Experimental and Therapeutic Medicine

Magnolol acts as a neurorestorative agent in an A‑induced mouse model of Alzheimer's disease
Yu Q, Shi Y, Wu Y, Liu R, Zhang H, Wu L and Ding M
Magnolol may have the potential to alleviate the progression of Alzheimer's disease (AD). The present study was conducted to investigate the broader mechanism of action of magnolol in AD pathogenesis. C57BL/6 mice were randomly divided into five groups (n=6 mice/group): i) Control; ii) AD model; iii) 5 mg/kg magnolol + AD model; iv) 10 mg/kg magnolol + AD model; and v) 20 mg/kg magnolol + AD model. A total of 7 days after modeling, the treatment groups were administered different doses of magnolol (5, 10 and 20 mg/kg) by gavage every day, and a Morris water maze test was conducted after 2 months of treatment. The impacts of magnolol on amyloid β (Aβ) plaque deposition and neuroinflammation were assessed using Congo red and immunofluorescence staining. Immunofluorescence staining results were supplemented with western blotting and reverse transcription-quantitative PCR to ascertain the role of magnolol in other pivotal pathological mechanisms, including the formation of intracellular neurofibrillary tangles, compromised synaptic plasticity, and astrocyte and microglia activation. Administration of magnolol effectively mitigated cognitive impairment, reduced Aβ plaque deposition and inhibited neuroinflammation in Aβ-induced mice. Moreover, hippocampal levels of tau, phosphorylated (p-)tau, glycogen synthase kinase 3β (GSK3β), p-GSK3β, synaptophysin, brain-derived neurotrophic factor, glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 revealed that magnolol also limited neurofibrillary tangle formation, repaired synaptic plasticity, and inhibited astrocyte and microglia activation. In conclusion, the present findings broaden the current understanding of the mechanisms explaining the neuroprotective effects of magnolol against AD progression. Notably, it may inhibit multiple manifestations of AD, including plaques and neuroinflammation, while also exhibiting the capacity to restore AD-related neurological damage.
Effectiveness of a single burr hole as a surgical technique for the management of chronic subdural hematoma: A clinical case series study
Fotakopoulos G, Gatos C, Georgakopoulou VE, Spandidos DA, Trakas N, Sklapani P and Fountas KN
Chronic subdural haematoma (chSDH) commonly affects the elderly population, and a number of factors are related to its recurrence. As regards the procedure, the percentage of its involvement in the chSDH recurrence must be clarified. Thus, the present study aimed to investigate the factors related to chSDH recurrence and to determine the efficacy and contribution of the single burr hole technique in preventing hematoma recurrence. The present study represents a single-center, retrospective study of chSDH cases who underwent surgical evacuation via single burr hole technique. Statistical analyses were executed using the Statistical Package for the Social Sciences. The Shapiro-Wilk test was used for the evaluation of the normality of the distribution of variables. Fisher's exact test was used for the categorical variables, and continuous data were evaluated with the Mann-Whitney U test. In total, 166 patients were divided into two groups: Group A (154 patients, 92.8%) without hematoma recurrence, and Group B (12 patients, 7.2%) with hematoma recurrence. All patients were re-operated on, only when they had clinical and radiological deterioration. In the present study, the hematoma recurrence rate using single burr hole surgery for chSDH evacuation was 7.2%, and was relatively small compared with other procedures reported in the literature. Overall, the patients who underwent single burr hole surgery for chSDH evacuation had an increased risk of hematoma recurrence, when this was in combination with anticoagulant use, history of a brain stroke event, and mixed hematoma density observed in CT scans. Notably, in the case of recurrence, the potential interval for recurrence was 16 days following the initial surgical evacuation of the hematoma.
