Startseite Medizin Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
Artikel Open Access

Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus

  • GuangZhi Li EMAIL logo und Dongmei Zhang
Veröffentlicht/Copyright: 17. März 2025
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Open Medicine
Aus der Zeitschrift Open Medicine Band 20 Heft 1

Abstract

Background

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and β-cell dysfunction. A hallmark of T2DM pathology is the accumulation of toxic amyloid polypeptides in and around pancreatic islet cells, leading to the progressive loss of β-cell populations. Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37-amino acid peptide hormone primarily produced by pancreatic β-cells. hIAPP aggregation and amyloid formation are strongly correlated with β-cell death and disease severity in T2DM patients.

Objectives

This article aims to review the current research progress on the correlation between hIAPP and T2DM, focusing on the molecular mechanisms and potential therapeutic strategies.

Methods

We conducted a comprehensive literature review covering recent studies on the molecular structure, physiological function, and pathological mechanisms of hIAPP. Key areas include biosynthesis, monomer structure, and the formation of hIAPP fiber structures. Additionally, we examined the mechanisms of hIAPP-induced β-cell death, including oxidative stress (OS), endoplasmic reticulum stress (ERS), impaired cell membrane and mitochondrial functions, and inflammatory factors.

Results

Our review highlights the critical role of hIAPP in the pathogenesis of T2DM. Specifically, we found that hIAPP biosynthesis and monomer structure contribute to its physiological functions, while hIAPP aggregation forms toxic amyloid fibers, contributing to β-cell dysfunction. OS, ERS, impaired cell membrane and mitochondrial functions, and inflammatory factors play significant roles in hIAPP-induced β-cell death. There is a strong correlation between hIAPP aggregation and the severity of T2DM, and potential therapeutic approaches using small molecule inhibitors to prevent hIAPP aggregation and fibrosis are discussed.

Conclusion

Understanding the molecular mechanisms of hIAPP in T2DM provides insights into potential therapeutic targets and preventive strategies. Future research should focus on developing more effective treatments targeting hIAPP aggregation and its downstream effects.

Keywords: islet amyloid peptides; type 2 diabetes mellitus; human

1 Introduction

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin (Ins) resistance and β-cell dysfunction [1]. A hallmark of T2DM pathology is the accumulation of toxic amyloid polypeptides in and around pancreatic islet cells, leading to the progressive loss of β-cell populations. Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37-amino acid peptide hormone primarily produced by pancreatic β-cells. hIAPP aggregation and amyloid formation are strongly correlated with β-cell death and disease severity in T2DM patients [2]. This article reviews the research progress on the correlation between hIAPP and T2DM, focusing on the molecular mechanisms and potential therapeutic strategies. The main feature of diabetes is abnormally high blood sugar levels. Diabetes has become one of the most widespread major diseases globally, affecting over 170 million people [1,2]. Globally, this number is projected to grow rapidly in developing countries in Africa, Asia, and South America, with an estimated increase of nearly 50% by 2023. The prevalence of diabetes in more developed societies has reached about 6%, and an even more alarming 4% of obese white adolescents have diabetes and 25% have abnormal blood sugar regulation [3,4]. Diabetes can lead to many serious complications, including blindness, kidney failure, and cardiovascular disease. Due to its high incidence and clinical complexity, diabetes, as a chronic disease, poses a significant medical and socioeconomic challenge to human society [4].

There are two main types of diabetes. Type 1 diabetes mellitus refers to Ins-dependent diabetes mellitus, where Ins production and beta-cell secretion in the islets are disrupted by the body’s autoimmune response, resulting in Ins deficiency at a young age. Type 2 diabetes (T2D), or non-Ins-dependent diabetes mellitus [5,6], involves initial defects primarily characterized by Ins resistance. In other words, Ins target cells, especially muscle and liver cells, do not respond normally to Ins, even when compensated with high levels of Ins. In the early stages of T2D, basal blood sugar levels may remain normal due to increased Ins production and secretion (hyperinsulinemia) [6,7]. Studies have found that more than 90% of patients with T2D have islet amyloidosis, which is more common than diabetes syndrome [8]. The extent of amyloid invasion and the number of affected islets determine the severity of diabetes. In contrast, only a very small number of islets are involved in healthy individuals, and while amyloid can be observed in the islets of the elderly, it is present in smaller quantities compared to T2D patients. Therefore, the vast majority of people with T2D have islet amyloid deposits, and amyloidosis is a hallmark of T2D [9].

