TNFα in the Trigeminal Nociceptive System Is Critical for Temporomandibular Joint Pain.

Previous studies have shown that tumor necrosis factor alpha (TNFα) is significantly increased in complete Freund's adjuvant (CFA)-treated temporomandibular joint (TMJ) tissues. However, it is unclear whether TNFα in the trigeminal nociceptive system contributes to the development of TMJ pain. In the present study, we investigated the role of TNFα in trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) in CFA-induced inflammatory TMJ pain.

B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex.

GARP, a cell surface docking receptor for binding and activating latent TGF-β, is highly expressed by platelets and activated Tregs. While GARP is implicated in immune invasion in cancer, the roles of the GARP-TGF-β axis in systemic autoimmune diseases are unknown. Although B cells do not express GARP at baseline, we found that the GARP-TGF-β complex is induced on activated human and mouse B cells by ligands for multiple TLRs, including TLR4, TLR7, and TLR9.

Physiological activation of mGlu5 receptors supports the ion channel function of NMDA receptors in hippocampal LTD induction in vivo.

Synaptic long-term depression (LTD) is believed to underlie critical mnemonic processes in the adult hippocampus. The roles of the metabotropic and ionotropic actions of glutamate in the induction of synaptic LTD by electrical low-frequency stimulation (LFS) in the living adult animal is poorly understood. Here we examined the requirement for metabotropic glutamate (mGlu) and NMDA receptors in LTD induction in anaesthetized adult rats.

AMPA receptor GluA1 Ser831 phosphorylation is critical for nitroglycerin-induced migraine-like pain.

Migraine is the third most common disease worldwide; however, the mechanisms underlying migraine headache are still not fully understood. Previous studies have demonstrated that α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor phosphorylation plays an important role in central sensitization of pain transmission. In the present study, we observed that AMPA receptor GluA1 Ser831 phosphorylation was enhanced in the spinal trigeminal nucleus caudalis (Sp5C) after intraperitoneal injection of nitroglycerin (NTG).

Immunoregulatory functions and the therapeutic implications of GARP-TGF-β in inflammation and cancer.

GARP (glycoprotein-A repetitions predominant) is a type I transmembrane cell surface docking receptor for latent transforming growth factor-β (TGF-β) that is abundantly expressed on regulatory T lymphocytes and platelets. GARP regulates the availability of membrane-bound latent TGF-β and modulates its activation. For this reason, GARP expression on immune and non-immune cells is involved in maintaining peripheral tolerance.

Thymidylate synthase prompts metastatic progression through the dTMP associated EMT process in pancreatic ductal adenocarcinoma.

As a fundamental metabolic enzyme, anti-Thymidylate synthase (TS) strategy has been shown to be an effective therapy for human cancers. However, the genuine effects of TS in pancreatic ductal adenocarcinoma (PDA) are still conflicting. We systemically assessed the prognostic value and whether TS associated with malignant progression in PDA.

Glycoprotein A repetitions predominant (GARP) positively regulates transforming growth factor (TGF) β3 and is essential for mouse palatogenesis.

Glycoprotein A repetitions predominant (GARP) (encoded by the gene) plays important roles in cell-surface docking and activation of TGFβ. However, GARP's role in organ development in mammalian systems is unclear. To determine the function of GARP , we generated a GARP KO mouse model.

CNPY2 is a key initiator of the PERK-CHOP pathway of the unfolded protein response.

The unfolded protein response (UPR) in the endoplasmic reticulum (ER) is a highly conserved protein-quality-control mechanism critical for cells to make survival-or-death decisions under ER-stress conditions. However, how UPR sensors are activated remains unclear. Here, we report that ER luminal protein canopy homolog 2 (CNPY2) is released from grp78 upon ER stress.

Platelets subvert T cell immunity against cancer via GARP-TGFβ axis.

Cancer-associated thrombocytosis has long been linked to poor clinical outcome, but the underlying mechanism is enigmatic. We hypothesized that platelets promote malignancy and resistance to therapy by dampening host immunity. We show that genetic targeting of platelets enhances adoptive T cell therapy of cancer.

Modulation of Endoplasmic Reticulum Stress Controls CD4 T-cell Activation and Antitumor Function.

The endoplasmic reticulum (ER) is an energy-sensing organelle with intimate ties to programming cell activation and metabolic fate. T-cell receptor (TCR) activation represents a form of acute cell stress and induces mobilization of ER Ca stores. The role of the ER in programming T-cell activation and metabolic fate remains largely undefined.

Spinal AMPA Receptor GluA1 Ser831 Phosphorylation Controls Chronic Alcohol Consumption-Produced Prolongation of Postsurgical Pain.

Previous studies have shown that excessive alcohol drinking is associated with chronic pain development; however, the molecular mechanism underlying this association is poorly understood. In this study, we investigated the effect of chronic alcohol consumption on plantar incision-induced postsurgical pain. We observed that 4-week ethanol drinking significantly prolonged plantar incision-induced mechanical pain, but not thermal pain.

PKMζ Is Not Required for Development of Postsurgical Pain.

Previous studies have shown that protein kinase M zeta (PKMζ), a brain-specific isoform of protein kinase C, is involved in the central processing of nociception in several pain models by using a synthetic zeta inhibitory peptide. In the present study, we investigated whether PKMζ contributes to the pathogenesis of postsurgical pain using both conditional and conventional PKMζ knockout mice. Our results showed that the expression of PKMζ in anterior cingulate cortex, but not spinal cord, of the conditional PKMζ knockout mice was inhibited following tamoxifen injection.

Application of optogenetics-mediated motor cortex stimulation in the treatment of chronic neuropathic pain.

