Aerobic exercise protects MI heart through miR-133a-3p downregulation of connective tissue growth factor.

OBJECTIVE: To investigate the effect of aerobic exercise intervention to inhibit cardiomyocyte apoptosis and thus improve cardiac function in myocardial infarction (MI) mice by regulating CTGF expression through miR-133a-3p. METHODS: Male C57/BL6 mice, 7-8 weeks old, were randomly divided into sham-operated group (S group), sham-operated +aerobic exercise group (SE group), myocardial infarction group (MI group) and MI + aerobic exercise group (ME group). The mice were anesthetized the day after training and cardiac function was assessed by cardiac echocardiography. Myocardial collagen volume fraction (CVF%) was analyzed by Masson staining. Myocardial CTGF, Bax and Bcl-2 were detected by Western blotting, and myocardial miR-133a-3p was measured by RT-qPCR. RESULTS: Compared with the S group, miR-133a-3p, Bcl-2 and EF were significantly decreased and CTGF, Bax, Bax/ Bcl-2, Caspase 3, Cleaved Caspase-3, LVIDd, LVIDs and CVF were significantly increased in the MI group. Compared with the MI group, miR-133a-3p, Bcl-2 and EF were significantly increased, cardiac function was significantly improved, and CTGF, Bax, Bax/ Bcl-2, Caspase 3, Cleaved Caspase-3, LVIDd, LVIDs and CVF were significantly decreased in ME group. The miR-133a-3p was significantly lower and CTGF was significantly higher in the H2O2 intervention group compared with the control group of H9C2 rat cardiomyocytes. miR-133a-3p was significantly higher and CTGF was significantly lower in the AICAR intervention group compared to the H2O2 intervention group. Compared with the control group of H9C2 rat cardiomyocytes, CTGF, Bax and Bax/Bcl-2 were significantly increased and Bcl-2 was significantly decreased in the miR-133a-3p inhibitor intervention group; CTGF, Bax and Bax/Bcl-2 were significantly decreased and Bcl-2 was significantly upregulated in the miR-133a-3p mimics intervention group. CONCLUSION: Aerobic exercise down-regulated CTGF expression in MI mouse myocardium through miR-133a-3p, thereby inhibiting cardiomyocyte apoptosis and improving cardiac function.

Mutational landscape of head and neck cancer and cervical cancer in Chinese and Western population.

BACKGROUND: We aimed to unbiasedly map the genetic mutation profile of HNSC and CESC associated with HPV status in the Chinese population (SYSU-cohort) and compare them with Western population (TCGA-cohort). METHODS: Fifty-one HNSC patients (SYSU-HNSC) and 38 CESC patients (SYSU-CESC) were enrolled in this study. Genomic alterations were examined, and the profile was produced using the YuanSuTM450 gene panel (OrigiMed, Shanghai, China). The altered genes were inferred and compared to Western patients from TCGA cohorts. RESULTS: Compared to the TCGA-HNSC cohort, FGFR3 mutation was identified as a novel target in SYSU-HNSC with therapeutic potential. Compared to the TCGA-CESC cohort, some epigenetic regulation-associated genes were frequently mutated in SYSU-CESC cohort (KMT2C, KMT2D, KDM5C, KMT2A). CONCLUSION: In summary, our study provides unbiased insights into the genetic landscape of HNSC and CESC in the Chinese population and highlights potential novel therapeutic targets that may benefit Chinese patients.

The roles EpCAM plays to enhance the malignancy of gastric cancer.

BACKGROUND: Gastric cancer (GC) remains a global challenge due to its high morbidity and mortality rates especially in Asia as well as poor response to treatment. As a member of the adhesion protein family and transmembrane glycoprotein, EpCAM expressed excessively in cancer cells including GC cells. The database assay showed that EpCAM is excessively expressed and easily mutated in cancers, especially in early stage of GC. METHODS: To explore the roles EpCAM plays in oncogenesis and progression of GC, the expression of EpCAM was deleted in GC cells with CRISPR/Cas9 method, and then the changes of cell proliferation, apoptosis, motility and motility associated microstructures in EpCAM-deleted GC cells (EpCAM-/-SGC7901) were detected to evaluate the rules EpCAM played. RESULTS: The results showed that EpCAM deletion caused cell proliferation, motility and the development of motility-relevant microstructures inhibited significantly, apoptotic trend and contact inhibition enhanced in EpCAM-deleted GC cells. The results of western blot suggested that EpCAM modulates the expression of epithelial/endothelial mesenchymal transition (EMT) correlated genes. All results as above indicated that EpCAM plays important roles to enhance the oncogenesis, malignancy and progression as a GC enhancer. CONCLUSIONS: Combining our results and published data together, the interaction of EpCAM with other proteins was also discussed and concluded in the discussion. Our results support that EpCAM can be considered as a novel target for the diagnosis and therapy of GC in future.