In T2D, amyloid is localized and deposited in islets (Figure 1). Congo red and thioflavin S staining show a green birefringent light under a polarized light microscope. Electron microscopy reveals that the amyloid deposits consist of fibers of varying lengths with an average diameter of 7–10 nm [10]. The amyloid is composed of islet amyloid polypeptide (IAPP), apolipoprotein E (ApoE), and heparan sulfate perlecan. IAPP is unique to islet amyloid, while ApoE and heparan sulfate perlecan are also found in other amyloidosis diseases and are common components of amyloid [11–13].

Figure 1 Micrograph of islets replaced by amyloid precipitate (a) and micrograph of individual islets (b).
Figure 1

Micrograph of islets replaced by amyloid precipitate (a) and micrograph of individual islets (b).

Amyloid deposits have a typical ultrastructure called filament: due to hydrogen bonding between regions of the protein molecule rich in a “beta-folded” structure, proteins stack on each other to form filament further amyloid deposits (Figure 2) [14,15].

Figure 2 Aggregation of amyloid polypeptides in human islets.
Figure 2

Aggregation of amyloid polypeptides in human islets.

hIAPP-derived aggregates or amyloid deposition have toxic effects on islet beta cells and are the main cause of T2DM. hIAPP, also known as amylin, is stored in islet beta cells along with Ins [15,16]. hIAPP deposition is present in 95% of T2DM patients, which is positively correlated with disease severity and reduces islet beta cell function. This article reviews the research progress on the correlation between hIAPP and T2DM [16].

2 Molecular structure and physiological function of hIAPP

2.1 Biosynthesis and monomer structure of hIAPP

The hIAPP gene is located on the short arm of chromosome 12, and IAPP is also included as a member of the calcitonin family due to its high sequence homology (46%) with calcitonin and calcitonin gene-related peptides, as well as the same signaling pathway as other members of the calcitonin family [17]. In the β cell, the IAPP precursor, PreproIAPP, containing 89 residues, is first synthesized. Then, PreproIAPP was hydrolyzed by signal peptidase in the endoplasmic reticulum (ER) to form ProIAPP containing 67 residues. The latter was digested by prohormone converting enzymes PC1/3 and PC2 into secretory vesicles in Golgi and then carboxypeptidase E (CPE). Further action of CPE and peptidylamdating monooxygenase (PAM) resulted in a mature IAPP composed of 37 amino acids (Figure 3) [18,19]. It is worth noting that the biosynthesis and secretion pathway of Ins is highly consistent with that of IAPP, and it is also formed by its precursor preproinsulin through the action of PC1/3, PC2, and CPE in turn. After undergoing the same biosynthesis and processing steps, Ins and IAPP are co-stored in secretory vesicles and secreted together with IAPP after stimulation, the only difference is that the synthesis of Ins does not require the action of PAM [19–21].

Figure 3 Biosynthesis of IAPP in β cells.
Figure 3

Biosynthesis of IAPP in β cells.

A large number of studies have shown that hIAPP monomer mainly exists in the form of random coil under physiological conditions, but sequence software analysis has found that some sequence fragments of hIAPP tend to form local secondary structures [21,22]. Experimental studies also found that the structure of the hIAPP monomer would change significantly under some solvent conditions. For example, some scholars applied circular dichroism and fluorescence studies and found that a large number of A-helix structures would be formed in trifluoroethanol under the hIAPP monomer [22,23].

2.2 Physiological function of hIAPP

hIAPP plays an important role in metabolism, especially blood sugar control. hIAPP inhibits food absorption and gastric emptying. In the same environment, the hIAPP knockout mice had accelerated gastric emptying and were 30% heavier than normal mice. Accelerated gastric emptying was present in patients with type 1 diabetes and T2D, but the rate of gastric emptying decreased significantly after IAPP injection [24,25].

hIAPP also inhibits Ins secretion. The study found that the cholinergic nervous system is involved in the regulation of Ins secretion by beta cells, and hIAPP can inhibit Ins secretion by blocking the cholinergic mechanism [26]. hIAPP is also able to inhibit the secretion of Ins caused by glucose stimulation, but only when IAPP concentrations are greater than 10 mmol/L. Given the low concentration of hIAPP circulating under normal physiological conditions (pmol/L level), this mechanism may not work under normal conditions [27,28].

hIAPP also has a certain inhibitory effect on glucagon secretion. Studies have found that IAPP can inhibit glucagon secretion by changing the plasma glucose concentration in the blood and inhibiting Ins secretion. However, hIAPP does not affect the normal function of glucagon, and glucagon can still play a normal role in hypoglycemia [28,29].

