Startseite Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review
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Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review

  • Changwei Chi , Shenghao Wu , Wenjin Zhou , Yingying Hu , Yanwei Lu und Shanshan Weng EMAIL logo
Veröffentlicht/Copyright: 27. Juni 2024
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Aus der Zeitschrift Open Life Sciences Band 19 Heft 1

Abstract

A congenital protein anomaly in the erythrocyte membrane skeleton causes a hereditary haemolytic illness known as hereditary spherocytosis (HS). The primary characteristic of HS is an increase in the number of tiny spherical red blood cells in the peripheral blood. The chief clinical features of HS include anaemia, jaundice, splenomegaly, spherical erythrocytosis in the blood, chronic anaemia with haemolysis, and recurrent acute attacks. Most patients have a family history; some have autosomal recessive inheritance, whereas most have autosomal dominant inheritance. In cases of severe hyperbilirubinemia disproportionate to haemolysis, other causes of hyperbilirubinemia should be considered. Gilbert syndrome (GS) is an autosomal dominant illness caused by the reduced activity of uridine diphosphate-glucuronosyl transferase lAl and is characterised by intermittent hyperbilirubinemia without any other signs or symptoms of liver disease. The possibility of the coexistence of HS and GS is very limited. Here we present the case of an elderly man with yellow skin and sclera recurring anaemia, and a final diagnosis of coexisting HS and GS.

Keywords: hereditary spherocytosis; Gilbert syndrome; jaundice

1 Background

Hereditary spherocytosis (HS) and Gilbert syndrome (GS) are autosomal dominant and recessive hereditary diseases, respectively. The probability of the simultaneous occurrence of these two hereditary diseases is extremely low, and its clinical manifestations is jaundice with elevated unconjugated bilirubin levels, which makes its diagnosis difficult.

GS is characterised by intermittent hyperbilirubinemia without liver disease or haemolysis. In patients with GS, the activity of uridine diphosphate-glucuronosyl transferase lAl (UGT1A1) decreased to less than 30% of that in normal individuals [1]. HS is the most common cause of congenital haemolytic anaemia, which leads to premature cell destruction due to erythrocyte membrane defects. Common clinical manifestations include anaemia, jaundice, and varying degrees of splenomegaly. SPTB, ANK1, and SLC4A1 variants are common in autosomal dominant HS, whereas new SPTB and ANK1 variants are more common in autosomal recessive HS. Thus, research on HS poses considerable challenges [2]. A unique HS variant spectrum exists in the Chinese population, with SPTB variants accounting for 45%, ANK1 variants accounting for 45%, and SLC4A1 variants accounting for 10% of case [3]. All variants were non-reproducible, but each was unique to a family member and specific to most Chinese populations. In some patients, multiple variants of related genes can produce synergistic or inhibitory effects, resulting in a complex HS pathogenesis. If HS is comorbid with GS, it can lead to obvious inconsistencies between the genotypes and phenotypes, leading to missed diagnoses and misdiagnoses of clinical HS. Here we present a case report of a patient with HS who harboured a heterozygous variant of the SPTB gene c.3449G＞A (p.Trp1150*) complicated by GS. After treatment, the symptoms of anaemia improved, whereas those of severe jaundice persisted. Finally, the diagnosis was confirmed by combining the clinical findings, laboratory examination results, and molecular sequencing of UGT1A1 with the hereditary polycythaemia genome set.

2 Case presentation

A 70-year-old man was admitted to our department for “dizziness and fatigue since 1 year, which were exacerbated with yellowing of the skin and sclera since 2 months.” One year prior, the patient developed dizziness and fatigue without any obvious cause that was not taken seriously. Two months prior, he experienced dizziness and fatigue, yellowing of the skin and sclera, and deepening of the urine colour. He was treated in other hospitals, and the relevant examination results were as follows: total bilirubin level, 91 μmol/L; direct bilirubin level, 12 μmol/L; indirect bilirubin level, 79 μmol/L; white blood cell count, 9.85 × 109/L; haemoglobin (Hb), 103 g/L; and platelet count, 318 × 109/L. A whole blood examination to identify abnormal red blood cell morphology revealed multiple stained red blood cells, a few large red blood cells, approximately 0.4% broken red blood cells, and approximately 60 spherical red blood cells. The serum-free Hb level was 7.4 mg/dL. The provisional diagnosis was HS and the patient was treated to promote red blood cell production, protect the liver, and eliminate the jaundice.

