AimThe aim of this study was to evaluate the relationship between platelet–lymphocyte ratio (PLR) and prognosis in small cell lung cancer (SCLC) patients.MethodA comprehensive search was carried out to collect related studies. Two independent investigators extracted the data of hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) or progression-free survival (PFS). A random-effect model was applied to analyze the effect of different PLR levels on OS and PFS in SCLC patients. Moreover, subgroup analysis was conducted to seek out the source of heterogeneity.ResultsA total of 26 articles containing 5,592 SCLC patients were included for this meta-analysis. SCLC patients with a high PLR level had a shorter OS compared with patients with a low PLR level, in both univariate (HR = 1.56, 95% CI 1.28–1.90, p < 0.0001) and multivariate (HR = 1.31, 95% CI 1.08–1.59, p = 0.007) models. SCLC patients with a high PLR level had a shorter PFS compared with patients with a low PLR level, in the univariate model (HR = 1.71, 95% CI 1.35–2.16, p < 0.0001), but not in the multivariate model (HR = 1.17, 95% CI 0.95–1.45, p = 0.14). Subgroup analysis showed that a high level of PLR shortened OS in some subgroups, including the Asian subgroup, the younger subgroup, the mixed-stage subgroup, the chemotherapy-dominant subgroup, the high-cutoff-point subgroup, and the retrospective subgroup. PLR level did not affect OS in other subgroups.ConclusionPLR was a good predictor for prognosis of SCLC patients, especially in patients received chemotherapy dominant treatments and predicting OS.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022383069.

Accumulating evidence indicates that lncRNAs are potential biomarkers and key regulators of tumor development and progression. The present study aimed to screen abnormal expression lncRNAs and investigate the mechanisms underlying the function in the progression of colorectal cancer (CRC). Potential CRC prognosis-associated dysregulated lncRNAs were screened and identified using bioinformatics analysis. Loss/gain-of-function experiments were performed to detect the biological roles of FAM222A-AS1 in CRC cell phenotypes in vitro and in vivo. The potential microRNAs that interact with FAM222A-AS1 were identified using online tools and were verified using qRT-PCR and luciferase reporter assay. The expression of FAM222A-AS1 is significantly upregulated in CRC tumor samples and cell lines. CRC patients with elevated FAM222A-AS1 expression in the tumor samples had unfavorable overall survival and disease-free survival. Silencing FAM222A-AS1 expression significantly inhibited CRC cell proliferation, migration, and invasion both in vitro and in vivo. Furthermore, FAM222A-AS1 was mainly distributed in the cytoplasm. It may directly bound to miR-let-7f and inhibit its expression and upregulate MYH9. In summary, FAM222A-AS1, as a novel oncogene in CRC, may promote the CRC progression by inhibiting miR-let-7f/MYH9 axis. The FAM222A-AS1/miR-let-7f/MYH9 signaling pathway may be a novel valuable target for inhibiting CRC.

目的 探索一种功能食品(五神)的抗肿瘤作用,并探讨该功能食品在抗肿瘤治疗中的应用前景.方法 取对数生长期Lewis细胞(鼠源性肺腺癌细胞系)悬液200μl(1×107/ml)接种于小鼠右后肢背部皮下构建肺癌Lewis皮下移植瘤模型.将小鼠分为以下四组:标准饮食饲养的对照组和顺铂组,添加功能食品饲料饲养的功能食品组及功能食品顺铂组,每组8只小鼠,顺铂组及功能食品顺铂组隔天按4 mg/kg体重腹腔注射顺铂,对照组与功能食品组注射等量生理盐水.实验过程中每周测量小鼠体重及移植瘤体积,按V=ab2π/6(a为最大直径,b为最小直径)计算,实验终点对瘤体称重,检测小鼠血清白蛋白、后肢肌围等营养指标,通过流式细胞仪检测小鼠脾脏、血清和肿瘤组织中相关免疫细胞亚群,ELISA检测试剂盒检测IL-6+T细胞及IL-10+T细胞等相关细胞因子,通过免疫组织化学检测瘤组织中微血管形成情况.结果 与对照组相比,功能食品组小鼠白蛋白及后肢肌围明显升高,但移植瘤体积及质量差异无统计学意义;与顺铂组相比,功能食品顺铂组移植瘤体积及质量明显降低,荷瘤小鼠免疫效应细胞亚群CD3+、CD4+T细胞,CD3+、CD8+T细胞,NK细胞的比例明显增高且差异有统计学意义;CD8+IFN-γ+、CD8+Perforin+T细胞和IL-10+T细胞比例降低,脾脏中抑制性免疫细胞亚群MDSCs和Treg细胞及肿瘤组织中的Treg细胞降低,但差异均无统计学意义.各组IL-6及IL-10差异无统计学意义.结论 功能食品能够增强顺铂的抗肿瘤疗效,这可能与改善小鼠营养状况、调节免疫等作用有关.

