Startseite Current research and evidence gaps on placental development in iron deficiency anemia
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Current research and evidence gaps on placental development in iron deficiency anemia

  • Shaoyang Lai , Weiwei Yu , Ying Liu , Yuxin Yang und Xueqin Zhang EMAIL logo
Veröffentlicht/Copyright: 21. Februar 2024

Abstract

Studying the effects of maternal iron deficiency anemia (IDA) is complex owing to its diverse causes, each independently impacting the placenta and fetus. Simple treatment with iron supplements does not always resolve the anemia. Therefore, delving into how IDA alters placental development at a molecular level is crucial to further optimize treatment. This review addresses the effects of IDA on placental structures and functions, including changes in oxygen levels, blood vessels, and the immune system. Profound understanding of physiological characteristics and regulatory mechanisms of placental development is key to explain the mechanisms of abnormal placental development in pregnancy-associated disorders. In turn, future strategies for the prevention and treatment of pregnancy complications involving the placenta can be devised. These studies are significant for improving human reproductive health, enhancing sociodemographic qualities, and even lifelong wellbeing, a focal point in future placental research.

1 Introduction

Recent evidence strongly shows that the intrauterine environment greatly influences the development of both the placenta and fetus. Placental structures and functions have been found to be altered in response to intrauterine conditions, including altitude hypoxia, maternal diabetes, and maternal anemia. These changes can lead to fetal growth retardation among other complications. They potentially represent placental adaptations, aimed at sustaining or optimizing its function amidst challenging conditions.

Figure 1 
               The latest theories of the placental development.
Figure 1

The latest theories of the placental development.

Iron is an essential nutrient for numerous biological processes. Physiologically, anemia is marked by the deficiency of hemoglobin content in red blood cells. Gestational anemia is mainly caused by maternal iron deficiency (ID) [1], attributed either to an unlikely cause of enigmatic deficiency of hemoglobin or mostly caused by a complex array of factors ranging from an orchestration of endogenous biological components including iron-elemental regulations to various exogenous supplementary, dietary, and socio-economic factors. Due to the high iron demand from the rapidly growing fetus and the expanding maternal blood volume, pregnant women are particularly vulnerable to ID. As per the World Health Organization, iron deficiency anemia (IDA) affects approximately half of the pregnant in developing countries [2], with Asia reporting the highest prevalence, with a percentage of 95% [3]. ID during pregnancy can result in serious risks for both the mother and her developing fetus. Iron-deficient mothers are at greater probability of requiring transfusion during parturition [4], and fetuses born to them have a higher risk of developmental delay, neonatal mortality, and morbidity [4]. Furthermore, infants born to these women could have long-lasting consequences with an increased risk of cardiovascular problems, diminished brain function, and compromised immune system development in adulthood [4]. The diverse causes of anemia complicate human studies into the effects of IDA, as different causes of anemia independently affect the placenta and fetus.

Figure 2 
               Proposed mechanisms by which IDA may influence the placental development.
Figure 2

Proposed mechanisms by which IDA may influence the placental development.

The mechanisms underlying these effects have not been clarified, although it seems that early pregnancy development may play a pivotal role. During gestation, the growing fetus depends on its mother for nutrition and waste disposal across the placenta. The placenta is not merely a passive mediator; it can also regulate the rates and amounts of nutrient transportation as well as iron transportation. Consequently, IDA may affect the placental development and, subsequently, affect the development of the fetus. Several potential biological mechanisms have been identified through which anemia or ID could affect pregnancy outcomes. Anemia caused by hypoxia and ID can induce both maternal and fetal stress. Any stress-altering placental development or function is likely to have consequences for the developing fetus. Notably, high prevalence of anemia in pregnant women and present observations about limited treatment show that monotreatment with iron supplementation cannot clinically cure the anemia [5]. It is pertinent to peruse and discuss the various plausible reasons along with underlying factors contributing to such unfortunate but sizable burden. Thus, this article consolidates current research on the biological mechanisms involved in the development of the placenta and explores ways in which IDA impacts them. Next, it is important to explore how the placental development is altered by IDA, precisely the molecular basis behind this placental dysfunction, and then aim to optimize treatments for this problem.

