Case report: One case of acute myeloid leukemia M3 with atypical morphology.

Acute promyelocytic leukemia (APL) is a type of acute myeloid leukemia. About 2% of APL is characterized by atypical rearrangements. Here we reported one APL case with atypical manifestations and morphology. A 35-year-old woman patient, mainly due to fatigue, poor appetite for over 10 days and intermittent fever for 3 days. combined with the results of flow cytometry, fusion gene and chromosome, the patient was diagnosed as AML-M3 with atypical morphology. Double induction therapy with retinoic acid and arsenous acid was immediately administrated. Idarubicin was administrated on the 18th day. A re-examination was performed in the 5th week, both the blood routine test and myelogram showed normal results, and the fusion gene turned negative, indicating complete remission. When atypical morphology occurs, peripheral blood POX staining may be performed to check the abnormal cells. Flow cytometry, chromosome analysis, and fusion gene analysis are also required for further diagnosis.

Vascular endothelial growth factor-D plasma levels in fluid overload and cardiac function evaluation of elderly patients with cardiovascular disease.

This study aimed to investigate the clinical significance of vascular endothelial growth factor (VEGF) subtypes and growth differentiation factor-15 (GDF-15) plasma levels in evaluating the fluid overload and cardiac function of elderly patients with cardiovascular disease. The plasma levels of VEGF-C, VEGF-D, and GDF-15 were measured using ELISA. Their correlations with N-terminal pro B-type natriuretic peptide (NT-Pro BNP) and echocardiography data were analyzed. 1. Higher plasma levels of VEGF-D and GDF-15 were observed in elderly patients with cardiovascular disease and heart failure(P < .01). VEGF-D plasma levels were higher in patients with chronic heart failure than those with acute myocardial infarction (P < .01). VEGF-D plasma levels were positively correlated with amino-terminal pro-B type natriuretic peptide (NT-pro BNP) (P < .001). VEGF-D plasma levels were positively correlated with echocardiographic parameters, including left atrial diameter, left ventricular end-diastolic diameter and left ventricular ejection fraction, in patients with cardiovascular disease (P < .01). 2. VEGF-C plasma levels were higher in acute myocardial infarction group (P < .05). The plasma levels of VEGF-C were not correlated with either VEGF-D or NT-pro BNP plasma levels. VEGF-C plasma levels had no correlation with echocardiographic parameters. 3. GDF-15 plasma levels were positively correlated with sera biomarkers of cardiac injury (creatine kinase isoenzyme MB and cardiac troponin I). GDF-15 plasma levels were positively correlated with urinary biomarkers of tubular injury (N-acetyl-ß-galactosidase and α1-microglobulin). Both GDF-15 and NT-pro BNP plasma levels were correlated with age, estimated glomerular filtration rate (eGFR), and nutritional biomarkers (albumin and hemoglobin plasma levels). VEGF-D plasma levels is a potential biomarker of fluid overload and cardiac function in elderly patients with cardiovascular disease. Age, nutrition, and kidney injury are factors influencing both GDF-15 and NT-pro BNP plasma levels in estimating cardiac function and fluid overload.

Reconstruction of large defects of anterior floor of mouth with free flaps using a novel individualized flap design method.

The purpose of this study was to introduce a novel individualized flap design method for large anterior floor of the mouth (AFOM) defect reconstruction, review experience with the use of this flap design method for large AFOM defect reconstruction, and assess its functional results. A retrospective study of patients who received large AFOM defect reconstruction with free flaps was conducted. There was a cohort of patients who were treated using the novel individualized flap design method and a cohort without flap design. Functional outcomes were evaluated with appropriate scales. Outcomes were analyzed, and a p-value <0.05 was considered significant. 22 patients received the individualized flap design, while 21 patients were treated without a special flap design. All flaps survived. All free flaps harvested with the novel individualized flap design method better matched AFOM defects. Relative to patients without flap design, patients in the novel individualized flap design group showed significant improvement in speech intelligibility (p = 0.036) and swallowing function (p = 0.019). Within the limitation of the study it seems that large AFOM defect reconstruction with the novel individualized flap design method can not only cover and close the wound to avoid oral-neck fistulae, but also maintains tongue mobility to achieve better functional outcomes than in patients without flap design.

