Effects of a 12-week walking intervention on circulating lipid profiles and adipokines in normal weight and abdominal obese female college students.

Background/objectives: Regular exercise such as aerobic exercise has been shown to reduce the risk of some diseases such as cardiovascular disease (CVD). However, only few studies have investigated the impact of regular aerobic exercise on non-obese and overweight/obese persons. Therefore, this study was designed to compare the effect of a 12-week 10,000 steps a day walking intervention on the body composition, serum lipids, adipose tissue function, and obesity-associated cardiometabolic risk between normal weight and overweight/obese female college students. Methods: Ten normal weight (NWCG) and 10 overweight/obese (AOG) individuals were recruited in this study. Both groups performed a regular 10,000 steps a day walk for 12 weeks. Their blood pressure, body mass index, waist-to-hip ratio, and blood lipid profiles were evaluated. Moreover, serum leptin and adiponectin levels were measured using an enzyme-linked immunosorbent assay. Results: Our results revealed that triglyceride (TG), TG/high-density lipoprotein cholesterol (HDL-C) ratio and leptin were significantly reduced in the AOG group after the 12-week walking intervention. However, total cholesterol, HDL-C, and adiponectin/leptin ratio were significantly increased in the AOG group. There was little or no change in these variables in the NWCG group after the 12-week walking intervention. Conclusions: Our study demonstrated that a 12-week walking intervention may help improve cardiorespiratory fitness and obesity-associated cardiometabolic risk by decrease resting heart rate, modulating blood lipid profiles, and inducing adipokine alterations in obese individuals. Therefore, our research encourages obese young adults to improve their physical health by participating in a 12-week walking program of 10,000 steps a day.

Exposure of Immunogenic Tumor Antigens in Surrendered Immunity and the Significance of Autologous Tumor Cell-Based Vaccination in Precision Medicine.

The mechanisms by which immune systems identify and destroy tumors, known as immunosurveillance, have been discussed for decades. However, several factors that lead to tumor persistence and escape from the attack of immune cells in a normal immune system have been found. In the process known as immunoediting, tumors decrease their immunogenicity and evade immunosurveillance. Furthermore, tumors exploit factors such as regulatory T cells, myeloid-derived suppressive cells, and inhibitory cytokines that avoid cytotoxic T cell (CTL) recognition. Current immunotherapies targeting tumors and their surroundings have been proposed. One such immunotherapy is autologous cancer vaccines (ACVs), which are characterized by enriched tumor antigens that can escalate specific CTL responses. Unfortunately, ACVs usually fail to activate desirable therapeutic effects, and the low immunogenicity of ACVs still needs to be elucidated. This difficulty highlights the significance of immunogenic antigens in antitumor therapies. Previous studies have shown that defective host immunity triggers tumor development by reprogramming tumor antigenic expressions. This phenomenon sheds new light on ACVs and provides a potential cue to improve the effectiveness of ACVs. Furthermore, synergistically with the ACV treatment, combinational therapy, which can reverse the suppressive tumor microenvironments, has also been widely proposed. Thus, in this review, we focus on tumor immunogenicity sculpted by the immune systems and discuss the significance and application of restructuring tumor antigens in precision medicine.

Surface Expression of Kynurenine 3-Monooxygenase Promotes Proliferation and Metastasis in Triple-Negative Breast Cancers.

Kynurenine 3-monooxygenase (KMO) is the pivotal enzyme in the kynurenine pathway and is located on the mitochondrial outer membrane. The dysregulation of KMO leads to various neurodegenerative diseases; however, it is rarely mentioned in cancer progression. Our previous study showed that KMO overexpression in canine mammary gland tumors (cMGT) is associated with poor prognosis in cMGT patients. Surprisingly, it was also found that KMO can be located on the cell membranes of cMGT cells, unlike its location in normal cells, where KMO is expressed only within the cytosol. Since cMGT and human breast cancer share similar morphologies and pathogenesis, this study investigated the possibility of detecting surface KMO in human breast cancers and the role of surface KMO in tumorigenesis. Using immunohistochemistry (IHC), flow cytometry (FC), immunofluorescence assay (IFA), and transmission electron microscopy (TEM), we demonstrated that KMO can be aberrantly and highly expressed on the cell membranes of breast cancer tissues and in an array of cell lines. Masking surface KMO with anti-KMO antibody reduced the cell viability and inhibited the migration and invasion of the triple-negative breast cancer cell line, MDA-MB-231. These results indicated that aberrant surface expression of KMO may be a potential therapeutic target for human breast cancers.

