The association of prealbumin, transferrin, and albumin with immunosenescence among elderly males.

OBJECTIVE: As people get older, the innate and acquired immunity of the elderly are affected, resulting in immunosenescence. Prealbumin (PAB), transferrin (TRF), and albumin (ALB) are commonly used markers to monitor protein energy malnutrition (PEM). However, their relationship with the immune system has not been fully explored. METHODS: In our study, a total of 93 subjects (≥65 years) were recruited from Tongji Hospital between January 2015 and February 2017. According to the serum levels of these proteins (PAB, TRF, and ALB), we divided the patients into the high serum protein group and the low serum protein group. Then, we compared the percent expression of lymphocyte subsets between two groups. RESULTS: All the low serum protein groups (PAB, TRF, and ALB) had significant decreases in the percentage of CD4+ cells, CD3+CD28+ cells, CD4+CD28+ cells and significant increases in the percentage of CD8+ cells, CD8+CD28- cells. PAB, TRF, and ALB levels revealed positive correlations with CD4/CD8 ratio, proportions of CD4+ cells, CD3+CD28+ cells, CD4+CD28+ cells, and negative correlation with proportions of CD8+ cells, CD8+CD28- cells. CONCLUSIONS: This study suggested PAB, TRF, and ALB could be used as immunosenescence indicators. PEM might accelerate the process of immunosenescence in elderly males.

Fufang-Zhenzhu-Tiaozhi Capsule reduces restenosis via the downregulation of NF-kappaB and inflammatory factors in rabbits.

BACKGROUND: To investigate the effects of a Chinese herbal medicine Fufang-Zhenzhu Tiaozhi Capsule (FTZ) on restenosis and elucidate the mechanism of action. METHODS: A restenosis model was established by balloon rubbing the endothelium of the abdominal aorta followed by high fat diet. Rabbits were divided into blank control group, restenosis group, FTZ group (0.66 mg/kg/day), atorvastatin group (5 mg/kg/day) and FTZ + atorvastatin group (n = 8). Vascular stenosis was analyzed by X-ray. Serum levels of chemokines and cytokines interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-12 (IL-12), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were measured by ELISA. The levels of NF-κB, IκB-α, P-IκBα, IKK-α, and P-IKKα/ß from injured abdominal arteries were detected by Western blotting. RESULTS: Restenosis was induced successfully via abdominal artery balloon injuries and high fat diet. Restenosis was significantly decreased in FTZ group compared with restenosis group (P < 0.05). FTZ group had markedly reduced serum lipid levels (P < 0.05). In addition, the levels of TNF-α, IL-1, IL-6, IL-8, IL-12, ICAM-1 and MCP-1 decreased by FTZ treatment (P < 0.05). The expression of NF-κB in the atherosclerotic lesions was significantly attenuated in FTZ group (P < 0.05). CONCLUSION: FTZ could reduce restenosis via reducing NF-κB activity and inflammatory factor expression within the atherosclerotic lesion in a rabbit restenosis model. FTZ may be a new therapeutic agent for restenosis.

Potential applications of prognostic and immunological marker transmembrane serine proteinase 2 in prediction, prevention and personalized treatment of lung cancer.

Transmembrane serine proteinase 2 (TMPRSS2), which is an essential serine protease for priming spike protein of SARS-CoV-2, was found in low expression in many cancer tissue including lung cancer. However, the mechanism of severely downregulated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) was not reported yet; the correlation between TMPRSS2 and prognosis in LUAD and LUSC is also not clear. In our present research, we found that TMPRSS2 was severely downregulated in LUAD and LUSC, and the expression of TMPRSS2 in LUAD is much lower than that of LUSC. Low TMPRSS2 expression was an independent prognostic factor for poor OS in LUAD, but not in LUSC patients. Promoter hypermethylation is one of the results of TMPRSS2 downregulated in LUAD and LUSC, whereas copy-number alteration is another reason for TMPRSS2 downregulated in LUAD but not LUSC. Then, low TMPRSS2 expression has higher prognostic value in LUAD and may be due to different immune environments and different enriched immune cells subgroups.

Wild­type KRAS inhibits the migration and invasion of pancreatic cancer through the Wnt/ß­catenin pathway.

Kirsten rat sarcoma virus (KRAS) mutation is considered to be the event that leads to the initiation of pancreatic ductal adenocarcinoma (PDAC), the mutation frequency of the KRAS gene in PDAC is 90­95%. Studies have shown that wild­type KRAS (KRASWT) has a survival advantage in PDAC and can antagonize the effect of mutated KRAS G12D (KRASG12D), leading to a low cell transformation efficiency. The present study focused on the differences in biological behavior between KRASWT and KRASG12D and explored the mechanism in pancreatic cancer. Overexpressed KRASWT and KRASG12D was transfected into cells through lentiviral transfection. The differences and mechanisms were explored using cell counting kit­8 (CCK­8), clone formation, wound healing and Transwell assays, as well as western blotting, immunohistochemistry and tumor formation in nude mice. In vitro, the proliferation of KRASWT group was reduced compared with PANC­1 group, while the proliferation of KRASG12D group was not significantly changed. In vivo, the proliferation of KRASWT group was reduced and that of KRASG12D group was enhanced compared with that in the PANC­1 group. The invasion and migration of KRASWT group were decreased, while the invasion and migration of KRASG12D group were increased. Western blotting showed that the expression of E­cadherin, α­E­catenin, MMP­3, MMP­9, STAT3 and phosphorylated STAT3 in KRASWT group was increased, while no significant difference was observed in KRASG12D group. The results of immunohistochemistry were consistent with those of western blotting. KRASWT group can inhibit the proliferation of pancreatic cancer in vitro and in vivo, while KRASG12D group can significantly promote proliferation in vivo, but not significantly in vitro. Wild­type KRAS may inhibit the invasion and migration of pancreatic cancer through the Wnt/ß­catenin pathway.

