Ultrathin Supratrochlear Artery Cutaneous Branch Flaps for Large Defects Around Eyebrows.

BACKGROUND: The key point of repairing large defects around eyebrows is to keep the eyebrow undistorted. The limited skin elevates the application difficulty of conventional methods such as direct suture or local flap. Forehead pedicle flaps do well in tension control. However, most of them are too thick for defects because the frontalis muscle must be included. Recently, 1 stable supratrochlear artery cutaneous branch was found, which provides an opportunity to make an ultrathin forehead flap with a good blood supply. This study aims to investigate whether the supratrochlear artery cutaneous branch flap could perform good esthetic reconstruction for defects around the eyebrow. METHODS: The authors retrospectively included 15 patients whose defect around the eyebrows was repaired by the supratrochlear artery cutaneous branch flap from June 2017 to June 2020. The authors followed up about their flap color and texture, scar, abnormal sensation, any complication, recurrence, and patient satisfaction for at least 6 months online or face-to-face. RESULTS: All of the flaps survived, without distortion of the eyebrows or inner canthi. Similar flap color, texture, and thickness with the nearby skin were obtained, except 2 patients reported pigmentation. Donor and receptor scars were acceptable. There was no recurrence or other complications. All of the patients were satisfied with the surgery effect. CONCLUSIONS: The supratrochlear artery cutaneous branch flap is a valuable alternative method to repair large defects around the eyebrows. It can avoid facial distortion and achieve good esthetic outcomes in single-stage surgery.

The TetR-type regulator AtsR is involved in multidrug response in Corynebacterium glutamicum.

BACKGROUND: The TetR (tetracycline repressor) family is one of the major transcription factor families that regulate expression of genes involved in bacterial antimicrobial resistance systems. NCgl0886 protein, designated as AtsR, is a member of the TetR family identified in Corynebacterium glutamicum, which is conserved in several species of the genera Corynebacterium, also including the well-known pathogen C. diphtheriae. AtsR is located at no far upstream of the identically oriented ncgl0884 gene, encoding a putative multidrug efflux pump protein, and in the same operon with ncgl0887, encoding a resistance, nodulation and cell division (RND) superfamily drug exporter. However, the role of AtsR is not clearly understood. RESULTS: Here we showed that dimeric AtsR directly repressed the expression of the ncgl0887-atsR operon, as well as indirectly controlled the ncgl0884 transcription. Antibiotics and toxic compounds induced the expression of ncgl0887-atsR operon. A perfect palindromic motif (5΄-TGCAA-N2-TTGCA-3΄; 12 bp) was identified in the upstream region of ncgl0887-atsR operon. Electrophoretic mobility shift assays (EMSAs) demonstrated specific binding of AtsR to this motif, and hydrogen peroxide (H2O2) blocked binding. H2O2 oxidized cysteine residues to form Cys123-Cys187 intermolecular disulfide bonds between two subunits in AtsR dimer, which altered its DNA-binding characteristics and caused its dissociation, thereby leading to derepression of the drug efflux protein. Deletion of ncgl0884 and ncgl0887 increased the susceptibilities of C. glutamicum for several toxic compounds, but overexpression of atsR decreased the drug tolerance of C. glutamicum. CONCLUSIONS: Our study revealed that AtsR was a redox regulator that sensed oxidative stress via thiol modification. The results obtained here will contribute to our understanding of the drug response mechanism not only in C. glutamicum but also in the related bacteria C. diphtheriae.

Mn-ZIF nanozymes kill tumors by generating hydroxyl radical as well as reversing the tumor microenvironment.

Tumor tissues are well known for their unique high hydrogen peroxide (H2O2) microenvironment. How to exploit this tumor microenvironment for tumor cell killing is a question. In this study, a Mn-doped metal-organic framework (Mn-ZIF) was constructed. It possesses good peroxidase (POD) activity, which can oxidize tumor-localized H2O2 into hydroxyl radicals (·OH), that possesses the ability to directly kill tumor cells. More surprisingly, in vivo experiments the researchers not only observed the tumor-killing effect of Mn-ZIF, but also found it changes in macrophage phenotype in the tumor region. There was an increase in macrophage polarization towards the M1 subtype. This suggests that the tumor-killing effect of Mn-ZIF not only comes from its POD activity, but also regulates the immune microenvironment in the tumor region. In conclusion, the preparation of Mn-ZIF provides a new way for comprehensive tumor therapy.

Development of sea urchin type silica stabilised zirconia nanospheres with enhanced antimicrobial and osteoactivity properties.