A novel flap design technique for subtotal tongue reconstruction with an "Individualized and Convenient Tongue Model".

BACKGROUND: To achieve improved functional outcomes in subtotal tongue reconstruction, a flap design with sufficient volume and appropriate shape is necessary. In this study, we introduce an "Individualized and Convenient Tongue Model" (ICTM) for flap design in subtotal tongue reconstruction. METHODS: By studying the anatomical morphology of the tongue, we found a similar geometry within the dorsum and body of the tongue as well as the mouth floor. This can be used to create an ICTM through folding and splicing. We can simulate tongue defects in the ICTM and transform defect shapes into guide plates for flap design. In this study, fifty-eight patients requiring subtotal tongue reconstruction were randomly divided into two groups: an ICTM group (35 patients) and a conventional group (31 patients). In the ICTM group, we individually designed profunda artery perforator flaps (PAPFs) or anterolateral thigh flaps (ALTFs) using the ICTM method. In the conventional group, the flap was designed according to the surgeon's clinical experience. Patient demographics, operative and follow-up data were recorded. Swallowing, speech intelligibility, and cosmetic results were assessed using appropriate scales. RESULTS: All flaps survived, although there were no significant differences in tumor size, operation time, flap size, and complication rate compared to the conventional group. Patients in the ICTM group had significantly improved speech intelligibility (p = 0.019), cosmetic appearance (p = 0.009), and swallowing ability (p = 0.003). CONCLUSIONS: The ICTM technique is an effective and convenient solution for subtotal tongue reconstruction that provides an individualized flap design and improves functional outcomes compared to the conventional design.

State of art on the mechanisms of laparoscopic sleeve gastrectomy in treating type 2 diabetes mellitus.

Obesity and type-2 diabetes mellitus (T2DM) are metabolic disorders. Obesity increases the risk of T2DM, and as obesity is becoming increasingly common, more individuals suffer from T2DM, which poses a considerable burden on health systems. Traditionally, pharmaceutical therapy together with lifestyle changes is used to treat obesity and T2DM to decrease the incidence of comorbidities and all-cause mortality and to increase life expectancy. Bariatric surgery is increasingly replacing other forms of treatment of morbid obesity, especially in patients with refractory obesity, owing to its many benefits including good long-term outcomes and almost no weight regain. The bariatric surgery options have markedly changed recently, and laparoscopic sleeve gastrectomy (LSG) is gradually gaining popularity. LSG has become an effective and safe treatment for type-2 diabetes and morbid obesity, with a high cost-benefit ratio. Here, we review the me-chanism associated with LSG treatment of T2DM, and we discuss clinical studies and animal experiments with regard to gastrointestinal hormones, gut microbiota, bile acids, and adipokines to clarify current treatment modalities for patients with obesity and T2DM.

Revisional One Anastomosis Gastric Bypass (OAGB) for Poor Response of Duodenal-Jejunal Bypass with Sleeve Gastrectomy (DJB-SG) (Video Report).

BACKGROUND: Bariatric surgery has actually focused not only on obesity but also more on the improvements or remission of the metabolic diseases. Therefore, revisional surgery is indicated for patients with poor response to the primary bariatric surgery to control weight and obesity-associated medical conditions. METHOD: In this video report, the patient was a 27-year-old Asian female with an initial BMI of 36.5 kg/m2 and poorly controlled type 2 diabetes (HbA1c: 11.9%). She underwent primary bariatric surgery of laparoscopic duodenal-jejunal bypass with sleeve gastrectomy (DJB-SG) in June 2019. She had a nadir BMI of 28.8 kg/m2 (corresponding body weight of 72 kg) in June 2020. However, she regained weight (BMI: 34 kg/m2) and had a relapse of diabetes with an HbA1c of 12.0% at the time of consultation for revisional bariatric surgery (RBS) in September 2022. After a multidisciplinary team evaluation, laparoscopic procedures of one anastomosis gastric bypass (OAGB) with resizing the gastric tube, removal of duodenal-jejunal anastomosis, and lengthening of the biliopancreatic limb were performed. RESULTS: The operative time was 186 min and blood loss was 50 ml. There were no intraoperative or postoperative complications. The patient had an uneventful postoperative course and was discharged on postoperative day 5. At the 3-month follow-up after RBS, the patient had lost 13 kg (weight dropped from 85 to 72 kg) and achieve remission of diabetes with HbA1c of 5.7%. CONCLUSION: Laparoscopic OAGB is technically feasible and practical as a revisional procedure for poor response of DJB-SG.

