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1.
Plant J ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935838

ABSTRACT

This review explores the integration of wild grass-derived alleles into modern bread wheat breeding to tackle the challenges of climate change and increasing food demand. With a focus on synthetic hexaploid wheat, this review highlights the potential of genetic variability in wheat wild relatives, particularly Aegilops tauschii, for improving resilience to multifactorial stresses like drought, heat, and salinity. The evolutionary journey of wheat (Triticum spp.) from diploid to hexaploid species is examined, revealing significant genetic contributions from wild grasses. We also emphasize the importance of understanding incomplete lineage sorting in the genomic evolution of wheat. Grasping this information is crucial as it can guide breeders in selecting the appropriate alleles from the gene pool of wild relatives to incorporate into modern wheat varieties. This approach improves the precision of phylogenetic relationships and increases the overall effectiveness of breeding strategies. This review also addresses the challenges in utilizing the wheat wild genetic resources, such as the linkage drag and cross-compatibility issues. Finally, we culminate the review with future perspectives, advocating for a combined approach of high-throughput phenotyping tools and advanced genomic techniques to comprehensively understand the genetic and regulatory architectures of wheat under stress conditions, paving the way for more precise and efficient breeding strategies.

2.
Plant Cell Physiol ; 63(12): 1848-1856, 2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36255097

ABSTRACT

Crop varieties with a high yield are most desirable in the present context of the ever-growing human population. Mostly, the yield traits are governed by a complex of numerous molecular and genetic facets modulated by various quantitative trait loci (QTLs). With the identification and molecular characterizations of yield-associated QTLs over recent years, the central role of phytohormones in regulating plant yield is becoming more apparent. Most often, different groups of phytohormones work in close association to orchestrate yield attributes. Understanding this cross talk would thus provide new venues for phytohormone pyramiding by editing a single gene or QTL(s) for yield improvement. Here, we review a few important findings to integrate the knowledge on the roles of auxin, brassinosteroid and cytokinin and how a single gene or a QTL could govern cross talk among multiple phytohormones to determine the yield traits.


Subject(s)
Oryza , Humans , Oryza/genetics , Brassinosteroids , Cytokinins , Plant Growth Regulators , Indoleacetic Acids
3.
Plant Biotechnol J ; 20(8): 1533-1545, 2022 08.
Article in English | MEDLINE | ID: mdl-35478430

ABSTRACT

The continuous growth of the global population and the increase in the amount of arid land has severely constrained agricultural crop production. To solve this problem, many researchers have attempted to increase productivity through the efficient distribution of energy; however, the direct relationship between the plant vasculature, specifically phloem development, and crop yield is not well established. Here, we demonstrate that an optimum increase in phloem-transportation capacity by reducing SIJUL expression leads to improved sink strength in tomato (Solanum lycopersicum L.). SIJUL, a negative regulator of phloem development, suppresses the translation of a positive regulator of phloem development, SlSMXL5. The suppression of SlJUL increases the number of phloem cells and sucrose transport, but only an optimal reduction of SlJUL function greatly enhances sink strength in tomato, improving fruit setting, and yield contents by 37% and 60%, respectively. We show that the increment in phloem cell number confers spare transport capacity. Our results suggest that the control of phloem-transport capacity within the threshold could enhance the commitment of photosynthates to instigate yield improvement.


Subject(s)
Phloem , Solanum lycopersicum , Biological Transport , Fruit/genetics , Fruit/metabolism , Solanum lycopersicum/genetics , Phloem/metabolism
4.
Int Psychogeriatr ; 34(10): 889-903, 2022 10.
Article in English | MEDLINE | ID: mdl-33757611