The patient was discharged after symptom improvement. At that time, the results of the genetic examination were not reported, and the diagnosis was unclear. After discharge, the patient’s symptoms recurred and became exacerbated. The patient was then referred to our hospital for treatment. A physical examination on admission revealed the following: stable vital signs, anaemia, yellow skin, and sclera, no liver palms or spider naevi, no cardiac or pulmonary abnormalities, a soft abdomen, no palpable liver or spleen under the ribs, negative Murphy’s sign, negative McBurney’s point tenderness, normal bowel sounds, negative mobile dullness, and no oedema in either lower limb. The pathological examination showed the following: white blood cell count, 4.3 × 109/L; Hb level, 68 g/L; red blood cell count, 1.75 × 1012/L; haematocrit, 21.4%; mean Hb content, 38.9 pg; mean corpuscular volume, 122.3 fL; red blood cell distribution width, 24.7%; platelet count, 366 × 109/L; and reticulocyte percentage, 16.0%. A peripheral blood smear examination revealed visible multicoloured and spherical red blood cells, with approximately 11.5% spherical red blood cells.

Liver function tests revealed the following: normal transaminase; total bilirubin level, 145.2 μmol/L; direct bilirubin level, 17.8 μmol/L; indirect bilirubin level, 127.4 μmol/L; lactate dehydrogenase level, 446 U/L; and urine iron-containing Hb, positive (+). The ferritin level was 635.9 μg/L, while the folate, vitamin B12, and glucose-6-phosphate dehydrogenase levels were normal. The antinuclear antibody spectrum test, Coombs direct and indirect tests, the paroxysmal nocturnal haemoglobinuria detection, the cold agglutinin test, and haemoglobin electrophoresis results were normal. Whole abdominal computed tomography revealed a possible left-lobe cyst in the liver and an enlarged spleen. A routine bone marrow examination showed a significant increase in the number of nucleated cells (G = 33.5%, E = 57.5%; granulocytes:erythrocytes = 0.6:1). Erythroid proliferation was significantly increased, with visible binucleated, enlarged erythroid cells, and Howell–Jolly bodies. Mature red blood cells of various sizes, polychromatic erythrocytes, and spherical red blood cells were also observed (Figure 1). Bone marrow flow cytometry and biopsies revealed no abnormalities. A bone marrow chromosomal examination revealed 47, XY, +8[20], an acquired genetic variation.

Figure 1 Peripheral blood smear (arrows show small spherical red blood cells) (HE staining).
Figure 1

Peripheral blood smear (arrows show small spherical red blood cells) (HE staining).

Considering the possibility of HS and myelodysplastic syndrome, haemolytic anaemia was diagnosed. After treatment, routine blood test results showed an Hb level of 94 g/L and an indirect bilirubin level of 101.7 μmol/L. After discontinuing the glucocorticoids, the patient continued treatment for liver protection and jaundice reduction. Genetic disease related gene sequencing of the patient’s genomic DNA using peripheral blood samples obtained at another hospital (Figures 2 and 3) showed SPTB c.3449G > A (p.Trp1150*) heterozygosity, ASXL1 c. 1275del (p.Tyr425*) suspected heterozygosity, a Chr8 duplication, UGT1A1 c. 211G > A(p.Gly71Arg) heterozygosity, and UGT1A1 c. 1091C > T (p.pro364Leu) heterozygosity. Based on the patient’s medical history and all case data, he was diagnosed with HS combined with GS. After discharge, the patient’s indirect bilirubin level decreased to 87 μmol/L after rest and liver protection therapy, and he is currently undergoing follow-up in the outpatient clinic.

Figure 2 Sanger sequencing results of SPTB and ASXL1 genes (the overlapping peaks caused by insertion mutation in the sequencing signal during unidirectional sequencing precisely indicate that a base is missing here).
Figure 2

Sanger sequencing results of SPTB and ASXL1 genes (the overlapping peaks caused by insertion mutation in the sequencing signal during unidirectional sequencing precisely indicate that a base is missing here).