Zirconia based ceramics are giving new hope in hard tissues replacement and implants application. Among the three forms of zirconia (ZrO2), tetragonal form (t-ZrO2) possess high mechanical stability in comparison with the other two which makes it suitable for fabricating biomedical implants with enhanced osteo activity. Here, tetragonal phase nanospheres consisting of silica stabilised zirconia (1:1) were prepared via sol gel method. The nanospheres exhibit sea urchin type morphology as observed from FESEM analysis. XRD patterns confirm the formation of t -SiO2-ZrO2 binary phase after high temperature calcination at 650°C. The immersion studies in SBF help in the formation of a layer of apatite in a gradual manner over the pallets for the period of 7, 14, 21 and 28 days which was confirmed by XRD, FTIR analysis. Moreover, t- SiO2 - ZrO2 samples were subjected to cytotoxicity tests through MTT assay on MG-63 cell lines. Antibacterial properties were investigated quantitatively using colony forming unit method against both gram positive as well as gram-negative bacteria.

Screening for MicroRNA combination with engineered exosomes as a new tool against osteosarcoma in elderly patients.

The most common primary malignant bone sarcoma is Osteogenic sarcoma (OS) which has a bimodal age distribution. Unfortunately, the treatment of OS was less effective for elderly patients than for younger ones. The study aimed to explore a new microRNA (miRNA) which can bind to combining engineered exosomes for treatment of older OS patients. Based on GSE65071 and miRNet 2.0, two up-regulated miRNAs (miR-328, miR-107) and seven down-regulated miRNAs (miR-133b, miR-206, miR-1-3p, miR-133a, miR-449a, miR-181daysay, miR-134) were selected. Next, we used FunRich software to predict the up-stream transcription factors (TFs) of differentially expressed miRNAs (DE-miRNAs). By comparing target genes predicted from DE-miRNAs with differentially expressed genes, we identified 12 down-regulated and 310 up-regulated mRNAs. For KEGG analysis, the most enriched KEGG pathway was Cell cycle, Spliceosome, and Protein digestion and absorption. By using protein-protein interactions network, topological analysis algorithm and GEPIA database, miR-449a /CCNB1 axis was identified. Experiments in vitro were conducted to confirm the results too. MiRNA-449a is down-regulated in osteosarcoma and suppresses cell proliferation by targeting CCNB1. Our findings not only reveal a novel mechanism of miR-449a /CCNB1 in OS but also had laid the groundwork for further investigation and analysis in the field of exosome engineering.

A Prognosis Marker Dynein Cytoplasmic 1 Heavy Chain 1 Correlates with EMT and Immune Signature in Liver Hepatocellular Carcinoma by Bioinformatics and Experimental Analysis.

Background: Liver hepatocellular carcinoma (LIHC) has had a continuous increase in incidence and mortality rates over the last 40 years. Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) is a protein coding gene which encodes the cytoplasmic dynein heavy chain family. This is the first investigation into the expression of DYNC1H1 and its mechanisms of action in LIHC patients. Methods: Based on the DYNC1H1 expression data from the TCGA database, we performed the DYNC1H1 expression, clinicopathological data, gene enrichment, and immune infiltration analysis. TIMER and CIBERSORT were used to assess immune responses of DYNC1H1 in LIHC. GEPIA, K-M survival analysis, and immunohistochemical staining pictures from the THPA were used to validate the results. In order to evaluate the diagnostic value of DYNC1H1, GEO datasets were analyzed by using ROC analysis. And quantitative real-time polymerase chain reaction was also carried out to evaluate the expression of DYNC1H1. Results: DYNC1H1 expression levels were associated with T classification, pathologic stage, histologic grade, and serum AFP levels. DYNC1H1 is an independent factor for a poor prognosis in patients with LIHC. Further study showed that high expression of DYNC1H1 was enriched in epithelial-mesenchymal transition (EMT) and the TGF ß signaling pathway by GSEA analysis enrichment, indicating that DYNC1H1 might play a key role in the progression of CRC through EMT and immune response, which also had been validated by the experimental assays. Conclusions: DYNC1H1 will provide a novel and important perspective for the mechanisms of LIHC by regulating EMT. This gene will be able to act as an efficacious tool for the early diagnosis and effective intervention of LIHC.

CD137 Regulates Bone Loss via the p53 Wnt/ß-Catenin Signaling Pathways in Aged Mice.