ABSTRACT

OBJECTIVE: This systematic review aims to identify published randomized controlled trials (RCTs) that evaluated the use of anticonvulsants for the prevention and/or treatment of delirium among older adults. METHODS: A comprehensive search of databases: MEDLINE ALL (Ovid), Embase (Ovid), PsycINFO (Ovid), Web of Science Core Collection and Cochrane Central Register of Controlled was conducted. RESULTS: The search identified four RCTs that evaluated the use of anticonvulsants among older adults with delirium. One RCT evaluated the perioperative use of gabapentin among individuals undergoing spinal surgery and the development of postoperative delirium. One RCT evaluated the relationship between the use of perioperative gabapentin and the development of postoperative delirium among individuals undergoing spinal surgery and hip and knee arthroplasty. Two post-hoc analyses of RCTs evaluated the use of gabapentin and pregabalin among individuals undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA). The perioperative use of gabapentin reduced the incidence of postoperative delirium among older adults undergoing spinal surgery. The perioperative use of gabapentin did not reduce the rates, severity or duration of postoperative delirium among older adults who were undergoing spine and hip and knee arthroplasty. The perioperative use of gabapentin did not reduce the incidence or duration of postoperative delirium among older adults undergoing elective TKA. The perioperative use of pregabalin did not reduce the incidence of postoperative delirium among older adults undergoing elective THA. Gabapentin and pregabalin were well tolerated among the individuals enrolled in these trials. There were no RCTs identified that evaluated the use of other anticonvulsants for the prevention and/or treatment of delirium among older adults. CONCLUSIONS: Based on current evidence, the routine use of anticonvulsants for the prevention and/or treatment of delirium among older adults cannot be recommended.


Subject(s)
Arthroplasty, Replacement, Hip , Delirium , Aged , Anticonvulsants/therapeutic use , Arthroplasty, Replacement, Hip/adverse effects , Delirium/chemically induced , Delirium/drug therapy , Delirium/prevention & control , Gabapentin/therapeutic use , Humans , Pregabalin/therapeutic use
5.
Int Environ Agreem ; 22(2): 393-409, 2022.
Article in English | MEDLINE | ID: mdl-35399805

ABSTRACT

Environmental justice issues have been incrementally but consistently covered within this journal in the last two decades. This article reviews theoretical and empirical approaches to justice in INEA scholarship in order to identify trends and draw lessons for the interpretation and implementation of the 2030 Agenda and for living within environmental limits. Our review traces how justice considerations were initially covered within new institutionalist scholarship on collective action and social practices, to conceptualizing justice as 'access and allocation', to newer notions of planetary justice. We link these trends to scholarship on diverse epistemologies and typologies of justice, including conservative, corrective, distributive and procedural justice, and examine their operationalization within the empirical domains of climate, water and sustainable development. In concluding, we draw out implications for the 2030 Sustainable Development Agenda. We argue that a just approach is essential to living within environmental limits, with greater synergies needed between collective action and social practice approaches. While justice can be unpacked for practical and political reasons into access and allocation, we find that (procedural) access considerations are more politically palatable in practice than a concern with allocation (distributive justice), which remains much more contested. As such, dominant approaches promote 'conservative' or thin market-based notions of justice. We conclude by noting that just allocation is a precondition to just access. A failure to prioritize and achieve more corrective and distributive forms of justice will, without doubt, contribute to exacerbating global ecological degradation.

6.
Int Psychogeriatr ; 33(2): 179-191, 2021 02.
Article in English | MEDLINE | ID: mdl-32600480

ABSTRACT

OBJECTIVE: To review the currently available data on the use of ketamine in the treatment of depression among older adults from randomized controlled studies. DESIGN: Randomized controlled trials. SETTING: Variable. PARTICIPANTS: 60 years and older with depression. INTERVENTION: Ketamine. MEASUREMENTS: Change in Montgomery-Asberg Depression Rating Scale (MADRS) scores. RESULTS: Two studies met the inclusion criteria. The first study showed a significant reduction in depression symptoms with use of repeated subcutaneous ketamine administration among older adults with depression. The second study failed to achieve significance on its primary outcome measure but did show a decrease in MADRS scores with intranasal ketamine along with a higher response and remission rates in esketamine group compared with the placebo group. The adverse effects from ketamine generally lasted only a few hours and abated spontaneously. No cognitive adverse effects were noted in either trial from the use of ketamine. CONCLUSIONS: The current evidence for use of ketamine among older adults with depression indicates some benefits with one positive and one negative trial. Although one of the trials did not achieve significance on the primary outcome measure, it still showed benefit of ketamine in reducing depressive symptoms. Ketamine was well tolerated in both studies with adverse effects being mild and transient.