In people with type 1 diabetes, the total amount of hIAPP and Ins secreted is insufficient due to the destruction of islet beta cells, leading to the development of diabetes symptoms [29]. Clinical studies have shown that increasing hIAPP levels in patients with type 1 diabetes have a good effect on weight control, postprandial blood glucose control, and long-term blood glucose control. Based on these studies, the American company Amylin developed the world’s first HiAPP-based analogue drug – Symlin (pramlintide acetate), which is currently mainly used as an Ins adjuvant in patients with type 1 diabetes [30,31].

In addition to regulating blood sugar, hIAPP also has some other physiological functions, such as dilating blood vessels and lowering blood calcium; activate the renin-angiotensin system; inhibit gastric acid secretion and keep gastric mucosa intact; inhibition of atrial natriuretic peptide secretion; help amino acids cross the blood–brain barrier, raise body temperature, etc. [31,32].

3 Structure formation of hIAPP fiber

hIAPP self-assembles amyloid fibers at micromolar concentrations through a classical nucleation growth mechanism that exhibits S-shaped aggregation dynamics characterized by lag, growth, and plateau periods. hIAPP nucleation occurs in the late stage of the assembly of soluble hIAPP monomers into oligomers, which is largely affected by temperature, peptide concentration, ionic strength, and pH value [33]. These nuclei further develop and elongate, forming fibrils during the growth phase. The fibril produces more fibril through secondary nucleation to catalyze new fibril and finally reaches homeostasis. The dynamic aggregation process of hIAPP involves the formation of a large number of different, transient oligomer intermediates and has a potential role in cytotoxicity and fibril formation [33,34].

4 Mechanism of hIAPP-induced death of pancreatic β cells

The fibril toxicity of hIAPP directly damages the islet beta cells, and the oligomer intermediates also damage the islet beta cells. The mechanisms of injury include oxidative stress (OS), ER stress (ERS), mitochondrial dysfunction, cell membrane rupture, islet inflammation, and injury, which aggravate the toxicity of islet beta cells [34,35].

4.1 OS

OS is associated with increased reactive oxygen species (ROS) in islet beta cells [36]. ROS are highly reactive molecules produced as a natural byproduct of normal metabolism and cellular processes. In healthy conditions, the body maintains a balance between ROS production and antioxidant defenses [37]. However, in pathological states such as T2DM, this balance is disrupted, leading to OS. The role of ROS in β-cell function is highly dependent on the timing and intensity of the signals [38]. β-cells are particularly susceptible to OS compared to other cell types because they have a limited capacity to scavenge oxidants [39]. Transient and moderate production of mitochondrial ROS is crucial for promoting β-cell function and glucose-stimulated Ins secretion, mimicking the effects of glucose [40]. However, chronic and sustained elevation of ROS due to inflammation or excessive glucose and fatty acid concentrations impairs β-cell function by inhibiting ROS signaling and inducing mitochondrial damage, which in turn leads to increased ROS production.

Increased mitochondrial superoxide production is activated by the peroxidation of mitochondrial phospholipids [6]. Morphological studies have shown that the number of β-cell mitochondria is similar in β-cells from patients with T2D and from non-diabetic donors [41]. However, diabetic pancreatic islets exhibit a significantly higher volume of mitochondrial density, which is associated with increased ROS production. Consistent with this observation, UCP2 protein levels are upregulated in pancreatic islets from T2D patients compared to non-diabetic patients [42].

Glucose is the main energy source for the electron transport chain in islet beta cells. In T2DM patients, elevated blood glucose levels lead to an increased flux of glucose through the electron transport chain, resulting in higher levels of ROS [43]. This excessive ROS production can damage cellular components, including proteins, lipids, and DNA, ultimately contributing to beta-cell dysfunction and impaired Ins secretion [44]. Glucose is the main energy source of the electron transport chain, and T2DM patients increase their energy source due to high blood sugar, resulting in higher levels of ROS [36]. Like other amyloid proteins, the formation and decomposition of hIAPP amyloid proteins are related to ROS production. The formation of hIAPP fibers and oligomers leads to the appearance of OS in pancreatic tissue and the loss of β cell mass in pancreatic islets. Inhibiting amyloid aggregation can reduce OS.

Furthermore, ROS can oxidize cardiolipin (CL) and other mitochondrial inner membrane phospholipids, leading to the permeabilization of the outer mitochondrial membrane and the subsequent release of cytochrome c into the cytosol. This process initiates apoptosis, ultimately resulting in a reduction of β-cell mass. The oxidation of CL disrupts the integrity of the mitochondrial membrane, causing the release of pro-apoptotic factors such as cytochrome c. These factors then activate caspase cascades, leading to the execution phase of apoptosis. As a result, β-cell mass is significantly reduced, contributing to impaired Ins secretion and the progression of T2D.