2 The latest theories of the placental development

Since it is the communication interface between the mother and her fetus, the normal development of the placenta is crucial for the growth and sustenance of the fetus. The factors relevant to the course of placental development include gender, epigenetics, and external environment [6]. Gender affects the expression of sex hormone genes in male or female fetal placenta, respectively. For example, the STS gene, the sex hormone synthesis gene in X-linked genes, expresses in the female fetal placenta [7]; and the cluster of LHB-CGB gene also expresses those expression products such as luteinizing hormone and hCG related to the growth, invasion, and angiogenesis of placenta [8]. Epigenetics refers to the phenomenon of transmitting non-DNA sequence genetic information through mitosis and meiosis, including DNA methylation, histone modification, and non-coding RNA. It can play an important role in placental trophoblast cell differentiation, invasion, and hormone secretion by regulating gene expression. The reconstruction of methylation affects the early development of the placenta, for example, the inhibition of DNA methylation during early embryonic development disrupts the proliferation and migration of trophoblasts [9]. In addition, the growth of placenta requires a hyperoxic environment, because a decline in oxygen level will directly impair placental volume, development, and maturation by inducing increased activity of hypoxia-inducible factor (HIF) [10]. Understanding these changes during placental development and their effects on the varied physiological function are reviewed here, which is essential for elucidating the mechanism of embryonic development and the maternal and infant safety as well.

Placental formation is a very complex process, mainly comprising of spiral artery remodeling and placental angiogenesis [11]. The course of spiral artery remodeling involves extravillous trophoblasts retrogradely infiltrating maternal spiral arterioles under the guidance of various factors, gradually replacing the vascular endothelium, and then, the vascular muscle layer is replaced by fibrous substances. Finally, the lumen elasticity disappears with the decreased resistance and the blood volume increases [12]. Placental angiogenesis refers to increased formation of blood vessels at the fetal interface, which ensures that more placental lobules are in contact and material exchange occurs with spiral arteries [13]. Disruptions of either spiral artery remodeling or placental angiogenesis may lead to placental ischemia and placental oxidative stress, hence resulting in the development of various placental-associated disorders. Therefore, exploring each individual step during the development of the placenta and its regulatory mechanisms is beneficial to the further understanding of the pathogenesis and treatment of placental-associated disorders (Figure 1).

In the first trimester physiological hypoxia is essential for the development of placenta owing to the immature antioxidant capacity. Abnormal oxidative responses to peroxidation at early gestation, and hypoxia at late gestation or reoxygenation after maternal compensation, may impair trophoblastic invasion and placental capillaries formation, resulting in placental dysfunctions. The biological function of trophoblast changes because of the complicated regulatory mechanisms of hypoxia and hypoxia response in different stages of pregnancy. Therefore, further research on hypoxia and hypoxic response should not only clarify the regulatory mechanism of placental development but also reveal the pathogenesis of pregnancy-associated conditions and provides new clues for treatment.

Placental development has a lot in common with tumor progression [14]. The development of placenta, similar to malignant tissue behavior, starts with the proliferation of trophoblast cells in the uterus which profoundly affect maternal immune tolerance. Structural and functional changes in the placenta in pregnancy with IDA have been reviewed here, including issues regarding oxygen content, vascular components, and the immune system. Exploring placental development, physiologically and pathologically, enables researchers to have a deeper understanding of the relevant mechanisms of IDA and finally contributes to improving treatments and prevention of maternal and neonatal diseases.

3 Progress of clinical research on the placental development in IDA

The maintenance of pregnancy depends on the normal development and function of the placenta. Multiple factors that could influence placental development have been extensively investigated. Some scholars argue that placental weight tends to increase with increasing severity of the anemia, which has been widely interpreted as evidence of compensatory hypertrophy in response to a reduced oxygen supply [15]. Studies demonstrated that placental hypertrophy was associated with a mild and moderate degree of IDA, with no significant differences in volume fractions or surface densities of placental structures across anemic, intermediate, and non-anemic groups [15]. This enlargement of placenta was uniform with proportional growth of placental components. This conclusion was also supported by the significantly larger absolute volumes of intervillous space, non-intervillous space, or branch villi per placenta in the anemic group [15].

