Mitophagy-related gene signature predicts prognosis, immune infiltration and chemotherapy sensitivity in colorectal cancer.

BACKGROUND: Mitophagy plays essential role in the development and progression of colorectal cancer (CRC). However, the effect of mitophagy-related genes in CRC remains largely unknown. AIM: To develop a mitophagy-related gene signature to predict the survival, immune infiltration and chemotherapy response of CRC patients. METHODS: Non-negative matrix factorization was used to cluster CRC patients from Gene Expression Omnibus database (GSE39582, GSE17536, and GSE37892) based on mitophagy-related gene expression. The CIBERSORT method was applied for the evaluation of the relative infiltration levels of immune cell types. The performance signature in predicting chemotherapeutic sensitivity was generated using data from the Genomics of Drug Sensitivity in Cancer database. RESULTS: Three clusters with different clinicopathological features and prognosis were identified. Higher enrichment of activated B cells and CD4+ T cells were observed in cluster III patients with the most favorable prognosis. Next, a risk model based on mitophagy-related genes was developed. Patients in training and validation sets were categorized into low-risk and high-risk subgroups. Low risk patients showed significantly better prognosis, higher enrichment of immune activating cells and greater response to chemotherapy (oxaliplatin, irinotecan, and 5-fluorouracil) compared to high-risk patients. Further experiments identified CXCL3 as novel regulator of cell proliferation and mitophagy. CONCLUSION: We revealed the biological roles of mitophagy-related genes in the immune infiltration, and its ability to predict patients' prognosis and response to chemotherapy in CRC. These interesting findings would provide new insight into the therapeutic management of CRC patients.

The relationship between cancer-related fatigue, quality of life and pain among cancer patients.

Objectives: This study aimed to select patients with cancer-related pain to further analyze the relationship between pain severity, fatigue severity, and quality of life. Methods: A cross-sectional study was conducted. A convenience sampling method was used to select 224 patients with cancer-related pain who were undergoing chemotherapy and met the inclusion criteria in two hospitals of two provinces from May to November 2019. All participants were invited to complete a general information questionnaire, the Brief Fatigue Inventory (BFI), the Numerical Rating Scale (NRS) for pain intensity, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Results: In the 24 h before completing the scales, 85 patients (37.9%) had mild pain, 121 (54.0%) had moderate pain, and 18 (8.0%) had severe pain. In addition, 92 (41.1%) patients had mild fatigue, 72 (32.1%) had moderate fatigue, and 60 (26.8%) had severe fatigue. Most patients with mild pain only experienced mild fatigue, and their quality of life was also at a moderate level. Patients with moderate and severe pain mostly had moderate or higher levels of fatigue and a lower quality of life. There was no correlation between fatigue and quality of life in patients with mild pain (r = -0.179, P = 0.104). There was a correlation between fatigue and quality of life in patients with moderate and severe pain (r = -0.537, P < 0.01; r = -0.509, P < 0.05). Conclusions: Patients with moderate and severe pain have more fatigue symptoms and lower quality of life than those with mild pain. Nurses should pay more attention to patients with moderate and severe pain, explore the interaction mechanism between symptoms, and carry out joint symptom intervention to improve the quality of life of patients.

[Inhibiting effects of interleukin-10 on expression of E-selectin and L-selectin in cerebral ischemia-reperfusion: experiment with rats].