4.2 ERS

The ER in β cells has a high capacity for protein synthesis and folding [45]. However, during Ins resistance, β cells must synthesize Ins beyond their normal folding and secretion capacity, thereby activating the unfolded protein response (UPR). The UPR is an adaptive signaling pathway designed to promote cellular survival when misfolded proteins accumulate in the ER. The UPR signaling sensors include inositol-requiring enzyme 1, PKR-like ER kinase, and activating transcription factor 6. If the UPR is chronically activated and the protein-folding demand in the ER exceeds its capacity, unfolded proteins begin to accumulate, leading to ER stress and ultimately cell death [46].

It has been reported that defects in ERS, ER-associated protein degradation, and the UPR can all contribute to β-cell death through the aggregation of hIAPP [47]. In cases where intracellular aggregates generate toxicity, proIAPP and partially processed proIAPP may be among the harmful species, as deficient processing of proIAPP has been demonstrated in diabetes [48]. Post-translational modifications are completed in the Golgi apparatus and Ins secretory granules [49]. The ERS signaling pathway activates protein kinase, transcription factor CHOP, etc., causing the UPR, which increases the intensity of ERS and decreases protein synthesis. If the UPR is unable to cope with the increase of hIAPP, the accumulation of hIAPP in cells can activate the apoptotic pathway, leading to the damage and death of islet beta cells.

4.3 Cell membrane and mitochondrial function are impaired

Mechanistic studies of IAPP-induced membrane disruption remain an active area of research, with various models being proposed. While some studies support a detergent or carpeting mechanism, others suggest a pore-like mechanism [50]. The toxic effect of hIAPP on islet beta cells was related to its ability to penetrate the cell membrane. Compared to the mature hIAPP fibrous structure, the oligomer intermediates have a higher membrane destruction capacity, and the hIAPP oligomer inserts into the membrane bilayer hydrophobic region, resulting in membrane rupture before fibril formation [51]. Therefore, hIAPP oligomers with high membrane permeability and low solubility can destroy the lipid accumulation on the membrane surface, increase the double-layer conductivity, thin and fracture the membrane, and then collapse the phospholipid bilayer [52]. In the islets of hIAPP transgenic mice and T2DM patients, cytoplasmic hIAPP oligomers were found near morphologically damaged mitochondria and ruptured mitochondrial membranes. The toxic effect of hIAPP on rat insulinoma beta cells can lead to mitochondrial rupture, mitochondrial membrane potential loss, and ATP depletion [53,54].

4.4 Inflammatory factor

Inflammatory stress plays a crucial role in the pathogenesis of T2DM. Indeed, mild inflammation within the pancreatic islets can be detected in patients with T2DM [55]. The use of anti-inflammatory drugs has been shown to produce a slight decrease in blood glucose levels, suggesting the involvement of inflammation in the development of T2DM. However, it remains unclear whether these anti-inflammatory drugs act directly on the pancreatic islets or through their effects on other relevant metabolic tissues.

This inflammation can arise from various sources, including nutritional overload, proinflammatory cytokines, pancreatic amylin accumulation, and ERS [56]. One of the organelles significantly affected by inflammation is the mitochondrion. Mitochondrial dysfunction leads to impaired ATP production and induces pro-apoptotic mechanisms, contributing to β-cell failure. Mitochondrial autophagy, also known as mitophagy, is an important mechanism that helps counteract the accumulation of damaged mitochondria following inflammatory processes. This process utilizes the autophagic mechanism to specifically remove dysfunctional mitochondria, thus maintaining cellular homeostasis. Any disruption in mitochondrial autophagy sensitizes pancreatic cells to inflammation, making them more vulnerable to OS and apoptosis [57].

Mitochondrial autophagy serves as a critical survival mechanism for pancreatic β-cells in response to inflammation. OS, characterized by an imbalance between ROS and antioxidant defenses, exacerbates mitochondrial dysfunction [58]. This leads to increased ROS production, further damaging mitochondrial integrity and ultimately resulting in β-cell failure. The accumulation of ROS due to impaired antioxidant defenses contributes to mitochondrial dysfunction and the progressive decline of pancreatic β-cell function. IL‑1β is an inflammatory cytokine associated with T2DM and is associated with cytotoxicity. Increased hIAPP activates inflammatory cells to produce IL‑1β, leading to islet beta cell death. Islet macrophages containing amyloid protein in hIAPP transgenic mice expressed higher levels of inflammatory factors such as IL-1β, IL-1α, and TNF‑α [41]. Studies involving T2DM, T2DM alone, and non-T2DM patients with islet amyloid deposition have shown that amyloid-rich islet beta cells are significantly damaged, and a large number of macrophages are mixed with OS-related DNA damage.