Conventionally, placental weight was regarded as an indicator of placental function. Stereological techniques have recently been applied to placentas from pregnancies exposed to long-term hypobaric hypoxia at high altitudes by measuring the values of key structural parameters to estimate the theoretic diffusing capacity of the organ [16]. Compared with lowland levels, the morphometric diffusing capacity is significantly increased at moderate altitudes despite considerable reduced growth of the fetal villous tree [16]. Although placental weight remained constant between the two groups there was a marked diminution rather than a hypertrophy in the villous tree in cases of maternal anemia [16].

Several large-scale studies have shown a notable negative correlation between maternal hemoglobin levels and placental sizes. IDA and maternal nutrition could influence the placental weight at birth [17]. Anemia itself rather than its type is the main factor of placental weight since there are no differences in their series comparing anemic women with thalassemia and those with IDA [18]. In some studies, there was not an association between hematological indices and placental size with discrepancies in study design and difficulty in standardizing the placental measurement at birth [19]. The maternal environment, more specifically maternal hemoglobin, could influence placental size in the mid-second trimester [20]. In some research, the placental volume was measured by three-dimensional (3D) ultrasound in the first and second trimesters [21], while similar placental measurement was obtained, they did not come to the same association between maternal hemoglobin levels and placental volume [22]. By 18 weeks of pregnancy, the placental volume may already be inversely correlated with maternal hemoglobin and serum ferritin concentrations, even in industrialized countries [22].

Contradictory studies have shown decreased villous surface area and a thinned harmonic mean thickness of the placental barrier [23]. Thus, they concluded that the placenta in the third trimester adapts to severe anemia by thinning the villous membrane so as to keep a normal diffusion capacity [23]. One study on term placentas from women with IDA has found a reduction in the size of the placental villous tree and a reduced thickness of the villous membrane. It meant that, overall, the diffusion capacity in these placentae was maintained despite the reduced size of the villous tree [23]. The results demonstrated that using placental size as an indicator of placental function can be unreliable since there may be changes in placental composition [23]. Another study has reported that placental vascularization increased in early gestation maternal anemia may reflect an adaptation to increased oxygen supply to the fetus [24].

In the light of the above observations, ID during pregnancy manifests a considerable variety of effects, culminating in placental dysplasia. Future fetal development depends on placental growth in early pregnancy and later differentiation might potentially have lifelong effects. Several reports suggest that inadequate prenatal growth patterns may be associated with problems later in life. At present, we cannot confirm that the outcome of pregnancy or later development will be compromised by ID, but future data will make it possible. Therefore, this review has good potential in advancing our understanding of how in utero nutrition relates to prenatal development.

4 Proposed mechanisms by which IDA may influence the placental development

Certain researchers propose that hypoxia might be the stimulus for the increased placental growth [25]. Some scholars have indicated that the levels of vascular endothelial growth factor (VEGF) stimulated by hypoxia correlate to the actual placental volume [13]. Moreover, it has been demonstrated that the maternal environment during the first and early second trimesters could affect placental growth.

However, further studies are needed to elucidate the physiological pathways involved.

The postulated biological mechanisms are outlined as follows (Figure 2).

4.1 Changes in the pattern of placental villous development in response to IDA

In the first trimester, placental villi undergo progressive vascularization by the process of branching angiogenesis within the stromal core under the influence of angiogenic growth factors, especially VEGF. Since VEGF transcription is upregulated in vitro by hypoxia, increased villous angiogenesis subsequent to maternal anemia may be mediated by an increased paracrine activity of VEGF [16]. Normal villous development during the second and early third trimesters is characterized by a gradual shift toward non-branching angiogenesis, resulting in the formation of gas exchanging peripheral villi [16]. Besides, a gradual decline in placental expression of VEGF and its FTR-1 receptor, in favor of increased placenta-like growth factor and KDR-receptor expression during pregnancy, may facilitate this switch to nonbranching angiogenesis [26]. Persistent branching angiogenesis could be the basis for the typical histological features of the anemic placenta at term [26] owing to “preplacental” hypoxia. Persistent branching angiogenesis within peripheral villi may therefore account for the epidemiological association between maternal anemia and placental characteristics [26].