Case report: A de novo ERBB3 mutation develops in a gallbladder cancer patient carrying BRCA1 mutation after effective treatment with olaparib.

Background: Gallbladder cancer (GBC) is highly lethal and resistant to most chemotherapeutic drugs. GBC was reported to carry multiple genetic mutations such as TP53, K-RAS, and ERBB2/3. Here, we unexpectedly identified a patient with GBC harboring germline BRCA1 p.Arg1325Lys heterozygous mutation. We sought to determine if olaparib, the poly ADP-ribose polymerase inhibitor (PARPi) commonly treated for BRCA mutation, can inhibit cancer development via a therapeutic trial on this patient. Case presentation: The patient received GBC R0 resection after an 8-week olaparib treatment. After surgery and 6-month follow-up treatment with olaparib, the patient's blood carbohydrate antigen 19-9 (CA19-9) level declined from 328 to 23.6 U/ml. No recurrence in CT scanning was observed, indicating a disease-free survival of 6 months with conventional therapy. Two months later, CT examination and CA19-9 level showed cancer relapse. A blood biopsy revealed a new ERBB3 p.Gly337Arg mutation. GBC cell lines ectopically expressing BRCA1 p.Arg1325Lys together with ERBB3 p.Gly337Arg mutations were challenged with olaparib and/or afatinib, an ERBB2/3 inhibitor. The dual mutation cells were more responsive to the combined olaparib with afatinib than a single drug in the cell proliferation assay. Conclusion: Olaparib is effective in a GBC patient with a BRAC1 mutation. The efficacy of olaparib and afatinib in both cultured BRAC1 and ERBB3 mutation cell lines suggests that a combined regimen targeting BRCA1/2 and ERBB2/3 mutations may be an optimal strategy to treat GBC patients who carry both gene mutations.

A Novel Fluorescent Aptamer Sensor with DNAzyme Signal Amplification for the Detection of CEA in Blood.

Carcinoembryonic antigen (CEA) is a tumor-specific biomarker; however, its low levels in the early stages of cancer make it difficult to detect. To address the need for analysis of ultra-low-level substances, we designed and synthesized a fluorescent aptamer sensor with DNAzyme signal amplification and used it for the detection of CEA in blood. In the presence of the target protein, the aptamer sequence in the recognition probe binds to the target protein and opens the hairpin structure, hybridizes with the primer and triggers a polymerization reaction in the presence of polymerase to generate double-stranded DNA with two restriction endonuclease Nb.BbvCl cleavage sites. At the same time, the target protein is displaced and continues to bind to another recognition probe, triggering a new round of polymerization reaction, forming a cyclic signal amplification triggered by the target. The experimental results show that the blood detection with CEA has a high sensitivity and a wide detection range. The detection range: 10 fg/mL~10 ng/mL, with a detection limit of 5.2 fg/mL. In addition, the sensor can be used for the analysis of complex biological samples such as blood.

Safety and Efficacy of Combined Imbrication Axle Reconstruction and Z-Type Titanium Plate Fixation for Hinge Fracture Displacement During Open-Door Laminoplasty.

