная оценка США

Задача. Оценка эффективности и безопасности лечения гормонами щитовидной железы беременных женщин с субклиническим гипотиреозом.Дизайн. Ретроспективное когортное исследование.Параметры. Большая административная база данных США в период с 1 января 2010 года по 31 декабря 2014 года.Участники. 5405 беременных женщин с субклиническим гипотиреозом, с концентрацией тиреотропного гормона (ТТГ) 2,5–10 мМЕ/л до лечения.Воздействие. Терапия гормонами щитовидной железы.Критерии оценки. Потеря беременности и другие заранее определенные неблагоприятные исходы, связанные с беременностью, как для матери, так и для плода.Результаты. Среди 5405 беременных женщин с субклиническим гипотиреозом 843 пациентки с концентрацией ТТГ до лечения 4,8 мМЕ/л (стандартное отклонение (СО) 1,7) получали гормоны щитовидной железы. 4562 пациентки со средней базовой концентрацией ТТГ 3,3 мМЕ/л (СО 0,9) не получали лечения (P&lt;0,01). По сравнению с группой без лечения пациентки, получавшие терапию, имели более низкую вероятность потери беременности (отношение шансов (ОШ) 0,62; 95% доверительный интервал (ДИ) от 0,48 до 0,82), однако более высокие шансы преждевременных родов (ОШ 1,60; ДИ от 1,14 до 2,24), гестационного диабета (ОШ 1,37; ДИ от 1,05 до 1,79) и преэклампсии (ОШ 1,61; ДИ от 1,10 до 2,37). Другие, связанные с беременностью, неблагоприятные исходы были схожи между двумя группами. Вероятность потери беременности была ниже у женщин, которые принимали лечение, чем у нелеченых пациенток, если концентрация ТТГ до начала лечения была 4,1–10 мМЕ/л (ОШ 0,45; ДИ от 0,30 до 0,65), но не тогда, когда она была 2,5–4,0 мМЕ/л (ОШ 0,91; ДИ от 0,65 до 1,23) (Р&lt;0,01).Заключение. Лечение гормонами щитовидной железы связано со снижением риска потери беременности у женщин с субклиническим гипотиреозом, особенно с концентрациями ТТГ до лечения 4,1–10 мМЕ/л. Тем не менее, повышенный риск развития других, связанных с беременностью, неблагоприятных исходов требует дополнительных исследований по оценке безопасности лечения гормонами щитовидной железы в этой популяции пациенток

Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: us national assessment

OBJECTIVE To estimate the effectiveness and safety of thyroid hormone treatment among pregnant women with subclinical hypothyroidism. DESIGN Retrospective cohort study. SETTING Large US administrative database between 1 January 2010 and 31 December 2014. PARTICIPANTS 5405 pregnant women with subclinical hypothyroidism, defined as untreated thyroid stimulating hormone (TSH) concentration 2.5-10 mIU/L. EXPOSURE Thyroid hormone therapy. MAIN OUTCOME MEASURE Pregnancy loss and other pre-specified maternal and fetal pregnancy related adverse outcomes. RESULTS Among 5405 pregnant women with subclinical hypothyroidism, 843 with a mean pre-treatment TSH concentration of 4.8 (SD 1.7) mIU/L were treated with thyroid hormone and 4562 with a mean baseline TSH concentration of 3.3 (SD 0.9) mIU/L were not treated (P&amp;lt; 0.01). Compared with the untreated group, treated women had lower adjusted odds of pregnancy loss (odds ratio 0.62, 95% confidence interval 0.48 to 0.82) but higher odds of preterm delivery (1.60, 1.14 to 2.24), gestational diabetes (1.37, 1.05 to 1.79), and pre-eclampsia (1.61, 1.10 to 2.37); other pregnancy related adverse outcomes were similar between the two groups. The adjusted odds of pregnancy loss were lower in treated women than in untreated women if their pre-treatment TSH concentration was 4.1-10 mIU/L (odds ratio 0.45, 0.30 to 0.65) but not if it was 2.5-4.0 mIU/L (0.91, 0.65 to 1.23) (P&amp;lt; 0.01). CONCLUSION Thyroid hormone treatment was associated with decreased risk of pregnancy loss among women with subclinical hypothyroidism, especially those with pre-treatment TSH concentrations of 4.1-10 mIU/L. However, the increased risk of other pregnancy related adverse outcomes calls for additional studies evaluating the safety of thyroid hormone treatment in this patient population