4.2 IDA may increase oxidative stress

The feto-placental unit is highly susceptible to oxidative damage induced by reactive oxygen species. Placental oxidant-antioxidant imbalance might cause the release of products of lipid peroxidation into the fetal circulation with subsequent damage to endothelial cell membranes [27]. When the effect of ID on lipid peroxidation and antioxidant enzyme activity was examined in rats, the IDA group had significantly lower liver production of malondialdehyde and activity of superoxide dismutase and higher catalase activity [26]. The investigators speculated that the iron-sufficient rats were more able to eliminate oxygen radicals, whereas ID increased susceptibility to oxidative stress [26]. Moreover, erythrocytes are usually protected from oxidative stress caused by free radicals released from the potentially dangerous combination of iron and oxygen [26]. Since ID may increase oxidative stress, erythrocytes are more susceptible to oxidative damage [26]. Therefore, oxidative stress is one potential mechanism considered to cause pregnancy-induced hypertension, pregnancy-induced diabetes.

4.3 The effect of IDA on cytokine levels in placenta

Placental function is regulated, at least in part, by a broad spectrum of cytokines, both locally and distally. To our knowledge, placental cytokine levels are altered in ID. The changes are specific to different parts of the placenta, which may give some indication regarding the consequences of the alterations in levels [28]. The regulation of TNFα expression at the maternofetal interface must be crucial for successful placental development and function. TNFα is produced at low levels in placental and decidual immune cells during normal and healthy pregnancies, which is thought to be beneficial for pregnancy. It induces apoptosis of placental cells by the TNF-R1 pathway and, therefore, may be important in trophoblast turnover and remodeling [29]. Data also suggested that TNFα may regulate placental steroid production by the placenta and downregulate amino acid transfer [29]. Furthermore, the production of TNFα in IDA was increased by lipo-polysaccharide-stimulated mononuclear cells [29].

Leptin, which was first identified as a placental hormone in 1997 [30], still has unclear functions. Human studies have shown a correlation between cord blood and placental leptin but not between maternal leptin and birth weight [30], suggesting that placental leptin may promote fetal growth. Leptin secretion by adipocytes is regulated by TNFα, acting through TNF-R1 [30]. Whether this mechanism operates in the placenta has yet to be determined. Interactions between these cytokines are currently under investigation.

4.4 Compensatory changes in the iron-transport mechanisms of the placenta

ID in the maternal rat results in compensatory changes in the iron-transport mechanisms of the placenta, which, in turn, minimizes the level of ID in the fetus [31]. Most, though not all, of the proteins involved in iron transfer show increases at both mRNA and protein levels, commensurating with the increase in iron flux [31]. Transferrin receptor mRNA and protein levels increase both in iron-deficient placentas and in BeWo cells [32]. Increased transferrin receptor levels, concurrent with the rise in DMT1 will, however, imply that the rate of uptake into the syncytiotrophoblast will increase [32]. This would help compensate for the decrease in iron-transferrin concentrations in the maternal serum.

Similarly, the efflux mechanism also shows compensatory changes. At present, the best hypothesis explaining how iron enters into the fetal circulation is that it exits the cell through IREG1 ferroportin1 as divalent iron [33]. It is then oxidized to Fe(iii) by the copper oxidase and is incorporated into fetal transferrin. It would be expected that oxidase would be located close to IREG1 to facilitate the oxidation of Fe(ii) [33]. Besides, there are other proteins involved in the efflux pathway, probably both in the regulated expression of the actual transport proteins and also in the relation between the iron-regulatory proteins and the translation apparatus of the syncytiotrophoblast.

Interestingly, IREG1 mRNA levels do not change in iron-deficient placentas.

5 Discussion

Ever since the inception of the “Human Placenta Project” by the National Institutes of Health (NIH) in 2015, there has been a notable surge in placental research. Scholars can now visualize the live dynamics of the development of placenta, structurally and functionally, in physiological and pathological conditions by multidisciplinary collaboration. Their aim is to identify good biomarkers for predicting and diagnosing disorders in early pregnancy, while developing novel intervention strategies for pregnancy-associated complications by specifically targeting the placenta.