Wushen (WS) is a mixed food containing 55 natural products that is beneficial to human health. This study aimed to reveal the preventive effect of WS on aging via a combined analysis of gut microbiome and metabolome. Senescence-accelerated mouse prone 8 (SAMP8) mice were used as aging model and senescence-accelerated mouse resistant 1 (SAMR1) mice as control. The mice were fed four diet types; control diet (for SAMR1 mice), standard diet (for SAMP8 mice, as SD group), WS diet, and fecal microbiota transplantation (FMT; transplanted from aging-WS mice). Our results showed that the weight, food intake, neurological function, and general physical conditions significantly improved in WS-fed mice compared to those fed with SD. The CA1 hippocampal region in WS-fed aged mice showed fewer shriveled neurons and increased neuronal layers compared to that of the SD group. WS-fed mice showed a decrease in malondialdehyde and an increase in superoxide dismutase levels in the brain; additionally, IL-6 and TNF-α levels significantly decreased, whereas IL-2 levels and the proportion of lymphocytes, CD3+CD8+ T, and CD4+IFNγ+T cells increased in WS-fed mice. After fed with WS, the abundance of Ruminococcus and Butyrivibrio markedly increased, whereas Lachnoclostridium and Ruminiclostridium significantly decreased in the aging mice. In addition, 887 differentially expressed metabolites were identified in fecal samples, among these, Butyrivibrio was positively correlated with D-glucuronic acid and Ruminococcus was positively associated with 5-acetamidovalerate. These findings provide mechanistic insight into the impact of WS on aging, and WS may be a valuable diet for preventing aging.

Purpose: This study aimed to investigate the potential antitumor effects and mechanisms underlying the action of a functional food containing 55 different natural food ingredients. Materials and Methods: Azoxymethane/dextran sulfate sodium was used to establish a mouse model of colorectal cancer. Serum levels of cytokines, diamine oxidase, D-lactate, and endotoxin were measured using enzyme-linked immunosorbent assays. Immune cells from the mouse spleen and tumor tissue were analyzed by flow cytometry. Finally, 16S rRNA gene sequencing and liquid chromatography-mass spectrometry were used to study the fecal microbiota and microbial metabolites, respectively. Results: The tumor growth was significantly lower in the FFD group than in the model group. The intestinal barrier function, fat mass, and lean body mass were significantly improved in the FFD group compared with the model group. The levels of interleukin-6 and tumor necrosis factor-a were significantly lower in the FFD group, while the proportions of total T cells, CD3(+) CD4(+), CD3(+) CD8(+), and interferon-gamma-producing CD4(+) T cells were significantly higher. Analysis of the diversity of the gut microbiota identified 60 differential bacterial genera between the FFD and model groups, with lower abundances of Desulfovibrio and unclassified Ruminococcaceae and higher abundances of the beneficial bacterial genera Bacteroides and Parasutterella in the FFD group. The fecal metabolite analysis revealed 635 differential metabolites between the FFD and model groups, with lower levels of deuteroporphyrin IX and citrulline and higher levels of acetic acid and ascorbic acid in the FFD group. Conclusion: Our results demonstrate that the functional food tested can inhibit the growth of colorectal cancer. This effect may be due to the ability of this food to improve nutritional status, enhance intestinal barrier function, and regulate the tumor microenvironment via changes in the intestinal microbiota and metabolites.

