Functional Deficiency Research Articles

TFAP2A drives non-small cell lung cancer (NSCLC) progression and resistance to targeted therapy by facilitating the ESR2-mediated MAPK pathway

Cancer is among the leading causes of death related diseases worldwide, and lung cancer has the highest mortality rate in the world. Transcription factors (TFs) constitute a class of structurally and functionally intricate proteins. Aberrant expression or functional deficiencies of transcription factors may give rise to abnormal gene expression, contributing to various diseases, including tumours. In this study, we propose to elucidate the potential role and mechanism of TFAP2A in NSCLC. We found that TFAP2A levels were significantly greater in tumour tissues than para-tumour tissues, and high expression of TFAP2A was associated with poor prognosis in NSCLC patients. Additionally, TFAP2A overexpression promoted NSCLC progression both in vivo and in vitro. Mechanistically, ESR2 is a potential target regulated by TFAP2A and that TFAP2A can bind to the promoter region of ESR2. Furthermore, the overexpression of both TFAP2A and ESR2 in NSCLC cells was associated with the overactivation of MAPK signalling, and the combination of PHTPP and osimertinib had a synergistic effect on suppressing tumour growth.

PPARγ Functional Deficiency Expedited Fatty Acid Utilization in the Liver: A Foundation of Inflammatory Adipokine-Induced Hypolipemia in Rheumatoid Arthritis.

Triglyceride (TG) and its derivatives tend to be decreased in rheumatoid arthritis (RA) patients' blood when inflammation progresses. Aside from the role as a lipid buffer, white adipose tissue (WAT) contributes to this abnormality via adipokines, which regulate many metabolic signals. This work investigated adipokine-caused hepatic changes and their involvement in RA-related hypolipemia. Given their immune similarities with RA and pathological representativeness, adjuvant-induced arthritis (AIA) rats and antigen-induced arthritis (AA) mice were adopted. Adipokine levels in the liver were quantified, and their hepatic conditions were assessed by oxidative/enzymatic indicators. Besides kit-based metabolite quantification, fatty acid levels in blood were accurately determined by GC-MS. Metabolic differences between healthy and AIA rats were further characterized by UPLC-MS2. In vitro, preadipocytes were stimulated by RA/AIA blood serum or together with rosiglitazone, a PPARγ agonist. The medium was used to culture HepG2 cells. Some AIA rats were subjected to adipectomy or rosiglitazone therapies. Being WAT-released mediators, IL-1β, IL-6, MCP-1, adiponectin, and visfatin were apparently increased in AIA/AA rodent models' liver, causing oxidative stress escalation, liver injuries, and fatty acid oxidation acceleration. This metabolic change was coincided to expression increase of CD36, FABP1, ATGL, and CPT-1A. PPARγ deficiency occurred both in vivo and in vitro under rheumatic conditions. RA serum reduced PPARγ expression and impaired its inhibition on NF-κB transcription activity in preadipocytes, which then led to excessive secretion of inflammatory adipokines. The corresponding medium down-regulated PPARγ and promoted expression of lipid catabolic enzymes in HepG2 cells. These effects were abrogated by rosiglitazone. Both the therapies impeded inflammatory secretion of WAT and fat catabolism of the liver. These data demonstrate that RA potentiates the capacity of WAT to secrete inflammatory adipokines. The resulting condition represses PPARγ expression and disrupts TG anabolism/catabolism balance in the liver. Because hepatocytes utilize more lipids but synthesize less, hypolipemia develops.

Progress in the mechanism of functional dyspepsia: roles of mitochondrial autophagy in duodenal abnormalities.

