Knockdown of MRPL35 promotes cell apoptosis and inhibits cell proliferation in non-small-cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a major pathological type of lung cancer. However, its pathogenesis remains largely unclear. MRPL35 is a regulatory subunit of the mitoribosome, which can regulate the assembly of cytochrome c oxidases and plays an important role in the occurrence of NSCLC. METHODS: The expression of MRPL35 in NSCLC was detected by tissue microarray and immunohistochemistry. H1299 cells were infected with lentivirus to knockdown MRPL35, and the cells were subjected to crystal violet staining to assess the results of colony formation assays. A549 cells were infected by lentiviral particles-expressing shMRPL35 or shControl, and then subcutaneously injected into nude mice. Tumorigenesis in mice was detected by in vivo imaging. The potential pathway of MRPL35 in NSCLC was assessed by Western blotting. RESULTS: MRPL35 was over-expressed in NSCLC tissue compared to para-cancerous and normal tissues. Knockdown of MRPL35 suppressed cell proliferation and decreased NSCLC progression both in vitro and in vivo. The possible molecular mechanisms were also clarified, which indicated that MRPL35 could be involved in cell apoptosis and proliferation by modulating the expression levels of CDK1, BIRC5, CHEK1, STMN1 and MCM2. Knockdown of MRPL35 activated p53 signaling pathway and inhibited cell cycle regulation. CONCLUSIONS: The oncogenic role of MRPL35 in NSCLC was potentially mediated through the cell cycle regulatory genes such as BIRC5, STMN1, CDK1, CHEK1 and MCM2, as well as activation of P53 signaling pathway.

Comparison of 18 F-FDG and 68 Ga-FAPI PET/CT in a Patient With Hepatic Perivascular Epithelioid Cell Neoplasm.

ABSTRACT: The prevalence of hepatic perivascular epithelioid cell neoplasm (PEComa) is extremely low, and imaging diagnosis is very difficult. We presented 18 F-FDG and 68 Ga-FAPI PET/CT findings in a 58-year-old woman with pathologically confirmed hepatic PEComa. The tumor showed intense 68 Ga-FAPI uptake but only mild 18 F-FDG activity on PET/CT studies. This case suggested that 68 Ga-FAPI PET/CT might be a useful tool for evaluation of hepatic PEComa with remarkable tumor-to-liver ratios.

Saturated fatty acid promotes calcification via suppressing SIRT6 expression in vascular smooth muscle cells.

BACKGROUND: This study aims to investigate the effects of saturated free fatty acid on calcification and SIRT6 expression in vascular smooth muscle cells (VSMCs) and the role of SIRT6 in regulating VSMC calcification. METHODS: Sprague-Dawley rats were randomly allocated to two groups: rats with normal diet (ND) and high-fat diet (HFD) from 4 to 12 weeks. At 12 weeks, part rats randomly selected from ND and HFD were administrated with vitamin D3 and nicotine to establish a model of vascular calcification. Thoracic aortas were collected from treatment rats at 16 weeks for assaying vascular calcification and related protein expression. Primary VSMCs isolated from Sprague-Dawley rats were used for investigating the effects of palmitic acid on VSMCs' calcification, apoptosis and target protein expression. RESULTS: HFD-facilitated calcification in medial aorta, with decreased SIRT6 expression in VSMCs of aortas. Palmitic acid decreased SIRT6 expression while increased calcification, apoptosis and protein expression of BMP2 and RUNX2 in primary VSMCs. Overexpression of SIRT6 could, partially or completely, rescue the palmitic acid-induced elevation of calcification, apoptosis and expression of BMP2 and RUNX2. CONCLUSION: This study demonstrated that vascular calcification induced by HFD was linked to the palmitic acid-induced downregulation of SIRT6. Overexpression of SIRT6 could decrease palmitic acid-induced calcification and apoptosis in VSMCs.

Lirilumab and Avelumab Enhance Anti-HPV+ Cervical Cancer Activity of Natural Killer Cells via Vav1-Dependent NF-κB Disinhibition.

BACKGROUND: We investigated the efficacy and mechanism of the anti-KIR immunotherapy lirilumab and anti-PD-L1 immunotherapy avelumab on natural killer (NK) cell activity against HPV+ cervical cancer. METHODS: NK cell-mediated lysis of autologous biopsy-derived malignant cervical squamous cells and normal cervical squamous cells were measured by europium-release cytotoxicity assays. Cytokine and granzyme B release were measured by ELISPOT effector-cell-based assays and ELISA. Murine cervical cancer tumor models were constructed to assess implanted tumor volumes over time and intratumoral immune cell infiltration. Receptor-crosslinking and plate-immobilized antibody stimulation studies, with or without p65 and Vav1 silencing, were used to investigate NF-κB pathway disinhibition in NK cells. RESULTS: Lirilumab and avelumab each enhanced NK cell disinhibition and NK cell-mediated lysis of autologous cervical cancer cells in vitro while reducing HPV+ tumor volumes and increasing intratumoral NK cell infiltration and cytolysis in vivo. Moreover, lirilumab and avelumab each promoted NK cell NF-κB disinhibition as well as stimulated cytokine and granzyme B expression in a NF-κB-dependent manner. Lirilumab+avelumab enhanced all aforementioned effects compared to either monotherapy. Vav1 silencing eliminated disinhibition of NF-κB signaling by lirilumab and avelumab, indicating their disinhibiting effects are Vav1-dependent. CONCLUSIONS: This study supports a novel approach to enhancing NK cell lysis against HPV+ cervical cancer cells through combining lirilumab and avelumab.

Abnormal expression of liver autophagy and apoptosis-related mRNA in fatty liver haemorrhagic syndrome and improvement function of resveratrol in laying hens.

