Sterol regulatory element binding transcription factor 1 promotes proliferation and migration in head and neck squamous cell carcinoma.

Background: Sterol-regulatory element-binding protein 1 (SREBP1) is a transcription factor involved in lipid metabolism that is encoded by sterol regulatory element binding transcription factor 1(SREBF1). SREBP1 overexpression is associated with the progression of several human tumors; however, the role of SREBP1 in head and neck squamous cell carcinoma (HNSC) remains unclear. Methods: SREBF1 expression in pan-cancer was analyzed using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data, and the association between SREBF1 expression and clinical characteristics of HNSC patients was examined using the UALCAN database. Enrichment analysis of SREBF1-related genes was performed using the Cluster Profiler R package. TCGA database was used to investigate the relationship between immune cell infiltration and SREBF1 expression. CCK-8, flow cytometry, and wound healing assays were performed to investigate the effect of SREBF1 knockdown on the proliferation and migration of HNSC cells. Results: SREBF1 was significantly upregulated in several tumor tissues, including HNSC, and SREBF1 overexpression was positively correlated with sample type, cancer stage, tumor grade, and lymph node stage in HNSC patients. Gene enrichment analysis revealed that SREBF1 is associated with DNA replication and homologous recombination. SREBF1 upregulation was positively correlated with the infiltration of cytotoxic cells, B cells, T cells, T helper cells, and NK CD56 bright cells in HNSC. Knockdown of SREBF1 inhibited the proliferation and migration of HNSC cells (Hep2 and TU212) and induced apoptosis by downregulating the expression of steroidogenic acute regulatory protein-related lipid transfer 4 (STARD4). Conclusions: SREBF1 may promote HNSC proliferation, migration and inhibit apoptosis by upregulating STARD4 and affecting the level of immune cell infiltration.

Melatonin Suppresses Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Signaling and Delays the Development of Hearing Loss in the C57BL/6J Presbycusis Mouse Model.

Melatonin supplementation has been shown to delay age-related hearing loss (ARHL) progression. Previously, melatonin was found to inhibit neuronal mitochondrial DNA (mtDNA) release, as well as inhibit cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling, thereby delaying the onset of central nervous system diseases. Therefore, we hypothesized that melatonin may delay the progression of hearing loss in the C57BL/6J presbycusis mouse model by inhibiting cGAS-STING signaling in the auditory pathway. Oral melatonin at 10 mg/kg/d was administered to 3-month-old C57BL/6J mice until 12 months of age. The auditory brainstem response (ABR) threshold was used to assess their hearing ability. By real-time polymerase chain reaction and Western blot analysis, the levels of cytosolic mtDNA, cGAS/STING, and cytokines were examined in the mouse cochlea, inferior colliculus, and auditory cortex. We found that the 12-month-old control mice exhibited significant hearing loss, increased cytosolic mtDNA, increased expression of inflammatory factors TNF-α, IL-6, IFN-ß, Cxcl10, and Ifit3, up-regulated cGAS and STING expression, and enhanced interferon regulatory factor 3 (IRF3) phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. Melatonin treatment significantly improved hearing, decreased cytosolic mtDNA, suppressed the expression of inflammatory cytokines TNF-α, IL-6, IFN-ß, Ifit3, and Cxcl10, down-regulated cGAS and STING expression, and attenuated IRF3 phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. This study suggested that melatonin had a protective effect on auditory function in the C57BL/6J presbycusis mouse model, which may be mediated through reducing mtDNA release, inhibiting the cGAS-STING signaling pathway in the auditory pathway.

Age-related Activation of Cyclic GMP-AMP synthase-Stimulator of Interferon Genes Signaling in the Auditory System is Associated with Presbycusis in C57BL/6J Male Mice.