Senile osteoporosis is a chronic skeletal disease, leading to increased bone brittleness and risk of fragile fractures. With the acceleration of population aging, osteoporosis has gradually become one of the most serious and prevalent problems worldwide. Bone formation is highly dependent on the proper osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in the bone marrow microenvironment, which is generated by the functional relationship among different cell types, including osteoblasts, adipogenic cells, and bone marrow stromal cells in the bone marrow. It is still not clear how osteoporosis is caused by its molecular mechanism. With aging, bone marrow is able to restrain osteogenesis. Discovering the underlying signals that oppose BMSC osteogenic differentiation from the bone marrow microenvironment and identifying the unusual changes in BMSCs with aging is important to elucidate possible mechanisms of senile osteoporosis. We used 3 gene expression profiles (GSE35956, GSE35957, and GSE35959) associated with osteoporosis. And a protein-protein interaction (PPI) network was also built to identify the promising gene CD137. After that, we performed in vivo experiments to verify its function and mechanism. In this experiment, we found that significant bone loss was observed in aged (18-month-old) mice compared with young (6-month-old) mice. The adipose tissue in bone marrow cavity from aged mice reached above 10 times more than young mice. Combining bioinformatics analysis and vivo experiments, we inferred that CD137 might be involved in the p53 and canonical Wnt/ß-catenin signaling pathways and thereby influenced bone mass through regulation of marrow adipogenesis. Importantly, osteoporosis can be rescued by blocking CD137 signaling in vivo. Our research will contribute to our understanding not only of the pathogenesis of age-related bone loss but also to the identification of new targets for treating senile osteoporosis.

Integrated Bioinformatics and Experimental Analysis Identified TRIM28 a Potential Prognostic Biomarker and Correlated with Immune Infiltrates in Liver Hepatocellular Carcinoma.

Background: Since the 1970s, liver hepatocellular carcinoma (LIHC) has experienced a constant rise in incidence and mortality rates, making the identification of LIHC biomarkers very important. Tripartite Motif-Containing 28 (TRIM28) is a protein-coding gene which encodes the tripartite motif-containing proteins (TRIMs) family and is associated with specific chromatin regions. TRIM28 expression and its prognostic value and impact on the immune system in LIHC patients are being investigated for the first time. Methods: The TRIM28 expression data from TCGA database was used to analyze TRIM28 expression, clinicopathological information, gene enrichment, and immune infiltration and conduct additional bioinformatics analysis. R language was used for statistical analysis. TIMER, CIBERSORT, and ssGSEA were used to assess immune responses of TRIM28 in LIHC. Next, the results were validated using GEPIA, ROC analysis, and immunohistochemical staining pictures from the THPA. GSE14520, GSE63898, and GSE87630 datasets were analyzed using ROC analysis to further evaluate TRIM28's diagnostic value. To ultimately determine TRIM28 expression, we performed qRT-PCR (quantitative real-time polymerase chain reaction). Results: High TRIM28 expression level was associated with T classification, pathologic stage, histologic grade, and serum AFP levels. In patients with LIHC, TRIM28 was an independent risk factor for a poor prognosis. The pathways ligand-receptor interaction, which is critical in LIHC patients, were closely associated with TRIM28 expression, and the function of DC could be suppressed by overexpression of TRIM28. As a final step, our results were validated by GEO data and qRT-PCR. Conclusions: TRIM28 will shed new light on LIHC mechanisms. As an effective diagnostic and intervention tool, this gene will be able to diagnose and treat LIHC at an early stage.

Efficacy and Safety of Brigatinib Compared With Crizotinib in Asian vs. Non-Asian Patients With Locally Advanced or Metastatic ALK-Inhibitor-Naive ALK+ Non-Small Cell Lung Cancer: Final Results From the Phase III ALTA-1L Study.

BACKGROUND: Brigatinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor with demonstrated efficacy in locally advanced and metastatic non-small cell lung cancer (NSCLC) in crizotinib-refractory and ALK inhibitor-naive settings. This analysis assessed brigatinib in Asian vs. non-Asian patients from the first-line ALTA-1L trial. PATIENTS AND METHODS: This was a subgroup analysis from the phase III ALTA-1L trial of brigatinib vs. crizotinib in ALK inhibitor-naive ALK+ NSCLC. The primary endpoint was progression-free survival (PFS) as assessed by blinded independent review committee (BIRC). Secondary endpoints included confirmed objective response rate (ORR) and overall survival (OS) in the overall population and BIRC-assessed intracranial ORR and PFS in patients with brain metastases. RESULTS: Of the 275 randomized patients, 108 were Asian. Brigatinib showed consistent superiority in BIRC-assessed PFS vs. crizotinib in Asian (hazard ratio [HR]: 0.35 [95% CI: 0.20-0.59]; log-rank P = .0001; median 24.0 vs. 11.1 months) and non-Asian (HR: 0.56 [95% CI: 0.38-0.84]; log-rank P = .0041; median 24.7 vs. 9.4 months) patients. Results were consistent with investigator-assessed PFS and BIRC-assessed intracranial PFS. Brigatinib was well tolerated. Toxicity profiles and dose modification rates were similar between Asian and non-Asian patients. CONCLUSION: Efficacy with brigatinib was consistently better than with crizotinib in Asian and non-Asian patients with locally advanced or metastatic ALK inhibitor-naive ALK-+ NSCLC. There were no clinically notable differences in overall safety in Asian vs. non-Asian patients.