A 4-Phenoxyphenol Derivative Exerts Inhibitory Effects on Human Hepatocellular Carcinoma Cells through Regulating Autophagy and Apoptosis Accompanied by Downregulating α-Tubulin Expression.

Hepatocellular carcinoma (HCC) is a leading cancer worldwide. Advanced HCCs are usually resistant to anticancer drugs, causing unsatisfactory chemotherapy outcomes. In this study, we showed that a 4-phenoxyphenol derivative, 4-[4-(4-hydroxyphenoxy)phenoxy]phenol (4-HPPP), exerts an inhibitory activity against two HCC cell lines, Huh7 and Ha22T. We further investigated the anti-HCC activities of 4-HPPP, including anti-proliferation and induction of apoptosis. Our results showed that higher dosage of 4-HPPP downregulates the expression of α-tubulin and causes nuclear enlargement in both the Huh-7 and Ha22T cell lines. Interestingly, the colony formation results showed a discrepancy in the inhibitory effect of 4-HPPP on HCC and rat liver epithelial Clone 9 cells, suggesting the selective cytotoxicity of 4-HPPP toward HCC cells. Furthermore, the cell proliferation and apoptosis assay results illustrated the differences between the two HCC cell lines. The results of cellular proliferation assays, including trypan blue exclusion and colony formation, revealed that 4-HPPP inhibits the growth of Huh7 cells, but exerts less cytotoxicity in Ha22T cells. Furthermore, the annexin V assay performed for detecting the apoptosis showed similar results. Western blotting results showed 4-HPPP caused the increase of pro-apoptotic factors including cleaved caspase-3, Bid and Bax in HCC cells, especially in Huh-7. Furthermore, an increase of autophagy-associated protein microtubule-associated protein-1 light chain-3B (LC3B)-II and the decrease of Beclin-1 and p62/SQSTM1 were observed following 4-HPPP treatment. Additionally, the level of γH2A histone family, member X (γH2AX), an endogenous DNA damage biomarker, was dramatically increased in Huh7 cells after 4-HPPP treatment, suggesting the involvement of DNA damage pathway in 4-HPPP-induced apoptosis. On the contrary, the western blotting results showed that treatment up-regulates pro-survival proteins, including the phosphorylation of protein kinase B (Akt) and the level of survivin on Ha22T cells, which may confer a resistance toward 4-HPPP. Notably, the blockade of extracellular signal-regulated kinases (ERK), but not Akt, enhanced the cytotoxicity of 4-HPPP against Ha22T cells, indicating the pro-survival role of ERK in 4-HPPP-induced anti-HCC effect. Our present work suggests that selective anti-HCC activity of 4-HPPP acts through induction of DNA damage. Accordingly, the combination of ERK inhibitor may significantly enhance the anti-cancer effect of 4-HPPP for those HCC cells which overexpress ERK in the future.

Prophylactic administration of fucoidan represses cancer metastasis by inhibiting vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in Lewis tumor-bearing mice.

Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has a wide assortment of protective activities against cancer, for example, induction of hepatocellular carcinoma senescence, induction of human breast and colon carcinoma apoptosis, and impediment of lung cancer cells migration and invasion. However, the anti-metastatic mechanism that fucoidan exploits remains elusive. In this report, we explored the effects of fucoidan on cachectic symptoms, tumor development, lung carcinoma cell spreading and proliferation, as well as expression of metastasis-associated proteins in the Lewis lung carcinoma (LLC) cells-inoculated mice model. We discovered that administration of fucoidan has prophylactic effects on mitigation of cachectic body weight loss and improvement of lung masses in tumor-inoculated mice. These desired effects are attributed to inhibition of LLC spreading and proliferation in lung tissues. Fucoidan also down-regulates expression of matrix metalloproteinases (MMPs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and vascular endothelial growth factor (VEGF). Moreover, the tumor-bearing mice supplemented with fucoidan indeed benefit from an ensemble of the chemo-phylacticity. The fact is that fucoidan significantly decreases viability, migration, invasion, and MMPs activities of LLC cells. In summary, fucoidan is suitable to act as a chemo-preventative agent for minimizing cachectic symptoms as well as inhibiting lung carcinoma metastasis through down-regulating metastatic factors VEGF and MMPs.

Euphorbia formosana root extract induces apoptosis by caspase-dependent cell death via Fas and mitochondrial pathway in THP-1 human leukemic cells.

Acute myeloid leukemia (AML), a very rare type of cancer, generally affects patients over 50 years old. While clinical drugs to treat advanced stages of AML exist, the disease becomes increasingly resistant to therapies. Euphorbia formosana Hayata (EF) is a native Taiwanese medicinal plant used to treat rheumatism, liver cirrhosis, herpes zoster, scabies, and photoaging, along with tumor suppression. However, the mechanisms by which it suppresses tumors have not been explored. Here, we provide molecular evidence that a hot-water extract of Euphorbia formosana (EFW) selectively inhibited the growth of human leukemic cancer cells more than other solid human cancer cell lines. Most importantly, the plant extract had limited toxicity toward healthy peripheral blood mononuclear cells (PBMCs). After THP-1 leukemic cells were treated with 50-100 µg/mL EFW for one day, the S phase DNA content of the cells increased, while treatment with 200-400 µg/mL caused the cells to accumulate in the G0/G1 phase. Notably, EFW did not affect A-549 lung cancer cells. The effectiveness of EFW against THP-1 cells may be through caspase-dependent apoptosis in leukemic cells, which is mediated through the Fas and mitochondrial pathways. The potent antileukemic activity of EFW in vitro warrants further investigation of this plant to treat leukemias and other malignancies.

Effects of freshwater clam extract supplementation on time to exhaustion, muscle damage, pro/anti-inflammatory cytokines, and liver injury in rats after exhaustive exercise.

The potent anti-inflammatory activities and tissue-protective effects of freshwater clams (Corbicula fluminea) have been well reported. The aim of this study was to determine the effects of freshwater clam extract (FCE) supplementation on time to exhaustion, muscle damage, pro- and anti-inflammatory cytokines, and liver injury in rats after exhaustive exercise. Thirty-two rats were divided into four groups: sedentary control (SC); SC group with FCE supplementation (SC+FCE); exhaustive exercise (E); and E group with FCE supplementation (E+FCE). The SC+FCE and E+FCE groups were treated with gavage administration of 20 mg/kg for seven consecutive days. Blood samples were collected for the evaluation of biochemical parameters. The cytokine levels of TNF-α and IL-10 were also examined. Twenty-four hours after exhaustive exercise, the rat livers were removed for H & E staining. The FCE supplementation could extend the time to exhaustion in exercised rats. The levels of CPK, LDH, AST, ALT, lactate, TNF-α and H & E stains of the liver injury were significantly decreased in the E+FCE group, but the blood glucose and IL-10 were significantly higher in comparison with the E group. This study suggests that FCE supplementation may improve endurance performance and reduce exercise-induced muscle damage, inflammatory stress and liver injury.

7,7''-Dimethoxyagastisflavone-induced apoptotic or autophagic cell death in different cancer cells.

