Annals of clinical and laboratory science最新文献

Objective: The screening and monitoring of lung adenocarcinoma (LUAD) is critical for its therapeutic efficiency. This study explored a novel biomarker of LUAD from the GSE146689 dataset and evaluated its function aiming to provide a potential therapeutic target for LUAD.

Methods: There were 126 LUAD patients, 75 benign lung disease patients, and 57 healthy individuals enrolled in this study. circ_0001681 levels were evaluated by PCR, and its significance in the diagnosis and prognosis of LUAD was assessed by ROC and Cox regression analysis. The effect of circ_0001681 on LUAD cells was investigated by CCK8 and transwell assays.

Results: Reduced circ_0001681 was observed in LUAD patients relative to benign lung disease patients and healthy individuals, which could discriminate LUAD patients. circ_0001681 downregulation was closely associated with the severity and malignancy of LUAD patients, and it also indicated the adverse prognosis of LUAD. In mechanism, circ_0001681 could negatively regulate miR-567, which was found to mediate the inhibitory effect of circ_0001681 on LUAD cell proliferation and motility.

Conclusion: Decreased circ_0001681 in LUAD served as a biomarker in tumor occurrence and development, which can be included in the formulation and adjustment of LUAD therapeutic strategy.

Objective: Recently, there has been much interest in quinazoline derivatives due to their unique anti-tumor effects. In this study, we aimed to investigate the effects of KZL204, an active trifluoromethylated quinazoline derivative, on a human glioblastoma multiforme (GBM) cell line U251MG. Additionally, we tried to identify the potential target of KZL204 for treating GBM.

Methods: Cell counting kit-8 (CCK-8) assay for cytotoxicity, 5-ethynyl-2-deoxyuridine (EdU) staining for cell proliferation, flow cytometry for cell apoptosis and cell cycle, wound scratch test for cell migration, and transwell assay for cell invasion were carried out on U251MG cells after exposing them to different concentrations of KZL204. In addition, western blot analysis, network pharmacology-based analysis, molecular docking assay, cellular thermal shift assay (CETSA), and cycloheximide chase assay were performed.

Results: Our results showed that KZL204 concentration-dependently inhibited U251MG cell proliferation, induced apoptosis, arrested cell cycle in the G2/M phase, and inhibited cell invasion and migration capacity. Further network pharmacology-based analysis revealed that epidermal growth factor receptor (EGFR), FYN, YES1, LYN, ephrin type-A receptor 2 (EPHA2), and EPHA4 are the top 6 core targets for inhibiting cell growth, apoptosis, cell cycle, and metastasis of the GBM cells. Molecular docking and CETSA showed that KZL204 had a strong targeting binding affinity with EPHA2. Cycloheximide chase assay and western blot results demonstrated that KZL204 could down-regulate the protein level of EPHA2.

Conclusions: KZL204 exhibits potent inhibitory activity for glioblastoma multiforme cells, which may be related to its role in promoting the degradation of EPHA2.

Objective: To evaluate the diagnostic and prognostic value of the Serum Procalcitonin (PCT) to Albumin (ALB) ratio in sepsis-associated ARDS patients.

Methods: We conducted a retrospective study including 349 septic patients (159 and 190 with and without ARDS, respectively). The serum PCT/ALB ratio was measured at admission, and participants' 28-day mortality and Sequential Organ Failure Assessment (SOFA) scores were compared.

Results: Compared to patients without sepsis-associated ARDS, sepsis-associated ARDS patients had a higher PCT/ALB ratio (P<0.001). Among sepsis-associated ARDS patients, non-survivors had a significantly higher PCT/ALB ratio than survivors (P<0.05). The AUC of the PCT/ALB ratio associated with the 28-day mortality in sepsis-associated ARDS patients on admission day was 0.62 (95% CI [0.54-0.69], P<0.001). In assessing the 28-day mortality in sepsis-associated ARDS patients, the AUC of the PCT/ALB ratio in combination with the oxygenation index and SOFA score rose from 0.62 to 0.78 (95% CI: 0.70-0.84; P<0.001). Moreover, survival analysis revealed that sepsis-associated ARDS patients with a higher PCT/ALB ratio (≥2.03 μg/g) had a significantly poorer prognosis than those with a low ratio (<2.03 μg/g).

Conclusions: The PCT/ALB ratio is a potential biomarker for the diagnosis and prognosis of sepsis-associated ARDS patients.

Objective: Estrogen may have a certain role in promoting lung cancer caused by tobacco. Our understanding of the carcinogenic effects and mechanisms of carcinogen mixture estrogen is limited and mostly relies on the findings from studying individual factors.