In summary, inflammatory stress and the resulting mitochondrial dysfunction play pivotal roles in the pathogenesis of T2DM. Targeting these pathways, particularly through the enhancement of mitochondrial autophagy and the reduction of OS, offers promising therapeutic strategies for managing and potentially reversing the progression of T2DM.

4.5 Block IAPP aggregation

Through the development of small molecule drugs or peptide inhibitors, researchers have identified substances that can bind to IAPP and prevent it from forming toxic aggregates. One notable study demonstrated the efficacy of a human monoclonal antibody that selectively targets IAPP oligomers. This antibody effectively neutralizes the aggregation toxicity of IAPP by preventing extracellular membrane destruction and reducing cell apoptosis. In experimental models, antibody therapy has shown promising results: when applied to male rats and mice with human IAPP gene transfer, as well as in mouse models of T2D transplanted with human islets, the treatment successfully triggered the clearance of IAPP oligomers. This not only protected the beta cells but also improved overall blood glucose control. These findings suggest that targeting IAPP oligomers with specific antibodies can be a viable therapeutic strategy for managing and potentially treating T2D [59].

4.6 Dietary patterns

One of the most effective strategies for controlling T2D is to follow a specific dietary pattern. Diets rich in whole grains, vegetables, fruits, nuts, and legumes, along with moderate alcohol consumption and less red/processed meats, refined grains, and sugary beverages, have been shown to be particularly beneficial. These dietary choices often lead to weight loss, which is associated with many positive health outcomes. For example, weight loss can significantly reduce cardiovascular risk and lower the risk of all-cause mortality. By promoting healthier body composition and improved metabolic function, these dietary modifications contribute to better overall health and well-being. The Okinawa-based Nordic diet for at least 3 months is sufficient to reduce circulating IAPP and IpuPO-IGA levels, which may be the main reason for controlling T2D [48].

5 Correlation between hIAPP and T2DM

In non-DM patients, hIAPP and Ins are co-produced and secreted by islets in a 1:100 molar ratio. Studies have found that hIAPP exists in the pancreas of patients with T2DM death, suggesting a correlation between hIAPP and T2DM. Amyloid polypeptide is a special protein aggregation that produces the characteristic β-folded fibril, Ins itself can be converted into fibril, and Ins or proinsulin is the origin of hIAPP. Protein molecular sequencing confirmed that hIAPP fibril was composed of unknown islet beta cell products [42,43].

hIAPP fiber is the main component of amyloid fiber deposition in islets and participates in T2DM by inducing islet β cell death. Primate studies support that islet amyloidosis and apoptosis of islet beta cells are key factors in islet dysfunction. Overexpression of IAPP leads to pancreatic amyloid formation and T2DM progression [43]. The formation of hIAPP amyloid deposition is related to the pathological mechanism of hyaline degeneration of islets in T2DM patients. hIAPP has been found in the brain and cerebrospinal fluid of both Alzheimer’s disease and T2DM patients, but it is uncertain whether it comes from the brain or the pancreas. hIAPP aggregation with nerve damage was also observed in Hiapp-expressing rat brains [44]. At present, there is no effective method to prevent hIAPP aggregation and toxicity in the human body. The mechanisms of hIAPP synthesis, secretion, and degradation are particularly important for exploring hIAPP aggregation in islet beta cells [36,44].