Subject(s)
Depression/drug therapy , Ketamine/therapeutic use , Aged , Antidepressive Agents/therapeutic use , Humans , Randomized Controlled Trials as Topic , Treatment Outcome
7.
J Exp Bot ; 71(2): 543-554, 2020 01 07.
Article in English | MEDLINE | ID: mdl-31232445

ABSTRACT

Crops such as wheat (Triticum spp.) are predicted to face more frequent exposures to heat stress as a result of climate change. Increasing the yield and sustainability of yield under such stressful conditions has long been a major target of wheat breeding, and this goal is becoming increasingly urgent as the global population increases. Exposure of wheat plants in their reproductive or grain-filling stage to high temperature affects the duration and rate of grain filling, and hence has a negative impact on wheat productivity. Therefore, understanding the plasticity of the response to heat stress that exists between wheat genotypes, especially in source-sink relationships at the reproductive and grain-filling stages, is critical for the selection of germplasm that can maintain high yields under heat stress. A broad understanding of metabolic dynamics and the relationships between metabolism and heat tolerance is required in order to achieve this goal. Here, we review the current literature concerning the effects of heat stress on sink-source relationships in a wide range of wheat genotypes, and highlight the current metabolomic approaches that are used to investigate high temperature responses in wheat.


Subject(s)
Adaptation, Physiological , Gene-Environment Interaction , Heat-Shock Response , Hot Temperature/adverse effects , Triticum/physiology , Climate Change , Genotype , Triticum/genetics
8.
Crit Rev Biotechnol ; 40(3): 320-340, 2020 May.
Article in English | MEDLINE | ID: mdl-31931629

ABSTRACT

Plants exposed to the combination of drought and pathogen infections are in a unique state, different from that of plants exposed to each stress alone. Plants undergo major hormonal changes during drought and/or pathogen infection, highlighting the importance of hormones as crucial mediators of plant stress responses. Evidence from individual stress studies has shown that drought and pathogen infection have both different and overlapping impacts on hormone metabolism and hormone-associated signal transduction pathways. Thus, under the combination of drought and pathogen infection, a reprograming of hormone levels and related signaling networks is inevitable. This process delivers data from plants exposed to individual stressors inadequate for predicting how hormone levels and related signaling networks will change in plants exposed to a combination of stressors. Furthermore, the yield of crop plants, determined by their capacity for stress acclimatization and resistance to pathogen infection, will be underpinned by interactions among the hormone pathways. Although many studies have been conducted to understand the molecular mechanisms associated with plant responses to combinations of stressors, the interactions that occur among hormones are far from being well-understood. We provide here an overview and evaluation of various reports on crosstalk or overlapping hormonal responses from individual stress studies and how the combination of drought and pathogen infection modulates hormone levels and their associated signaling pathways in plant responses to these combined stresses. We also give a brief overview of the importance of overlapping plant responses for the production of crop plants resistant to individual and combined stressors under natural environmental conditions.


Subject(s)
Droughts , Plant Diseases , Plant Growth Regulators/metabolism , Plants/metabolism , Abscisic Acid/metabolism , Cell Wall/metabolism , Gene Expression Regulation, Plant , Glucans/metabolism , Homeostasis , Host-Pathogen Interactions/physiology , Osmoregulation , Plant Diseases/microbiology , Plant Stomata , Pseudomonas syringae/pathogenicity , Signal Transduction , Stress, Physiological
9.
Ann Clin Psychiatry ; 32(2): 114-127, 2020 05.
Article in English | MEDLINE | ID: mdl-32343283

ABSTRACT

BACKGROUND: Benzodiazepines are currently the most commonly prescribed medication for the treatment of anxiety in older adults, although there is a dearth of good-quality data on this subject. The aim of this review was to systematically review studies examining the efficacy and tolerability of benzodiazepines for the treatment of anxiety disorders among older adults. METHODS: The authors conducted a systematic review, searching PubMed, Ovid MEDLINE, Ovid Embase, Web of Science, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. All searches were limited to English-language articles. The quality of each study was appraised using criteria developed by the Centre for Evidence-Based Medicine for randomized controlled trials. RESULTS: A total of 8,785 citations were retrieved and pooled in EndNote and de-duplicated to 3,753. This set was uploaded to Covidence for screening. Two separate screeners (AG and SAF) evaluated the titles, abstracts, and full text of the eligible articles. Five studies met the inclusion criteria. Across all studies, benzodiazepines were associated with decreased anxiety at the end of the study period. The limited tolerability data show mild adverse effects from the benzodiazepines studied. Limitations of the trials included limited data on the long-term use of benzodiazepines for anxiety and a preponderance of trials examining generalized anxiety disorder, with relatively less data on other anxiety disorders. CONCLUSIONS: Benzodiazepines are effective for treating anxiety disorders in late life, at least in the short term, but more data is needed to establish tolerability and their long-term benefits.