Effect of F11R Gene Knockdown on Malignant Biological Behaviors of Pancreatic Cancer Cells.

F11R receptor (F11R/junctional adhesion molecule-A/F11R-A) is preferentially concentrated at tight junctions and influences epithelial cell morphology and migration. Numerous studies have shown that the aberrant expression of F11R contributes to tumor progression including pancreatic cancer. However, the significance of F11R in various tumors is controversial, and the role of F11R in regulating the malignant behaviors of human pancreatic cancer is unknown. To investigate the role of F11R in the carcinogenesis of pancreatic cancer and the potential targets of F11R as a therapeutic target for pancreatic cancer, we knocked down F11R in the pancreatic cancer cell line PANC-1 using lentiviral approaches. We found that F11R silencing led to decreased cell proliferation, a loss of cell invasiveness, cell cycle arrest in the G1 phase, and enhanced cell apoptosis. The present results suggest that F11R may be a promising therapeutic target for pancreatic cancer.

miR-205 and HMGB1 expressions in chronic periodontitis patients and their associations with the inflammatory factors.

OBJECTIVE: This paper sets out to investigate the miR-205 and HMGB1 expressions in chronic periodontitis (PO) patients and their associations with the inflammatory factors. METHODS: From February 2016 to May 2018, 68 PO patients treated in our hospital were recruited for the study and placed in a patient group (PG), and 60 healthy volunteers were also recruited and placed in a healthy group (HG). Serum samples were collected from both groups for the identification of miR-205 using qPCR, as well as to determine the HMGB1 and inflammatory factor (IL-1ß, IL-6, TNF-α) expression levels using ELISA. The correlations of the miR-205 and HMGB1 expression levels with the periodontal clinical indicators and the inflammatory factors were analyzed using a correlation analysis. RESULTS: In comparison with the HG expression, the serum miR-205 expression was lower, and the HMGB1 was elevated in PG (P < 0.05). An ROC curve analysis showed that the areas under the curve (AUCs) of the serum miR-205 and HMGB1 expressions in diagnosing PO were 0.936 and 0.955 respectively. However, the serum miR-205 expression in PG increased while the HMGB1 expression decreased post treatment (P < 0.05). A correlation analysis revealed an inverse association between the serum miR-205 expression levels and the periodontal clinical indicators [bleeding index (BI), probing depth (PD), plaque index (PLI), and attachment loss (AL)], and the inflammatory factors [interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α)], but there was a positive association between the HMGB1 expression level and these parameters. CONCLUSIONS: miR-205 and HMGB1 are closely related to the progression of PO, and may be candidate biomarkers for the diagnosis and treatment of PO.

Identification of Target Genes of Antiarrhythmic Traditional Chinese Medicine Wenxin Keli.

Wenxin Keli (WXKL) is a traditional Chinese medicine drug approved for the treatment of cardiovascular diseases. This study aimed to identify WXKL-targeting genes involved in antiarrhythmic efficacy of WXKL. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) technology platform was used to screen active compounds of WXKL and WXKL-targeting arrhythmia-related genes. A pig model of myocardial ischemia (MI) was established by balloon-expanding the endothelium of the left coronary artery. Pigs were divided into the model group and WXKL group (n = 6). MI, QT interval, heart rate, and arrhythmia were recorded, and the mRNA expression of target genes in myocardial tissues was detected by PCR. Eleven active ingredients of WXKL and eight WXKL-targeting arrhythmia-related genes were screened. Five pathways were enriched, and an "ingredient-gene-path" network was constructed. WXKL markedly decreased the incidence of arrhythmia in the MI pig model (P < 0.05). The QT interval was significantly shortened, and the heart rate was slowed down in the WXKL group compared with the model group (P < 0.05). In addition, the expression of sodium channel protein type 5 subunit alpha (SCN5A) and beta-2 adrenergic receptor (ADRB2) was downregulated, while muscarinic acetylcholine receptor M2 (CHRM2) was upregulated in the WXKL group (P < 0.05). In conclusion, WXKL may shorten the QT interval and slow down the heart rate by downregulating SCN5A and ADRB2 and upregulating CHRM2 during MI. These findings provide novel insight into molecular mechanisms of WXKL in reducing the incidence of ventricular arrhythmia.