6 Small molecule inhibitor of hIAPP aggregation and fibrosis

The aggregation potential of hIAPP in islets is related to the clinical characteristics of T2DM patients, and hIAPP aggregation is less in non-DM patients. There may be effective natural inhibitors of hIAPP oligomerization and fibrosis in human islets, and Ins, C‑P, and zinc ions (Zn2+) may be important intracellular factors that help prevent hIAPP aggregation, and the B chain of Ins is the active component that inhibits hIAPP aggregation [45,46]. The inhibition of amyloid formation by metal ions may be due to the different molecular coordination between hIAPP residues, the HIS-18 imidazole ring in hIAPP is the most significant, which reduces the assembly rate of amyloid protein, and the binding of Zn2+ with His18 induces the local destruction of hIAPP secondary structure. C‑P, Zn2+, and hIAPP form a stable soluble metal–peptide complex to prevent oligomerization and fibrosis, and Zn2+ is also a cofactor for Ins to inhibit hIAPP aggregation [46]. Copper ions reduce the toxic effects of hIAPP by preventing the transition of hIAPP from random curling to β-fold-rich oligomers and aggregates to avoid HiAPP aggregation in islet beta cells. Low molecular weight metal-HIAPP complexes are not cytotoxic, and transition metals or chelates may accelerate hIAPP aggregation and toxicity. Many natural products and derivatives, such as small molecule polyphenol compounds isolated from plants, have been shown to inhibit hIAPP aggregation in vitro and intracellular [46,47]. It has been found that Tat-CIAPIN1 protein improves the pathological changes of pancreatic beta cells and reduces fasting blood glucose, body weight, and hemoglobin Alc levels in T2DM mouse models. Tat-CIAPIN1 has a protective effect on β-cells and T2DM by inhibiting hIAPP toxicity and regulating MAPK signaling pathway, suggesting that CIAPIN1 may be a therapeutic protein candidate for beneficial regulation of T2DM. On the other hand, biflavonoids are natural compounds with a wide range of biological activities. A study investigating the inhibitory effects of two biflavonoids (arylflavonoids (1) and arylflavonoids (2)) on the formation of hIAPP protofibrils and their interaction mechanisms found that they significantly prevented the self-assembly behavior of hIAPP and disassembled the aged aggregates into small oligomers and monomers. Both compounds showed strong binding affinity for hIAPP mainly through hydrophobic and hydrogen bonding interactions, and the hydroxyl substitution in 1 was superior to the methoxy substitution in 2 for hindering hIAPP aggregation at the same C8 position. 1 and 2 also reduced hIAPP-induced cytotoxicity by decreasing peptide oligomerization.

7 Summary and outlook

In summary, hIAPP serves as the primary component of amyloid deposition in islet tissue, assisting Ins in regulating blood glucose levels in non-diabetic individuals and playing a crucial role in the pathogenesis of T2D. Understanding the cytotoxic mechanisms of hIAPP will further elucidate the pathogenesis of T2D. Additionally, as a typical representative of amyloid deposition proteins, studying hIAPP provides valuable insights into the pathogenesis of other amyloid deposition diseases. To expand our understanding of hIAPP, future research should focus on investigating its role and effects in diverse populations, including different ethnicities and age groups. Specifically, studies should explore the genetic and environmental factors that influence hIAPP expression and toxicity across different ethnicities, such as Asian, Caucasian, African, and Hispanic populations, which could reveal unique patterns and potential therapeutic targets. For instance, comparative studies between these ethnic groups might uncover distinct genetic variants that affect hIAPP aggregation and toxicity, providing a basis for ethnicity-specific therapeutic approaches. Additionally, studying hIAPP in various age groups, from pediatric to elderly populations, can help identify age-specific mechanisms and risk factors. Pediatric studies could uncover early biomarkers of hIAPP-related dysfunction, while geriatric studies might reveal the cumulative effects of hIAPP on islet function over time, leading to more targeted interventions and personalized treatment strategies. Given the critical role of hIAPP in T2D, it presents a promising therapeutic target, and future research should focus on developing inhibitors or modulators that can specifically target hIAPP aggregation and toxicity, potentially enhancing the efficacy of existing treatments. By addressing these research prospects, we aim to gain a comprehensive understanding of hIAPP’s role in diverse populations and its potential as a therapeutic target for T2D and related amyloid deposition diseases.

  1. Funding information: The authors state no funding involved.

  2. Author contributions: Dongmei Zhang: conceptualization, methodology, software; GuangZhi Li: data curation, writing – original draft preparation; Dongmei Zhang: visualization, investigation; GuangZhi Li: supervision.

  3. Conflict of interest: The authors state no conflicts 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: 2024-07-17
Revised: 2024-10-27
Accepted: 2024-11-28
Published Online: 2025-03-17

© 2025 the author(s), published by De Gruyter

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

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  195. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  196. Letter to the Editor
  197. Role of enhanced external counterpulsation in long COVID
  198. Expression of Concern
  199. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  200. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  201. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  202. Corrigendum
  203. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  204. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  205. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  206. Retraction
  207. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  208. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  209. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  210. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  211. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  212. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  213. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  214. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  215. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  216. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  217. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  218. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  219. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  220. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  221. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  222. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  223. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  224. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  225. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  226. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  227. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  228. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  229. A review of brain research on T2DM-related cognitive dysfunction
  230. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  231. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  232. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
https://doi.org/10.1515/med-2024-1124
Schlagwörter für diesen Artikel
islet amyloid peptides; type 2 diabetes mellitus; human
Creative Commons
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Artikel in diesem Heft