7,7''-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from the needles of Taxus × media cv. Hicksii, was evaluated for its antiproliferative and antineoplastic effects in three human cancer cell lines. Interestingly, DMGF caused cell death via different pathways in different cancer cells. DMGF induced apoptosis, activated caspase-3 activity and changed the mitochondrial membrane potential in HT-29 human colon cancer cells. However, the apoptotic pathway is not the major pathway involved in DMGF-induced cell death in A549 human lung cancer cells and HepG2 human hepatoma cells. Treatment with 3-MA, an inhibitor of autophagy, significantly decreased DMGF-induced cell death in HepG2 and A549 cells, but did not affect DMGF-induced cell death in HT-29 cells. Following DMGF treatment, the HepG2 cells increased expression of LC3B-II, a marker used to monitor autophagy in cells. Thus, DMGF induced apoptotic cell death in HT-29 cells, triggered both apoptotic and autophagic death in A549 cells and induced autophagic cell death in HepG2 cells.

A rapid and convenient method to enhance transgenic expression in target cells.

Gene therapy provides a novel strategy and a new hope for patients with cancer. Unfortunately, the specifics of the delivery systems or the promoters have not achieved the specified efficacy so far, and the perfection of either system will be extremely difficult. In this study, we introduce a simple concept that a combination of a partially specific delivery system and a partially specific promoter activity may achieve a more specific effect on transgenic expression in target cells. The first section describes tumor-related transcription factors that were assayed in tumors or rapidly proliferating cells to determine their activities. The activities of nuclear factor (NF)-κB, CREB, and HIF-1 were higher, and three copies of each response element were used to construct a transcription factor-based synthetic promoter (TSP). The results showed that the expression of the TSP was active and partially specific to cell types. As described in the second section, the multifunctional peptide RGD-4C-HA was designed to absorb polyethyleneimine (PEI) molecules, and this complex was targeted to integrin αvß3 on B16F10 cells. The results indicated that RGD-4C-HA could associate with PEI to mediate specific targeting in vitro. Finally, the combination of the PEI-peptide complex and TSP could enhance the specifically transgenic expression in B16F10 cells. This strategy has been proven to work in vitro and might potentially be used for specific gene therapy in vivo.

Integrative Multiomics Evaluation of IIDH1 Metabolic Enzyme as a Candidate Oncogene That is Correlated with Poor Prognosis and Immune Infiltration in Prostate Adenocarcinoma.

Mutations in the isocitrate dehydrogenase gene (IDH1) are involved in the progression of tumors. Although IDH1 has a role in various tumors, its clinical relevance and its expression in response to the immune response have not been investigated in prostate adenocarcinoma (PRAD). In the present study, we investigated the utility of IDH1 as a prognostic biomarker for PRAD by analyzing IDH1 mRNA expression and its association with patient survival and immune cell infiltration. IDH1 mRNA expression was significantly higher in PRAD tissue than in normal tissue, and Kaplan-Meier survival analysis showed that IDH1 expression was significantly associated with poor prognosis in PRAD patients. To elucidate the mechanisms involved, the correlation between IDH1 expression and the level of immune cell infiltration, in particular of immunosuppressive cells such as CD8+ T-cells, CD4+ T-cells, and macrophages, was further analyzed by single-cell RNA sequencing. We also screened a pharmacogenetic database for IDH1-specific drugs that inhibited high expression in PRAD. In the present study, we used a combination of databases to identify a significant correlation between IDH1 expression and cellular infiltration and to explain the mechanism by which IDH1 confers poor prognosis in PRAD, thus demonstrating the relevance of IDH1 expression as a prognostic biomarker with clinical utility in PRAD patients.

The Lysosome in Malignant Melanoma: Biology, Function and Therapeutic Applications.

Lysosomes are membrane-bound vesicles that play roles in the degradation and recycling of cellular waste and homeostasis maintenance within cells. False alterations of lysosomal functions can lead to broad detrimental effects and cause various diseases, including cancers. Cancer cells that are rapidly proliferative and invasive are highly dependent on effective lysosomal function. Malignant melanoma is the most lethal form of skin cancer, with high metastasis characteristics, drug resistance, and aggressiveness. It is critical to understand the role of lysosomes in melanoma pathogenesis in order to improve the outcomes of melanoma patients. In this mini-review, we compile our current knowledge of lysosomes' role in tumorigenesis, progression, therapy resistance, and the current treatment strategies related to lysosomes in melanoma.