Mitochondria are the main source of energy for cellular activity. Their functional damage or deficiency leads to cellular deterioration, which in turn triggers autophagic reactions. Taking mitochondrial autophagy as a starting point, the present review explored the mechanisms of duodenal abnormalities in detail, including mucosal barrier damage, release of inflammatory factors, and disruption of intracellular signal transduction. We summarized the key roles of mitochondrial autophagy in the abnormal development of the duodenum and examined the in-depth physiological and pathological mechanisms involved, providing a comprehensive theoretical basis for understanding the pathogenesis of functional dyspepsia. At present, it has been confirmed that an increase in the eosinophil count and mast cell degranulation in the duodenum can trigger visceral hypersensitive reactions and cause gastrointestinal motility disorders. In the future, it is necessary to continue exploring the molecular mechanisms and signaling pathways of mitochondrial autophagy in duodenal abnormalities. A deeper understanding of mitochondrial autophagy provides important references for developing treatment strategies for functional dyspepsia, thereby improving clinical efficacy and patient quality of life.

Hypoxia-inducible factor activators: a novel class of oral drugs for the treatment of anemia of chronic kidney disease.

Anemia is a hallmark of chronic kidney disease (CKD), worsens with disease progression, and profoundly affects a patient's well-being. Major pathogenic factors are inadequate kidney erythropoietin (EPO) production and absolute and functional iron deficiency. The 2 mainstays of current anemia treatment are a) replacement therapy with recombinant EPO or 1 of its glycosylated derivatives, administered subcutaneously or intravenously, and b) intravenous (IV) iron injections. Over the past 5 years, hypoxia-inducible factor (HIF)-prolyl hydroxylase inhibitors (HIF-PHIs) have been approved in many countries for the management of anemia in both nondialysis and dialysis-dependent patients with CKD. Due to cardiovascular safety concerns, only 2 HIF-PHIs, daprodustat and vadadustat, have been approved for marketing in the United States, and only for patients on maintenance dialysis. HIF-PHIs are oral agents that are effective at improving and maintaining hemoglobin levels by activating HIF signaling in anemic patients with CKD. They stimulate the production of endogenous EPO, increase total iron-binding capacity through their direct effects on transferrin gene transcription, lower plasma hepcidin indirectly, and have beneficial effects on red blood cell parameters. Here, we discuss the mechanisms of action and pharmacologic properties of different HIF-PHIs. We discuss unwanted on-target and off-target effects, review cardiovascular and other safety concerns, and provide a benefit/risk-based perspective on how this new class of oral drugs might impact current anemia management in CKD. A clinical case is presented that highlights the clinical complexities and therapeutic challenges in managing anemia in CKD.

Inhibition of alternative complement system and prolyl hydroxylase ameliorates anaemia of inflammation.

Chronic diseases associated with inflammation cause early destruction of RBCs. Complement system, part of innate immunity, is involved in such RBC destruction. Persistent inflammation causes kidney injury, leading to reduced erythropoietin release and functional iron deficiency, causing anaemia. We have investigated effect of iptacopan, a factor B inhibitor, and desidustat, a prolyl hydroxylase inhibitor in anaemia induced by peptidoglycan polysaccharide (PGPS) treatment in rats. Inflammation, haemolysis and its diagnostic markers (LDH, total bilirubin, and RBC lifespan) were evaluated after three days of PGPS challenge. Haemoglobin, RBC, iron homeostasis, and RBC destruction were evaluated fourteen days after PGPS challenge. Desidustat (15mg/kg) and iptacopan (20mg/kg) were given along with PGPS and continued for two weeks. Iptacopan and its combination with desidustat prevented LDH, total bilirubin, complement protein-C3a and haemolysis. Combination treatment caused an early normalization of haemoglobin and RBC. Combination also reduced WBC, alkaline phosphatase, aspartate aminotransferase, and rat paw volume. Serum iron was increased by desidustat and its combination treatment. Spleen weight, tissue iron, and serum hepcidin were reduced by combination treatment. Effect of desidustat alone was prominent on iron (serum and tissue) and hepcidin. Thus, combination of iptacopan and desidustat can be a potentially useful therapeutic option for treatment of anaemia of inflammation.