Methods: To test this hypothesis, an in-vitro study was used to investigate the effects of 17 β-estradiol (E₂) on benzo[a]pyrene (Bap)-induced lung cancer cell A549 proliferation.

Results: We first found that E₂ was increased in serum samples from lung adenocarcinoma cancer (LUAD) patients, even to a small extent. We found that Bap could enhance colony formation ability, up-regulate proliferating cell nuclear antigen (PCNA) and B-cell lymphoma-2 (Bcl-2) expression, induce cell proliferation and inhibit apoptosis in A549 cells. E₂ promoted these effects of Bap. Moreover, E2 and Bap co-exposure promoted lung cancer cell proliferation by activating the aryl hydrocarbon receptor (AHR)/protein kinase B (AKT)/extracellular regulated protein kinases (ERK1/2) signaling pathway. Inhibition of the AKT and ERK1/2 signaling pathways suppressed E₂ and Bap co-exposure's effect on A549 cells proliferation and apoptosis.

Conclusions: Collectively, we conclude that E₂ could promote the proliferative and antiapoptotic effects of Bap on A549 cells, and activation of the AHR/AKT/ERK1/2 pathway may be involved in this process.

Objective: Osteosarcoma is the most common malignant bone cancer and is typically associated with poor prognosis. Histone deacetylase 8 (HDAC8) presents as an effective target in anti-tumor treatment in various tumors. As the functions of HDAC8 in osteosarcoma have not been studied thoroughly, our study aims to explore the effects of HDAC8 in osteosarcoma proliferation.

Methods: HDAC8 expression was analyzed in The Cancer Genome Atlas (TCGA)-pan-cancer dataset. The expression of HDAC8 in osteosarcoma cell lines was detected by western blot. TM-2-51, an activator of HDAC8, was taken to promote HDAC8 expression in osteosarcoma cells. Cell Counting Kit-8 (CCK-8) assay was applied to analyze cell viability changes and colony formation while 5-ethynyl-29-deoxyuridine (EdU) assays were used to evaluate cell proliferation. The migration and invasion abilities were analyzed by transwell assay, the distributions of cell cycle were analyzed by flow cytometry, and xenograft models were used to study the effect of HDAC8 activation in vivo. Furthermore, the mechanism underlying HDAC8's influence in osteosarcoma was analyzed by western blot assay.

Results: Our study demonstrated that activation of HDAC8 in osteosarcoma cells can suppress cell viability, proliferation, migration, invasion, and arrest cell cycle of the osteosarcoma cells via TP53 and STAT3/ERK signaling pathway. Xenograft models confirmed that HDAC8 activation can reduce tumor growth in vivo.

Conclusion: The activation of HDCA8 could contribute negatively to osteosarcoma proliferation, and HDAC8 may represent a valuable therapeutic target in osteosarcoma therapy.

Objective: The current study aimed to investigate the correlation between HPV16/18 infection and the microecological characteristics of the female reproductive tract and cervical lesions and to explore the risk factors associated with cervical precancerous lesions (CIN) and cervical cancer (CC).

Methods: A total of 326 women were selected for HPV screening, with 121 testing negative for HPV, 113 infected with HPV16/18, and 92 infected with other types of HPV. Microecological characteristics of the vaginal flora in all subjects were analyzed. Liquid-based thin layer cell (TCT) tests, genitourinary tract infection pathogen (STDs) assessments, HPV typing, and colposcopic pathological biopsies of exfoliated cervical cells were conducted.

Results: Among patients with HPV infection, there was a higher detection rate of abnormal microecological indicators such as bacterial vaginosis (BV) and vaginal cleanliness. Additionally, an increased proportion of vaginal microbiota (VM) imbalance was observed. Ureaplasma urealyticum (Uu) infection in the reproductive tract was closely associated with HPV 16/18 infection and showed co-infection. Moreover, patients with BV infection and high expression of HPV mRNA were at a higher risk of persistent HPV16/18 positive infection. BV infection, Uu infection, and HPV16/18 positive infection were identified as risk factors for CIN and CC. Furthermore, BV and Uu infections promoted the development of CIN/CC in patients infected with HPV16/18.

Conclusions: Changes in vaginal microecology are strongly linked to HPV16/18 infection. BV infection, Uu infection, HPV viral load, and HPV16/18 infection are risk factors for CIN/CC. Timely treatment of BV and Uu infections, restoration of a normal vaginal microecological environment, and improvement of HPV16/18 outcomes can delay the occurrence and progression of CIN/CC.