Background Nitric oxide (NO) plays an important role in lung cancer. However, the results of previous studies about NO in the occurrence, progress and therapy were not consistent. Therefore, we conducted a meta-analysis to evaluate the relationship between NO and lung cancer. Method We carried out comprehensive search in the databases, and collected related studies. The data of fraction of exhaled nitric oxide (FeNO) or blood NO in different populations (lung cancer patients and control subjects) and different time points (before therapy and after therapy) were extracted by two investigators. A random effect model was applied to analyze the differences of FeNO and blood NO in different populations and different time points. To further compare NO level of each subgroup with different pathological types and different stages, a network meta-analysis (NMA) was performed. Results Fifty studies including 2551 cases and 1691 controls were adopted in this meta-analysis. The FeNO (SMD 3.01, 95% CI 1.89-4.13, p < 0.00001) and blood NO (SMD 1.34, 95% CI 0.84-1.85, p < 0.00001) level in lung cancer patients was much higher than that in control subjects. NMA model indicated blood NO level in each cancer type except SCLC was higher than that in control patients. There was no significant difference of blood NO level among four kinds of lung cancer patients. Blood NO level in LCC patients (SUCRA = 83.5%) was the highest. Blood NO level in advanced stage but not early stage was higher than that in control subjects. Patients in advanced stage (SUCRA = 95.5%) had the highest blood NO level. No significant difference of FeNO (SMD -0.04, 95% CI -0.46-0.38, p > 0.05) and blood NO level (SMD -0.36, 95% CI -1.08-0.36, p > 0.05) was observed between pretreatment and posttreatment in all patients. However, FeNO level elevated (SMD 0.28, 95% CI 0.04-0.51, p = 0.02) and blood NO level decreased in NSCLC patients (SMD -0.95, 95% CI -1.89-0.00, p = 0.05) after therapy. Conclusion FeNO and blood NO level would contribute to diagnosis of lung cancer and evaluation of therapy effect, especially for NSCLC patients.

Objective To investigate the sensitivity of pancreatic cancer cells to mannose under various glucose concentrations and the mechanisms. Methods CCK-8 cell viability and proliferation kit was used to detect the proliferation of pancreatic cancer cells under different concentrations of glucose and mannose. Trypan blue staining was used to calculate the survival rate of mannose-cultured cells. Western blot was used to observe the expression of PMI enzyme. A subcutaneous xenograft tumor model was established to test the efficacy of ketogenic diet combined with mannose. Results With the decrease of glucose concentration, the concentration of mannose required for the significant inhibition of pancreatic cancer cell proliferation was also significantly reduced; mannose significantly induced the expression of PMI enzymes in high glucose culture, and the induction effect was weakened in low glucose. The ketogenic diet had an effect on lowering blood sugar and raising blood ketones, and the inhibitory effect on the xenograft combined with mannose was significant. Conclusion Low glucose concentration enhances the tumor inhibitory effect of mannose, and the combination of ketogenic diet and mannose could improve the antitumor effect.

This study aims to investigate the antitumor effect and the possible mechanism of a microecological preparation (JK5G) in mice. The mice treated with AOM/DSS were then randomly divided into the two model groups and the JK5G group, and the blank control group was included. Fecal samples were used for liquid chromatography-mass spectrometry and 16S rRNA gene sequencing analyses to reveal metabolic perturbations and gut flora disorders to demonstrate the effects of JK5G. Compared with the mice in the control group, the weight and food intake of mice after JK5G treatment were both upregulated. Moreover, JK5G could inhibit the growth of colon tumors and prolong the survival rate of mice, as well as inhibit the levels of cytokines in serum. The proportions of lymphocytes, T cells, CD3+CD4+ T cells, and CD3+CD8+ T cells in the spleen of the JK5G mice were all significantly increased compared to those in the control group (p < 0.05). Similarly, compared with the model group, the proportions of lymphocytes, B cells, T cells, natural killer T cells, CD3+CD4+ T cells, and CD3+CD8+ T cells in the intestinal tumors of the JK5G mice were significantly increased (p < 0.05). Furthermore, 16S rRNA high-throughput sequencing data revealed that Alloprevotella in the JK5G group was significantly upregulated, and Ruminiclostridium, Prevotellaceae_UCG_001, and Acetitomaculum were significantly downregulated. Fecal and serum metabolite analysis detected 939 metabolites, such as sildenafil and pyridoxamine, as well as 20 metabolites, including N-Palmitoyl tyrosine and dihydroergotamine, which were differentially expressed between the JK5G and model groups. Integrated analysis of 16s rRNA and metabolomics data showed that there were 19 functional relationship pairs, including 8 altered microbiota, such as Ruminiclostridium and Prevotellaceae_UCG_001, and 16 disturbed metabolites between the JK5G and model groups. This study revealed that JK5G treatment was involved in the growth of colorectal cancer, which may be associated with the role of JK5G in improving the nutritional status of mice and regulating the tumor microenvironment by regulating the changes of intestinal microbiota and metabolite bands on different pathways.