BACKGROUND: Open-door laminoplasty is a classical decompression method used to treat cervical spondylotic myelopathy. However, hinge fracture displacement (HFD) is a common occurrence during this procedure. The current study aimed to investigate the safety and efficacy of a combined imbrication axle reconstruction and Z-type titanium plate fixation method for HFD during open-door laminoplasty. METHODS: In total, 617 patients with cervical spondylotic myelopathy who underwent C3-C7 open-door laminoplasty from March 2015 to October 2018 were included in this retrospective study. Overall, 73 patients developed HFD during surgery. Of these, 43 underwent combined imbrication axle reconstruction and Z-type titanium plate fixation (IRZF group) and 30 underwent traditional titanium plate fixation (TF group). Data such as the operative time, intraoperative blood loss volume, and distribution of fractured hinges were recorded. Both groups were compared in terms of improvement in neurologic function, cervical curvature index, hinge fusion rate, incidence of C5 palsy, severity of axial symptoms, and development of complications. RESULTS: The operative time and intraoperative blood loss were slightly higher in the IRZF group than in the TF group; however, the differences were not significant (p > 0.05). Furthermore, there was no significant difference between the groups in terms of the number of fractured segments and the distribution of fractured hinges (p > 0.05). The cervical curvature index did not decline in the two groups (p > 0.05). The IRZF group had a higher hinge fusion rate than the TF group at 3 (79.6 vs. 57.1%) and 12 (93.9 vs. 74.3%) months postoperatively (p < 0.05). There was no significant difference in the incidence of C5 palsy between the two groups (9.3 vs. 6.7%; p > 0.05). However, the TF group had more severe axial symptoms than the IRZF group (p < 0.05). The neurologic function of the two groups increased postoperatively as per the Japanese Orthopaedic Association scoring system (p < 0.05). Nevertheless, there was no significant difference in terms of neurologic function at any observational time point (p > 0.05). One patient in the TF group with hinge nonunion underwent laminectomy due to lamina displacement into the spinal canal and nerve root compression. CONCLUSION: In patients with HFD, IRZF facilitates a more intimate contact between the lamina and the lateral mass and, therefore, achieves fractured hinge fusion without additional surgical trauma. This technical improvement can significantly promote neurologic recovery, decrease the severity of axial symptoms, and prevent the development of spinal cord or nerve root recompression.

Novel Three-Holed Titanium Plate Fixation during Open Door Laminoplasty for Cervical Spondylotic Myelopathy: Comparison with Conventional Titanium Plate.

OBJECTIVE: For reconstructing the posterior cervical muscular-ligament complex, attachment points and various modified techniques were designed and applied in clinical practice. This study investigated the clinical and radiographic outcomes of open door laminoplasty with modified centerpiece mini-plate fixation and extensor attachment point reconstruction in the treatment of cervical spondylotic myelopathy (CSM). METHODS: Sixty-nine patients with CSM who underwent C3-C7 open door laminoplasty at our hospital from January 2016 to May 2018 were divided into two groups: 37 and 32 patients underwent laminoplasty with modified and conventional centerpiece titanium plate fixation (MPF and CPF groups), respectively. Changes in cervical spinal angle (CSA), cervical range of motion (ROM), posterior cervical muscle atrophy, neurological function (Japanese Orthopaedic Association [JOA] score), Neck Disability Index (NDI), and axial symptom severity were compared between the two groups. RESULTS: There were no significant differences in operative duration (136.7 ± 23.9 vs 128.3 ± 21.5 min, t = 1.525, p > 0.05), volume of intraoperative blood loss (275.9 ± 33.1 vs 268.2 ± 31.6 ml, t = 0.984, p > 0.05), lamina open angle (41.2° ± 4.5° vs 39.4° ± 4.1°, t = 1.726, p > 0.05), and spinal cord drift distance (2.4 ± 0.3 vs 2.3 ± 0.4 mm, t = 1.184, p > 0.05) between the two groups. After surgery, JOA score significantly increased (p < 0.05), and neurological recovery rates were similar (62.7% vs 63.4%, t = 0.208, p > 0.05). The NDI score was significantly decreased in both the groups (p < 0.05); however, the MPF group recovered to a greater degree than the CPF group (8.3 ± 1.2 vs 9.8 ± 1.4) (t = 4.793, p < 0.05). There was no significant change in cervical ROM postoperatively compared with preoperatively in either group (p > 0.05). CSA decreased from 21.7° ± 2.8° to 18.3° ± 2.1°, and posterior cervical muscle cross-sectional area decreased from 35.2 ± 4.9 cm2 to 31.0 ± 4.1 cm2 in the CPF group (p < 0.05), but no significant change was observed in the MPF group (20.6° ± 2.5° to 20.4° ± 2.6°and 35.9 ± 5.1 to 34.1 ± 4.6 cm2 , respectively) (p > 0.05). Postoperative axial symptom severity was significantly worse in the CPF group than in the MPF group (Z = -2.357, p < 0.05). CONCLUSIONS: As an improvement to the conventional titanium plate, the modified centerpiece titanium plate effectively provides an attachment point for the posterior muscle-ligament complex, reducing posterior cervical muscle atrophy and improving neck function, without inflicting additional surgical trauma.

