Acquired factor XIII deficiency presenting with multiple intracranial hemorrhages and right hip hematoma:A case report

BACKGROUND Factor XIII(FXIII)deficiency is a rare yet profound coagulopathy.FXIII plays a pivotal role in hemostasis,and deficiencies in this factor can precipitate unchecked or spontaneous hemorrhaging.Immunological assays for detecting FXIII inhibitors are indispensable for diagnosing acquired FXIII deficiency;however,the availability of suitable testing facilities is limited,resulting in prolonged turnaround times for these assays.CASE SUMMARY In this case study,a 53-year-old male devoid of significant medical history presented with recurrent intracranial hemorrhages and a hematoma in the right hip.Subsequent genetic analysis revealed a homozygous mutation in the ACE gene,confirming the diagnosis of acquired FXIII deficiency.CONCLUSION This case underscores the significance of considering acquired deficiencies in clotting factors when evaluating patients with unexplained bleeding episodes.

Vitamin B12 deficiency in dialysis patients:risk factors,diagnosis,complications,and treatment:A comprehensive review

Vitamin B12 deficiency is a significant concern among patients with end-stage renal disease undergoing dialysis.However,there hasn’t been extensive research conducted on this particular patient group.The reported incidence rates vary widely,ranging from 20%to 90%,reflecting the complexity of its diagnosis.Dialysis patients often face multiple nutritional deficiencies,including a lack of essential vitamins,due to factors such as dietary restrictions,impaired absorption,and nutrient loss during dialysis.Diagnosing vitamin B12 deficiency in these patients is challenging,and addressing it is crucial to prevent complications and improve their overall quality of life.This review paper delves into the available body of evidence on vitamin B12 deficiency in dialysis patients,examining the contributing risk factors,diagnostic challenges,potential complications,and available treatment options.It provides a well-rounded perspective on the topic,making it a valuable resource for researchers,healthcare practitioners,and policymakers interested in addressing the nutritional needs of dialysis patients.

Alpha-1 antitrypsin deficiency and Pi^(*)Z allele as important co-factors in the development of liver fibrosis

BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant mutation.AIM To evaluate the impact of clinical parameters and AATD phenotypes,particularly the Pi*Z allele,in liver fibrosis.METHODS Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation.RESULTS Included 69 patients,49.3%had Pi*MZ phenotype and 10.1%Pi*ZZ.An age≥55 years,age at diagnosis≥41 years and AAT at diagnosis<77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,P<0.001;AUC=0.836,P<0.001;AUC=0.681,P=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,P<0.001;AUC=0.795,P<0.001).Patients with hypertension,type 2 diabetes mellitus(DM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(P<0.001,P=0.002,P=0.008,P<0.001,P=0.033).Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement≥7.1 kPa(P=0.040).CONCLUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one Pi*Z allele,and AAT value at diagnosis<77 mg/dL.We created an algorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.

Research Progress on the Influencing Factors and Preventive Interventions of Iron Deficiency

Iron is an important element that maintains the normal operation of the body.It not only participates in various physiological reactions as a component of various enzymes,but also is an indispensable component in the synthesis of hemoglobin(Hb)and myoglobin,which transport oxygen.About two-thirds of the iron in the body is stored in the Hb of red blood cells,with a small amount present in myoglobin in muscle tissue and enzymes required for various metabolic reactions.The remaining amount is mostly in the form of ferritin as a mobilized iron reserve.When dietary iron intake is limited and the stored iron in the body is insufficient or depleted,iron deficiency occurs.Iron deficiency can be further divided into three stages based on their severity,namely iron deficiency(ID),iron deficiency erythropoiesis(IDE),and iron deficiency anemia(IDA).This study aims to explore the prevalence,diagnosis and differentiation,influencing factors,and preventive interventions of iron deficiency.