Effective local control of a giant calvarial hemangioma in a child by proton beam therapy: A case report and literature review
Shen Z, Mizumoto M, Oshiro Y, Jin Y, Wang J, Zhang S, Liu C, Wang Z, Wang W, Li Y, Wang W, Zhao J and Shimizu Xiangxing SQ
Intraosseous hemangiomas are rare, benign tumors, predominantly affecting the vertebrae, calvarium and other bones. These lesions, although slow progressing, can lead to complications such as visual disturbances and structural deformities. Standard management includes surgical interventions and more recently, advanced radiation therapies such as proton beam therapy (PBT) have been explored due to their precision and minimized damage to surrounding tissues. The current study presents a compelling case of a 10-year-old female patent diagnosed with a giant calvarial hemangioma located at the cranio-orbital junction. Although it was initially managed with surgery and chemotherapy, the tumor recurred. Given the recurrence and proximity to critical structures, PBT was employed. The treatment was administered over 28 fractions, with a total dose of 50.4 Gy. The patient exhibited good tolerance to the treatment, experiencing only minor acute side effects such as hair loss and skin pigmentation. At 14 months post-PBT, a marked reduction in tumor size was revealed with no further progression, indicating effective local control of the hemangioma. In addition, the side effects had improved markedly, highlighting the long-term benefits and efficacy of PBT in managing this challenging case. This is the first case in which PBT has been used to manage a calvarial hemangioma in children to the best of the authors' knowledge. The current case highlights the potential of PBT in treating complex intraosseous hemangiomas where conventional therapies are ineffective. Further research into long-term outcomes is necessary to establish PBT as a crucial approach for similar cases.
m1A regulator‑mediated methylation modifications and gene signatures and their prognostic value in multiple myeloma
Fu J, Han X, Gao W, Yu M and Cui X
N-methyladenosine (m1A), a methylation of RNA, is gaining attention for its role in diverse biological processes. However, the potential roles of m1A regulatory-mediated methylation modifications in multiple myeloma (MM) remain unclear. The mRNA expression of m1A regulators in normal plasma (NP; n=9) and MM (n=174) bone marrow plasma cells was investigated and the m1A modification patterns of 559 MM samples based on the expression of 10 m1A-related regulatory genes were comprehensively evaluated. Univariate Cox regression, Kaplan-Meier survival curve, unsupervised clustering and gene enrichment analyses were used to explore the associations between m1A-related regulatory genes and MM patient survival/prognosis. The m1A score model was subsequently constructed to quantify the m1A modification patterns of individual tumours, and its predictive performance was further assessed via receiver operating characteristic curves. Immunohistochemistry, Cell Counting Kit-8, flow cytometry and m1A dot blot assays were performed to investigate the potential role of YTH domain-containing family protein 2 (YTHDF2) in MM. Moreover, bioinformatics analysis was performed to predict the potential downstream regulatory mechanism of YTHDF2. In total, seven differentially expressed genes [tRNA methyltransferase 61A/B (TRMT61A/B), YTH N-methyladenosine RNA binding protein (YTHD)F1/F2/F3/C1 and Alkb homolog 1, histone H2A dioxygenase (ALKBH1)] were identified in MM samples compared with those in NP samples. The forest map and Kaplan-Meier curve revealed that the expression of m1A-related regulatory genes could be favourable prognostic factors for patients with MM. A total of three distinct m1A modification patterns were determined, and Cluster B exhibited the worst outcome, which was accompanied by increased expression of YTHDF2, tRNA methyltransferase 6 non-catalytic subunit (TRMT6), tRNA methyltransferase 10 homolog C (TRMT10C) and TRMT61B. The m1Ascore model was subsequently constructed. A high m1A score was associated with clinical benefit and an improved treatment response. High expression of the reader protein YTHDF2 was associated with poor survival in patients with MM and was superior to other assessed proteins in terms of prognosis. Subsequent cell experiments demonstrated that YTHDF2 promoted the proliferation and inhibited the apoptosis of U266 cells. Notably, an evident increase in the m1A level was observed when YTHDF2 was overexpressed. A total of 150 genes related to YTHDF2 were identified, and these genes were enriched in the peroxisome proliferator-activated receptor signalling pathway, protein export, positive regulation of protein targeting to the membrane, and gamma-delta intraepithelial T-cell differentiation. Serine and arginine rich splicing factor 10 (SRSF10) was subsequently selected because SRSF10 expression was significantly positively correlated with YTHDF2 expression and was also associated with poor prognosis in patients with MM. The present study revealed the modification patterns and high prognostic value of m1A regulators and demonstrated that the reader protein YTHDF2 is a potentially crucial target for MM.