The Unmet Needs of Lysosomal Storage Disorders from Early Diagnosis to Caregiving Pathways: An Italian Perspective

Background/Objective: Lysosomal storage diseases (LSDs) are a group of rare, inborn, metabolic errors characterized by deficiencies in normal lysosomal function and by the intralysosomal accumulation of undegraded substrates, resulting in the damage of multiple organ systems. The spectrum of clinical manifestations is extremely heterogeneous. LSD diagnosis and management still present many issues. Methods: A group of Italian experts and patients’ representatives met to discuss some critical aspects, and among the most impactful are early diagnosis, the transition of the patient from pediatric to adult age, territorial management, and the multidisciplinary approach. Results: Possible solutions to diagnostic delays may be a widespread newborn screening and screening programs on selected populations. The lack of a structured transition process could be helped by the drafting of shared diagnostic and therapeutic care pathways beyond the availability of databases accessible to the different levels that manage a patient. Territorial management could benefit from telemedicine, but a homogeneous diffusion of home therapy, not yet everywhere possible, is essential. A fundamental role is played by the patient associations, which should be increasingly involved in the political choices. It is also crucial to create structured multidisciplinary teams of experts for disease management and comorbidities. A transversal need appears to be greater training on LSDs. In Italy, the “Statement of Udine” was developed to guide further steps towards improvements in inherited metabolic medicine in adults, referencing the experience from the United Kingdom. Conclusions: Much can be done for the early diagnosis and management of LSDs with an effective treatment, but many aspects need improvement for the overall management of the patient. An investment in dedicated resources, formal recognition, and training is needed to address these unmet needs.

Associations of anaemia and iron deficiency with health-related quality of life in patients with chronic kidney disease stage G3b-5 in Japan: sub analysis of the Reach-J CKD cohort study

BackgroundIron deficiency is a major contributor to anaemia in chronic kidney diseases. The association of anaemia and iron deficiency with health-related quality of life in Japanese patients with non-dialysis chronic kidney disease has not been examined. In this study, we evaluated anaemia and iron deficiency in patients with chronic kidney disease G3b-5 and examined their associations with health-related quality of life.MethodsThis nationwide cohort study included 2,249 patients with advanced chronic kidney disease receiving nephrologist care from 31 representative facilities throughout Japan; they were randomly selected through stratification by region and facility size and aligned with the Chronic Kidney Disease Outcomes and Practice Patterns Study. Using baseline patient data, we assessed the association of anaemia and iron deficiency with health-related quality of life, employing the 36-item Kidney Disease Quality of Life Questionnaire.ResultsThe mean mental and physical component summary scores for all patients were 49 and 47, respectively. Patients with haemoglobin levels < 10 g/dL had worse three kidney disease subscale, mental component summary, physical component summary, and subdomain scores than those with haemoglobin levels > 12 g/dL. Patients with absolute iron deficiency (TSAT < 20% and ferritin < 100 ng/mL) had worse three kidney disease subscale and mental component summary scores than those with functional iron deficiency (TSAT < 20% and ferritin ≥ 100 ng/mL).ConclusionsJapanese patients with chronic kidney disease G3b-5 with anaemia or absolute iron deficiency had worse health-related quality of life. Our results provide clinical evidence of renal anaemia in Japan and will be useful for international comparisons.

In Vivo Functional Assessment of Rat Masseter Muscle Following Surgical Creation of a Volumetric Muscle Loss (VML) Injury.

Volumetric Muscle Loss (VML) is prevalent in civilian and military populations and represents a debilitating skeletal muscle injury surpassing the body's natural regenerative capacity. These injuries disrupt not only muscle fibers but also nerves, blood vessels, and the extracellular matrix, overwhelming the regenerative capacity of skeletal muscle and leading to severe fibrosis and permanent deficiencies in muscle structure and function. Current clinical management has many limitations, and thus, research is ongoing to develop more effective therapeutic approaches. Notably, however, much of the preclinical emphasis on VML injuries has focused on limb and trunk muscles, with limited investigation into craniofacial muscles. Differences in developmental biology and regenerative capacity between craniofacial and limb/trunk muscles may provide crucial insights that drive more injury-specific VML treatment options. Moreover, evaluation of functional recovery is critical to establishing therapeutic efficacy. In this regard, in vivo testing of muscle contraction with percutaneous nerve stimulation is a minimally invasive method that allows for repeated functional assessment over the course of a study - in the same animal. In light of these considerations, this paper describes a method for the in vivo assessment of muscle function in the rat masseter muscle before and after a VML injury. This protocol is the first published instance to detail the creation and functional evaluation of a biologically relevant craniofacial VML injury in the rat.