Figure 3 Sequencing results of UGT1A1 gene.
Figure 3

Sequencing results of UGT1A1 gene.

  1. Informed consent: Informed consent has been obtained from all individuals included in this study.

  2. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.

3 Discussion

HS is mostly inherited in an autosomal dominant manner, with some cases being inherited in an autosomal recessive manner. This is caused by variants in the genes located on chromosomes 6 or 8. Owing to membrane defects in the red blood cells, they become spherical, and are destroyed in large quantities when passing through the spleen, resulting in haemolytic jaundice characterised by increased indirect bilirubin levels. Typical clinical manifestations include anaemia, jaundice, and splenomegaly, with some patients having gallstones [4]. The incidence rate in this population is approximately 1/2,000.

HS exhibits significant heterogeneity in its genetics, molecular genetics, biochemical phenotypes, and clinical manifestations. Approximately 25% of patients have no family history and their conditions are associated with gene variants, phenotypic variations, or autosomal recessive inheritance [5]. HS is caused by variants in genes encoding erythrocyte membrane and cytoskeletal proteins. Five genes associated with HS, including SPTA1, SPTB, ANK1, SLC4A1, and EPB42. HS is caused by at least one variants of an HS-related gene [6]. These variants reduce the levels of proteins that link the endomembrane skeleton of red blood cells to the outer layer of the lipid bilayer, resulting in the formation of microvesicles in the red blood cell membrane and the gradual spherical transformation of the red blood cells. Spherocytes are susceptible to haemolysis through reduced erythrocyte deformability and phagocytosis by splenic macrophages, and the loss of spectrin appears to be particularly associated with haemolysis severity [7].

The updated HS diagnostic process guidelines for 2021 suggest that a preliminary diagnosis can be made based on typical clinical manifestations and laboratory test findings, such as peripheral reticulocytosis, increased unconjugated bilirubin level, and increased microspherocytic red blood cell counts. The diagnosis can be confirmed if a child has a definite family history. If the child’s family history is negative, relevant screenings, such as the acidified glycerol lysis test, red blood cell osmotic fragility test, and genetic testing, can be performed to assist in the diagnosis. The eosin-5-maleimide binding test is currently recognised as the most convenient, highly sensitive, specific diagnostic method and new guidelines have listed it as a new diagnostic approach [8]. Asymptomatic carriers and patients with mild HS do not require special treatment, whereas patients with moderate to severe HS require a total or partial splenectomy and/or splenic artery embolisation [9].

Our patient had no family history of HS. A preliminary diagnosis of HS was made based on clinical manifestations and laboratory test findings. Subsequently, genetic tests performed at an external hospital revealed SPTB c.3449G > A (p.Trp1150*) heterozygosity, suspected ASXLI c. 1275del (p.Tyr425*) heterozygosity, and Chr8 duplication. We know that c.3449G > A (p.Trp1150*) is a nonsense variant in the coding region of the SPTB gene, which can theoretically lead to the loss of normal protein function through nonsense-mediated mRNA degradation or premature termination of the encoded amino acid sequence. This variant was not reported previously in the gnomAD. In some patients, multiple variants in related genes can produce synergistic or inhibitory effects, leading to a complex HS pathology. Based on the available evidence, we excluded other diseases of the blood system and finally considered the diagnosis of HS. Moreover, the patient experienced disease onset at an old age, and no similar condition was reported in his immediate family; therefore, we identified a high possibility of SPTB-acquired variants.

GS, a benign, familial disorder of bilirubin metabolism that often occurs in adolescents and adults, has a higher incidence in men. Because of the reduced UGT1A1 activity, the ability of liver cells to process Ibil decreases, causing congenital non-haemolytic jaundice characterised by elevated Ibil levels. The primary clinical manifestation is chronic, intermittent hyperbilirubinemia, without haemolytic or liver disease symptoms [10,11]. Its reported prevalence is 2–5%. GS, which is usually undetectable, can be exacerbated by alcohol consumption, fatigue, infection, trauma, pregnancy, or other triggers. The total serum bilirubin level of patients with GS is usually <3 mg/dL, and the condition is mild with a good prognosis. Treatment is generally not necessary, and any symptoms can be alleviated by avoiding triggers. Phenobarbital treatment is reportedly effective.