Some researchers believe that placental growth impairment and abnormal pregnancy adaptation might trigger excessive oxidative stress and placenta-derived cytokines acting on the circulatory system and exert permanent structural changes on the heart or arteries, which in turn may cause long-term cardiovascular diseases. Normal pregnancy is itself regarded as a physiological stress for mother. Abnormal pregnancy adaptation is not only one of the significant causes of maternal symptoms but also reflects certain maternal subclinical abnormalities, and clinical manifestations appear with pregnancy stress. The pregnant and parturient with pregnancy-related disorders are at high risk of developing other chronic diseases. Therefore, an appropriate and effective intervention and prevention strategy is needed.

Given the high prevalence of IDA, the profound subsequent complications, and the grim dilemma of treatment, greater emphasis should be paid to antenatal examination during pregnancy, early diagnosis, and timely treatment of IDA. This emphasis aims at promoting normal placental development, improving the current treatment effectiveness, and ultimately preventing adverse pregnancy outcomes. However, the available experimental evidence is still limited. There is an important bottleneck that our understanding of the regulation of human placenta development has not been discussed enough. Previous studies have proposed that placentas from IDA patients have physiological and pathological changes, including changes in the pattern of placental villous development, triggered oxidative stress, elevated levels of placental cytokines, and compensatory changes in the iron-transport mechanisms. Most studies at present are nearly cross-sectional, mainly focusing on the prevalence, the sociodemographic factors, the impact on maternal and fetal complications, and the efficacy of iron supplementation on IDA. The pathogenesis of IDA is mainly conducted on the change of iron conversion mechanism. The oral iron-supplement therapy is still the main clinical treatment of IDA, yet it might not consistently solve the problem. Consequently, the effective prediction and early diagnosis of diseases and then drawing up active and effective interventions is still unclear in this domain.

Prenatal anemia and ID are recognized as one of the preventable risk factors for disease with a substantial disease burden [34]. This calls for a rigorous evaluation of the effectiveness of existing antenatal care programmes in high-burden countries to identify gaps in policy and programme implementation. Targeted interventions to strengthen the infrastructure of antenatal care should be used. Future research to explore feasible strategies of ID in a country setting and evaluation of the effectiveness of other strategies, such as fortification and dietary diversification, should be explored.

Through the research on the mechanism of placental development, the current pregnancy management of IDA should be improved, and new treatment methods targeting the placenta should be devised to improve placental function and reduce the occurrence of long-term diseases of placental origin. However, there are still some limitations in the current research that are limited to animal models, lack of the support from large sample and multi-centre prospective research, and lack of a unified standard for the evaluation of placental function. And most studies are still in the basic experimental stage. Translation of these basic studies into clinical application will be the future research focus of placental medicine.

The effects of IDA on placental structures and functions by various factors have been reviewed, including changes in oxygen content, blood vessels, and immune system during the development of placenta. A deep insight into physiological characteristics and regulatory mechanisms of placental development was discussed, with the explanation of the mechanistic roles of abnormal placental development in pregnancy-associated disorders. Finally, strategies for the prevention and treatment of pregnancy-related complications targeting the placenta were explored. Investigating these aspects could vigorously promote great breakthroughs in the field of pregnancy maintenance and maternal–fetal health research. Such studies have crucial implications for improving human reproductive health, and sociodemographic factors, and even ensuring lifelong health maintenance. These remain pivotal areas of focus for our forthcoming placental research endeavors.

Acknowledgments

We would like to acknowledge the Science and Technology Bureau of Xiamen and the Fujian Provincial Department of Science and Technology for providing financial support.

  1. Funding information: This work was supported by the Xiamen Health Care Projects (3502Z20209199) and the Natural Science Foundation of Fujian Province (2023J011613).