Fatty liver haemorrhagic syndrome (FLHS) is characterized by hepatic rupture and haemorrhage leading to sudden death in laying hens. Resveratrol (Res) is a natural polyphenol with antioxidant and anti-inflammatory effects that can ameliorate chronic liver disease. The aim of this study was to investigate the improved effect of Res on the altered expression of autophagy and apoptosis-related genes in laying hens with FLHS. A total of 144 healthy 150-day-old laying hens were randomly divided into four groups: control group (standard diet), HELP group (high-energy-low-protein (HELP) diet), HELP + Res group (HELP diet with 400 mg/kg Res) and Res group (standard diet with 400 mg/kg Res). Histopathological lesions of the liver and the mRNA levels of Beclin-1, Atg5, Atg7, p62, Bcl-2, Bax and Caspase-3 on days 40, 80, and 120 were measured. The results showed that lipid accumulation and hepatocyte damage in the HELP group were more serious than those in the HELP + Res group. The mRNA levels of Beclin-1, Atg5, Atg7, and Bcl-2 in the HELP and HELP + Res groups were strikingly declined (P < 0.01) compared to the control group, and their mRNA levels were markedly higher in HELP group than those in the HELP + Res group (P < 0.05). Additionally, the mRNA levels of p62, Bax and Caspase-3 were significantly increased in the HELP and HELP + Res groups (P < 0.01 or P < 0.05), but their mRNA levels in the HELP group were higher than those in the HELP + Res group (P < 0.05). Collectively, FLHS could induce severe lipid accumulation, abnormal mRNA levels of liver autophagy and apoptosis-related genes. Res as a dietary supplement could attenuate these abnormal changes.

Bioinspired sensor chip for detection of miRNA-21 based on photonic crystals assisted cyclic enzymatic amplification method.

Cancer, as the most invasive disease in the world, has led to an increasing amount of death year by year, so it is highly desired to develop a portable device to monitor the aberrant expression of biomarker in cancer patient. Here, we present a bio-photonic periodic nanostructures sensor chip assisted cyclic enzymatic amplification method to detect miRNA-21 with a detection limit of 55 fM. By employing biocompatible polydopamine nanospheres (PDANs) and DNaseⅠto construct an target-recycling amplification process on the photonic crystals, the output fluorescence signal can be strengthened selectively and short amplification time is needed. Benefiting from the synergy of the enhancement of photonic crystals and enzymatic cycle amplification, we realize high sensitivity detection of miRNA-21 with a detection range of 1 pM-10 nM and a detection limit of about four orders of magnitudes lower than the method employs no amplification, showing an expectable prospect in the early diagnosis of cancer.

Tanshinone IIA protects against pulmonary arterial hypertension in broilers.

This investigation was conducted to study the effects of tanshinone IIA (TIIA) on pulmonary arterial hypertension (PAH) in broilers. Two-hundred newly hatched Arbor Acre commercial broilers were randomly divided into 3 groups. All groups, with the exception of the control group (tap water), were given NaCl water (0.3%) starting on the d 15, and broilers in the protected group were fed a diet supplemented with TIIA (2.5 g/kg) starting on the d 15. On d 28, 35, 42, and 49, the ratio of the right ventricular weight to the total ventricular weight (RV: TV) and the values of other biochemical indicators for each group chickens were determined. The concentrations of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), nuclear factor kappa (NF-κB), and P38 (a mitogen-activated protein kinase) were measured using enzyme-linked immune sorbent assays (ELISA). The results showed that the proportion of chickens in the diseased group with an RV:TV ratio in the range of 0.250 to 0.299 (10%) was significantly higher (25 to 30%) compared to that of the other groups (P < 0.05), and the proportion in all chickens was 28%. In addition, the IL-6, IL-1ß, NF-κB, and P38 protein concentrations were higher in the diseased group, whereas there were no differences between the control group and the protected group. Moreover, the measurements of body weight, liver function, kidney function and electrolytes showed significant differences between the diseased group and the other groups. These findings suggest that tanshinone IIA may protect broilers from PAH, which is an important piece of information for the poultry industry.

Effects of Different Levels of Molybdenum on Rumen Microbiota and Trace Elements Changes in Tissues from Goats.

Molybdenum (Mo) is an essential trace element for animals and human beings. However, the negative effects on rumen function and distribution of trace elements in tissues induced by excessive Mo have not been well understood. Therefore, the purpose of present study was to investigate the impact of Mo on rumen microbiota, distribution of trace elements in various organs, and hematological parameters of goats. A total of 36 goats were randomly distributed into three groups with equal number and low-Mo and high-Mo groups were orally administered ammonium molybdate at 15 and 45 mg · Mo · kg-1 · BW respectively, while the control group received corresponding quantitative deionized water. The results showed that the total number of ciliate and protozoa protein concentration decreased significantly (P < 0.01) on days 25 and 50. Concentrations of ammonia nitrogen and bacterial protein were significantly higher (P < 0.05) in low-Mo group, while they were lower (P < 0.05) in high-Mo group than the control group on days 25 and 50. In addition, Mo accumulated in serum and all detected tissues. Copper (Cu) and zinc (Zn) contents significantly decreased (P < 0.05) in hair and serum on days 25 and 50, while Cu contents increased (P < 0.05) and the change of Zn contents were not obvious (P > 0.05) in other tissues on days 25 and 50. Besides, there was no obvious variation in iron (Fe) contents during whole experiment period (P > 0.05). Furthermore, excessive Mo content had no significant effect on red blood cell (RBC) counts and hemoglobin (HGB) concentration (P > 0.05) on days 25 and 50, while white blood cell (WBC) counts increased significantly (P < 0.05) on day 50. These results indicated that excessive Mo content could impact the balance of ruminal microorganisms and interfere with the absorption and distribution of Mo and Cu mainly.