Pedigree-based study to identify GOLGB1 as a risk gene for bipolar disorder.

Bipolar disorder (BD) is a complex psychiatric disorder with strong heritability. Identification of new BD risk genes will help determine the mechanism underlying disease pathogenesis. In the present study, we carried out whole genome sequencing for a Chinese BD family with three affected members and three unaffected members, and identified multiple candidate causal variations, including a frameshift mutation in the GOLGB1 gene. Since a GOLGB1 missense mutation was also found in another BD pedigree, we carried out functional studies by downregulating Golgb1 expression in the brain of neonatal mice. Golgb1 deficiency had no effect on anxiety, memory, and social behaviors in young adult mice. However, we found that young adult mice with Golgb1 deficiency exhibited elevated locomotor activity and decreased depressive behaviors in the tail suspension test and the sucrose preference test, but increased depressive behaviors in the forced swim test, resembling the dual character of BD patients with both mania and depression. Moreover, Golgb1 downregulation reduced PSD93 levels and Akt phosphorylation in the brain. Together, our results indicate that GOLGB1 is a strong BD risk gene candidate whose deficiency may result in BD phenotypes possibly through affecting PSD93 and PI3K/Akt signaling.

Recent Updates on the Anticancer Activity of Quinoxaline Hybrids (Jan. 2017-Jan. 2022).

Cancer being one of the leading causes of death among non-communicable diseases, has already posed a heavy burden on the world health system. Chemotherapy is one of the most effective approaches for cancer treatment, but multidrug resistance, lack of efficacy, and toxic side effects hamper efficacious cancer chemotherapy, creating an urgent need to develop novel, more effective and less toxic anticancer therapeutics. Quinoxalines, as fascinating structures, constitute an important class of heterocycles in drug discovery. Quinoxaline hybrids could exert anticancer activity through diverse mechanisms and possess profound in vitro and in vivo efficacy against various cancers, including multidrug-resistant forms. Thus, quinoxaline hybrids represent useful templates for the control and eradication of cancer. The purpose of the present review article is to provide an emphasis on the recent developments (Jan. 2017-Jan. 2022) in quinoxaline hybrids with insights into their in vitro and in vivo anticancer potential as well as structure-activity relationships (SARs) to facilitate further rational design of more effective candidates.

CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma.

PURPOSE: This study aimed to investigate the impact of CC chemokine receptor 7 (CCR7) on the recruitment and polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC). METHODS: We analyzed CCR7 expression pattern, clinicopathological significance, and its association with M2 macrophage infiltration in OSCC by bioinformatic methods. Small interfering RNA (siRNA) was utilized to silence CCR7 in OSCC cells. Conditioned media (CM) was harvested from transfected OSCC cells to establish a co-culture model of THP-1 derived macrophages and OSCC cells. Transwell assay and cell adhesion assay were performed to examine the effect of CCR7 on macrophages recruitment and adhesion. Cytoskeleton was labelled by phalloidin to observe macrophage morphological changes. Moreover, phenotypic alteration of macrophages was measured using quantitative real-time PCR (qRT-PCR), flow cytometry, and immunofluorescence (IF) staining. Ultimately, recombinant human CCL19 and CCL21 were added into the medium of THP-1 derived macrophages to explore their effects on polarization in vitro. RESULTS: In OSCC patients, the overexpression of CCR7 positively correlated with lymph node metastasis and M2 macrophage infiltration. Macrophage not only exhibited enhanced migration, invasion and adhesion abilities, but also appeared more spindle and branched in vitro when treated with CM from OSCC cells. However, these phenomena were abrogated with knockdown of CCR7. We also discovered that inhibition of CCR7 in OSCC cells suppressed TAMs polarization to an M2 phenotype. In addition, recombinant human CCL19 and CCL21 promoted macrophage M2-polarization in vitro. CONCLUSION: CCR7 in OSCC cells promoted recruitment and M2-polarization of THP-1 derived macrophages in vitro by regulating production of CCL19 and CCL21.

Influence of fixed titanium plate position on the effectiveness of open-door laminoplasty for cervical spondylotic myelopathy.