Subject(s)
Anxiety Disorders/drug therapy , Benzodiazepines/therapeutic use , Randomized Controlled Trials as Topic , Aged , Humans , Middle Aged
10.
Int J Mol Sci ; 21(20)2020 Oct 11.
Article in English | MEDLINE | ID: mdl-33050569

ABSTRACT

Sensing of pathogen infection by plants elicits early signals that are transduced to affect defense mechanisms, such as effective blockage of pathogen entry by regulation of stomatal closure, cuticle, or callose deposition, change in water potential, and resource acquisition among many others. Pathogens, on the other hand, interfere with plant physiology and protein functioning to counteract plant defense responses. In plants, hormonal homeostasis and signaling are tightly regulated; thus, the phytohormones are qualified as a major group of signaling molecules controlling the most widely tinkered regulatory networks of defense and counter-defense strategies. Notably, the phytohormone jasmonic acid mediates plant defense responses to a wide array of pathogens. In this review, we present the synopsis on the jasmonic acid metabolism and signaling, and the regulatory roles of this hormone in plant defense against the hemibiotrophic bacterial pathogen Pseudomonas syringae. We also elaborate on how this pathogen releases virulence factors and effectors to gain control over plant jasmonic acid signaling to effectively cause disease. The findings discussed in this review may lead to ideas for the development of crop cultivars with enhanced disease resistance by genetic manipulation.


Subject(s)
Cyclopentanes/metabolism , Host-Pathogen Interactions , Oxylipins/metabolism , Plant Diseases/immunology , Plant Diseases/microbiology , Plant Immunity , Pseudomonas syringae/pathogenicity , Cyclopentanes/pharmacology , Disease Resistance/immunology , Host-Pathogen Interactions/immunology , Metabolic Networks and Pathways , Oxylipins/pharmacology , Plant Growth Regulators/metabolism , Plant Immunity/drug effects , Signal Transduction , Virulence
11.
Ann Clin Psychiatry ; 31(4): 277-291, 2019 11.
Article in English | MEDLINE | ID: mdl-31369663

ABSTRACT

BACKGROUND: Anxiety in late-life is a frequently encountered condition. The aim of this review is to systematically examine the efficacy and tolerability of antidepressants for treating anxiety disorders among older adults. METHODS: Electronic searches of The Cochrane Central Register of Controlled Trials and the standard bibliographic databases PubMed, MEDLINE, EMBASE, and PsycINFO were performed in August 2018 and updated in October 2018 for randomized controlled trials (RCTs) evaluating antidepressants for late-life anxiety. The quality of each study was appraised using criteria developed by the Centre for Evidence-Based Medicine. RESULTS: Data from 12 papers describing 10 RCTs of antidepressants for late-life anxiety are included in this review. There were 2 studies each of sertraline, escitalopram, and duloxetine, and 1 study each of citalopram, paroxetine, venlafaxine, and imipramine. Across all trials, antidepressants were associated with a significant reduction in anxiety symptoms at the end of the study period. Limitations of the trials include a preponderance of generalized anxiety disorder and relatively less data on other anxiety disorders, and limited data on long-term use of antidepressants for anxiety. CONCLUSIONS: Antidepressants are beneficial for treating anxiety disorders in late life and are generally well tolerated.


Subject(s)
Antidepressive Agents/therapeutic use , Anxiety Disorders/therapy , Late Onset Disorders , Randomized Controlled Trials as Topic , Selective Serotonin Reuptake Inhibitors/therapeutic use , Aged , Citalopram , Duloxetine Hydrochloride , Humans , Paroxetine , Sertraline
12.
Pediatr Res ; 84(1): 118-124, 2018 07.
Article in English | MEDLINE | ID: mdl-29795200

ABSTRACT

BACKGROUND: Prodromal symptoms are frequently reported in the atypical form of Hemolytic uremic syndrome (aHUS) suggesting implication of infectious triggers. Some pathogens may also play a role in the mechanisms of production of autoantibody directed against Factor H (FH), a complement regulator, leading to aHUS. METHODS: The presence of 15 gastrointestinal (GI) pathogens was investigated by using xTAG-based multiplex PCR techniques on stools collected at the acute phase in a cohort of Indian HUS children classified according to the presence or absence of anti-FH autoantibodies. RESULTS: Prevalence of pathogens in patients with anti-FH antibody (62.5%) was twice that in those without (31.5%). Different pathogens were detected, the most frequent being Clostridium difficile, Giardia intestinalis, Salmonella, Shigella, Rotavirus, Norovirus and Entamoeba histolytica. No stool was positive for Shigatoxin. CONCLUSION: This study reveals a higher prevalence of GI pathogens in anti-FH positive than in negative patients. No single pathogen was implicated exclusively in one form of HUS. These pathogens may play a role in the disease initiation by inducing complement activation or an autoimmune response.