MicroRNA‑4327 regulates TGF‑β1 stimulation of matrix metalloproteinase‑13 expression via CREB‑binding protein‑mediated Runx2 acetylation in human osteoblasts
Kolipaka R, Magesh I, Karthik S, Ashok Bharathy MR, Saranya I, Preetha D and Selvamurugan N
Transforming growth factor beta 1 (TGF-β1), a multifunctional cytokine, induces the expression of bone remodeling gene matrix metalloproteinase-13 (MMP-13). CREB-binding protein (CBP), a co-activator and runt-related transcription factor 2 (Runx2), a bone transcription factor, play critical roles in regulating bone-remodeling genes. Recent advances in non-coding RNAs have revealed the significance of microRNAs (miRNAs) and their target genes in bone physiology. The present study hypothesized that TGF-β1 stimulated MMP-13 expression by downregulating CBP-targeting miRNAs and activating CBP-mediated Runx2 acetylation in human osteoblastic cells. TGF-β1-downregulated miRNAs that potentially target CBP were identified. Among these miRNAs, TGF-β1 significantly downregulated miR-4327 in these cells. TGF-β1 stimulated CBP, acetylated Runx2 and MMP-13 protein expression levels in human osteoblastic cells and this effect was decreased by overexpressing miR-4327 in these cells. In human osteoblastic cells, miR-4327 was found to directly bind to the 3'-untranslated region of CBP using a dual-luciferase gene reporter assay. Thus, the present study indicated that the TGF-β1/miR-4327/CBP/Runx2 plays a key role in MMP-13 expression, suggesting the clinical relevance of this axis for treating bone-related disorders.
Diagnosis of acute Q fever using targeted next‑generation sequencing: A case report
Jiang Z, Yan Z, Yang Y, Tian Y, Zhao X, Liu X, Bai Y, Zhang L, Yang J, Ma R, Geng Y, He L and Wang Y
Acute Q fever, caused by , is a zoonotic infection presenting with non-specific symptoms such as high fever, severe headache and myalgia, making it challenging to diagnose. Traditional diagnostic methods often fall short due to their time-consuming nature and limited sensitivity. A 26-year-old male presented with severe headache, persistent high fever and nausea following a hiking trip. Initial tests, including serology and PCR, were inconclusive. Targeted next-generation sequencing (tNGS) identified within 24 h, leading to a prompt diagnosis of acute Q fever. This rapid identification facilitated the initiation of appropriate antibiotic therapy, resulting in significant clinical improvement. This case underscores the diagnostic utility of tNGS in rapidly identifying rare pathogens and highlights its potential to influence clinical decision-making and improve patient outcomes. This case highlights the effectiveness of tNGS in diagnosing acute Q fever, particularly in regions where the disease is uncommon. The use of tNGS facilitated rapid identification and treatment, underscoring its potential as a valuable diagnostic tool in clinical practice.
[Retracted] MicroRNA‑195‑5p inhibits the progression of hemangioma via targeting SKI
Sun B, Huang Z, Yang H and Zhao X
[This retracts the article DOI: 10.3892/etm.2021.11088.].
Unveiling the depths of pelvic organ prolapse: From risk factors to therapeutic methods (Review)
Gao J, Li Y, Hou J and Wang Y
Pelvic organ prolapse (POP) is a condition where one or more pelvic organs (such as the uterus, bladder and rectum) descend from their normal anatomical positions into the vagina, primarily due to the weakening of the pelvic floor support structures. While not life-threatening, POP can substantially diminish the patient's quality of life and lead to serious social and psychological complications. Researchers have explored novel directions regarding the etiology, mechanism and treatment of POP. However, existing literature on the subject often lacks comprehensive and systematic overviews. To address this gap and enhance researchers' understanding of POP, the present study reviewed the risk factors and molecular mechanisms of POP [including matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs, transforming growth factor β, advanced glycation end products (AGEs)/receptor for AGE, phosphoinositide 3-kinase/protein kinase B, fibulin, lysyl oxidase-like 1, homeobox A11, collagen α-1 (XVIII) chain, Wnt signaling pathways and estrogen receptor α], as well as therapeutic approaches, such as lifestyle interventions, physical methods, pharmacotherapy, stem cell transplantation and surgical techniques. The present review aims to provide new insights for future research and contribute to the advancement of diagnosis and treatment strategies for POP.