Fufang-Zhenzhu-Tiaozhi capsule ameliorates rabbit's iliac artery restenosis by regulating adiponectin signaling pathway.

BACKGROUND AND PURPOSE: Fufang-Zhenzhu-Tiaozhi Capsule (FTZ), a traditional Chinese medicine, has been shown obvious effects on the treatment of dyslipidemia and atherosclerosis. The aim of this study was to evaluate whether FTZ can ameliorate rabbit iliac artery restenosis after angioplasty by regulating adiponectin signaling pathway. EXPERIMENTAL APPROACH: The rabbit iliac artery restenosis model was established through percutaneous iliac artery transluminal balloon angioplasty and a high-fat diet. Twenty eight male New Zealand rabbits (8-week-old) were divided into sham operation group (Group Ⅰ), model group (Group Ⅱ), atorvastatin group (Group Ⅲ) and FTZ group (Group Ⅳ), with 7 rabbits in each group. Vascular stenosis was analyzed with Digital Subtraction Angiography. Level of adiponectin (APN), and inflammatory factor including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) as well as monocyte chemoattractant protein-1 (MCP-1) was measured by Enzyme Linked Immunosorbent Assay; and injured iliac artery was collected for Hematoxylin-eosin staining and Western Blotting detection of expression of peroxisome proliferator-activated receptor-alpha (PPAR-α), adenosine 5'-monophosphate -activated protein kinase (AMPK) and phosphorylated adenosine 5'-monophosphate -activated protein kinase (p-AMPK). Besides, we evaluated FTZ's safety for the first time. KEY RESULTS: Percutaneous iliac artery transluminal balloon angioplasty and high-fat diet result in inflammatory response and restenosis. Compared with Group Ⅱ, iliac artery restenosis was significantly ameliorated in Group Ⅳ (P < 0.05). Treated with FTZ, serum lipids were significantly decreased (P < 0.01), while the level of APN was elevated significantly (P < 0.01). Western blotting detection of the injured iliac artery showed that the expressions of PPAR-α, AMPK and p-AMPK were significantly increased in Group Ⅳ (P < 0.01) than that in Group Ⅱ. Besides, before and after taking drugs, liver and kidney function indicators, creatine kinase, as well as measurement of echocardiography were of no statistical difference in four groups(P > 0.05). CONCLUSIONS AND IMPLICATIONS: FTZ could effectively reduce serum lipids and ameliorate rabbit's iliac artery restenosis after angioplasty, and its mechanism may be related to activation of APN signaling pathway.

IL10-modified Human Mesenchymal Stem Cells inhibit Pancreatic Cancer growth through Angiogenesis Inhibition.

In the present study, we constructed the recombinant plasmid IL10-PEGFP-C1 and successfully transfected into human mesenchymal stem cells. After culturing for 72 h, the levels of IL6 and TNF-α in the supernatant of the MSCs-IL10 group were significantly lower than the vector group and the control group (17.6 ± 0.68vs73.8 ± 0.8 and 74.4 ± 1.5) µg/L and (65.05 ± 3.8 vs 203.2 ± 2.4 and 201.3 ± 3.7) µg/L, respectively (p < 0.001) .The animal experiments showed that the volume of subcutaneous tumors in the MSCs-IL10 group in vivo was a significantly less level compared to that in MSC control and the blank control groups (76.84 ± 20.11) mm3 vs (518. 344 ± 48.66) mm3, (576.99± 49.88) mm3, (P < 0. 05) and they have a longer life time. Further we found the mass concentrations of IL6 and TNF-α in the blood serum of MSC-IL10 group were lower than the vector group and the control group (64.42 ± 10.9 vs120.83 ± 15.52 and 122.65 ± 13.71) and (40.05 ± 5.63 vs 126.78 ±1.89 and 105.83 ± 2.16) µg/L respectively (p < 0.001). CD31 immunohistochemistry and alginate encapsulation experiments showed tumor angiogenesis were inhibited in MSCs-IL10 group in comparison to the control and vector group (P < 0.001), FITC-labeled dextran intake was also lower than the other groups (P < 0.01). Collectively, this study suggested IL10 could inhibit the growth of the transplanted tumor in vivo and prolong survival of mice, and the primary mechanism may be the indirect inhibition of pro-inflammatory cytokines IL6 and TNF-α secretion and tumor angiogenesis formation.

Left atrial myxoma complicated with multi-system embolization.

BACKGROUND: Atrial myxoma accounts for approximately 50% of all cardiac tumors. The majority of myxomas are located in the left atrium and present variable clinical manifestation. CASE PRESENTATION: A young man was transferred to our hospital with sudden onset of resting pain, pallor and numb in right leg. An atrial mobile mass was detected by transthoracic echocardiography. Anticoagulant and antithrombotic therapy were administered, a timely surgery was performed and the mass was confirmed as a myxoma. The patient did not discharge any discomfort post-operation. CONCLUSION: For patients with atrial myxoma, early diagnosis is essential, anticoagulant or antithrombotic therapy and surgery have a great importance to prevent further embolism.