Valsartan decreases TGF-ß1 production and protects against chlorhexidine digluconate-induced liver peritoneal fibrosis in rats.

Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of valsartan on chlorhexidine digluconate-induced PF by decreasing TGF-ß1 production in rats. PF was induced in Sprague-Dawley rats by daily administration of 0.5 ml 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis (PD) tube for 1 week. Rats received daily intravenous injections of low dose valsartan (1 mg/kg) or high dose valsartan (3 mg/kg) for 1 week. After 7 days, conventional 4.25% Dianeal (30 ml) was administered via a PD catheter with a dwell time of 4 h and assessed of peritoneal function. At the end of dialysis, rats were sacrificed and the liver peritoneum was harvested for microscopically and immunohistochemistry. There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D4/P(4Urea) level was reduced, the D4/D0 glucose level, serum and dialysate transforming growth factor-ß1 (TGF-ß1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-ß1, alpha-smooth muscle actin (α-SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF) were elevated in the PF group compared with the vehicle group. High dose of valsartan decreased the serum and dialysate TGF-ß1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-ß1, α-SMA, fibronectin, collagen, and VEGF-positive cells in liver peritoneum. The low dose of valsartan did not protect against chlorhexidine digluconate-induced PF in rat. Valsartan protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-ß1 production.

Antibodies against Helicobacter pylori heat shock protein 60 aggravate HSP60-mediated proinflammatory responses.

Anti-Helicobacter pylori heat shock protein 60 (HpHSP60) antibodies are usually found in H. pylori-infected patients and are known to be associated with the progression of gastric diseases. However, the effects of these antibodies on the functions of HpHSP60 have not been identified. This study aims to investigate the effects of the interaction between anti-HSP60 antibodies and HpHSP60 on inflammatory responses. Anti-HpHSP60 polyclonal sera and monoclonal antibodies (mAbs) were produced to evaluate their effects on HpHSP60-induced IL-8 and TNF-α activity. The results indicated that anti-HpHSP60 polyclonal sera collected from patients infected with H. pylori or from rabbit and mice immunized with HpHSP60 could significantly enhance HpHSP60-mediated IL-8 and TNF-α secretion from monocytic THP-1 cells. Similar effects were also found with anti-HpHSP60 mAbs. Further analysis revealed that this phenomenon was only carried out by anti-HpHSP60 antibody but not by other non-specific mAbs. Moreover, the non-specific mAbs decreased the synergism of HpHSP60 and anti-HpHSP60 mAbs in proinflammatory cytokine induction. Herein, we have examined the role of anti-HpHSP60 antibody in host immune responses for the first time. This study demonstrated that H. pylori HSP60/mAbs could modulate helicobacterial pathogenesis by increasing IL-8 and TNF-α production. The pathogen-specific antibodies may execute potential immune functions rather than recognize or neutralize microbes.

Molecular Machinery and Pathophysiology of Mitochondrial Dynamics.

Mitochondria are double-membraned organelles that exhibit fluidity. They are the main site of cellular aerobic respiration, providing energy for cell proliferation, migration, and survival; hence, they are called "powerhouses." Mitochondria play an important role in biological processes such as cell death, cell senescence, autophagy, lipid synthesis, calcium homeostasis, and iron balance. Fission and fusion are active processes that require many specialized proteins, including mechanical enzymes that physically alter mitochondrial membranes, and interface proteins that regulate the interaction of these mechanical proteins with organelles. This review discusses the molecular mechanisms of mitochondrial fusion, fission, and physiopathology, emphasizing the biological significance of mitochondrial morphology and dynamics. In particular, the regulatory mechanisms of mitochondria-related genes and proteins in animal cells are discussed, as well as research trends in mitochondrial dynamics, providing a theoretical reference for future mitochondrial research.