Acute superior mesenteric artery embolism: A case report
Wang Y and Du P
The incidence rate of superior mesenteric artery embolism (SMAE) is low and its mortality rate is high due to its rapid onset and progression. Due to its clinical manifestations being similar to other acute abdominal diseases, such as gastrointestinal perforation, acute appendicitis and acute pancreatitis, its misdiagnosis rate can reach 75-90%. Reducing the mortality rate of this disease is dependent upon an early diagnosis and timely surgical intervention. In the present case report, the diagnosis and treatment process of a female patient aged 83 years with SMAE were reported. The patient recovered well following timely and effective intervention. The patient was admitted due to acute abdominal pain, and computed tomography angiography (CTA) examination showed filling defect in the superior mesenteric artery (SMA). The patient was diagnosed with SMAE and underwent emergency surgical treatment for a thrombectomy and thrombolysis of the SMA under general anesthesia. After surgery, recanalization of the SMA was achieved. The patient was followed up six months later, and SMA CTA revealed that the main trunk and branches of the SMA were well visualized. In addition, relevant literature was reviewed to improve the understanding and treatment of SMAE among clinicians. If patients experience severe abdominal pain that cannot be relieved by antispasmodic drugs, SMAE should be suspected. Patients with history of atrial fibrillation, valvular heart disease and atherosclerosis need further examination. At present, there is a lack of highly sensitive and specific serological indicators. CTA can provide a diagnosis with high sensitivity and specificity.
Superficial mucoceles as a sequel to Stevens‑Johnson syndrome during treatment of cutaneous squamous cell carcinoma with cemiplimab: A case report and review of literature
Chwiałkowska V, Słowińska M, Płatkowska A, Kania J, Parciak K, Czarnecka A, Teterycz P and Owczarek W
Superficial mucoceles (SM) are small, benign, translucent vesicles, which develop in the oral mucosa, mainly on the lower lip, due to a rupture of minor salivary gland ducts and the extravasation of saliva. The use of immune checkpoint blockade treatment may lead to dermatologic immune-related adverse events in 40-50% of patients and with severe dermatologic immune adverse events of Common Terminology Criteria for Adverse Events of grade G3-G4 in 1-2% of patients. The present study described the case of a patient with squamous cell carcinoma treated with cemiplimab with the adverse effect of Stevens-Johnson syndrome. The patient developed multiple SM, which made it challenging for the patient to speak and eat. Ablative treatment using a plasma device (Plasma IQ) and electrocoagulation were used to remove all lesions, which achieved a precise and timely therapeutic effect without any remainder of scarring. Through the publication of the present case report and literature review, the present article aimed to enhance the understanding of this condition, providing valuable diagnostic and therapeutic information about the spectrum of mucosal involvement among drug-related toxicities of current oncological treatment.
[Retracted] SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF‑κB pathway
Gong S, Xiong L, Luo Z, Yin Q, Huang M, Zhou Y and Li J
[This retracts the article DOI: 10.3892/etm.2022.11430.].
Development and validation of a nomogram for predicting bacterial infections in patients with acute exacerbation of chronic obstructive pulmonary disease
Wang X, Yuan W, Zhong D and Chen X
Bacterial infection is a significant contributory factor in the pathogenesis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and it has a pivotal role in exacerbating symptoms and precipitating mortality among patients with chronic obstructive pulmonary disease (COPD). The early identification of bacterial infection in individuals with COPD remains a challenge. Therefore, the present study aimed to create and validate a risk assessment tool using easily accessible serum biomarkers to predict bacterial infection in individuals with AECOPD. A retrospective cohort study was carried out at Pingxiang People's Hospital (Pingxiang, China) from January 2023 to December 2023, involving individuals diagnosed with AECOPD. A total of 544 patients with AECOPD were randomly allocated to the two following groups: The training set, which included 70% (n=384) of the patients, and the validation set, which included 30% (n=160) of the patients. Subsequently, a nomogram model was constructed using multivariate logistic regression analysis in the training set. Its discriminatory ability and calibration were internally validated, while decision curve analyses were employed to assess the clinical utility of the nomogram. The incidence of bacterial infection in hospitalized patients with AECOPD was 50% in the training set and 48.1% in the validation set. The nomogram model incorporated independent factors associated with bacterial infection, including C-reactive protein, neutrophil elastase, procalcitonin and eosinophils, identified by univariate and multivariate logistic regression analyses. The area under the curve of the nomogram model was 0.835 [95% confidence interval (CI): 0.795-0.875] in the training set and 0.785 (95% CI: 0.715-0.856) in the validation set. The model demonstrated excellent discrimination and calibration in the validation set [c-statistic: 0.79 (95% CI: 0.68-0.90)]. Furthermore, the discrimination and overfitting bias of the model were assessed through internal validation, revealing a C-index of 0.836 for the initial group and 0.788 for the subsequent validation set. The straightforward risk prediction model for early identification of bacterial infections is valuable for hospitalized patients with AECOPD.