Presbycusis, or age-related hearing loss (ARHL), is primarily associated with sensory or transduction nerve cell degeneration in the peripheral and/or central auditory systems. During aging, the auditory system shows mitochondrial dysfunction and increased inflammatory responses. Mitochondrial dysfunction promotes leakage of mitochondrial DNA (mtDNA) into the cytosol, which activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway to induce type I interferon and inflammatory responses. However, whether this pathway is involved in the occurrence and development of ARHL is unknown. This study aimed to determine whether there are age-related changes in the levels of cytosolic mtDNA and cGAS-STING pathway activation in the auditory pathway and to explore their relationship with ARHL. The results showed that cGAS-positive immunoreactive cells were observed in the cochlea, inferior colliculus, and auditory cortex. Levels of cytosolic mtDNA, cGAS, STING, phosphorylated interferon regulatory factor 3, and cytokines were significantly increased in the cochlea, inferior colliculus, and auditory cortex of 6-, 9-, and 12-month-old mice compared with 3-month-old mice. These findings suggested that cytosolic mtDNA may play an important role in the pathogenesis of ARHL by activating cGAS-STING-mediated type I interferon and inflammatory responses.

MiRNA-27b Regulates Angiogenesis by Targeting AMPK in Mouse Ischemic Stroke Model.

Stroke is a leading cause of mortality and serious disability worldwide with limited treatment options. Angiogenesis has been reported to be involved in post-stroke recovery. Although the molecular mechanisms that regulate angiogenesis remain ambiguous, microRNAs have emerged as effective regulators of angiogenesis, involved in neurological function outcome. The present study aims to investigate the regulatory effects of miRNA-27b on post-stroke angiogenesis. In primary cultured brain microvascular endothelial cells (BMECs), the inhibition of miRNA-27b induced the activation of adenosine monophosphate-activated protein kinase (AMPK), which increased tube formation and migration. This action was attenuated when AMPKα2 was knocked down. Mice were subjected to middle cerebral artery occlusion (MCAo) surgery and administrated with Lentivirus miR-27b inhibitor. Enhanced angiogenesis in ischemic boundary zone (IBZ) was observed, and the neurological outcome during the entire study period was improved. The number of phosphate-AMPKα2+ cells that co-expressed endothelial cell marker CD31 was significantly increased. Taken together, the present study demonstrated that downregulated miRNA-27b promoted recovery after ischemic stroke via AMPK stimulus.

Delayed active bleeding after radical evacuation of injected polyacrylamide hydrogel and immediate implant based breast reconstruction.

BACKGROUND: Polyacrylamide hydrogel (PAAG) was used in breast augmentation surgery in China during 1997-2006. Its application has led to increasing complications such as localized lumps, asymmetry, diffuse stiffness, infections, and localized tenderness or myalgia. Hence, many patients have sought for surgical gel evacuation in the following years. CASE PRESENTATION: A 37-year-old G2P0A2 slim (BMI = 18.3) woman who had received injected PAAG bilateral breast augmentation in China 15 years ago, visited our hospital for gel removal due to left upper quadrant breast tenderness with burning sensation. We performed simple mastectomy and immediate breast augmentation with silicone prostheses. Her postoperative course was uneventful. However, subcutaneous hematoma formed right after she started breast massage on the day 14 post operatively. The patient promptly received a CT-guided drainage followed by exploratory surgery with coagulation of the lesion located at the second intercostal space 2 cm to the right of the sternum. DISCUSSION: Delayed bleeding in our patient might be contributed to below reasons. First, the usage of PAAG might cause degeneration of muscle tissue structure which made it more fragile than normal muscle tissue. Secondly, the lack of sufficient coverage, cushion and protection of the muscle tissue in slim patient in addition to the external compression and shearing force of massage. CONCLUSION: In slim patients, we suggest that the postoperative breast massage should be postponed for months until the tissue is recovered, or delayed breast reconstruction could also be considered.

A study on anticancer activity of Caulis Spatholobi extract on human osteosarcoma Saos-2 cells.