Monocarboxylate transporters MCTs are important transmembrane transporters responsible for monocarboxylate metabolites such as pyruvate lactate ketone bodies.They promote nutrient absorption of these substances and maintain the metabolic balance of cells.The expression of MCT in tumors is significantly up-regulated which is closely related to glucose metabolism lipid metabolism energy metabolism and the formation of tumor microenvironment and plays an essential role in maintaining the high glycolytic state of tumor cells.In some tumors lactic acid is produced by glycolytic cells in the hypoxic region excreted into the tumor microenvironment by MCT4 and then taken up by peripheral oxidized cells expressing MCT1 finally enters the TCA cycle and becomes a fuel for respiration.Pyruvate is also effluxed out of tumor cells by MCT1 and MCT2 while pyruvate in the tumor microenvironment promotes lung metastasis of breast cancer.At the same time MCT promotes the formation of acidic tumor microenvironment which is not only conducive to the growth proliferation and metastasis of tumors but also causes the death of normal cells around the tumor.The immunosuppression of tumors is also related to this.A number of studies have proved that the high expression of MCT1 and MCT4 is positively correlated with tumor malignancy and prognosis.Inhibition of MCT expression influences tumor growth proliferation and metastasis which provides potential therapeutic targets for targeted therapy.Currently MCT inhibitors such as CHC AR-C155858 and AZD3965 are lack of selectivity for MCT subtypes but have shown good therapeutic effects.While developing new MCT inhibitors exploring strategies for joint application with traditional tumor therapies has a good clinical application prospect.

“Warburg效应”是肿瘤细胞重要的代谢特征之一,肿瘤细胞在氧气充足的条件下仍进行糖酵解,亦称“有氧糖酵解”.愈来愈多的研究表明肿瘤是一种代谢性疾病.因此探索肿瘤代谢变化及机制,以及靶向肿瘤代谢的肿瘤治疗成为近年来肿瘤研究的热点.目前基于肿瘤代谢的一些治疗方法(如生酮疗法、大剂量维生素C等)逐步引起基础研究和临床研究工作者的重视.最近有研究报导,甘露糖可以抑制肿瘤生长、增加阿霉素抗癌效果和延长荷瘤小鼠生存期.其主要作用机制是干扰葡萄糖代谢、促进肿瘤细胞凋亡以及增强化疗药物顺铂和阿霉素的抗肿瘤作用.此外,甘露糖还有调节免疫平衡等作用.甘露糖作为一种营养素,对人体健康无害,有望成为一种重要肿瘤代谢调节治疗的营养素,并且可与一线肿瘤治疗(化疗和放疗)配合来提高抗肿瘤治疗效果,具有重要的临床意义和应用前景.

: Objective To establish a lung cancer dormancy mouse model and verify the effects of Wushen (WS), a formula food, on postoperative recurrence. Methods We established a Lewis cell tumor dormancy model system that definitively links surgery and the subsequent wound-healing response to the outgrowth of lung cancer cells. We used this model to observe the effects of WS on the postoperative recurrence and the nutritional status of the mice. Finally, the immunocyte subtypes and cytokine levels in the serum and spleens of mice were detected by flow cytometry and ELISA. Results The recurrence rate in the WS group was obviously lower than that in the control group. Wushen increased the body weights and serum albumin levels of the mice. The levels of NK, Gr1 + CD11b + CD3 + CD8 + and CD3 + CD4 + T cells in the spleens of mice in the WS group were also increased. Compared with the control group, the levels of CD4 + IFN-γ + , CD4 + IL-2 and CD4 + /IL-10 + in the spleens of mice in the WS group were decreased. Wushen also seemed to decrease the levels of IL-6 and TNF-α, but the decrease was not significant. Conclusion The postoperative lung cancer recurrence model was successfully established. Wushen inhibited postoperative recurrence, apparently by regulating the level of immune cell subtypes and cytokines in the serum and spleen.