The Tai Chi Flap: A Novel Design for the Radial Forearm Flap.

OBJECTIVE: Tai Chi is an ancient philosophy used to explain the universe. The Tai Chi symbol is represented by Yin/Yang fishes. The authors describe a novel radial forearm flap (RFF) design for the reconstruction of circular defects based on the Tai Chi symbol. METHODS: Eleven consecutive patients with craniofacial skin or mucus defects underwent reconstruction with a Tai Chi RFF. Patient perioperative and follow-up information was collected. RESULTS: The diameter of the Tai Chi RFF was 5 to 6 cm. All flaps healed uneventfully without ischemic problems, and all donor site defects were closed primarily without skin grafts. Remarkably, 2 patients received a tattoo to mark the Tai Chi symbol and greatly appreciate the shape of the flap. CONCLUSIONS: The Tai Chi flap is an economically friendly flap design that can be used to prevent skin grafts while providing psychological comfort to patients.

Single-cell profiling of tumor-infiltrating TCF1/TCF7+ T cells reveals a T lymphocyte subset associated with tertiary lymphoid structures/organs and a superior prognosis in oral cancer.

OBJECTIVES: Despite substantial advances in treatment, clinical outcomes for oral squamous cell carcinoma (OSCC) remain unsatisfactory. Tumor-infiltrating lymphocytes (TILs) are an important prognostic factor for patients and are heterogeneous. Some studies have suggested that TCF1/TCF7+ T cells and tertiary lymphatic structure/organ (TLS) play an important role in tumor immunity. However, how they affect tumor immunity and whether they are related to prognosis in OSCC have not been reported in detail. MATERIALS AND METHODS: We isolated OSCC cells and performed single-cell RNA sequencing (scRNA-seq). We used immunohistochemistry (IHC) to analyze the relationship between TLSs and prognosis. Multiplex immunohistochemistry (MIHC), flow cytometry (FCM) and spatial analysis were performed to verify the characteristics of TCF1/TCF7+ T cells. The prognostic significance and upstream regulatory network of the TCF1/TCF7+ T cell subpopulation were determined by multivariate analysis and Scenic software. RESULTS: We found a strong association between TCF1/TCF7+ T cell subsets, TLSs and prognosis. The results suggested that TCF1/TCF7+ T cells express high levels of TLS-related genes and low levels of immune checkpoint molecules. Finally, we found that TCF1/TCF7+ T cells were significantly associated with favorable outcomes. We also describe the upstream drivers that these cells rely on. CONCLUSIONS: TCF1/TCF7+ T cells could be used as a new therapeutic target to regulate the immune response of OSCC and are expected to be a new prognostic marker.

A Pan-Histone Deacetylase Inhibitor Enhances the Antitumor Activity of B7-H3-Specific CAR T Cells in Solid Tumors.