Fine particulate matter‑induced cardiac developmental toxicity (Review)
Meng X, Du W and Sun Z
Fine particulate matter (PM) has become an important risk factor threatening human health. Epidemiological and toxicological investigations have revealed that PM not only leads to cardiovascular dysfunction, but it also gives rise to various adverse health effects on the human body, such as cardiovascular and cerebrovascular diseases, cancers, neurodevelopmental disorders, depression and autism. PM is able to penetrate both respiratory and placental barriers, thereby resulting in negative effects on fetal development. A large body of epidemiological evidences has suggested that gestational exposure to PM increases the incidence of congenital diseases in offspring, including congenital heart defects. In addition, animal model studies have revealed that gestational exposure to PM can disrupt normal heart development in offspring, although the potential molecular mechanisms have yet to be fully elucidated. The aim of the present review was to provide a brief overview of what is currently known regarding the molecular mechanisms underlying cardiac developmental toxicity in offspring induced by gestational exposure to PM.
[Retracted] TFAP4 promotes the growth of prostate cancer cells by upregulating FOXK1
Gu Y, Jiang J and Liang C
[This retracts the article DOI: 10.3892/etm.2021.10734.].
Clinical characteristics of patients with maintenance hemodialysis affected by COVID‑19: A single‑center retrospective study
Zhang G, Ma D, Li B, Bao L, Luo H, Cao S and Zheng Y
The coronavirus disease 2019 (COVID-19) is spreading continuously worldwide. Maintenance hemodialysis (MHD) patients are a particular group at higher risk of contracting COVID-19. The aim of the present study was to investigate the various risk factors that contribute to the occurrence of co-infection with COVID-19 among patients with MHD. A retrospective analysis was conducted on 171 patients with MHD. The characteristics and outcomes were examined among patients with MHD who were infected with COVID-19 and those who were not. Moreover, risk factors associated with survival or mortality among the COVID-19-infected patients with MHD were analyzed. The results of the present study revealed that the mean level of 25-hydroxyvitamin D [25(OH)D] in patients with MHD was 22.3±11.28 ng/ml. However, there was no significant difference in the levels of 25(OH)D between patients with MHD with and without COVID-19. Logistic regression analysis revealed that decreased levels of intact parathyroid hormone (iPTH) and increased levels of serum ferritin were associated with an increased risk of COVID-19 in these patients. Additionally, the levels of 25(OH)D and albumin were decreased in the deceased patients. Similarly, logistic regression analysis was performed to identify risk factors for mortality in patients with MHD with COVID-19, which revealed that decreased levels of 25(OH)D were associated with an increased risk of mortality in these patients. The results of the present study indicated that iPTH and serum ferritin levels could potentially increase the risk of COVID-19 among patients with MHD. Additionally, 25(OH)D levels may influence the mortality rate among patients with MHD who have been infected with COVID-19.
Potential role of G protein‑coupled receptor 124 in cardiovascular and cerebrovascular disease (Review)
Lin WY, Dong YL, Lin Y, Sunchuri D and Guo ZL
G protein-coupled receptor 124 (GPR124) has a key role in regulating the proliferation and differentiation of endothelial cells, activating inflammatory bodies and promoting angiogenesis and other processes, thus affecting various pathological and physiological processes in the body. GPR124 is vital for promoting the development of the nervous system and maintaining the stability of the blood-brain barrier, and is also associated with cardiovascular and cerebrovascular diseases and cancer. This article will elaborate on the biological information regarding GPR124 published in recent years and its possible related signaling pathways in the field of diseases and provide a reference for further revealing the role of GPR124 in the occurrence and development of diseases.