  2. Author contributions: We declare that this work was completed by the authors named in this article. Ying Liu, Yuxin Yang, and Weiwei Yu designed the study and supervised data collection. Shaoyang Lai and Xueqin Zhang prepared the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript. The authors applied the SDC approach for the sequences of the authors.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2023-10-10
Revised: 2023-12-19
Accepted: 2023-12-22
Published Online: 2024-02-21

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  15. Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model
  16. Preparation of Cu2+/TA/HAP composite coating with anti-bacterial and osteogenic potential on 3D-printed porous Ti alloy scaffolds for orthopedic applications
  17. Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging
  18. Current research and evidence gaps on placental development in iron deficiency anemia
  19. Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis
  20. Pheochromocytoma-induced myocardial infarction: A case report
  21. Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O‐GlcNAcylation of β-catenin
  22. Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase
  23. Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner
  24. KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1
  25. Current state of research on copper complexes in the treatment of breast cancer
  26. Exploring antioxidant strategies in the pathogenesis of ALS
  27. Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients
  28. IL-33/soluble ST2 axis is associated with radiation-induced cardiac injury
  29. The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery
  30. Carrying SNP rs17506395 (T > G) in TP63 gene and CCR5Δ32 mutation associated with the occurrence of breast cancer in Burkina Faso
  31. P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy
  32. Probiotics for inflammatory bowel disease: Is there sufficient evidence?
  33. Identification of KDM4C as a gene conferring drug resistance in multiple myeloma
  34. Microbial perspective on the skin–gut axis and atopic dermatitis
  35. Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery
  36. Highly specific vaginal microbiome signature for gynecological cancers
  37. Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography
  38. The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats
  39. Fabrication and characterization of gold nanoparticles using alginate: In vitro and in vivo assessment of its administration effects with swimming exercise on diabetic rats
  40. Mitigating digestive disorders: Action mechanisms of Mediterranean herbal active compounds
  41. Distribution of CYP2D6 and CYP2C19 gene polymorphisms in Han and Uygur populations with breast cancer in Xinjiang, China
  42. VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway
  43. Factors influencing spontaneous hypothermia after emergency trauma and the construction of a predictive model
  44. Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
  45. Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis
  46. Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine
  47. Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
  48. Preliminary investigation into the genetic etiology of short stature in children through whole exon sequencing of the core family
  49. Cystic adenomyoma of the uterus: Case report and literature review
  50. Mesoporous silica nanoparticles as a drug delivery mechanism
  51. Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice
  52. Vitamin D deficiency and inflammatory markers in type 2 diabetes: Big data insights
  53. Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells
  54. Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma
  55. Mitochondrial DNA drives neuroinflammation through the cGAS-IFN signaling pathway in the spinal cord of neuropathic pain mice
  56. Application value of artificial intelligence algorithm-based magnetic resonance multi-sequence imaging in staging diagnosis of cervical cancer
  57. Embedded monitoring system and teaching of artificial intelligence online drug component recognition
  58. Investigation into the association of FNDC1 and ADAMTS12 gene expression with plumage coloration in Muscovy ducks
  59. Yak meat content in feed and its impact on the growth of rats
  60. A rare case of Richter transformation with breast involvement: A case report and literature review
  61. First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province
  62. Rhodococcus equi and Brucella pulmonary mass in immunocompetent: A case report and literature review
  63. Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway
  64. Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease
  65. The role of Phafin proteins in cell signaling pathways and diseases
  66. Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report
  67. Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review
  68. Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells
  69. Exploratory evaluation supported by experimental and modeling approaches of Inula viscosa root extract as a potent corrosion inhibitor for mild steel in a 1 M HCl solution
  70. Imaging manifestations of ductal adenoma of the breast: A case report
  71. Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects
  72. Isomangiferin promotes the migration and osteogenic differentiation of rat bone marrow mesenchymal stem cells
  73. Prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer
  74. Circular RNAs as potential biomarkers for male severe sepsis
  75. Knockdown of Stanniocalcin-1 inhibits growth and glycolysis in oral squamous cell carcinoma cells
  76. The expression and biological role of complement C1s in esophageal squamous cell carcinoma
  77. A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report