GS and HS are genetic diseases caused by different gene variants, and their co-occurrence is low. According to international data for GS and HS, the theoretical incidence rate of the comorbid conditions is 15–35 per 100,000 people [1,12]; however, the actual incidence rate statistics have not been reported. Only a few cases have been reported in China, an incidence that is lower than the theoretical incidence rates in other countries. In addition to being related to race, this could be related to missed diagnoses because of insufficient clinical knowledge. The genetic variant sites of the two genetic diseases differ, and the specific mechanism of their comorbidity remains unclear. There is no evidence that these two proteins have a specific biological relevance [13,14]. GS and HS can co-occur during infancy or old age [15]. When the two conditions coexist, patients first experience a mismatch between the degrees of bilirubinaemia and anaemia; some patients with HS have relatively mild anaemia but high bilirubin levels. Therefore, special attention should be paid to the coexistence of these two diseases. Patients with GS show no signs of extravascular haemolysis such as splenomegaly. In patients with HS, if the characteristics of jaundice become significantly aggravated after exertion and significantly alleviated after rest and hyperbilirubinemia is not relieved after treatment, the possibility of comorbid GS should be considered.

Our patient was diagnosed with late-onset HS and GS and had no relevant family history. The diagnosis of HS could explain his splenomegaly, anaemia, and elevated reticulocyte levels. The increased reticulocyte proportion suggested haemolysis. After hormone treatment, the anaemia improved but the jaundice remained severe, and the degree of haemolysis did not match the increase in total and indirect bilirubin levels. Haemolytic jaundice caused by HS alone does not provide adequate justification considering that hyperbilirubinemia is common in cases of UGT1A1 variants. UGT1A1 gene screening results reported by another hospital suggested a co-heterozygous variant of UGT1A1 c. 211G > A (p.Gly71Arg) and UGT1A1 c. 1091C > T (p.pro364Leu), a widely mutated gene in the Han Chinese population with GS [16].

In summary, the diagnostic process in this case suggests that the diagnosis of hyperbilirubinemia should be combined with the patient’s clinical manifestations and comprehensive screening should be conducted to determine whether a patient has haemolytic disease or UGT1A1 gene abnormalities. Upon the diagnosis of haemolytic jaundice, the possibility of genetic and acquired haemolytic anaemia should be considered. Upon the diagnosis of UGT1A1 gene abnormalities, GS and Crigler-Najjar syndrome should be considered. When elevated bilirubin levels do not match the provisional diagnosis, the coexistence of multiple diseases should be considered. As HS and GS are both genetic diseases, a timely and accurate diagnosis can provide guidance for future genetic counselling.

  1. Funding information: This study was supported in part by Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (Grant No. 2021KY1078).

  2. Author contributions: Shanshan Weng, Changwei Chi, Shenghao Wu, Wenjin Zhou, Yingying Hu, and Yanwei Lu discussed and wrote the manuscript. All authors reviewed this manuscript and agreed to submit this manuscript.

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

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

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Received: 2024-02-24
Revised: 2024-05-23
Accepted: 2024-06-03
Published Online: 2024-06-27

© 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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  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?
https://doi.org/10.1515/biol-2022-0904
Schlagwörter für diesen Artikel
hereditary spherocytosis; Gilbert syndrome; jaundice
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Biomedical Sciences
  2. Constitutive and evoked release of ATP in adult mouse olfactory epithelium
  3. LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior
  4. PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications
  5. Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons
  6. The role and mechanism of esketamine in preventing and treating remifentanil-induced hyperalgesia based on the NMDA receptor–CaMKII pathway
  7. Brucella infection combined with Nocardia infection: A case report and literature review
  8. Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance
  9. Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous
  10. PTTG1 induces pancreatic cancer cell proliferation and promotes aerobic glycolysis by regulating c-myc
  11. Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features
  12. Effectiveness and safety of a mumps containing vaccine in preventing laboratory-confirmed mumps cases from 2002 to 2017: A meta-analysis
  13. Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms
  14. A case of Trousseau syndrome: Screening, detection and complication
  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?
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