The objective of the present study was to investigate the anticancer activity of Chinese medicine Caulis Spatholobi extract on multicentric osteosarcoma cells. Ultraviolet spectrophotometry was used to determine the total flavonoid content in each sample; vanillin sulphuric acid assay was used to determine the condensed tannin content in each sample; and the varying degrees of inhibitory activities of ethanol, ethyl acetate and n-butanol extracts of Caulis Spatholobi on human osteosarcoma Saos-2 cells were studied. The results showed that the inhibitory activity of ethyl acetate extract was the highest among the four extracts. The condensed tannin contents of 1.2 mg/mL Caulis Spatholobi water extract, ethanol extract, ethyl acetate extract and petroleum ether extract were 26.23%, 48.36%, 70.18% and 40.51% respectively; and condensed tannin content of 1.5 mg/mL Caulis Spatholobi water extract, ethanol extract, ethyl acetate extract and petroleum ether extract were 4.15%, 5.81%, 8.76% and 7.30% respectively.

Study on anti-tumor effect of total glycosides from Radix paeoniae rubra in S180 tumor-bearing mice.

The objective of the paper was to study the anti-tumor effect of total glycosides from Radix paeoniae rubra in S180 tumor-bearing mice, and to preliminarily explore its mechanism of action. Mice were made into S180 solid tumor model, grouped and administered with the extracts; tumor inhibition rate was measured by harvesting the tumors, and serum IL-2 and IL-4 levels were measured by taking blood samples. Total glycosides of Radix paeoniae rubra significantly inhibited the growth of tumor cells in tumor-bearing organisms, enhanced the cytotoxic activity of NK cells, and increased the serum IL-2 and IL-4 levels. Total glycosides of Radix paeoniae rubra have some anti-tumor effect in vivo, which might have been accomplished through the regulation of the immune system.

Recurrent upper quadrant pain: a fish bone secondary to gastric perforation and liver abscess.

A 60-year-old male patient was admitted to our hospital for recurrent upper quadrant pain for 1 month. He had a past history of coronary artery disease. After admission, he repeatedly suffered from high-grade fever, chills and upper quadrant pain. Computed tomography (CT) showed a round hypodense mass in the left lobe of the liver, approximately 2.7 × 2.2 cm in size, and a fish bone was confirmed by surgery in the left lobe of liver. The patient was cured completely after surgical removal of the fish bone and liver abscess. CT scan 1 month after discharge showed that the liver abscess had disappeared completely.

[Expression of lung resistance protein and multidrug resistance protein genes in bone marrow cells of acute leukemia patients and its clinical significance].

To study the expression of lung resistance protein (LRP) and multidrug resistance protein (MRP) genes in bone marrow cells in patients with acute leukemia and its clinical significance, expression of LRP and MRP mRNA in bone marrow cells from 47 cases of acute leukemia, including 10 refractory or relapsed cases, and 7 normal individuals were determined by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). The result s showed that expression of LRP gene was negative in normal individuals. LRP mRNA level in newly treated cases of acute myelocytic leukemia and refractory or relapsed cases was significantly higher than that in normal individuals, increased LRP mRNA level has correlation with lower sensitivity to initial chemotherapy and was associated with reduced overall survival rate. Complete remission (CR) rate in LRP positive patients was lower than that in negative cases. The level of LRP expression was correlated with that of MRP mRNA. In conclusion, the expression of LRP mRNA can predict the treatment outcome and prognosis for acute myelocytic leukemia, prognosis was even worse in LRP and MRP linked expression cases, therefore, LRP was an important resistant factor, determination of LRP and MRP expression can help us to evaluate the prognosis and choose chemotherapy program.

[Expression of nm23-H(1) mRNA in Bone Marrow Cells from Patients with Myelodysplastic Syndrome and Its Clinical Implication]

The purpose of this investigation was to explore the expression of nm23-H(1) gene in patients with myelodysplastic syndrome (MDS) and evaluate the relationship between nm23-H(1) expression and therapeutic outcomes. Semi-quantitative RT-PCR was used to detect the expression of nm23-H(1) mRNA in marrow mononuclear cells from 28 MDS patients and 15 normal subjects. nm23-H(1)/GAPDH ratio >/= 0.5 was believed to a positive case. The expression of nm23-H(1) was positive in 24 of 28 MDS patients, and the average level was 0.89 +/- 0.56. nm23-H(1) mRNA was negative in normal controls. The overexpression of nm23-H(1) mRNA in MDS patients could predict outcome of treatment and prognosis for MDR patients.