BACKGROUND: During open-door laminoplasty, the position of the bone gutter is not fixed, and when the gutter migrates inward, the outer end of the titanium plate must be fixed on the lamina edge. It is unclear whether this will affect the clinical efficacy. This study aimed to observe the influence of the titanium plate fixation position on the effectiveness of open-door laminoplasty for cervical spondylotic myelopathy (CSM). METHODS: A total of 98 patients with CSM who underwent open-door laminoplasty from August 2016 to October 2019 were included in this retrospective study. Fifty-five patients had the titanium plate fixed on the lateral mass (lateral mass group), and 43 patients had the titanium plate fixed on the lamina edge (lamina group). The opening angle, opening width, occurrence of hinge fracture, spinal cord drift distance, cervical curvature index (CCI), neurological function recovery (JOA score), neck function (NDI), C5 palsy and severity of axial symptoms were observed and compared between the two groups. RESULTS: The opening angle in the lamina group was significantly larger than that in the lateral mass group, while the opening width and the spinal cord drift distance were significantly smaller than those in the lateral mass group (P < 0.05). The occurrence of hinge fracture in the lamina group was significantly higher than that in the lateral group (25.6% and 9.1%, respectively) (P < 0.05). The CCI was maintained well in both groups (P > 0.05), and there was no significant difference between the groups (P > 0.05). After surgery, the JOA score significantly increased in both groups (P < 0.05), and the neurological recovery rates were similar between the two groups (62.6% vs. 64.5%). The NDI score significantly decreased in both groups (P < 0.05), but the lateral mass group recovered to a greater degree than the lamina group (P < 0.05). The occurrence of C5 palsy was 2.3% in the lamina group and 14.5% in the lateral mass group, and there was a significant difference between the groups (P < 0.05). Postoperative axial symptom severity was significantly worse in the lamina group than in the lateral mass group (P < 0.05). CONCLUSIONS: In open-door laminoplasty, it is feasible to fix the titanium plate on the lateral mass or to the lamina due to the same neurological function recovery. However, fixing it to the lamina will increase the opening angle and decrease the opening width, making the hinge prone to fracture and increasing the severity of postoperative axial symptoms.

The Overexpression of Fibronectin 1 Promotes Cancer Progression and Associated with M2 Macrophages Polarization in Head and Neck Squamous Cell Carcinoma Patients.

Purpose: This study aimed to investigate the biological roles of fibronectin 1 (FN1) in head and neck squamous cell carcinoma (HNSCC) and its effects on macrophage M2 polarization. Methods: We analyzed FN1 expression pattern and examined its clinical relevance in HNSCC progression by bioinformatic analysis. Small interfering RNA (siRNA) was utilized to silence FN1 in HNSCC cells. Cell counting kit-8 (CCK-8) assay, colony formation assay, Transwell assay and wound healing assay were performed to reveal the effect of FN1 on malignant behaviors of HNSCC cells. Moreover, a co-culture model of macrophages and HNSCC cells was established to investigate whether FN1 induce macrophage M2 polarization. Finally, we used bioinformatic methods to explore the possible FN1-related pathways in HNSCC. Results: FN1 is significantly overexpressed in HNSCC patients and has been obviously correlated with higher pathological stage and poor prognosis. Downregulation of FN1 suppressed the proliferation, migration and invasion of HNSCC cells, and inhibited macrophage M2 polarization in vitro. In addition, "PI3K-Akt" and "MAPK" signaling pathways may be involved in the malignant process of FN1 in HNSCC. Conclusion: The overexpression of FN1 promotes HNSCC progression and induces macrophages M2 polarization. FN1 may serve as a promising prognostic biomarker and therapeutic target in HNSCC.

[Long intergenic non-coding RNA 01121 promotes metastasis of prostate cancer cells by activating the EMT process].

OBJECTIVE: To investigate the expression, biological function and potential mechanism of long intergenic non-coding RNA 01121 (LINC01121) in PCa. METHODS: Using real-time quantitative polymerase chain reaction (qRT-PCR), we detected the expression of LINC01121 in PCa cell lines and the efficiency of small interfering RNA (siRNA) in knocking down LINC01121. We examined the biological function of LIC01121 in the PCa cells by CCK8, cell cloning, and Transwell migration and invasion assays, and determined the expressions of epithelial-mesenchymal transition (EMT)-related proteins in the PCa cells by Western blot. RESULTS: The relative expression of LINC01121 was significantly higher in the PCa than in the WPMY1 human normal prostate matrix immortalized cells (P < 0.05). Knocking down the expression of LINC01121 significantly reduced the proliferation, cloning, migration and invasiveness of the PCa cells (P < 0.05), down-regulated the expressions of the N-cadherin and vimentin proteins and up-regulated that of E-cadherin in the PCa cells (P < 0.05). CONCLUSION: LINC01121 is overexpressed in PCa cell lines, which may promote the proliferation, migration and invasiveness of the cells by activating the EMT process.