Acetyl Coenzyme A Synthase 2 Acts as a Prognostic Biomarker Associated with Immune Infiltration in Cervical Squamous Cell Carcinoma.

Cervical squamous cell carcinoma (CESC) is one of the most common malignant tumors in women worldwide with a low survival rate. Acetyl coenzyme A synthase 2 (ACSS2) is a conserved nucleosidase that converts acetate to acetyl-CoA for energy production. Our research intended to identify the correlations of ACSS2 with clinical prognosis and tumor immune infiltration in CESC. ACSS2 is highly expressed in many tumors and is involved in the progression and metastasis of these tumors. However, it is not clear how ACSS2 affects CESC progression and immune infiltration. Analysis of the cBioPortal, GEPIA2, UALCAN, and TCGA databases showed that ACSS2 transcript levels were significantly upregulated in multiple cancer types including CESC. Quantitative RT-PCR analysis confirmed that ACSS2 expression was significantly upregulated in human cervical cancer cells. Here, we performed tissue microarray analysis of paraffin-embedded tissues from 240 cervical cancer patients recorded at FIGO/TNM cancer staging. The results showed that ACSS2 and PDL1 were highly expressed in human CESC tissues, and its expression was associated with the clinical characteristics of CESC patients. TIMER database analysis showed that ACSS2 expression in CESC was associated with tumor infiltration of B cells, CD4+ and CD8+ T cells, and cancer-associated fibroblasts (CAF). Kaplan-Meier survival curve analysis showed that CESC with high ACSS2 expression was associated with shorter overall survival. Collectively, our findings establish ACSS2 as a potential diagnostic and prognostic biomarker for CESC.

Multi-Omics Reveals the Immunological Role and Prognostic Potential of Mitochondrial Ubiquitin Ligase MARCH5 in Human Breast Cancer.

E3 ubiquitin-linked enzyme MARCH5, also known as membrane-associated circular finger 5, is an enzyme encoded by the human MARCH5 gene. The main objective of this study was to visualize the prognosis of MARCH5 in breast cancer and to determine the relationship between MARCH5 expression and tumor immunity. MARCH5 expression was significantly higher in several cancers, including breast cancer (BRCA), compared with corresponding normal tissues. Not only was high MARCH5 expression associated with poorer overall survival, but also MARCH5 expression was positively correlated with the number of tumor-infiltrating immune cells in BRCA malignant tissues. Furthermore, MARCH5 expression showed a strong correlation with various immune markers of BRCA, suggesting its role in regulating tumor immunity. MARCH5 is a useful prognostic biomarker in several cancers, and its expression is highly correlated with tumor immune cell infiltration, and increased MARCH5 expression may serve as a new biomarker for BRCA diagnosis and prognosis.

Pathogenesis and Potential Therapeutic Targets for Triple-Negative Breast Cancer.

Triple negative breast cancer (TNBC) is a heterogeneous tumor characterized by early recurrence, high invasion, and poor prognosis. Currently, its treatment includes chemotherapy, which shows a suboptimal efficacy. However, with the increasing studies on TNBC subtypes and tumor molecular biology, great progress has been made in targeted therapy for TNBC. The new developments in the treatment of breast cancer include targeted therapy, which has the advantages of accurate positioning, high efficiency, and low toxicity, as compared to surgery, radiotherapy, and chemotherapy. Given its importance as cancer treatment, we review the latest research on the subtypes of TNBC and relevant targeted therapies.

Kynurenine 3-monooxygenase (KMO), and signal transducer and activator of transcription 3 (STAT3) expression is involved in tumour proliferation and predicts poor survival in canine melanoma.

