The Warburg effect or aerobic glycolysis is a hallmark of cancer. Lactate dehydrogenase (LDH), which catalyzes conversion of pyruvate into lactate, serves a critical role during Warburg effect. LDH A chain (LDHA), a member of the LDH family, is upregulated in multiple types of cancer and serves a vital role in tumor growth and progression. However, its expression and function in cervical cancer has not been characterized. The present study evaluated LDHA expression in The Cancer Genome Atlas database and found that LDHA was upregulated in cervical cancer compared with normal tissue. To clarify the role of LDHA in cervical cancer HeLa and SiHa cells, lentiviral shRNA was used to stably knockdown LDHA and oxamate, a small‑molecule inhibitor of LDHA, was used to inhibit the activity of LDHA. Glucose uptake assay, lactate production measurement and ATP detection assay demonstrated LDHA inhibition notably decreased glucose consumption, lactate production and ATP levels in both HeLa and SiHa cells. Furthermore, the effect of LDHA inhibition on cell proliferation, cell cycle and apoptosis was investigated by MTT, BrdU incorporation, colony formation assay, flow cytometry and western blotting; LDHA knockdown or oxamate treatment led to decreased cell proliferation and increased apoptosis. Inhibition of LDHA induced G2/M cell cycle arrest and activated the mitochondrial apoptosis pathway. Mechanistically, the JNK signaling pathway was key for LDHA inhibition‑mediated cell cycle arrest and apoptosis. Collectively, these results indicated that LDHA was involved in cervical cancer pathogenesis and may be a promising therapeutic target for treatment.

Background/Aims: The Hippo-Yap pathway is associated with tumor development and progression. However, little evidence is available concerning its role in cancer cell apoptosis and migration via mitochondrial homeostasis. Here, we identify mitochondrial fission as a regulator of the Hippo–Yap pathway in human rectal cancer tumorigenesis and metastasis. Methods: In this study, we performed loss-of function assays concerning Yap in RCC via shRNA. Cellular viability and apoptosis were measured via MTT, the TUNEL assay and trypan blue staining. Mitochondrial function was assessed via JC1 staining, the mPTP opening assay, mitochondrial respiratory function analysis, electron microscopy and immunofluorescence analysis of HtrA2/Omi. Mitophagy and mitochondrial fission were assessed via western blots and immunofluorescence. Cell migration was evaluated via the Transwell assay, wound-healing assay and immunofluorescence analysis of F-actin. The interaction between JNK and Yap was detected via co-immunoprecipitation and Yap recombinant mutagenic plasmid transfection. Western blots were used to analyze signaling pathways in conjunction with JNK inhibitors or HtrA2/Omi siRNA. Results: Yap is upregulated in human rectal cancer cells, where its expression correlates positively with cell survival and migration. Functional studies established that silencing of Yap drove JNK phosphorylation, which induced Drp1 activation and translocation to the surface of mitochondria, initiating mitochondrial fission. Excessive mitochondrial fission mediated HtrA2/Omi leakage from the mitochondria into the cytoplasm, where HtrA2/Omi triggered cellular apoptosis via the mitochondrial apoptosis pathway. Moreover, released HtrA2/Omi also phosphorylated cofilin and inhibited cofilin-mediated F-actin polymerization. F-actin collapse perturbed lamellipodia formation and therefore impaired cellular migration and invasion. Conclusion: Collectively, our results demonstrate that Hippo-Yap can serve as a tumor promoter in human rectal cancer and acts by restricting JNK/Drp1/mitochondrial fission/ HtrA2/Omi, with potential implications for new approaches to human rectal cancer therapy.

Mast cells play a significant role in urticaria pathogenesis. It's evidenced that vitamin D has positive impact in chronic spontaneous urticaria (CSU) recently, but underlying mechanisms remain unclear. In this study, isobaric tag for relative and absolute quantification-liquid chromatography-mass spectrometer/mass spectrometer was used to detect the expression of proteins in sera of CSU patients and healthy subjects. Thirty-one differentially expressed proteins were identified, in which vitamin D binding protein (VDBP) was higher in CSU patients than that in healthy subjects after verification. Our results indicated that sera of CSU patients induced the production of vascular endothelial growth factor (VEGF) in mast cells through PI3K/Akt/p38 MAPK/HIF-1α axis in an IgE-depended way, and 25(OH)D3 suppressed the expression of VEGF by inhibiting this signaling pathway axis in this process. Collectively, these results suggest VDBP to be a potential biomarker and propose a potential mechanism of benefit for vitamin D therapy in CSU.

To predict the prognosis by observing the dynamic change of C-reactive protein (CRP) and procalcitonin (PCT) for hospitalized community-acquired pneumonia (CAP). The data were collected from January to December 2017 from the first affiliated Hospital of Zhengzhou University. Demographic and clinical patient information including age, length of hospital stay and Charlson Comorbidity Index (CCI) were recorded. Blood samples were taken for CRP, PCT, and white blood cell count (WBC). Receiver Operating Characteristic (ROC) curve was used to verify each biomarker’s association with the prognosis of pneumonia. A total of 350 patients were enrolled in the study. The 30-day mortality was 10.86%. Serial serum CRP3, CRP5, PCT3, PCT5 and PCT5c levels were statistically lower in CAP survivors than non-survivors. CRP3c < 0, CRP5c < 0 and PCT5c < 0 were observed with a statistically lower frequency in patients with 30-day mortality and initial treatment failure. The AUC for 30-day mortality for serial CRP levels combined with CRP clearances was 0.85 (95% CI 0.77–0.92), as compared to an AUC of 0.81 (95% CI 0.73–0.9) for serial PCT levels combined with PCT clearances. Serum serial CRP and PCT levels had moderate predictive value for hospitalized CAP prognosis. The dynamic CRP and PCT changes may potentially be used in the future to predict hospitalized CAP prognosis.

Histone deacetylase (HDAC)‑mediated epigenetic modification plays crucial roles in numerous biological processes, including cell cycle regulation, cell proliferation and apoptosis. HDAC inhibitors demonstrate antitumor effects in various cancers, including glioblastoma and breast cancer. HDAC inhibitors are therefore promising antitumor drugs for these tumors. The tumorigenesis and development of esophageal squamous cell carcinoma (ESCC) involve genetic and epigenetic mechanisms. However, the effects of the HDAC inhibitor on ESCC are not fully investigated. In the present study, ESCC cells were treated with trichostatin A (TSA) and its antitumor effects and related mechanisms were investigated. The results indicated that TSA suppressed the proliferation of ESCCs and caused G1 phase arrest by inducing the expression of p21 and p27. TSA also induced cell apoptosis by enhancing the expression of pro‑apoptotic protein Bax and decreasing the expression of anti‑apoptotic protein Bcl‑2. Furthermore, TSA inhibited the expression of phosphatidylinositol‑3‑kinase (PI3K) and reduced the phosphorylation of Akt and extracellular signal‑regulated kinase (ERK)1/2 in EC9706 and EC1 cell lines. High levels of acetylated histone H4 were detected in TSA‑treated ESCC cell lines. Overall, these results indicate that TSA suppresses ESCC cell growth by inhibiting the activation of the PI3K/Akt and ERK1/2 pathways. TSA also promotes cell apoptosis through epigenetic regulation of the expression of apoptosis‑related protein.