Subject(s)
Atypical Hemolytic Uremic Syndrome/immunology , Autoantibodies/immunology , Complement Activation , Atypical Hemolytic Uremic Syndrome/microbiology , Atypical Hemolytic Uremic Syndrome/parasitology , Atypical Hemolytic Uremic Syndrome/virology , Child , Child, Preschool , Clostridioides difficile , Cohort Studies , Complement Factor H/immunology , Entamoeba histolytica , Female , Giardia lamblia , Humans , India , Infant , Intestines/microbiology , Intestines/parasitology , Intestines/pathology , Intestines/virology , Male , Multiplex Polymerase Chain Reaction , Mutation , Norovirus , Rotavirus , Salmonella , Shigella
13.
Cancer Control ; 25(1): 1073274818806900, 2018.
Article in English | MEDLINE | ID: mdl-30375235

ABSTRACT

Despite guidelines recommending annual low-dose computed tomography (LDCT) screening for lung cancer, uptake remains low due to the perceived complexity of initiating and maintaining a clinical program-problems that likely magnify in underserved populations. We conducted a survey of community providers at Federally Qualified Health Centers (FQHCs) in Santa Clara County, California, to evaluate provider-related factors that affect adherence. We then compared these findings to academic providers' (APs) LDCT screening knowledge, behaviors, and attitudes at an academic referral center in the same county. The 4 FQHCs enrolled care for 80 000 patients largely of minority descent and insured by Medi-Cal. Of the 75 FQHC providers (FQHCPs), 36 (48%) completed the survey. Of the 36 providers, 8 (22%) knew screening criteria. Fifteen (42%) FQHCPs discussed LDCT screening with patients. Compared to 36 APs, FQHCPs were more concerned about harms, false positives, discussion time, patient apathy, insurance coverage, and a lack of expertise for screening and follow-up. Yet, more FQHCPs thought screening was effective (27 [75%] of 36) compared to APs ( P = .0003). In conclusion, provider knowledge gaps are greater and barriers are different for community clinics caring for underserved populations compared to their academic counterparts, but practical and scalable solutions exist to enhance adoption.


Subject(s)
Academic Medical Centers/statistics & numerical data , Clinical Competence , Community Health Centers/statistics & numerical data , Early Detection of Cancer/standards , Lung Neoplasms/diagnostic imaging , Practice Patterns, Physicians'/statistics & numerical data , California , Early Detection of Cancer/adverse effects , Early Detection of Cancer/statistics & numerical data , False Positive Reactions , Female , Guideline Adherence/statistics & numerical data , Humans , Lung/diagnostic imaging , Lung/radiation effects , Male , Practice Guidelines as Topic , Practice Patterns, Physicians'/standards , Surveys and Questionnaires/statistics & numerical data , Tomography, X-Ray Computed/adverse effects , Tomography, X-Ray Computed/standards , Tomography, X-Ray Computed/statistics & numerical data
14.
Kidney Int ; 92(1): 248-257, 2017 07.
Article in English | MEDLINE | ID: mdl-28318625

