Annals of clinical and laboratory science最新文献

Objective: The prevalence and the clinical significance of gastric foveolar metaplasia (GFM) of duodenal mucosa in pediatric patients are undetermined. The aim was to investigate the event of GFM in duodenal biopsies and its association with gastrointestinal tract disorders in pediatric patients.

Methods: We performed a chart review of the characteristics and pathologic findings in patients with GFM described in the pathology reports during 2020 to 2022.

Results: Sixty-five out of 3,857 patients (1.7%) had GFM observed in a total of 70/4,778 (1.5%) cases with duodenal biopsies. The ages ranged from 3 to 19 years. The duodenal bulb with GFM was identified in 65 out of 70 cases (92.9%). 17/70 (24.3%) biopsies had coexisting chronic duodenitis, and 52/70 (74.3%) had isolated GFM in duodenum. 48/70 (68.6%) cases had pathologic findings in other parts of the gastrointestinal tract, including 20 (28.6%) inflammatory bowel disease (IBD) and four (5.7%) H. pylori gastritis. Of all 4,778 cases, 136 (2.8%) and 92 (1.9%) cases were diagnosed as IBD and H. pylori gastritis, which had an odds ratio for GFM at 15.8 and 3.2 respectively (p<0.05).

Conclusion: Both H. pylori gastritis and IBD are associated with GFM in pediatric patients, while isolated GFM itself in the duodenal bulb has limited clinical implications.

Objective: Cell division cycle 42 (CDC42) modulates inflammation and multiple organ dysfunction by regulating T-cell differentiation and macrophage polarization. This research intended to explore the association of blood CDC42 expression with septic risk, multi-organ dysfunctions, and mortality.

Methods: 145 sepsis patients and 50 health controls were recruited, then CDC42 expression in peripheral blood mononuclear cell (PBMC) from them was measured by RT-qPCR.

Results: CDC42 was decreased in sepsis patients versus health controls (P<0.001); meanwhile, the receiver operating characteristic (ROC) curve showed that CDC42 had a certain value to predict sepsis risk with an area under the curve (AUC) (95% confidence interval (CI): 0.797 (0.725-0.869). Furthermore, CDC42 was negatively correlated with C-reactive protein (P<0.001), tumor necrosis factor-alpha (P<0.001) and interleukin-17A (P<0.001) but less with interleukin-6 (P=0.056). Moreover, CDC42 was negatively related to the SOFA score (P<0.001) and its several subscales (respiratory system, liver, cardiovascular, and renal system) (P<0.05). Furthermore, CDC42 was lower in septic deaths versus survivors (P<0.001); meanwhile, the ROC curve exhibited a certain ability of CDC42 in estimating 28-day mortality with an AUC (95%CI) of 0.766 (0.676-0.855).

Conclusion: Circulating CDC42 exhibits potency to be a prognostic biomarker reflecting multi-organ dysfunctions and higher mortality risk in sepsis.

Objective: To study the effect of dexmedetomidine (Dex) on myocardial injury induced by acute kidney injury (AKI) in diabetes mellitus rats and explore the potential mechanisms.

Methods: The Type 2 diabetes mellitus (T2DM) model was prepared in 40 adult male Wistar rats. These rats were randomly divided into four groups (n=10/group), including the control (Con) group, AKI group, Dex preconditioning (DPreC) group, and resveratrol (Res) combined with Dex preconditioning (Res+DPreC) group. The AKI model was prepared in the AKI, DPreC, and Res+DPreC group. The DPreC group received Dex, while the Con and AKI group received normal saline. The Res+DPreC group received Res in addition to Dex preconditioning. Histopathologic, apoptotic, enzymatic, and inflammatory changes in myocardial tissue were observed or detected.

Results: Histopathologic, apoptotic, and enzymatic changes in myocardial tissue demonstrated that AKI induced myocardial injury in T2DM rats; Dex preconditioning could mitigate this injury; and RES enhanced this effect. Inflammatory changes suggested that Dex alleviated the inflammatory response induced by AKI in T2DM rats via regulating the expressions of SIRT1, TNF-α, IL-17A, and IL-10.

Conclusions: Dex could alleviate myocardial injury induced by AKI in DM rats via regulating the inflammatory response associated with SIRT1, TNF-α, IL-17A, and IL-10, and Res could enhance this protective effect.

Objective: Finding methods that can interfere with Wnt/β-catenin signaling has become an important research direction in inhibiting colon cancer metastasis. Mesoporous silica nanoparticles can efficiently carry and release drugs. Therefore, combining ligustrazine, miR-570, and mesoporous silica nanoparticles as carriers will provide a theoretical basis for development of new therapeutic strategies and drugs.

Methods: We herein prepared mesoporous silica-loaded ligustrazine nanoparticles and used them to culture HT-29 cells; we observed biological behavior of HT-29 and explored the levels of miR-570 and Wnt2/β-catenin.