Vitamin D deficiency and increased inflammatory factor intercellular cell adhesion molecule-1 indicate severe leukoaraiosis in northern China

Background and objective:Commonly plaguing in the frigid zone of the world,vitamin D deficiency,as indicated by low levels of 25-hydroxyvitamin D,exacerbated inflammatory responses and impaired endothelial function.Leukoaraiosis(LA)is a prevalent cause of cognitive dysfunction in the elderly and is potentially associated with inflammatory responses.This study aimed to investigate the impact of vitamin D on the severity of LA.Methods:Patients with LA were categorized based on 3.0 T brain MRI findings into mild(N=43),moderate(N=40),or severe groups(N=29)using the Fazekas scale(scoring 1-6).A control group consisting of 41 healthy individuals was included.Serum fibrinogen C,homocysteine,plasma 25-hydroxyvitamin D,and intercellular cell adhesion molecule-1(ICAM-1)levels were measured using ELISA.Results:All LA severity groups exhibited lower plasma 25-hydroxyvitamin D levels compared to the control group,with a more pronounced decrease observed as LA severity increased.Low plasma 25-hydroxyvitamin D was identified as an independent risk factor for LA(P<0.05)according to Multiple logistic regression analysis.Additionally,a negative association was observed between 25-hydroxyvitamin D and vascular inflammatory factor ICAM-1.Conclusions:Disease severity positively correlated with levels of the inflammatory marker ICAM-1,worsening as plasma 25-hydroxyvitamin D concentration decreased.Low 25-hydroxyvitamin D emerged as an independent risk factor for LA,potentially exacerbating the inflammatory response.These findings suggest 25-hydroxyvitamin D supplementation as a potential therapeutic approach for LA.

Ethylene accelerates maize leaf senescence in response to nitrogen deficiency by regulating chlorophyll metabolism and autophagy

Leaf senescence is an orderly and highly coordinated process,and finely regulated by ethylene and nitrogen(N),ultimately affecting grain yield and nitrogen-use efficiency(NUE).However,the underlying regulatory mechanisms on the crosstalk between ethylene-and N-regulated leaf senescence remain a mystery in maize.In this study,ethylene biosynthesis gene ZmACS7 overexpressing(OE-ZmACS7)plants were used to study the role of ethylene regulating leaf senescence in response to N deficiency,and they exhibited the premature leaf senescence accompanied by increased ethylene release,decreased chlorophyll content and F_v/F_m ratio,and accelerated chloroplast degradation.Then,we investigated the dynamics changes of transcriptome reprogramming underlying ethylene-accelerated leaf senescence in response to N deficiency.The differentially expressed genes(DEGs)involved in chlorophyll biosynthesis were significantly down-regulated,while DEGs involved in chlorophyll degradation and autophagy processes were significantly up-regulated,especially in OE-ZmACS7 plants in response to N deficiency.A gene regulatory network(GRN)was predicted during ethylene-accelerated leaf senescence in response to N deficiency.Three transcription factors(TFs)ZmHSF4,Zmb HLH106,and ZmEREB147 were identified as the key regulatory genes,which targeted chlorophyll biosynthesis gene ZmLES22,chlorophyll degradation gene ZmNYC1,and autophagy-related gene ZmATG5,respectively.Furthermore,ethylene signaling key genes might be located upstream of these TFs,generating the signaling cascade networks during ethylene-accelerated leaf senescence in response to N deficiency.Collectively,these findings improve our molecular knowledge of ethylene-accelerated maize leaf senescence in response to N deficiency,which is promising to improve NUE by manipulating the progress of leaf senescence in maize.

Role of bisphosphonates in osteoporosis caused by adult growth hormone deficiency

In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.

Abnormal ACT in a Patient with Prekallikrein Deficiency Undergoing Cardiopulmonary Bypass

Prekallikrein deficiency is a disorder that often remains undiagnosed. Prekallikrein activates factor XII, which initiates the intrinsic coagulation pathway. Prekallikrein deficiency results in prolonged Partial Thromboplastin Time and Activated Clotting Time in absence of anticoagulants or active bleeding. This case report describes the anesthesia management of a patient with Prekallikrein deficiency who underwent cardiac surgery with Cardiopulmonary Bypass for correction of a congenital cardiac malformation. We highlight the importance of understanding the different tests available for the diagnosis of coagulation factors deficiency during administration of heparin in the setting of cardiovascular procedures under general anesthesia.