ABSTRACT

Studies of nephrotic syndrome show that substitution of calcineurin inhibitors by mycophenolate mofetil (MMF) enables sustained remission and corticosteroid sparing and avoids therapy associated adverse effects. However, controlled studies in patients with steroid resistance are lacking. Here we examined the effect of switching from therapy with tacrolimus to MMF on disease course in an open-label, one-to-one randomized, controlled trial on children (one to 18 years old), recently diagnosed with steroid-resistant nephrotic syndrome, at a referral center in India. Following six months of therapy with tacrolimus, patients with complete or partial remission were randomly assigned such that 29 received MMF while 31 received tacrolimus along with tapering prednisolone on alternate days for 12 months. On intention-to-treat analyses, the proportion of patients with a favorable outcome (sustained remission, infrequent relapses) at one year was significantly lower (44.8%) in the MMF group than in the tacrolimus group (90.3%). The incidence of relapses was significantly higher for patients treated with MMF than tacrolimus (mean difference: 1.05 relapses per person-year). While there was no difference in the proportion of patients with sustained remission, the risk of recurrence of steroid resistance was significantly higher for patients receiving MMF compared to tacrolimus (mean difference: 20.7%). Compared to tacrolimus, patients receiving MMF had a significantly (71%) lower likelihood of a favorable outcome and significantly increased risk of treatment failure (frequent relapses, steroid resistance). Thus, replacing tacrolimus with MMF after six months of tacrolimus therapy for steroid-resistant nephrotic syndrome in children is associated with significant risk of frequent relapses or recurrence of resistance. These findings have implications for guiding the duration of therapy with tacrolimus for steroid-resistant nephrotic syndrome.


Subject(s)
Immunosuppressive Agents/therapeutic use , Mycophenolic Acid/therapeutic use , Nephrotic Syndrome/congenital , Tacrolimus/therapeutic use , Adolescent , Age Factors , Child , Child, Preschool , Drug Substitution , Drug Therapy, Combination , Female , Glucocorticoids/therapeutic use , Humans , Immunosuppressive Agents/adverse effects , India , Infant , Kaplan-Meier Estimate , Male , Mycophenolic Acid/adverse effects , Nephrotic Syndrome/diagnosis , Nephrotic Syndrome/drug therapy , Nephrotic Syndrome/immunology , Prednisolone/therapeutic use , Prospective Studies , Recurrence , Remission Induction , Tacrolimus/adverse effects , Time Factors , Treatment Outcome
15.
Plant Mol Biol ; 87(3): 249-60, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25537646

ABSTRACT

Diamine putrescine (Put) and polyamines; spermidine (Spd) and spermine (Spm) are essential component of every cell because of their involvement in the regulation of cell division, growth and development. The aim of this study is to enhance the levels of Put during fruit development and see its implications in ripening and quality of tomato fruits. Transgenic tomato plants over-expressing mouse ornithine decarboxylase gene under the control of fruit-specific promoter (2A11) were developed. Transgenic fruits exhibited enhanced levels of Put, Spd and Spm, with a concomitant reduction in ethylene levels, rate of respiration and physiological loss of water. Consequently such fruits displayed significant delay of on-vine ripening and prolonged shelf life over untransformed fruits. The activation of Put biosynthetic pathway at the onset of ripening in transgenic fruits is also consistent with the improvement of qualitative traits such as total soluble solids, titratable acids and total sugars. Such changes were associated with alteration in expression pattern of ripening specific genes. Transgenic fruits were also fortified with important nutraceuticals like lycopene, ascorbate and antioxidants. Therefore, these transgenic tomatoes would be useful for the improvement of tomato cultivars through breeding approaches.


Subject(s)
Ornithine Decarboxylase/genetics , Solanum lycopersicum/enzymology , Solanum lycopersicum/genetics , Animals , Biogenic Polyamines/metabolism , Ethylenes/biosynthesis , Food, Genetically Modified , Fruit/enzymology , Fruit/genetics , Fruit/growth & development , Genes, Plant , Solanum lycopersicum/growth & development , Mice , Nutritive Value , Plants, Genetically Modified/enzymology , Plants, Genetically Modified/genetics , Plants, Genetically Modified/growth & development , Promoter Regions, Genetic , Putrescine/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Plant/genetics , RNA, Plant/metabolism , Recombinant Proteins/genetics , Up-Regulation
16.
Pediatr Nephrol ; 30(3): 451-7, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25217328