  78. Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy
  79. HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway
  80. IgG4-related disease complicated by PLA2R-associated membranous nephropathy: A case report
  81. Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma
  82. Metformin mitigates osteoarthritis progression by modulating the PI3K/AKT/mTOR signaling pathway and enhancing chondrocyte autophagy
  83. Evaluation of the activity of antimicrobial peptides against bacterial vaginosis
  84. Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation
  85. Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review
  86. Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
  87. Refractory hypertension complicated with Turner syndrome: A case report
  88. Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma
  89. Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease
  90. Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects
  91. The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein
  92. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential diagnostic markers for rebleeding in patients with esophagogastric variceal bleeding
  93. G protein-coupled receptor 1 participating in the mechanism of mediating gestational diabetes mellitus by phosphorylating the AKT pathway
  94. LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1
  95. The analgesic effect of paeoniflorin: A focused review
  96. Chemical composition’s effect on Solanum nigrum Linn.’s antioxidant capacity and erythrocyte protection: Bioactive components and molecular docking analysis
  97. Knockdown of HCK promotes HREC cell viability and inner blood–retinal barrier integrity by regulating the AMPK signaling pathway
  98. The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes
  99. Laryngeal non-Hodgkin lymphoma: Report of four cases and review of the literature
  100. Clinical value of macrogenome next-generation sequencing on infections
  101. Overview of dendritic cells and related pathways in autoimmune uveitis
  102. TAK-242 alleviates diabetic cardiomyopathy via inhibiting pyroptosis and TLR4/CaMKII/NLRP3 pathway
  103. Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age
  104. Profile and antimicrobial susceptibility patterns of bacteria isolated from effluents of Kolladiba and Debark hospitals
  105. The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients
  106. A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi
  107. PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
  108. Analysis of MDA, SOD, TAOC, MNCV, SNCV, and TSS scores in patients with diabetes peripheral neuropathy
  109. SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling
  110. The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells
  111. Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma
  112. PHB2 alleviates retinal pigment epithelium cell fibrosis by suppressing the AGE–RAGE pathway
  113. Anti-γ-aminobutyric acid-B receptor autoimmune encephalitis with syncope as the initial symptom: Case report and literature review
  114. Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua
  115. Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells
  116. Electroacupuncture on GB acupoints improves osteoporosis via the estradiol–PI3K–Akt signaling pathway
  117. Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy
  118. Review: Dicranostigma leptopodum: A peculiar plant of Papaveraceae
  119. Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway
  120. Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report
  121. Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats
  122. Gastrointestinal health anti-diarrheal mixture relieves spleen deficiency-induced diarrhea through regulating gut microbiota
  123. Myriad factors and pathways influencing tumor radiotherapy resistance
  124. Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
  125. Screening of prognostic core genes based on cell–cell interaction in the peripheral blood of patients with sepsis
  126. Coagulation factor II thrombin receptor as a promising biomarker in breast cancer management
  127. Ileocecal mucinous carcinoma misdiagnosed as incarcerated hernia: A case report
  128. Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway
  129. The debate between electricity and heat, efficacy and safety of irreversible electroporation and radiofrequency ablation in the treatment of liver cancer: A meta-analysis
  130. ZAG promotes colorectal cancer cell proliferation and epithelial–mesenchymal transition by promoting lipid synthesis
  131. Baicalein inhibits NLRP3 inflammasome activation and mitigates placental inflammation and oxidative stress in gestational diabetes mellitus
  132. Impact of SWCNT-conjugated senna leaf extract on breast cancer cells: A potential apoptotic therapeutic strategy
  133. MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro
  134. Major ozonated autohemotherapy promoted functional recovery following spinal cord injury in adult rats via the inhibition of oxidative stress and inflammation
  135. Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
  136. Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model
  137. The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review
  138. BA inhibits LPS-stimulated inflammatory response and apoptosis in human middle ear epithelial cells by regulating the Nf-Kb/Iκbα axis
  139. Role of circRMRP and circRPL27 in chronic obstructive pulmonary disease
  140. Investigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway
  141. Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies
  142. Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence
  143. Ecology and Environmental Science
  144. Screening of different growth conditions of Bacillus subtilis isolated from membrane-less microbial fuel cell toward antimicrobial activity profiling