OBJECTIVE: To investigate the inhibiting effects of interleukin-10 (IL-10) on the expression of E-selectin and L-selectin in cerebral ischemia-reperfusions. METHODS: Seventy-two adult male Sprague-Dawley rats were randomly divided into 4 equal groups, cerebral ischemia-reperfusion (I/R) group undergoing middle cerebral artery occlusion with Longa's thread method, IL-10 group undergoing lateral ventricle injection of IL-10 after the establishment of I/R model, Vehicle group undergoing lateral ventricle injection of normal saline after the establishment of I/R model, and sham operation (Sham) group. Twenty-four hours later the rats were killed with their brains taken out. Immunohistochemistry, RT-PCR and Western blotting were used to detect the mRNA and protein expression of E-selectin and L-selectin. RESULTS: The E-selectin and L-selectin expression levels of the I/R group were significantly up-regulated compared with the Sham group (both P < 0.05). The numbers of E-selectin and L-selectin positive vessels of the IL-10 group were 18.8 +/- 1.9/10 HP fields and 15.8 + 2.4/10 HP fields respectively, both significantly less than those of the vehicle group (24.7 +/- 2.4/10 HP fields and 20.9 + 3.3/10 HP fields respectively, both P < 0.05). The E-selectin and L-selectin gene mRNA expression levels of the IL-10 group were (0.431 +/- 0.029) and (0.318 +/- 0.048) respectively, both significantly lower than those of the Vehicle group [(0.497 +/- 0.019) and (0.433 +/- 0.087) respectively, both P < 0.05]. The E-selectin and L-selectin protein expression levels of the IL-10 group were (0.349 +/- 0.037) and (0.296 +/- 0.035) respectively, both significantly lower than those of the Vehicle group [(0.421 +/- 0.043,) and (0.348 +/- 0.044) respectively, both P < 0.05]. CONCLUSIONS: IL-10 suppresses the expression of E-selectin and L-selectin in cerebral ischemia-reperfusion.

[Effects of adipose-derived stem cell transplantation on the angiogenesis and the expression of bFGF and VEGF in the brain post focal cerebral ischemia in rats].

AIM: To investigate the effects of adipose-derived stem cell (ADSC) transplantation on the angiogenesis in the brain post focal cerebral ischemia in rats. METHODS: 72 male adult Sprague-Dawley rats were randomly divided into 4 groups: sham-operated group, middle cerebral artery occlusion (MCAO) group, vehicle group and MCAO+ADSC-treated group (n=18). A permenant focal cerebral ischemia model was established with the modified Longa's method. ADSC were labeled by DAPI before transplantation. One day after right MCAO, 30 muL of cell suspension containing 1x10(6) cells were injected into the lateral ventricle of MCAO+ADSC-treated group and the same dose of PBS was given to the vehicle group. On D4, D7 and D14 after MCAO, the rats were killed to detect the regeneration of microvessel and the expression of bFGF and VEGF in ischemic region by immunohistochemistry and RT-PCR. RESULTS: A lot of microvessel proliferate in the injured cortex reached peak in 2 weeks. The microvessel density in the brain tissues of rats treated with ADSC was higher than that in MCAO group and vehicle group (P<0.01). The expression of bFGF and VEGF in the brain tissues of MCAO+ADSC-treated group was higher than that in MCAO group and vehicle group on D4, D7 and D14 post MCAO. CONCLUSION: The transplantation of ADSC can promote the revascularization of cerebral ischemia in rats partly by enhancing bFGF and VEGF synthesis in brain.

[Effects of bone marrow-derived mesenchymal stem cells transplantation on recovery of neurological functions and expression of synaptophysin in focal cerebral infarction in rats].

AIM: To investigate the effects of bone marrow-derived mesenchymal stem cells (BMSC) transplantation on the recovery of neurological functions and the expression of synaptophysin in focal cerebral infarction in rats. METHODS: 72 male adult Sprague-Dawley rats were randomly divided into 4 groups (18 in each group): shamoperated group, middle cerebral artery occlusion (MCAO) roup,vehicle group and MCAO+BMSC-treated group. A permanent focal cerebral ischemia model was established using modified Longa's method. BMSC was labeled by DAPI before the transplantation. One day after right middle cerebral artery occlusion(MCAO), 1 x 10(6) cells were injected into the lateral ventricle of rats in BMSCs-treated group and the same dose of PBS was given to the rats in vehicle group. Before sacrificed and at 4 d, 7 d and 14 d after MCAO, the neurological functions were tested by balance beam, rota-rod and screen prehensile and the synaptophysin was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical method. RESULTS: DAPI stained positive cells were observed around the cerebral infarcted area in the BMSC-treated group. Compared with the MCAO group and the vehicle group,the neurological functions in BMSC-treated group were better on 7 d and 14 d after MCAO (P<0.05 or P<0.01), and the synaptophysin around the cerebral infarcted area was significantly upregulated on 4 d, 7 d and 14 d after MCAO (all P<0.01). CONCLUSION: BMSC transplantation can improve the neurological functions by upregulating the expression of synaptophysin after MCAO in rats.