ABSTRACT

BACKGROUND: Anti-complement factor H (anti-CFH) antibody-associated hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury in Indian children. While management comprises plasma exchange and immunosuppression, information on the impact on serial antibody titers and outcomes is limited. METHODS: This retrospective study included 45 patients with anti-CFH-associated HUS who were followed for ≥12 months. Following the initial plasma exchange sessions, patients received prednisolone and either intravenous (IV) cyclophosphamide (n = 31) or IV rituximab (n = 14), followed by maintenance immunosuppression. RESULTS: The median anti-CFH antibody titers fell from 3,215.5 [interquartile range (IQR) 1,977.9-8,453.9 to 414.6 (IQR 251.6-1,368.2) AU/ml with plasma exchange therapy (P < 0.0001), and the decline was similar with three, five, or seven plasma exchange sessions (P = 0.08). Serial anti-CFH titers were similar in patients receiving IV cyclophosphamide- and rituximab-based regimens during the 12-month follow-up (P = 0.63). Renal outcomes and relapse frequencies at the 15.4-month follow-up were comparable. Seven patients relapsed 6.5 (IQR 2.2-12.3) months from treatment onset. Patients with relapse had higher antibody titers during remission (P = 0.017). Titers of ≥1,300 AU/ml at 6 months predicted subsequent relapses. CONCLUSIONS: Our patients with anti-CFH antibody-associated HUS showed a significant fall in antibody titers following daily plasma exchange sessions. Therapy with cyclophosphamide- or rituximab-based regimens was associated with similar outcomes and a comparable decline in antibody titers.


Subject(s)
Autoantibodies/blood , Complement Factor H/immunology , Hemolytic-Uremic Syndrome/blood , Hemolytic-Uremic Syndrome/drug therapy , Plasma Exchange , Child , Combined Modality Therapy , Female , Hemolytic-Uremic Syndrome/immunology , Humans , Immunosuppressive Agents/therapeutic use , Male , Retrospective Studies , Treatment Outcome
17.
Kidney Int ; 85(3): 649-58, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24429405

ABSTRACT

In this prospective study, we measured serum levels of the soluble urokinase receptor (suPAR) in pediatric patients with nephrotic syndrome of various etiologies. Mean levels of suPAR were 3316 pg/ml in 99 patients with steroid-resistant focal segmental glomerulosclerosis and 3253 pg/ml in 117 patients with biopsy-proven minimal change disease, which were similar to that of 138 patients with steroid-sensitive nephrotic syndrome (3150 pg/ml) and 83 healthy controls (3021 pg/ml). Similar proportions of patients in each group had suPAR over 3000 pg/ml. Compared with controls, suPAR levels were significantly higher in patients with focal segmental glomerulosclerosis (FSGS) and estimated glomerular filtration rate (eGFR) under 30 ml/min per 1.73 m(2) (6365 pg/ml), congenital nephrotic syndrome (4398 pg/ml), and other proteinuric diseases with or without eGFR under 30 ml/min per 1.73 m(2) (5052 and 3875 pg/ml, respectively; both significant). There were no changes following therapy and during remission. Levels of suPAR significantly correlated in an inverse manner with eGFR (r=-0.36) and directly with C-reactive protein (r=0.20). The urinary suPAR-to-creatinine ratio significantly correlated with proteinuria (r=0.25) in 151 patients and controls. Using generalized estimating equations approach, serum suPAR significantly correlated with eGFR (coefficient=-13.75), age at sampling (2.72), and C-reactive protein (39.85). Thus, serum suPAR levels in nephrotic syndrome are similar to controls, and do not discriminate between FSGS, minimal change disease, or steroid-responsive illness.


Subject(s)
Glomerulosclerosis, Focal Segmental/blood , Nephrotic Syndrome/blood , Receptors, Urokinase Plasminogen Activator/blood , C-Reactive Protein/analysis , Child , Child, Preschool , Female , Glomerular Filtration Rate , Glomerulosclerosis, Focal Segmental/drug therapy , Glomerulosclerosis, Focal Segmental/physiopathology , Humans , Immunosuppressive Agents/therapeutic use , Infant , Infant, Newborn , Male , Nephrotic Syndrome/etiology , Nephrotic Syndrome/physiopathology , Prospective Studies , Proteinuria/urine
18.
Kidney Int ; 85(5): 1151-60, 2014 May.
Article in English | MEDLINE | ID: mdl-24088957