Study on improving hematopoietic function of rats with blood deficiency syndrome by Shengxuebao mixture

Background:Shengxuebao mixture(SXBM)is a novel herbal drug approved by China State Food and Drug Administration for the treatment of Leukopenia and iron deficiency anemia caused by radiotherapy and chemotherapy.Methods:To explore the mechanism of SXBM in treating blood deficiency syndrome(BDS).Firstly,network pharmacology and in vivo experiments were used to screen candidate targets and important signaling pathways of SXBM,GO functional enrichment and KEGG pathway analysis were performed.Secondly,a BDS rat model was established to verify the results of the analysis of network pharmacological enrichment.Histopathology and routine peripheral blood examination were observed.The expressions of tumor necrosis factor-α,interleukin(IL)-6,HIF-1αand NF-κB were detected by Western blot,and the expressions of IL-6,IL-1βwere detected by ELISA.Results:62 bioactive components,66 potential targets and 131 signaling pathways of BDS were successfully identified by network pharmacology.Molecular docking simulation techniques showed that key targets tumor necrosis factor-α,IL-6,IL-1βcan dock well with crucial components,and the BDS-related signaling pathways HIF-1 and JAK-STAT play a vital role.The combined model experiment of acetylphenylhydrazine and cyclophosphamide showed that the model group had obvious blood deficiency,and the histopathology and blood routine were effectively restored after administration.Our findings indicate that SXBM’s therapeutic effect on BDS primarily involves the mediation of the HIF-1α/NF-κB signaling pathway and the regulation of hematopoietic factor expression.Conclusion:This study not only affirmed the protective properties of SXBM against BDS but also provided insights into a potential mechanism for blood replenishment in the treatment of BDS using SXBM.

Parenteral iron therapy in children with iron deficiency anemia

Iron deficiency anemia(IDA)continues to be a global public health problem.Oral iron is the universally accepted first-line therapy,and most children have a prompt and favorable response to oral formulations.In subsets of children who fail to respond due to intolerance,poor adherence,or inadequate intestinal absorption,parenteral iron is indicated.Despite numerous studies in adults with IDA of diverse etiologies,pediatric studies on parenteral iron use are very limited.Although mostly retrospective and small,these studies have documented the efficacy and safety profile of intravenous iron formulations.In this editorial the author comments on the most important published data and underscores the need to seriously consider parenteral iron use in children unresponsive to oral therapy.

A Budd-Chiari Syndrome Due to C Protein Deficiency: A Case Report at YaoundéGeneral Hospital (Cameroon)

Primary Budd-Chiari syndrome (BCS) is a spontaneously fatal disease characterized by an obstruction of the hepatic venous outflow tract due to thrombosis or a primary disease of the venous wall. The primary form of BCS is extremely rare. This is a disease mainly affecting young adults of both sexes. Clinical manifestations are variable;they can be asymptomatic, acute, or subacute but mostly chronic. Several causes have been identified, such as myeloproliferative syndrome, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria, and inherited thrombotic disorders. Data on primary BCS in Sub-Saharan Africa is rare as most publications available are case reports. In these reports, the causes are unknown with poor prognosis in most cases often leading to patient death. We herein present a case report of a male patient diagnosed with a primary BCS at Yaoundé General Hospital (Cameroon) caused by a Protein C deficiency who presented with ascites decompensating liver cirrhosis. Treatment was based on anticoagulants, diuretics and laxatives administration. Two years after the diagnosis, the patient is alive with clinical and paraclinical improvement.