  145. Degradation of a mixture of 13 polycyclic aromatic hydrocarbons by commercial effective microorganisms
  146. Evaluation of the impact of two citrus plants on the variation of Panonychus citri (Acari: Tetranychidae) and beneficial phytoseiid mites
  147. Prediction of present and future distribution areas of Juniperus drupacea Labill and determination of ethnobotany properties in Antalya Province, Türkiye
  148. Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing
  149. A comparative analysis of dendrometric, macromorphological, and micromorphological characteristics of Pistacia atlantica subsp. atlantica and Pistacia terebinthus in the middle Atlas region of Morocco
  150. Macrofungal sporocarp community in the lichen Scots pine forests
  151. Assessing the proximate compositions of indigenous forage species in Yemen’s pastoral rangelands
  152. Food Science
  153. Gut microbiota changes associated with low-carbohydrate diet intervention for obesity
  154. Reexamination of Aspergillus cristatus phylogeny in dark tea: Characteristics of the mitochondrial genome
  155. Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach
  156. Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera
  157. Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017–2020)
  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
  159. Utility of dairy microbiome as a tool for authentication and traceability
  160. Agriculture
  161. Enhancing faba bean (Vicia faba L.) productivity through establishing the area-specific fertilizer rate recommendation in southwest Ethiopia
  162. Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control
  163. Perspectives of pteridophytes microbiome for bioremediation in agricultural applications
  164. Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a “3414” field trial
  165. Improving the productivity and profitability of maize (Zea mays L.) using optimum blended inorganic fertilization
  166. Application of leaf multispectral analyzer in comparison to hyperspectral device to assess the diversity of spectral reflectance indices in wheat genotypes
  167. Animal Sciences
  168. Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway
  169. Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases
  170. Exploration of the genetic influence of MYOT and MB genes on the plumage coloration of Muscovy ducks
  171. Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism
  172. Comparison of nutritional value of the wild and cultivated spiny loaches at three growth stages
  173. Transcriptomic analysis of liver immune response in Chinese spiny frog (Quasipaa spinosa) infected with Proteus mirabilis
  174. Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
  175. Plant Sciences
  176. Effect of long-term in-row branch covering on soil microorganisms in pear orchards
  177. Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole–calcifuge behaviors of three Camellia species
  178. Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation
  179. Bioinformatics, expression analysis, and functional verification of allene oxide synthase gene HvnAOS1 and HvnAOS2 in qingke
  180. Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield
  181. Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots
  182. Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells
  183. Revealing the effects of amino acid, organic acid, and phytohormones on the germination of tomato seeds under salinity stress
  184. Combined effects of nitrogen fertilizer and biochar on the growth, yield, and quality of pepper
  185. Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
  186. Impact of “3414” fertilization on the yield and quality of greenhouse tomatoes
  187. Exploring the coupling mode of water and fertilizer for improving growth, fruit quality, and yield of the pear in the arid region
  188. Metagenomic analysis of endophytic bacteria in seed potato (Solanum tuberosum)
  189. Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract
  190. Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells
  191. Enhanced osmotic dehydration of watermelon rind using honey–sucrose solutions: A study on pre-treatment efficacy and mass transfer kinetics
  192. Effects of exogenous 2,4-epibrassinolide on photosynthetic traits of 53 cowpea varieties under NaCl stress
  193. Comparative transcriptome analysis of maize (Zea mays L.) seedlings in response to copper stress
  194. An optimization method for measuring the stomata in cassava (Manihot esculenta Crantz) under multiple abiotic stresses
  195. Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
  196. Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization
  197. Bioengineering and Biotechnology
  198. Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration
  199. New advances in protein engineering for industrial applications: Key takeaways
  200. An overview of the production and use of Bacillus thuringiensis toxin
  201. Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma
  202. Bioelectrochemical biosensors for water quality assessment and wastewater monitoring
  203. PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
  204. Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells
  205. Erratum
  206. Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
  211. Special Issue on Advances in Neurodegenerative Disease Research and Treatment
  212. Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson’s disease
  213. Special Issue on Multi-omics
  214. Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma
  215. Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?
Heruntergeladen am 27.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/biol-2022-0827/html
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