  1. Research Articles
  2. Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
  3. Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
  4. Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
  5. Risk factors for severe adverse drug reactions in hospitalized patients
  6. Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with Fonsecaea monophora based on single-cell sequencing
  7. Development and validation of headspace gas chromatography with a flame ionization detector method for the determination of ethanol in the vitreous humor
  8. CMSP exerts anti-tumor effects on small cell lung cancer cells by inducing mitochondrial dysfunction and ferroptosis
  9. Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
  10. Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
  11. Comparison of the effectiveness of nurse-led preoperative counseling and postoperative follow-up care vs standard care for patients with gastric cancer
  12. Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
  13. Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
  14. Association between statin administration and outcome in patients with sepsis: A retrospective study
  15. Exploration of the association between estimated glucose disposal rate and osteoarthritis in middle-aged and older adults: An analysis of NHANES data from 2011 to 2018
  16. A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
  17. Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function
  18. Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
  19. Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition
  20. Hydromorphone reduced the incidence of emergence agitation after adenotonsillectomy in children with obstructive sleep apnea: A randomized, double-blind study
  21. Vitamin D replacement therapy may regulate sleep habits in patients with restless leg syndrome
  22. The first-line antihypertensive nitrendipine potentiated the therapeutic effect of oxaliplatin by downregulating CACNA1D in colorectal cancer
  23. Health literacy and health-related quality of life: The mediating role of irrational happiness
  24. Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis
  25. Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics
  26. Examination of the causal role of immune cells in non-alcoholic fatty liver disease by a bidirectional Mendelian randomization study
  27. Clinical analysis of ten cases of HIV infection combined with acute leukemia
  28. Investigating the cardioprotective potential of quercetin against tacrolimus-induced cardiotoxicity in Wistar rats: A mechanistic insights
  29. Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis
  30. Diagnostic value of ratio of blood inflammation to coagulation markers in periprosthetic joint infection
  31. Sex-specific associations of sex hormone binding globulin and risk of bladder cancer
  32. Core muscle strength and stability-oriented breathing training reduces inter-recti distance in postpartum women
  33. The ERAS nursing care strategy for patients undergoing transsphenoidal endoscopic pituitary tumor resection: A randomized blinded controlled trial
  34. The serum IL-17A levels in patients with traumatic bowel rupture post-surgery and its predictive value for patient prognosis
  35. Impact of Kolb’s experiential learning theory-based nursing on caregiver burden and psychological state of caregivers of dementia patients
  36. Analysis of serum NLR combined with intraoperative margin condition to predict the prognosis of cervical HSIL patients undergoing LEEP surgery
  37. Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
  38. The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
  39. Tetrahydropalmatine improves mitochondrial function in vascular smooth muscle cells of atherosclerosis in vitro by inhibiting Ras homolog gene family A/Rho-associated protein kinase-1 signaling pathway
  40. A cross-sectional study: Relationship between serum oxidative stress levels and arteriovenous fistula maturation in maintenance dialysis patients
  41. A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
  42. Identifying early screening factors for depression in middle-aged and older adults: A cohort study
  43. Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
  44. Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
  45. High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
  46. RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
  47. Impact of peripheral conditioning on reperfusion injury following primary percutaneous coronary intervention in diabetic and non-diabetic STEMI patients
  48. Clinical efficacy of azacitidine in the treatment of middle- and high-risk myelodysplastic syndrome in middle-aged and elderly patients: A retrospective study
  49. The effect of ambulatory blood pressure load on mitral regurgitation in continuous ambulatory peritoneal dialysis patients
  50. Expression and clinical significance of ITGA3 in breast cancer
  51. Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy
  52. rSIG combined with NLR in the prognostic assessment of patients with multiple injuries
  53. Toxic metals and metalloids in collagen supplements of fish and jellyfish origin: Risk assessment for daily intake
  54. Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study
  55. Gender beliefs and legitimization of dating violence in adolescents
  56. Effect of serum IL-6, CRP, and MMP-9 levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal hernia
  57. Effect of smoking and smoking cessation on hematological parameters in polycythemic patients
  58. Pathogen surveillance and risk factors for pulmonary infection in patients with lung cancer: A retrospective single-center study
  59. Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway
  60. Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
  61. Cord-lamina angle and foraminal diameter as key predictors of C5 palsy after anterior cervical decompression and fusion surgery
  62. GATA1: A key biomarker for predicting the prognosis of patients with diffuse large B-cell lymphoma
  63. Influencing factors of false lumen thrombosis in type B aortic dissection: A single-center retrospective study
  64. MZB1 regulates the immune microenvironment and inhibits ovarian cancer cell migration
  65. Integrating experimental and network pharmacology to explore the pharmacological mechanisms of Dioscin against glioblastoma
  66. Trends in research on preterm birth in twin pregnancy based on bibliometrics
  67. Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma
  68. Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype
  69. Acute pancreatitis risk in the diagnosis and management of inflammatory bowel disease: A critical focus
  70. Effect of subclinical esketamine on NLRP3 and cognitive dysfunction in elderly ischemic stroke patients
  71. Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
  72. CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
  73. Efficacy of a novel drainage catheter in the treatment of CSF leak after posterior spine surgery: A retrospective cohort study
  74. Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
  75. Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
  76. Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
  77. Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
  78. Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
  79. Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
  80. The law on oncological oblivion in the Italian and European context: How to best uphold the cancer patients’ rights to privacy and self-determination?
  81. The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
  82. Factors affecting the measurements of peripheral oxygen saturation values in healthy young adults