Results: Mesoporous silica nanoparticles loaded with Ligustrazine were successfully prepared. Ligustrazine inhibited metastasis of HT-29 cells. Mesoporous silica nanoparticles carrying ligustrazine increased the expression of miR-570 and reduced Wnt/β-catenin in HT-29 cells. Moreover, overexpression of miR-570 inhibited HT- 29 cancer cell metastasis and Wnt/β-catenin inhibition led to inhibition of HT-29 cell metastasis, while inhibiting miR-570 expression reversed the effect of mesoporous silica nanoparticles carrying ligustrazine, thereby accelerating HT-29 cell metastasis.

Conclusion: miR-570 can inhibit Wnt/β-catenin expression. Mesoporous silica nanoparticles carrying ligustrazine can promote miR-570 to inhibit Wnt/β-catenin expression, leading to inhibition of HT029cell metastasis.

Objective: To investigate the molecular mechanism by which DNA damage induced apoptosis suppressor (DDIAS) regulates STAT3/CCL2 to enhance macrophage polarization to M1 type in Kawasaki disease (KD).

Methods: A KD vascular model was established by culturing human coronary artery endothelial cells (HCAECs) in vitro. Small interfering RNA of DDIAS (si-DDIAS) was transfected into the KD cell model. The human macrophage cell line THP-1 was induced into M1 macrophages using phorbol myristate acetate (PMA) and lipopolysaccharide (LPS) and co-cultured with the endothelial cells using the HCAECs medium. Western blot analysis was utilized to assess cellular DDIAS, p-STAT3, STAT3, and CCL2 protein expression. MTT was utilized to detect cell proliferation. ELISA was utilized to assess the expression levels of TNF-α, IL-4, IL-6, IL-8 and CCL2 in cell supernatants. Flow cytometry was utilized to examine cell apoptosis and the expression of M1 macrophage surface marker CD86.

Results: The expression level of DDIAS was elevated in the KD group compared to the Control group. Serum inhibition of HCAEC proliferation in the KD group was concentration-dependent and pro-inflammatory cytokines were substantially elevated, while the anti-inflammatory cytokines were substantially reduced (P<0.05). Compared to the si-NC group, cell proliferation was considerably enhanced; pro-inflammatory cytokines were substantially reduced; anti-inflammatory cytokines were substantially elevated, and the expression of p-STAT3 and CCL2 was lowered in the si-DDIAS group (P<0.05). The percentage of M1 macrophages was substantially elevated in the THP-1+LPS group compared to the THP-1 group (P<0.05). Compared to the THP-1+LPS+si-NC group, macrophage CCL2 expression was decreased in the THP-1+LPS+si-DDIAS group; the percentage of M1 macrophages was substantially lowered (P<0.05); and the levels of pro-inflammatory cytokines and CCL2 in the cell supernatant were substantially reduced. Incubation of macrophages with STAT3 agonist reversed these changes, which were exacerbated by the addition of neutralizing antibody CCL2.

Conclusions: Downregulation of DDIAS inhibits macrophage polarization toward the M1 type through inhibition of the STAT3/CCL2 signaling pathway and can ameliorate vascular injury and inflammation in KD coronary arteries.

Objective: Osteoporosis is a common bone disease. miR-26b regulates OA-induced osteogenesis and induces osteoporosis. miR-26b is elevated in bone marrow stromal cells (BMSCs) during bone formation; however, we haven't fully revealed whether it is directly involved in this process, which was the aim of this study.

Methods: An oophorectomized rat model of osteoporosis was used. BMSCs were detected by electron microscopy of exosomes, and mir-26b levels were detected by RT-PCR. The correlation between mir-26b and sirt2 was detected by bioinformatics and luciferase activity analysis. Bone microstructure and cartilage moisture content were also measured. The proliferation ability of mir-26b and sirt2 on chondrocytes was detected by cell viability test and flow cytometry.

Results: Western blotting further proved that the surface markers of isolated granular exosomes were positive for CD63 and CD81. Further analysis showed that exosomes' diameters ranged from 50 to 150 nm. Mir-26b is elevated in BMSC, and its mimics can promote proliferation. Luciferase showed that mir-26b targets sirt2 and the effect of elevated mir-26b on chondrocytes was completely reversed by silencing sirt2. The proliferation ability of C28/I2 chondrocytes in Mir MICs group was lower than other two groups, while that in Mir inhibition group had stronger proliferation ability than in the Mir NC group. mir-26b was highly expressed in BMSC, indicating that mir-26b comes from secretion of BMSC.

Conclusion: Mir-26 is highly expressed in OP. mir-26b can therefore target sirt2 to promote proliferation and inhibit apoptosis of OP chondrocytes. It may offer a possibility of a treatment of OP in the future.