Canine melanoma is a malignant tumour that exhibits aggressive behaviour, and frequently metastasizes to regional lymph nodes and distant sites. Currently, there are no effective treatments or practical prognostic biomarkers for canine melanoma. The enzyme kynurenine 3-monooxygenase (KMO), which plays a central role in the tryptophan metabolism, has previously been identified as the main pathogenic factor in neurodegenerative diseases; however, it has recently been found to be positively associated with tumour malignancy in human hepatocellular carcinoma and canine mammary tumours. Signal transducer and activator of transcription 3 (STAT3) is a well-known oncoprotein contributing to the proliferation, survival, invasiveness and metastasis of a variety of cancers. Although whether STAT3 and KMO collaborate in tumorigenesis needs to be further verified, our previous findings showed that inhibition of KMO activity reduced activation of STAT3. This study investigated the expressions of KMO and STAT3/phosphorylated (pSTAT3) by immunohistochemical analysis in 85 cases of canine melanoma, showing their expression levels were high within highly mitotic melanoma cells. KMO Overexpression was significantly associated with increased STAT3 and pSTAT3 expressions. Melanoma tissues with higher KMO, STAT3 and pSTAT3 protein expressions were correlated with reduced survival rates of the canine patients. Moreover, inhibition of KMO activity in canine melanoma cells resulted in reduced cell viability, in addition to decreased expressions of STAT3 and pSTAT3. Our results indicated the significance of KMO and the potential role of KMO/STAT3 interaction in enhancing tumour development. Additionally, KMO and STAT3/pSTAT3 may be viewed as useful biomarkers for the prediction of prognosis of canine melanoma.

Identification of Novel Biomarkers and Candidate Drug in Ovarian Cancer.

This paper investigates the expression of the CREB1 gene in ovarian cancer (OV) by deeply excavating the gene information in the multiple databases and the mechanism thereof. In short, we found that the expression of the CREB1 gene in ovarian cancer tissue was significantly higher than that of normal ovarian tissue. Kaplan-Meier survival analysis showed that the overall survival was significantly shorter in patients with high expression of the CREB1 gene than those in patients with low expression of the CREB1 gene, and the prognosis of patients with low expression of the CREB1 gene was better. The CREB1 gene may play a role in the occurrence and development of ovarian cancer by regulating the process of protein. Based on differentially expressed genes, 20 small-molecule drugs that potentially target CREB1 with abnormal expression in OV were obtained from the CMap database. Among these compounds, we found that naloxone has the greatest therapeutic value for OV. The high expression of the CREB1 gene may be an indicator of poor prognosis in ovarian cancer patients. Targeting CREB1 may be a potential tool for the diagnosis and treatment of OV.

Positive Effects of Preventive Nutrition Supplement on Anticancer Radiotherapy in Lung Cancer Bearing Mice.

(1) Background: Radiotherapy (RT) is one of the major treatments for non-small cell lung cancer, but RT-associated toxicities usually impede its anticancer effect. Nutrient supplementation has been applied for cancer prevention or a complementary measure to anticancer therapy. Here, we explored the influence of total nutrition supplementation before and after cancer occurrence on the anticancer benefit and side effects of RT. (2) Methods: C57BL/6JNarl mice were inoculated with Lewis lung carcinoma cells and then treated with radiotherapy. TNuF, a total nutrition formula, was prescribed by oral gavage. In the preventive groups, TNuF supplementation started from seven days before tumor inoculation. In the complementary groups, TNuF supplementation began after tumor inoculation. (3) Results: TNuF successfully enhanced the anticancer effect of RT against primary tumor and lung metastasis. Additionally, the complementary supplement improved the high serum TNF-α level and the wasting of sartorius muscle in mice receiving RT. In histologic and molecular analysis, TNuF was observed to modulate EGFR, apoptosis, and VEGF and PD-1/PD-L1 pathways. Furthermore, the anticancer benefit of the preventive supplement was comparable to that of the complementary administration. (4) Conclusions: Our results demonstrated that the prescription of the TNuF total nutrition formula before and after cancer diagnosis attains similar benefits in testing subjects with typical anticancer RT. TNuF is also a potential sensitizer to anti-PD-1 immune therapy.