  83. Comparison and correlations between findings of hysteroscopy and vaginal color Doppler ultrasonography for detection of uterine abnormalities in patients with recurrent implantation failure
  84. The effects of different types of RAGT on balance function in stroke patients with low levels of independent walking in a convalescent rehabilitation hospital
  85. Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study
  86. Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
  87. Correlation of serum calprotectin with outcome of acute cerebral infarction
  88. Comparison of computed tomography and guided bronchoscopy in the diagnosis of pulmonary nodules: A systematic review and meta-analysis
  89. Curdione protects vascular endothelial cells and atherosclerosis via the regulation of DNMT1-mediated ERBB4 promoter methylation
  90. The identification of novel missense variant in ChAT gene in a patient with gestational diabetes denotes plausible genetic association
  91. Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance
  92. Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study
  93. Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis
  94. Analysis of serum metabolomics in patients with different types of chronic heart failure
  95. Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis
  96. Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease
  97. Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19
  98. METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2
  99. The predictive significance of anti-RO-52 antibody in patients with interstitial pneumonia after treatment of malignant tumors
  100. Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian randomization
  101. Development and validation of potential molecular subtypes and signatures of ocular sarcoidosis based on autophagy-related gene analysis
  102. Widespread venous thrombosis: Unveiling a complex case of Behçet’s disease with a literature perspective
  103. Uterine fibroid embolization: An analysis of clinical outcomes and impact on patients’ quality of life
  104. Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head
  105. Serum-derived exomiR-188-3p is a promising novel biomarker for early-stage ovarian cancer
  106. Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
  107. Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
  108. Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
  109. Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
  110. Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
  111. HALP score in Demodex blepharitis: A case–control study
  112. Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
  113. Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
  114. Comparison of the two intestinal anastomosis methods in pediatric patients
  115. Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
  116. Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
  117. Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
  118. Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
  119. Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
  120. Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
  122. Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
  124. Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Influence of sevoflurane combined with propofol anesthesia on the anesthesia effect and adverse reactions in children with acute appendicitis
  157. Review Articles
  158. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  159. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  160. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  161. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  162. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  163. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  164. The application of augmented reality in robotic general surgery: A mini-review
  165. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  166. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  167. Plant polyphenols, terpenes, and terpenoids in oral health
  168. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  169. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  170. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  171. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  172. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  173. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  174. Giant borderline ovarian tumours – review of the literature
  175. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  176. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  177. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  178. Supplement strategies for infertility in overweight women: Evidence and legal insights
  179. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  180. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  181. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  182. Strategies for hyperkalemia management in dialysis patients: A systematic review
  183. C-reactive protein-to-albumin ratio in peripheral artery disease
  184. Case Reports
  185. Delayed graft function after renal transplantation
  186. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  187. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  188. Giant right atrial hemangioma presenting with ascites: A case report
  189. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  190. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  191. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  192. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  193. Rapid Communication
  194. Biological properties of valve materials using RGD and EC
  195. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  196. Letter to the Editor
  197. Role of enhanced external counterpulsation in long COVID
  198. Expression of Concern
  199. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  200. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  201. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  202. Corrigendum
  203. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  204. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  205. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  206. Retraction
  207. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  208. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  209. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  210. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  211. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  212. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  213. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  214. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  215. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  216. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  217. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  218. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  219. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  220. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  221. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  222. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  223. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  224. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  225. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  226. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  227. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  228. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  229. A review of brain research on T2DM-related cognitive dysfunction
  230. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  231. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  232. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
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