Objective: Multiple myeloma (MM) is caused by abnormal cloning of plasma cells. miR-184 is abnormally expressed in several types of tumors, but its expression and role in MM have not been reported.

Methods: The bone marrow samples of healthy controls and MM patients were collected, and plasma cells were sorted. The multiple myeloma cell line OPM-2 was cultured and assigned into miR-NC+siRNA-NC group, miR-184 inhibitor+siRNA-NC group, and miR-184 inhibitor+siRNA-Notch1 group. Cell proliferation was assessed by MTT assay. Clone formation was evaluated by colony formation assay. Cell apoptosis activity was tested with flow cytometry. Notch1 and cleaved caspase3 protein expressions were detected.

Results: MiR-184 expression was increased in myeloma plasma cells (P<0.05). Transfection of miR-184 inhibitor can downregulate miR-184 expression, increase the levels of Notch1 and cleaved caspase3, inhibit OPM-2 cell proliferation, restrain colony formation, enhance caspase3 activity, and suppress tumor cell invasion (P<0.05). However, administration of siRNA-Notch1 retarded the effect of miR-184 inhibitor by decreasing the expressions of Notch1 and cleaved caspase3, enhancing colony formation and tumor cell invasion, as well as inhibiting caspase3 activity and cell proliferation.

Conclusion: Our data indicated that miR-184 expression is increased in myeloma plasma cells. Down-regulation of miR-184 promotes MM cell apoptosis and inhibits proliferation and colony formation by regulating Notch1 expression.

Objective: The JR blood group system, officially designated ISBT JR 032, consists of a single antigen called Jr^a. This is a high frequency antigen in most populations. The Jr(a-) phenotype is more prevalent in Japanese and Asian populations. Individuals with the Jr(a-) blood type can be recognized incidentally by the production of anti-Jr(a) antibodies and verified by the existence of two null ABCG2 alleles.

Methods: We used direct sequencing to analyze the genotype frequency of the ABCG2 null allele (c.376C>T, rs72552713) and compared it with East Asian genomic databases. We developed tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), which is a simple, precise method for determining an individual's genotype and suitable for clinical use, and analyzed a cohort of 300 healthy Koreans.

Results: Using direct sequencing, we found that 14 individuals in the cohort carried a heterozygous ABCG2 null allele. We optimized the ARMS-PCR technique to detect and identify this null allele precisely. We identified the presence of this null allele in a heterozygous state using ARMS-PCR.

Conclusion: The minor allele frequency of the ABCG2 null allele in the Korean cohort was 2.3%. The estimated genotype frequencies of homozygotes and heterozygotes for this null allele are 0.05% and 4.56%, respectively. The newly developed ARMS-PCR assay would be useful for determining the Jr(a-) antigen status in patients who produce anti-Jr(a) antibodies as well as for selecting Jr(a-) blood donors.

Objective: Rheumatoid arthritis (RA) is a common chronic autoimmune inflammatory disease. The pathogenesis of RA is complex, and RA lacks effective therapeutic drugs. Heme oxygenase 1 (HO-1) is found to be reduced in RA. However, the role of HO-1 in RA and related mechanisms have not been elucidated.

Methods: RA rat model was established. The expression of HO-1 was upregulated by hemin. The increase weight rate, the degree of toe swelling, and the arthritis index were analyzed to evaluate the therapeutic effect of HO-1 on RA. In vitro RAW264.7 inflammatory cell model was established using 5 ng/mL IL-1. SnPP or hemin were used to inhibit or upregulate HO-1 expression. Tetrazolium salt colorimetric assay (MTT) was selected to test cell proliferation. ELISA was used to determine the concentrations of cellular inflammatory factors IL-1 and IL-6. Reactive oxygen species (ROS) activity was assessed. Western blot was performed to analyze NF-[Formula: see text]B and MMP-3 expressions.

Results: The expression of HO-1 was decreased in RA rats, and hemin increased HO-1 level in arthritic rats, which elevated the increase weight rate and decreased toe swelling degree and arthritis index (P<0.05). Hemin significantly upregulated HO-1 expression, inhibited inflammatory cell proliferation, decreased IL-1 and IL-6 expressions, declined ROS level, restrained NF-[Formula: see text]B expression, and enhanced MMP-3 expression in Raw264.7 cells induced by LPS (P<0.05). SnPP obviously inhibited the expression of HO-1, promoted cell proliferation, elevated IL-1 and IL-6 secretions, increased ROS level, promoted NF-[Formula: see text]B expression, and decreased MMP-3 level compared with LPS group (P<0.05).

Conclusion: Upregulation of HO-1 can improve arthritis symptoms by reducing ROS expression, inhibiting NF-[Formula: see text]B signaling pathway, elevating MMP-3 expression, attenuating inflammatory factor secretion, and suppressing inflammatory cell proliferation.