ABSTRACT

Antibodies to complement factor H are an uncommon cause of hemolytic uremic syndrome (HUS). Information on clinical features and outcomes in children is limited. In order to explore this we studied a multicenter cohort of 138 Indian children with anti-complement factor H antibody associated HUS, constituting 56% of patients with HUS. Antibody titers were high (mean 7054 AU/ml) and correlated inversely with levels of complement C3, but not complement factor H. Homozygous deletion of the CFHR1 gene was found in 60 of 68 patients. Therapies included dialysis in 119 children, 105 receiving plasma exchanges and 26 intravenous immunoglobulin. Induction immunosuppression consisted of 87 children receiving prednisolone with or without intravenous cyclophosphamide or rituximab. Antibody titers fell significantly following plasma exchanges and increased during relapses. Adverse outcome (stage 4-5 CKD or death) was seen in 36 at 3 months and 41 by last follow up, with relapse in 14 of 122 available children. Significant independent risk factors for adverse outcome were an antibody titer over 8000 AU/ml, low C3 and delay in plasma exchange. Combined plasma exchanges and induction immunosuppression resulted in significantly improved renal survival: one adverse outcome prevented for every 2.6 patients treated. Maintenance immunosuppressive therapy, of prednisolone with either mycophenolate mofetil or azathioprine, significantly reduced the risk of relapses. Thus, prompt use of immunosuppressive agents and plasma exchanges are useful for improving outcomes in pediatric patients with anti-complement factor H-associated HUS.


Subject(s)
Autoantibodies/blood , Blood Proteins/immunology , Complement C3b Inactivator Proteins/immunology , Hemolytic-Uremic Syndrome/therapy , Immunosuppressive Agents/therapeutic use , Plasma Exchange , Time-to-Treatment , Age Factors , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Azathioprine/therapeutic use , Biomarkers/blood , Blood Proteins/genetics , Case-Control Studies , Child , Child, Preschool , Combined Modality Therapy , Complement C3b Inactivator Proteins/genetics , Cyclophosphamide/therapeutic use , Drug Therapy, Combination , Female , Gene Deletion , Hemolytic-Uremic Syndrome/blood , Hemolytic-Uremic Syndrome/diagnosis , Hemolytic-Uremic Syndrome/genetics , Hemolytic-Uremic Syndrome/immunology , Homozygote , Humans , Immunosuppressive Agents/adverse effects , India , Infant , Male , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Plasma Exchange/adverse effects , Prednisolone/therapeutic use , Recurrence , Risk Factors , Rituximab , Time Factors , Treatment Outcome
19.
Plant Physiol Biochem ; 206: 108193, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38029615

ABSTRACT

In the aftermaths of global warming, plants are more frequently exposed to the combination of heat stress and drought in natural conditions. Jasmonic acid (JA) has been known to modulate numerous plant adaptive responses to diverse environmental stresses. However, the function of JA in regulating plant responses to the combined effects of heat and drought remains underexplored. In this study, we elucidated the functions of JA in enhancing the combined heat and drought tolerance of soybean (Glycine max). Our results showed that priming with JA improved plant biomass, photosynthetic efficiency and leaf relative water content, which all together contributed to the improved performance of soybean plants under single and combined heat and drought conditions. Exposure to single and combined heat and drought conditions caused oxidative damage in soybean leaves. Priming soybean plants, which were exposed to single and combined heat and drought conditions, with JA, on the other hand, substantially quenched the reactive oxygen species-induced oxidative burden possibly by bolstering their antioxidant defense system. Together, our findings provide direct evidence of the JA-mediated protective mechanisms in maintaining the optimal photosynthetic rate and plant performance under combined heat and drought conditions.


Subject(s)
Antioxidants , Cyclopentanes , Glycine max , Oxylipins , Antioxidants/metabolism , Droughts , Photosynthesis
20.
Plant Sci ; 340: 111937, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38043729

ABSTRACT

Due to the increasing demand for high-quality and high fiber-yielding cotton (Gossypium spp.), research into the development of stress-resilient cotton cultivars has acquired greater significance. Various biotic and abiotic stressors greatly affect cotton production and productivity, posing challenges to the future of the textile industry. Moreover, the content and quality of cottonseed oil can also potentially be influenced by future environmental conditions. Apart from conventional methods, genetic engineering has emerged as a potential tool to improve cotton fiber quality and productivity. Identification and modification of genome sequences and the expression levels of yield-related genes using genetic engineering approaches have enabled to increase both the quality and yields of cotton fiber and cottonseed oil. Herein, we evaluate the significance and molecular mechanisms associated with the regulation of cotton agronomic traits under both normal and stressful environmental conditions. In addition, the importance of gossypol, a toxic phenolic compound in cottonseed that can limit consumption by animals and humans, is reviewed and discussed.


Subject(s)
Gossypium , Gossypol , Humans , Gossypium/metabolism , Cottonseed Oil/metabolism , Cotton Fiber , Gossypol/metabolism , Genomics
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