Anthrax meningoencephalitis: A case report
Zhou L, Liu K, Yang X and Chong Z
The present study describes the case of a patient with anthrax meningoencephalitis with the aim of providing a scientific basis for the control of this disease. The cerebrospinal fluid and blood of the patient were tested for genes and was detected. The patient's meningitis was cured following treatment. Tracing the route of infection, anthrax was detected on the chopping board of the rural cattle and sheep butcher shop where the patient had purchased meat. In 2018, the patient complained of intermittent nasal discharge for 11 days after brain injury and came to the Second People's Hospital of Liaocheng (Linqing, China). Considering the existence of cerebrospinal fluid rhinorrhea, the patient's cerebrospinal fluid biochemistry was assessed and showed low sugar and high protein levels, resulting in a diagnosis of bacterial encephalitis. This encephalitis was considered to be related to bacterial retrograde infection after cerebrospinal fluid rhinorrhea. It is required to strengthen the training of medical personnel according to guidelines and laws and improve the level of early detection, reporting and diagnosis, as well as timely treatment at medical institutions. There is an urgent need to intensify the education of the population regarding the awareness and prevention of the disease. For individuals involved in the breeding, slaughtering and processing of livestock, multiple measures need to be taken to comprehensively intervene and to enhance occupational protection awareness and disease prevention capabilities.
[Retracted] Toll‑like receptor 2 downregulates the cholesterol efflux by activating the nuclear factor‑κB pathway in macrophages and may be a potential therapeutic target for the prevention of atherosclerosis
Li Y, Shen S, Ding S and Wang L
[This retracts the article DOI: 10.3892/etm.2017.5404.].
Investigating a middle‑step COVID‑19 unit in Greece
Verykokou G, Papaioannou AI, Apollonatou V, Kavatha D, Boumpas D, Papiris SA, Manali ED and Loukides S
During the coronavirus disease-19 (COVID-19) pandemic, there was an unprecedented requirement for hospital bed availability. The present study aimed to examine the characteristics and outcomes of patients hospitalized in a COVID-19 unit that operated as a novel middle-step unit in Greece. The present study aimed to determine whether the middle-step unit supported the central general hospitals; thus, highlighting the potential of these models in future pandemics. During the 9-month period of operation, a total of 631 patients were admitted. In addition, 539 (85.4%) patients were discharged, 57 (9%) patients were referred to surrounding hospitals for further management and 35 (5.6%) patients succumbed. Based on the results of the present study, an algorithm for patient referral to middle-step units was outlined for future pandemics.
KL‑6, ET‑1 and S100A9 levels in patients with idiopathic pulmonary fibrosis and obstructive sleep apnea
Bouloukaki I, Michelakis S, Tsitoura E, Vasarmidi E, Koutoulaki C, Tzanakis N, Schiza S and Antoniou KM
Obstructive sleep apnea (OSA) and idiopathic pulmonary fibrosis (IPF) frequently coexist. Elevated levels of Krebs von den Lungen-6 (KL-6), endothelin-1 (ET-1) and S100 calcium-binding protein A9 (S100A9) have been observed in patients with IPF, suggesting their potential role as biomarkers for lung fibrosis. The aim of the present study was to measure the levels of KL-6, ET-1 and S100A9 in patients with IPF-OSA and to test the potential of these biomarkers as a characteristic OSA signature with diagnostic and prognostic potential for IPF. A total of 55 subjects with newly-diagnosed IPF participated in the present cross-sectional study. In addition to performing overnight attended polysomnography and pulmonary function tests, serum and bronchoalveolar lavage (BAL) levels of KL-6, along with serum levels of ET-1 and S100A9, were also assessed. A total of 15 patients with IPF and 40 patients with IPF-OSA were included. Age, sex, comorbidities and pulmonary function tests did not differ between the groups. Although there was no significant difference between groups in the levels of KL-6, ET-1 and S100A9 (P>0.05), the serum ET-1 levels tended to be elevated in patients with OSA-IPF compared with patients with IPF (1.78 vs. 1.07 pg/ml; P=0.06). Additionally, a significant association was observed between serum KL-6 levels and the severity of IPF, and also between BAL KL-6 levels and nocturnal mean SaO levels, even after taking into account factors such as obesity and smoking. S100A9 levels were associated with the oxygen desaturation index, even after adjustments for obesity, smoking and the gender-age-physiology index, only in the IPF-OSA group. Conclusively, the present findings suggested significant associations between serum ET-1, S100A9 and BAL KL-6 levels and specific OSA severity parameters in the IPF-OSA group. This evidence suggested that these molecules could serve as biomarkers for the identification of patients with IPF-OSA, offering a distinct OSA signature that has diagnostic and potential treatment value. Larger studies are crucial to substantiate the present findings and reinforce this hypothesis.