The Mutual Relationship between Thyroid Hormones, Kidney Function, and Vitamin D3 Deficiency

The Mutual Relationship between Thyroid Hormones, Kidney Function, and Vitamin D3 Deficiency

Anaemia during pregnancy: could riboflavin deficiency be implicated?

Anaemia affects more than 36% of all pregnancies globally and is associated with significant maternal and neonatal morbidity and mortality. Iron deficiency is widely recognised as the most common nutritional cause of anaemia but other nutrient deficiencies are also implicated, including the B vitamin riboflavin, albeit its role is largely under-investigated and thus typically overlooked. Riboflavin, in its cofactor forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), is required for numerous oxidation-reduction reactions, antioxidant function, and in the metabolism of other B vitamins and iron. While clinical deficiency of riboflavin is largely confined to low-income countries, sub-clinical (functional) deficiency is much more widespread, including in high-income countries, and is particularly common among women of reproductive age and during pregnancy. Limited observational evidence from high-income populations suggests that suboptimal riboflavin status contributes to an increased risk of anaemia. Furthermore, randomised controlled trials in pregnant women from low- and middle-income countries have demonstrated beneficial effects of riboflavin on haematological status and anaemia. Various mechanisms have been proposed to explain the contribution of riboflavin deficiency to anaemia, with the strongest evidence pointing to an adverse effect on iron metabolism, given that riboflavin co-factors are required for the release of iron from storage ferritin in the production of red blood cells. Overall, this review investigates riboflavin intakes and status during pregnancy in different populations and evaluates the available evidence for the under-recognised role of riboflavin in the maintenance of haemoglobin concentrations together with its potential to protect against the development of anaemia during pregnancy.

Absolute versus functional iron deficiency.

Absolute versus functional iron deficiency.

Improvements to the bonding condition of ultra-thin concrete overlays for airport rigid pavements

ABSTRACT Ultra-thin concrete overlay (UTO) is an effective solution for repairing functional deficiencies in airport rigid pavements, with interface bonding properties critical to pavement performance and longevity. This study systematically investigates methods to enhance UTO interface bond strength under heavy dynamic loads. Aircraft dynamic simulations were performed to analyze stress states during landing, taxiing, and turning, identifying the required ultimate bond strength to prevent interface failure. Laboratory tests measured the shear and pull-out strengths of new and old concrete interfaces. A styrene–butadiene rubber (SBR) modified cement quartz mortar adhesive was developed with optimal curing conditions, and the effects of grooving intervals on bonding strength were assessed. Results demonstrated that the interface treatment increased the safety factor for tensile failure from 0.69 to 1.25 and for shear resistance from 0.61 to 1.12 under dynamic loads. This research provides a scientific basis for enhancing UTO applications in the functional rehabilitation of airport rigid pavements, offering a practical solution to improve safety and durability in high-stress environments.

Foot Progression Angle in Relation to Spatiotemporal Parameters of Gait in Children with Cerebral Palsy

OBJECTIVE: This study assessed the difference in the foot progression angle and measure spatiotemporal parameters of gait of children with diplegic cerebral palsy and to examine the relation among foot progression angle of right and left lower limb and spatiotemporal parameters of gait. DESIGN: Cross-sectional and Correlation study. SUBJECTS: Sixty children with spastic diplegia, aged 5 to 8 years. The participants were categorized into 3 age groups of equivalent number: group A (5 to 6 years), group B (6 to 7 years), as well as group C (7 to 8 years). METHODS: Foot progression angle and spatiotemporal parameters of the gait for both feet were evaluated utilizing a dynamic footprint. RESULTS: a moderate negative significant correlation was noted among left FPA and right step length, and right stride length. There was moderate positive significant correlation among left FPA and cadence . A weak non-significant correlation was observed among right and left FPA and gait parameters among three groups. CONCLUSION: foot progression angle assessment and spatiotemporal measurements and the correlation among them can give objective and quantitative data that could be utilized in rehabilitation and clinical evaluations to identify functional deficiencies.