Analysis of Phenotypes Associated with Deficiency of PAX6 Haplotypes in Chinese Aniridia Families

Objective To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency.Methods A comprehensive questionnaire and ophthalmological assessments were administered to both affected patients and unaffected relatives.The clinical feature analysis included the evaluation of visual acuity,intraocular pressure,slit-lamp anterior segment examination,fundus photography,and spectral domain optical coherence tomography.To identify the mutation responsible for aniridia,targeted next-generation sequencing was used as a beneficial technique.Results A total of 4 mutations were identified,consisting of two novel frameshift mutations(c.314delA,p.K105Sfs*33 and c.838_845dup AACACACC,p.S283Tfs*85),along with two recurring nonsense mutations(c.307C>T,p.R103X and c.619A>T,p.K207*).Complete iris absence,macular foveal hypoplasia,and nystagmus were consistent in these PAX6 haplotype-deficient Chinese aniridia families,while corneal lesions,cataracts,and glaucoma exhibited heterogeneity both among the families and within the same family.Conclusion In our study,two novel PAX6 mutations associated with aniridia were identified in Chinese families,which expanded the phenotypic and genotypic spectrum of PAX6 mutations.We also analyzed the clinical characteristics of PAX6 haplotype deficiency in Chinese aniridia families.

Exogenous testosterone therapy on choroid in androgen deficiency

AIM:To investigate the effects of exogenous testosterone treatment on the choroidal parameters in patients with androgen deficiency.METHODS:Right eyes of 24 patients with androgen deficiency and 31 healthy volunteers were included in the study.The eyes were scanned for subfoveal choroidal thickness(SFCT),choroidal vascularity index(CVI),choroidstromal area(C-SA),choroid-luminal area(C-LA),choroidstromal to luminal area ratio(CSLR),and the choroidal parameters within central 1500μm of the macula(CVI1500,C-LA1500,C-SA1500,and CSLR1500)by enhanced-depth imaging optical coherence tomography(EDI-OCT)at baseline,6th and 18th weeks of the exogenous testosterone treatment.RESULTS:The mean SFCT values of the androgen deficient groups and healthy controls were 307.7±27.0 and 303.2±37.2μm(P=0.8).However,CVI,C-SA,CSLR,CVI1500,C-LA1500,and CSLR1500 were significantly different between the groups(all P<0.01).At the 6th week visit after exogenous testosterone treatment,SFCT,CVI,C-LA,and C-SA were significantly decreased,and these parameters returned to baseline levels at the 18th-week visit(all P>0.05).However,CVI1500 and LA1500 significantly increased at the end of the follow-up period(P<0.001).CONCLUSION:CVI is lower in androgen-deficient patients than in healthy subjects.The alterations in the choroid during the testosterone peak are transient in the treatment of patients with androgen deficiency.However,the increase in CVI within the central 1500μm of the macula persists even after 4mo.

Changes in Metabolites and Allelopathic Effects of Non-Pigmented and Black-Pigmented Lowland Indica Rice Varieties in Phosphorus Deficiency

Phosphorus(P) levels alter the allelopathic activity of rice seedlings against lettuce seeds. In this study, we investigated the effect of P deficiency on the allelopathic potential of non-pigmented and pigmented rice varieties. Rice seedlings of the white variety Khao Dawk Mali(KDML105, non-pigmented) and the black varieties Jao Hom Nin(JHN, pigmented) and Riceberry(RB, pigmented) were cultivated under high P(HP) and low P(LP) conditions. Morphological and metabolic responses to P deficiency were investigated. P deficiency inhibited shoot growth but promoted root growth of rice seedlings in all three varieties. Moreover, P deficiency led to decreased cytosolic phosphate(Pi) and total P concentrations in both shoot and root tissues. The subsequent reduction in internal P concentration enhanced the accumulation of phenolic compounds in both shoot and root tissues of the seedlings. Subsequently, allelopathy-based inter-and intra-specific interactions were assessed using water extracts from seedlings of the three varieties grown under HP and LP conditions. These extracts were tested on seeds of lettuce, the weed Dactyloctenium aegyptium, and the same rice variety. The shoot and root extracts from P-deficient seedlings reduced the germination of all recipient plants. Specifically, the shoot extract from P-deficient KDML105 seedlings reduced the germination index(GI) of lettuce seeds to 1%, while those from P-deficient RB and JHN seedlings produced GIs of 32% and 42%, respectively. However, when rice seeds were exposed to their own LP shoot and root extracts, their GIs increased up to 4-fold, compared with the HP extracts. Additionally, the shoot extracts from P-deficient plants also stimulated the germination of D. aegyptium by about 2–3-fold, whereas the root extracts did not have this effect. Therefore, P starvation led to the accumulation and exudation of phenolics in the shoots and roots of rice seedlings, altering their allelopathic activities. To adapt to P deficiency, rice seedlings potentially release signaling chemicals to suppress nearby competing species while simultaneously promoting their own germination and growth.