PURPOSE: The limited efficacy of chimeric antigen receptor (CAR) T-cell therapies with solid malignancies prompted us to test whether epigenetic therapy could enhance the antitumor activity of B7-H3.CAR T cells with several solid cancer types. EXPERIMENTAL DESIGN: We evaluated B7-H3 expression in many human solid cancer and normal tissue samples. The efficacy of the combinatorial therapy with B7-H3.CAR T cells and the deacetylase inhibitor SAHA with several solid cancer types and the potential underlying mechanisms were characterized with in vitro and ex vivo experiments. RESULTS: B7-H3 is expressed in most of the human solid tumor samples tested, but exhibits a restricted expression in normal tissues. B7-H3.CAR T cells selectively killed B7-H3 expressing human cancer cell lines in vitro. A low dose of SAHA upregulated B7-H3 expression in several types of solid cancer cells at the transcriptional level and B7-H3.CAR expression on human transgenic T-cell membrane. In contrast, the expression of immunosuppressive molecules, such as CTLA-4 and TET2, by T cells was downregulated upon SAHA treatment. A low dose of SAHA significantly enhanced the antitumor activity of B7-H3.CAR T cells with solid cancers in vitro and ex vivo, including orthotopic patient-derived xenograft and metastatic models treated with autologous CAR T-cell infusions. CONCLUSIONS: Our results show that our novel strategy which combines SAHA and B7-H3.CAR T cells enhances their therapeutic efficacy with solid cancers and justify its translation to a clinical setting.

Correlation of Cerebral White Matter Lesions with Carotid Intraplaque Neovascularization assessed by Contrast-enhanced Ultrasound.

PURPOSE: Carotid atherosclerotic plaque is closely associated with cerebral white matter lesions (WMLs), while intraplaque neovascularization (IPN) contributes significantly to arterial remodeling and plaque vulnerability. In this study, we aim to evaluate the correlation of carotid IPN with cerebral WMLs. METHODS: The presence of IPN and WMLs were assessed by contrast-enhanced ultrasound (CEUS) and MRI respectively. IPN was evaluated utilizing semi-quantification visual grading scale and WMLs was divided according to Fazekas grading scale. We investigated the baseline data, Fazekas grades, and IPN grades among 269 participants. We explored the influences of each variable on Fazekas grades using ordinal logistic regression and evaluated the relationship between IPN grades and WMLs Fazekas grades. RESULTS: Increased age (OR: 1.06, P<0.001), hypertension (OR: 2.17, P=0.002), cerebral infarction (OR: 1.74, P=0.046), and elevated carotid IPN grading were significantly associated with aggravated Fazekas grades (grade 2 or 3). To be specific, people having grade 3, 2, and 1 carotid IPN were 25.84 (P<0.001), 10.64 (P<0.001), and 5.96 (P=0.010) times as likely to have elevated Fazekas grades compared with those who having grade 0 carotid IPN. CONCLUSION: Increased carotid IPN is independently correlated with aggravated cerebral WMLs.

Diode laser combined with intradiscal vancomycin for iatrogenic discitis: an experimental study in rabbits.

OBJECTIVE: The purpose of this study was to assess the efficacy of diode laser combined with intradiscal vancomycin for iatrogenic discitis (ID) infected with Staphylococcus aureus. BACKGROUND DATA: In vivo and in vitro studies have reported that diode laser has a potential bactericidal effect on S. aureus. METHODS: The rabbit ID model was induced by injecting S. aureus into the intervertebral discs (IVDs). The animals were classified into the following groups: Group M, model; Group N, non-treatment; Group O, operation; Group V, vancomycin; Group L, laser; and Group C, laser with vancomycin. The rabbits were killed when paraplegia occurred and target IVD regions were removed for histopathological examination. RESULTS: In Group M, MRI findings revealed narrowing of the disc space, with changed T1 and T2 signals. In Group N, pathological examination showed a narrowed disc space, inflammatory changes in disc tissue, extensive erosion and hyperostosis of bony end plates, and an epidural abscess. Narrowed disc space and bone fusion were observed in Group O. In Group V, narrowed disc spaces, focal inflammatory changes of the disc tissue, and focal erosion and hyperostosis of bony end plates were seen. In Groups L and C, cavitation, inflammatory lesions, focal erosion, and hyperostosis of bony endplates were observed. However, in Group C, fibrosis was found in the nucleus region, with a smaller area of cavitation and better preservation of IVD structure than in Group L. The ID score was lowest in Group O, at 9.7 ± 0.95. The ID scores in Groups V and L were 12.2 ± 1.32 and 12.6 ± 0.97, respectively, significantly less than in Group N. The Group C ID score of 10.9 ± 0.99 was significantly less than that of Groups N, V, and L. CONCLUSIONS: High power diode laser combined with intradiscal vancomycin contained the pathological process of ID in this rabbit model.