EZH1/2 plays critical roles in oocyte meiosis prophase I in mice

Backgroudabnormalities or defects in oocyte meiosis can result in decreased oocyte quality, reduced ovarian reserve, and female diseases. However, the mechanisms of oocyte meiosis remain largely unknown, especially epigenetic regulation. Here, we explored the role of EZH1/2 (histone methyltransferase of H3K27) in mouse oocyte meiosis by inhibiting its activity and deleting its gene.Resultswith embryonic ovary cultured in vitro, EZH1/2 was demonstrated to be essential for oocyte development during meiosis prophase I in mice. Activity inhibition or gene knockout of EZH1/2 resulted in cell apoptosis and a reduction in oocyte numbers within embryonic ovaries. By observing the expression of some meiotic marker protein (γ-H2AX, diplotene stage marker MSY2 and synapsis complex protein SCP1), we found that function deficiency of EZH1/2 resulted in failure of DNA double-strand breaks (DSBs) repair and break of meiotic progression in fetal mouse ovaries. Moreover, Ezh1/2 deficiency led to the suppression of ATM (Ataxia Telangiectasia Mutated kinase) phosphorylation and a decrease in the expression of key DNA repair proteins Hormad1, Mre11, Rad50, and Nbs1 in fetal mouse ovaries, underscoring the enzyme’s pivotal role in initiating DNA repair. RNA-seq analysis revealed that Ezh1/2-deletion induced abnormal expression of multiple genes involved into several function of oocyte development in embryonic ovaries. Knockout of Ezh1/2 in ovaries also affected the levels of H3K9me3 and H4K20me2, as well as the expression of their target genes L3mbtl4 and Fbxo44.Conclusionsour study demonstrated that EZH1/2 plays a role in the DSBs repair in oocyte meiosis prophase I via multiple mechanisms and offers new insights into the physiological regulatory role of histone modification in fetal oocyte guardianship and female fertility.

Iron deficiency anemia and anemia of chronic disease – what is known?

Anemia is the most common disease in the world, affecting about 30–40% of people. Children, adolescents, and women are most often affected by anemia. The main causes of true iron deficiency (ID and IDA) are insufficient iron intake, increased iron loss (chronic bleeding), increased iron requirement, and impaired iron absorption (gastrointestinal diseases). Chronic diseases, inflammatory conditions, autoimmune diseases, obesity cause an increase in the synthesis of hepcidin in the liver and block the entry of iron into the bloodstream, leading to functional iron deficiency. Anemia of chronic diseases (ACD) or anemia of chronic inflammation (the second most common anemia) is associated with the fact that iron is present in the body, but the absorption of iron in various areas is limited. Until recently, it was believed that treatment with iron supplements in the absence of iron deficiency does not bring benefit to patients with ACD. The opinion has been repeatedly expressed about the harm of iron therapy, since iron is necessary for the growth of some pathogenic microorganisms and tumor cells. However, the real clinical significance of these mainly theoretical provisions is unknown. Therefore, the prescription of iron preparations for anemia is justified and logical. Ferrous sulfate (ferrous iron) is most often prescribed orally due to its low cost, high bioavailability and effectiveness. The drug Tardiferon, containing iron sulphate 247.25 mg (in terms of iron (II) 80.00 mg), is widely used in patients with IDA and ID, since divalent iron has a high ability to overcome the intestinal barrier by “passive” transport and quickly create high concentrations in the blood, restoring the level of hemoglobin and iron stores in the body. The drug Tardiferon has a relatively low dose of iron – 80 mg with slow-release technology to avoid irritating effects on the intestine, contributing to good tolerability. A number of studies confirmed a high safety profile – patients did not refuse to take the drug due to side effects. Timely examination and identification of patients with anemia allows you to prescribe an effective correction. The drug Tardiferon promotes rapid restoration of hemoglobin and iron stores in the body and has good tolerability.

Does hypersialylation compensate the functional Alpha1-AntiTrypsin (A1AT) deficiency in all critically ill patients?