A comparison of the effect of alendronate and You-Gui-Wan on osteoporosis in female rats with kidney-yang deficiency

Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.

Is magnesium deficiency the major cause of needle chlorosis of Pinus taeda in Brazil?

Needle chlorosis(NC)in Pinus taeda L.systems in Brazil becomes more frequent after second and third harvest rotation cycles.In a study to identify factors contributing to yellowing needle chorosis(YNC),trees were grown in soils originating from contrasting parent materials,and soils and needles(whole,green and chlorotic portions)from 1-and 2-year-old branches and the first and second needle flush release at four sites with YNC on P.taeda were analyzed for various elements and properties.All soils had very low base levels(Ca^(2+),Mg^(2+)and K^(+))and P,suggesting a possible lack of multiple elements.YNC symptoms started at needle tips,then extended toward the needle base with time.First flush needles had longer portions with YNC than second flush needles did.Needles from the lower crown also had more symptoms along their length than those higher in the canopy.Symptoms were similar to those reported for Mg.In chlorotic portions,Mg and Ca concentrations were well below critical values;in particular,Mg levels were only one third of the critical value of 0.3 g kg^(-1).Collectively,results suggest that Mg deficiency is the primary reason for NC of P.taeda in various parent soils in Brazil.

Effect of Artemisia annua (Asteraceae) Extracts on Hemolysis in Individuals with G6PD-Deficiency

Individuals with Glucose-6-phosphate dehydrogenase (G6PD) deficiency are susceptible to hemolytic anemia when exposed to pro-oxidant substances. This study investigates the hemolytic impact of Artemisia annua (A. annua) extracts in G6PD-deficient subjects through a mixed experimental approach. In the in vitro phase, red blood cells from G6PD-deficient individuals and rats induced with Dehydroepiandrosterone (DHEA) were exposed to various concentrations of A. annua infusion, with distilled water and physiological saline as positive and negative controls respectively. The in vivo study involved G6PD-deficient Wistar rats divided into three groups receiving A. annua infusion, quinine (positive control), and distilled water (negative control) via gavage. Blood samples were collected for biochemical and hematological analyses. Notably, at a 40% concentration of A. annua infusion, there was a significant increase in the hemolysis rate of G6PD-deficient red blood cells compared to controls (p A. annua exhibited elevated aspartate aminotransferase (129.25 ± 4.55 U/L vs. 80.09 ± 4.03 U/L;p A. annua infusion tested positive for saponins. These findings underscore the risk of hemolysis in G6PD-deficient individuals upon ingesting A. annua.

Iron-Deficiency Anemia Management in Gynecological Surgery: A Review of Current Evidence and Best Practices

Purpose: Due to the high prevalence of iron deficiency anemia in women undergoing gynecological surgeries and its association with worse postoperative results, it is necessary to identify and treat anemia preoperatively. However, although anemia and iron deficiency are significant global health problems, there are still disparities in the recognition and implementation of “Patient Blood Management” (PBM) as a comprehensive approach to mitigating the risks associated with these diseases. The purpose of the study is to review best practices for the treatment of anemia based on the Enhanced Recovery After Surgery (ERAS) protocol and PBM recommendations. Methods: This study reviewed the literature on preoperative iron deficiency anemia in patients undergoing gynecological surgery. We identified references through searches in PubMed using relevant search terms. Results: Among the various strategies used in PBM, perhaps the most important is the early detection and management of anemia. In gynecological surgery, there are several approaches to reducing perioperative blood loss, highlighting the use of gonadotropin-releasing hormone (GnRH) agonists (aGnRh) and antifibrinolytics. Oral and intravenous iron supplementation can be performed in addition to blood transfusion to treat anemia. Conclusion: Addressing preoperative and postoperative anemia through systematic correction, following the guidelines of the ERAS protocol and PBM guidelines, is essential to improving perioperative outcomes in women undergoing gynecological surgery.