MKP-1 is required to limit myeloid-cell mediated oral squamous cell carcinoma progression and regional extension.

Mitogen-activated protein kinases (MAPKs) require MAPK phosphatases (MKPs) for deactivation of MAPK intracellular signaling. MKP-1 (encoded by Dusp1) is a key negative regulator of MAPKs and prior reports have indicated that MKP-1 regulates oral cancer-associated inflammation and leukocyte infiltration. OBJECTIVE: To determine the significance of myeloid-based expression of MKP-1 in oral cancer. METHODS: The Cancer Genome Atlas (TCGA) was used to address DUSP1 expression in oral squamous cell carcinoma (OSCC). Syngeneic and carcinogen-induced mouse models using global and myeloid-specific Dusp-1 deficient mice with immunophenotypic, histologic, and transcriptomic analyses and in vitro migration assays. RESULTS: Data from TCGA indicates the DUSP1 expression is inversely related to oral cancer burden and nodal involvement. Using murine models of OSCC, the role of MKP-1 signaling in tumor associated macrophages (TAMs) was assessed. Dusp1-deficient mice had increased tumor burden and TAM infiltrate with increased M2 macrophage polarization. Transcriptomic signatures of TAMs from Dusp1-deficent mice indicated a pro-metastatic phenotype as well as concomitant differences in myeloid-associated genes, cytokine/chemokine signaling, and Notch signaling consistent with tumor progression. In vitro and in vivo assays revealed mouse OSCC cells had a higher migration rate using TAM cell-free supernatant from Dusp1 deficiency mice compared to controls with enhanced regional cervical lymph node metastasis, respectively. To validate TAM studies using implantable mouse models, an OSCC progression model with conditional myeloid-specific Dusp-1 deficient mice demonstrated enhanced OSCC disease progression, characterized by advanced onset, histological stage, and tumor burden. CONCLUSION: Myeloid-based Dusp1-deficiency increases OSCC burden and metastasis through alteration in TAM recruitment, gene profile, and polarity suggesting that MKP-1 could be a viable target to reprogram TAM to limit local/regional OSCC extension.

ITRAQ-based proteomics analysis of tanshinone IIA on human ectopic endometrial stromal cells of adenomyosis.

PURPOSE: Adenomyosis is a diffuse or localized disease. Our previous study has indicated that tanshinone IIA (TSIIA) inhibits the proliferation, migration, and induces apoptosis of ectopic endometrial stromal cells (EESCs) of adenomyosis. However, the complex molecular mechanism of TSIIA in adenomyosis remains unclear. The objective of this study was to explore the complex molecular mechanism of TSIIA on EESCs. METHODS: In our present study, we used the proteomics approach iTRAQ (isobaric tags for relative and absolute quantitation) combined with LC-MS/MS (liquid chromatography-mass spectrometry) to investigate changes in the protein profile of EESCs treated with TSIIA. Differential proteins were analyzed by employing bioinformatics tools and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In TSIIA treated EESCs, the protein expression levels of TNFRSF10D, PLEKHM1, FECH, and TPM1A were detected by western blotting. RESULTS: Quantitative results revealed 267 significantly differential proteins in TSIIA pretreated EESCs. Gene Ontology (GO) analysis presented an overview of dysregulated proteins in the biological process (BP), cell component (CC), and molecular function (MF) categories. Interestingly, we observed that differential proteins in the extracellular matrix (ECM)-receptor interaction pathway and estrogen signaling pathway were all involved in the focal adhesion pathway, which plays essential roles in the TSIIA-mediated inhibition of EESC proliferation and migration. Furthermore, some significantly differential proteins, which may be potential targets for the treatment of adenomyosis in the future, were validated by western blotting. CONCLUSIONS: Our study provides a useful method to detect the detailed mechanism underlying the efficacy of TSIIA on EESCs.