Alpha-1 antitrypsin (A1AT) is the major circulating serine protease inhibitor. Hypersialylated glycoforms (HSG) are produced to boost A1AT anti-inflammatory and anti-protease properties. Their occurrence and prognostic impact outside severe COVID-19 or community-acquired pneumonia are unknown. Our aim was to clarify the occurrence of A1AT functional deficiency and HSG in patients admitted into intensive care unit (ICU) for any cause. A1AT and elastase inhibitory capacity (EIC) were measured in serum. Functional A1AT deficiency was defined by a measured EIC/calculated EIC Ratio ≤0.85. HSG were identified by isoelectrofocusing and quantified by gel densitometry. A total of 248 serum samples was analyzed, 173 from COVID-19 and 75 from non COVID-19 patients. A functional A1AT deficiency occurred 3-fold more frequently in non-COVID-19 than in COVID-19 patients: 18.7 % vs 6.9 % and was not associated with more frequent S/Z deficient alleles. Functional deficiency was also more frequent in deceased than alive patients in COVID-19 group. M0 and M1 HSG of A1AT occurred in around half of patients but the relative proportion of M1 significantly increased in deceased vs alive patients only in the non-COVID-19 group explaining the absence of worsening of the functional deficiency. In conclusion, our study shows that a functional A1AT deficiency is more frequently observed in patients admitted to the ICU for a cause unrelated to COVID-19, as well as in those with an unfavorable evolution. Among the latter, only those admitted for non-COVID-19 tried to compensate the functional deficiency by increasing the proportion of M1 HSG of A1AT.

Hip Fracture in the Sportive Adult: Case Report of Complete Functional Recovery After Removal of Hardware.

Pertrochanteric hip fractures in sportive young adults are mainly caused by a high-energy trauma and treated in the same way as in the older population, using an osteosynthesis immediately followed by a rehabilitation program for several months. The current standard is not to remove osteosynthesis material, similar to the case of older patients. A 45-year-old male cyclist experienced a right pertrochanteric femoral fracture, treated with cephalomedullary nails. After 9months of adequate rehabilitation, weakness of the quadriceps musculature and functional complaints persisted, objectified through an isokinetic strength test and a significantly reduced score on the Hip Disability and Osteoarthritis Outcome Score questionnaire. The patient was unable to return to his previous level of cycling performance. After exclusion of structural bone complications, nerve injury, and central sensitization, the functional complaints and strength deficiency were hypothesized to be related to the osteosynthesis material. Therefore, the hardware was removed 9months after the first surgery, and the rehabilitation was continued for another 20weeks. Very soon after the removal of the hardware, the functional complaints disappeared with a remarkable improvement of the Hip Disability and Osteoarthritis Outcome Score. The isokinetic strength test showed complete recovery of muscle strength 20weeks after osteosynthesis removal, and preinjury cycling performance values were obtained 9months posthardware removal. Despite an adequate rehabilitation following a hip fracture, sporty young adults may fail to reach their previous level of functioning. Osteosynthesis removal may be indicated in this sportive population to reach complete muscle strength and functional recovery. The management of hip fractures in the sportive young adult and the identification of patients who may benefit from removal of the hardware require more research.

B-TBM: A Novel Deep Learning Model with Enhanced Loss Function for HAZOP Risk Classification Using Natural Language Statistical Laws

HAZOP is a paradigm of industrial safety, and the introduction of deep learning-based HAZOP text categorization marks the arrival of an intelligent era of safety analysis. However, existing risk analysis methods have limitations in processing complex texts and extracting deep risk features. To solve this problem, this paper proposes a novel HAZOP risk event classification model based on BERT, BiLSTM, and TextCNN. The complexity of HAZOP text is revealed by introducing statistical laws of natural language, such as Zipf’s law and Heaps’ law, and the outputs of different levels of BERT are further combined linearly to collaborate with BiLSTM and TextCNN to capture long-term dependency and local contextual information for a more accurate classification task. Meanwhile, an improved loss function is proposed to effectively solve the deficiencies of the traditional cross-entropy loss function in the mislabeling process and improve the generalization ability of the model. It is experimentally demonstrated that the accuracy of the model is improved by 3% to 4% compared to the traditional BERT model in the task of severity and possibility classification of HAZOP reports. This study not only improves the accuracy and efficiency of HAZOP risk analysis, but also provides new ideas and methods for the application of natural language processing in industrial safety.