Overexpression of ELF1 combined with MMP9 is associated with prognosis and tumor microenvironment in gastric cancer
Zhang X, Ren X, Zhang S and Wang Y
Gastric cancer (GC) is a prevalent malignancy of the digestive system. E74-like factor 1 (ELF1) is a transcription factor that is specific to T cells and belongs to the Ets family. They are typically expressed in numerous tumor cells, such as pancreatic cancer, oral squamous cell, endometrial carcinoma, nasopharyngeal carcinoma and prostate and colorectal cancer, where they can promote cell invasion and migration. MMP9 is an important protease of the MMP family, since it serves a vital role in tumor progression and prognostic evaluation in colorectal cancer, uveal melanoma and clear cell renal cell carcinoma. The present study aimed to investigate the expression, correlation with MMP9 and clinical significance of ELF1 in GC. In addition, it aimed to explore the possible mechanisms. The ELF1 mRNA expression profile was first assessed using the GEPIA database and R4.2.1 software (Limma package). Reverse transcription-quantitative PCR (RT-qPCR) was used then to validate ELF1 mRNA expression levels in fresh GC samples from 40 patients. The clinical diagnostic value of ELF1 was also assessed using RT-qPCR. Tissue microarray immunohistochemistry (TMA-IHC) was utilized to examine the expression levels of ELF1 and MMP9 proteins in 355 paraffin-embedded GC samples. Subsequently, the present study further investigated the relationship between ELF1 and MMP9 and their possible effects on the clinicopathological features and prognosis of patients with GC. Gene correlation analysis was conducted using the GEPIA database and complemented with Tumor Immune Estimation Resource (TIMER) and CIBERSORT analyses to explore associations with immune infiltration. A significantly higher expression of ELF1 mRNA was found in GC tissues compared with that in adjacent normal tissues (P<0.05). High ELF1 expression in GC tumor cells was found to distinguish GC tissues from adjacent normal tissues with a sensitivity of 87.5% and specificity of 77.5%. ELF1 and MMP9 proteins also showed higher expression in 355 GC compared with adjacent normal tissues, where they were significantly positively correlated (P<0.001). The two were closely associated with various clinicopathological features, including infiltration depth, lymph node involvement, metastasis, TNM staging, microscopic venous invasion, lymphatic invasion and blood serum carcinoembryonic antigen levels in GC. Furthermore, ELF1 and MMP9 expression levels were negatively associated with the overall survival of patients with GC. Prognostic analysis using the Cox proportional hazards model identified high ELF1 expression [hazards ratio (HR), 2.555; 95% CI, 1.546-4.224; P=0.002], high MMP9 expression (HR, 3.813; 95% CI, 2.406-6.041; P<0.001), advanced TNM stage (P=0.001) and advanced N stage (P=0.011) to be independent prognostic factors for patients with GC. Correlation analysis results from the GEPIA database indicated significant associations of ELF1 expression with various GC-related genes, including MutL homolog 1, erythroblastic leukemia viral oncogene homolog 2, PI3K catalytic subunit α, and tumor suppressor protein 53, MMP-9, Cadherin 1, TIMP1, growth factor A and kinase insert domain receptor. In addition, immune infiltration correlation analysis on TIMER and CIBERSORT revealed ELF1 positive relationship with specific infiltrating immune cell types, including naive B, memory-activated CD4 and gamma delta T cells, and activated NK cells (P<0.05). This observation was further confirmed using immunohistochemistry, showing that ELF1 was associated with CD19 (B-cells) (P<0.001) and CD4 (CD4+ T cells, P=0.002). In conclusion, results from the present study suggest that ELF1 is overexpressed in GC. ELF1 combined with MMP9 can serve as a predictor of malignant biological behavior in GC and therefore a prognostic indicator for patients, due to its association with the tumor microenvironment.