Invasive fungal infections remain a devastating and potentially deadly complication in the setting of immunocompromised patients, such as in the setting of cancer, transplants, and other immune deficiencies. Infection with dematiaceous molds remains a less common but clear and present etiology. We present here a patient with relapsed acute myeloid leukemia who was neutropenic for a prolonged period. Symptoms worsened during the hospital course, including left-sided sinus swelling, which was also noted on imaging. ENT performed a bedside endoscopy and biopsied an eschar forming in the left nasal cavity. This was ultimately found to be acute invasive rhinosinusitis due to infection with the mold Exserohilum rostratum The patient was started on Posaconazole and Amphotericin B. He eventually also underwent surgical debridement. Infections with this organism are very uncommon, as noted in our literature search. In the diagnostic methods employed in this case, we utilized pathology, culture and microscopy, as well as mass spectrometry which was used to confirm the diagnosis.

Objective: Coagulopathy is a common complication in patients with decompensated cirrhotic portal hypertension (DCPH), presenting a significant clinical challenge. Nonetheless, there is limited understanding of the coagulation profile of portal venous blood in DCPH patients. The objective of this study was to evaluate the coagulation characteristics of portal venous blood in DCPH patients by collecting blood samples through a transjugular intrahepatic portosystemic shunt (TIPS).

Methods: A total of 48 DCPH patients were enrolled to measure the activities of pro- and anticoagulant factors in both portal and peripheral venous blood. A correlation analysis between the activities of coagulation factors and the Child-Pugh scores and classes was performed.

Results: Collecting portal venous blood via TIPS achieved a 100% success rate. In portal venous blood, all pro- and anticoagulant factors tested exhibited lower activities. The activity of protein C (PC) was negatively correlated with the Child-Pugh scores, and the activities of FII, FVII, and PC were negatively correlated with the Child-Pugh classes.

Conclusions: The collection of portal venous blood via TIPS is a safe and feasible method for studying coagulation characteristics in DCPH patients. The parallel reduction of both pro- and anticoagulant factors in DCPH patients results in a rebalanced but fragile coagulation system, which may lead to portal vein hemorrhage and thrombosis. Furthermore, as the Child-Pugh scores or classes increase, the situation will probably get worse due to FII, FVII, and PC deficiencies.

Coffin-Siris syndrome (CSS) is a rare congenital disorder characterized by coarse facial features, intellectual disability or developmental delay, and aplasia or hypoplasia of the tips of the fifth finger and/or toes. Mutations in genes affecting the switch/sucrose non-fermenting ATP-dependent chromatin remodeling complex are reported to cause CSS. Here, we describe three CSS patients. Two girls aged 3 and 2 years old presented with global developmental delay, poor growth, and a dysmorphic face. Whole-exome sequencing (WES) was performed and they were diagnosed with CSS due to heterozygous frameshift variants (c.3443_3444del, p.Lys1148ArgfsTer9 and c.2869_2890del, p.Pro957CysfsTer20) in ARID1B A 2-year-old girl presented with gross motor delay and dysmorphic face. She was diagnosed with CSS due to a novel heterozygous frameshift variant (c.4942_4943del: p.Gln1648GlyfsTer8) in ARID2.

Objective: Chronic infection of the hepatitis B virus (HBV) is associated with the dysfunction and exhaustion of CD8+ T cells, which are crucial in controlling HBV. While clinical parameters provide insight into the state of HBV infection, the relationship between HBV biochemical parameters and CD8+ T cell exhaustion remains poorly understood. This study aimed to evaluate the expression of activation, exhaustion, and function-related markers in CD8+ T cells of HBV carriers, and to determine the potential of HBV clinical parameters as biomarkers for CD8+ T cell exhaustion.

Methods: We enrolled 93 patients with HBV and measured the expression levels of CD160, T cell Ig and mucin-domain containing-3 (Tim-3), programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), CD28, CD137, granzyme B, and perforin in CD8+ T cells using flow cytometry. HBV clinical parameters including, HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, HBV DNA load, ALT, AST, ABil, and ALB, were measured in the blood samples.

Results: Patients were divided into two groups, HBV DNA+, and HBV DNA-, based on whether their HBV DNA load was below the test baseline; ALT, AST, and CD160+CD8+ T cell percentages were significantly higher in the HBV DNA+ group than in the HBV DNA- group (P=0.0323; P=0.0072; P=0.0458). However, the granzyme B-expressing CD8+ T cell percentage in the HBV DNA-group was higher than the HBV DNA+ group (P=0.0497). In the HBV DNA+ group, CD160, Tim-3, CD28, and perforin were significantly correlated with ALT, granzyme B was significantly correlated with AST; however, there was no correlation with HBV DNA load.

Conclusion: It is possible to infer the level of CD8+ T cell exhaustion in patients with an HBV DNA load >10² copies/mL based on clinical parameters (such as ALT, AST, and ABIL).