Hepcidin, GDF-15 and their Impact on Iron Metabolism in CKD

Background Anemia is an important complication in chronic kidney disease (CKD). We studied the diagnostic accuracy of hepcidin and growth differentiation factor-15 (GDF-15) as early markers of iron deficiency anemia (IDA) in non-dialysis (ND-CKD) patients. Materials and Methods This was a cross-sectional, case-control study comprising 100 cases of CKD (newly diagnosed and non-dialyzed) and 40 healthy controls. Serum levels of hepcidin and GDF-15 were estimated using ELISA-based assays. Receiver operator characteristics were used to evaluate the diagnostic validity of hepcidin and GDF-15 for absolute and functional iron deficiency anemia. Results About 33% of the cases were females with a mean age of 47.64 (± 13.68) years. The predictive value of hepcidin for diagnosing functional IDA in CKD was found to be 69.1% (95% CI: 52.5% to 82.7%), and that of GDF-15 was found to be 68.8% (95% CI: 52.6% to 82.1%). Hepcidin significantly correlated with hemoglobin (r = 0.278, p = 0.005) and serum iron (r = 0.222; p = 0.025). GDF-15 positively correlated with ferritin (r = 0.346, p &lt; 0.0001) and hsCRP (r = 0.223, p = 0.0088) and negatively correlated with eGFR (r = -0.462, p &lt; 000001), Hb (r = -0.481, p &lt; 0.00001) and TIBC (r = -0.353, p &lt; 0.0001). Conclusion Hepcidin and GDF-15 could predict functional IDA in our patients but not absolute IDA.

Ultrastructural changes in the adrenal gland in terms of age and gender-related

Objectives: The adrenal glands are endocrine organs that synthesise hormones with crucial functions in the body. This irreplaceable structure performs multiple functions, from metabolism of carbohydrates, fats and proteins to sex development. Any disorder concerning the adrenal glands can give rise to life-threatening conditions. The aging process inevitably affects the adrenal glands. The effects of ageing are marked by a rise in cortisol secretion in the zona fasciculata and a decrease in androgen secretion in the zona reticularis. Elevated cortisol levels in the blood disturb most bodily systems in favour of catabolism, amplifying the cellular decline and destruction that accompanies ageing. The deterioration of the adrenal glands relates not just to spongiocytes and chromaffin cells, but also to the endothelium, which enables circulation. It is clear that a decline in vascular function will have a negative impact on endocrine activities. Our study aims to explore the influence of ageing on the adrenal glands in rats, analysing sex-specific ultrastructural scales. Materials and Methods: A total of 28 Sprague-Dawley rats, 14 males and 14 females, were planned to be used in the study. Of these 28 rats, 4 females and 4 males will constitute the control group. The rats in the control group will be approximately 10 weeks old, and the rats in the experimental group, which will represent the aged group, will be 19 weeks old. All animals in the study will be anaesthetised and then sacrificed by removal of the heart. The right and left common carotid arteries were removed from the sacrificed animals. Collected vessels prepared for TEM examination. For each animal, at least four TEM images were taken from four different sections from the same block. Results: Our findings demonstrate that the ageing process not only affects spongiocytes within the adrenal gland, but also contributes to the deterioration of endothelial cells. As anticipated, our results indicate the presence of senescence and apoptosis in endothelial cells. The observed vascular separations and ruptures are due to the endothelial deterioration. Spongiocytes experienced hypertrophy to compensate for the functional deficiencies following a decrease in their number due to ageing. Elevated levels of lipofuscin, lipid droplets, and lysosomes were discovered in spongiocytes. Impaired endothelium potentially contributes to certain changes in spongiocytes. Conclusions: While ageing-related changes appear similar in both genders, males tend to be more impacted.