Carbon Monoxide Modulates Auxin Transport and Nitric Oxide Signaling in Plants under Iron Deficiency Stress

Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in modulating the plant’s response to iron deficiency.Iron deficiency leads to an increase in the activity of heme oxygenase(HO)and the subsequent generation of CO.Additionally,it alters the polar subcellular distribution of Pin-Formed 1(PIN1)proteins,resulting in enhanced auxin transport.This alteration,in turn,leads to an increase in NO accumulation.Furthermore,iron deficiency enhances the activity of ferric chelate reductase(FCR),as well as the expression of the Fer-like iron deficiency-induced transcription factor 1(FIT)and the ferric reduction oxidase 2(FRO2)genes in plant roots.Overexpression of the long hypocotyl 1(HY1)gene,which encodes heme oxygenase,or the CO donor treatment resulted in enhanced basipetal auxin transport,higher FCR activity,and the expression of FIT and FRO2 genes under Fe deficiency.Here,a potential mechanism is proposed:CO and NO interact with auxin to address iron deficiency stress.CO alters auxin transport,enhancing its accumulation in roots and up-regulating key iron-related genes like FRO2 and IRT1.Elevated auxin levels affect NO signaling,leading to greater sensitivity in root development.This interplay promotes FCR activity,which is crucial for iron absorption.Together,these molecules enhance iron uptake and root growth,revealing a novel aspect of plant physiology in adapting to environmental stress.

Distinct and Additive Effects of Alcohol and Thiamine Deficiency in the Developing Brain: Relevance to Fetal Alcohol Spectrum Disorder

Background: Neurodevelopmental abnormalities in fetal alcohol spectrum disorder (FASD) are linked to brain insulin resistance and oxidative stress. However, the role of thiamine deficiency as a distinct or additive factor in the pathogenesis of the neurodevelopmental and metabolic derangements in FASD has not been determined. Methods: Control and ethanol-exposed human PNET2 cerebellar neuronal cells and rat cerebellar slice cultures were treated with vehicle or pyrithiamine (Pyr) to assess independent and additive effects of thiamine deficiency on ethanol-mediated neurotoxicity, mitochondrial dysfunction, insulin resistance, inhibition of neuronal and glial genes, and oxidative stress. Results: Pyr treatments (0 - 200 µM) caused dose-dependent cell loss (Crystal Violet assay) and reduced mitochondrial function (MTT assay) in PNET2 neuronal cultures. Ethanol alone (100 mM) significantly reduced PNET2 neuronal viability, MTT activity, and ATP production. Over the broad dose range of Pyr treatment, ethanol significantly reduced ATP content and cell number and increased mitochondrial mass (MitoTracker Green). Ex vivo cerebellar slice culture studies revealed ethanol-induced developmental architectural disruption that was substantially worsened by Pyr. The adverse effects of ethanol were linked to increased lipid peroxidation and inhibition of asparatyl-asparaginyl-β-hydroxylase (ASPH) expression. The independent and additive effects of Pyr were associated with increased cytotoxicity, lipid peroxidation, Caspase 3 activation, and Tau accumulation. Conclusions: During development, alcohol exposure and thiamine deficiency exert distinct but overlapping molecular pathologies that ultimately impair the structure and function of cerebellar neurons. While both insults drive cell loss and mitochondrial dysfunction with increased lipid peroxidation, ethanol’s additional inhibitory effects on ASPH reflect impairments in insulin and IGF signaling. In contrast, Pyr’s main adverse effects were likely due to neurotoxicity and the activation of apoptosis cascades. The findings suggest that FASD severity may be reduced by thiamine supplementation, but without additional support for insulin/IGF signaling networks, FASD would not be prevented.