Motor cortex stimulation provides an alternate approach for intractable pain treatment. Optogenetic manipulation can produce gain- or loss-of-function in specific type of cells following light application. This state-of-the-art technology may be used in motor cortex stimulation to produce circuit-specific neuromodulation and regulate neuronal activities in motor cortex, thereby treating pain in the clinic.

Primary tumor site and anti-EGFR monoclonal antibody benefit in metastatic colorectal cancer: a meta-analysis.

Aim: This meta-analysis aimed to document the impact of primary tumor site on anti-EGFR monoclonal antibody (mAb) benefit in metastatic colorectal cancer.

Materials & Methods: Tumors with metastatic left-sided colorectal cancer (LCC) were compared with tumors with metastatic right-sided colon cancer (RCC) with respect to anti-EGFR mAb objective response rate (ORR), overall survival (OS) and progression-free survival (PFS) benefit.

Results: Comparing LCC with RCC, LCC was found to have significantly superior anti-EGFR mAb ORR (p < 0.

Is CD47 an innate immune checkpoint for tumor evasion?

Cluster of differentiation 47 (CD47) (also known as integrin-associated protein) is a ubiquitously expressed glycoprotein of the immunoglobulin superfamily that plays a critical role in self-recognition. Various solid and hematologic cancers exploit CD47 expression in order to evade immunological eradication, and its overexpression is clinically correlated with poor prognoses. One essential mechanism behind CD47-mediated immune evasion is that it can interact with signal regulatory protein-alpha (SIRPα) expressed on myeloid cells, causing phosphorylation of the SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and recruitment of Src homology 2 domain-containing tyrosine phosphatases to ultimately result in delivering an anti-phagocytic-"don't eat me"-signal.

ANGPTL4 Correlates with NSCLC Progression and Regulates Epithelial-Mesenchymal Transition via ERK Pathway.

Purpose Lung cancer remains the leading cause of cancer deaths with intricate mechanisms. In the present study, we evaluated the clinical significance and biological role of ANGPTL4 in non-small cell lung cancer (NSCLC), the most common lung cancer subtype. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used for examining the mRNA level of ANGPTL4 in NSCLC tissues and adjacent non-tumor tissues, NSCLC cell lines, and the immortalized human bronchial epithelial cell line HBE, respectively.

Upregulation of Chemokine CXCL12 in the Dorsal Root Ganglia and Spinal Cord Contributes to the Development and Maintenance of Neuropathic Pain Following Spared Nerve Injury in Rats.

Emerging evidence indicates that CXCL12/CXCR4 signaling is involved in chronic pain. However, few studies have systemically assessed its role in direct nerve injury-induced neuropathic pain and the underlying mechanism. Here, we determined that spared nerve injury (SNI) increased the expression of CXCL12 and its cognate receptor CXCR4 in lumbar 5 dorsal root ganglia (DRG) neurons and satellite glial cells.

Inhibition of hepatitis B virus replication by targeting ribonucleotide reductase M2 protein.

Chronic hepatitis B virus (HBV) infection is a key factor for hepatocellular carcinoma worldwide. Ribonucleotide reductase (RR) regulates the deoxyribonucleoside triphosphates biosynthesis and serves as a target for anti-cancer therapy. Here, we demonstrate that RR is essential for HBV replication and the viral covalently-closed-circular DNA (cccDNA) synthesis in host liver cells.

Protein N-arginine methyltransferase 5 promotes the tumor progression and radioresistance of nasopharyngeal carcinoma.

Radiotherapy resistance is the main cause of the the poor prognosis of some nasopharyngeal carcinoma (NPC) patients. Yet, the exact mechanism is still elusive. In the present study, we explored the clinical and biological role of protein arginine methyltransferase 5 (PRMT5) in NPC.

Ubiquitin-conjugating enzyme E2C regulates apoptosis-dependent tumor progression of non-small cell lung cancer via ERK pathway.

The oncogenic role of ubiquitin-conjugating enzyme E2C (UBE2C) had been identified in some types of human tumors, while the clinical and biological role of UBE2C in non-small cell lung cancer (NSCLC) is still elusive. Here, we have determined the specific role of UBE2C in NSCLC. Western blot and qRT-PCR were used for detecting the mRNA level and protein level of UBE2C in NSCLC samples and cell lines, respectively.

Mesenchymal stem cells promote liver regeneration and prolong survival in small-for-size liver grafts: involvement of C-Jun N-terminal kinase, cyclin D1, and NF-κB.

Background: The therapeutic potential of mesenchymal stem cells (MSCs) has been highlighted recently for treatment of acute or chronic liver injury, by possibly differentiating into hepatocyte-like cells, reducing inflammation, and enhancing tissue repair. Despite recent progress, exact mechanisms of action are not clearly elucidated. In this study, we attempted to explore whether and how MSCs protected hepatocytes and stimulated allograft regeneration in small-for-size liver transplantation (SFSLT).

Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2.

Stat3 alters the expression of its downstream genes and is associated with tumor invasion and metastasis in several human cancers. Its role in esophageal squamous cell carcinoma (ESCC) has not been well characterized. We examined the tumor sections of 100 cases of ESCC by immunohistochemistry and observed significant overexpression of Stat3 in the cytoplasm of 89% of ESCC cells and of phosphorylated Stat3 (p-Stat3) in the nuclei of 71% of ESCC when compare with normal esophageal mucosa (72%, p = 0.

Use a simple lower limb outrigger frame in intramedullary nailing fixation of a floating knee.

Closed intramedullary nailing is a classical therapeutic approach for floating knee injuries. An appropriate positioning is critical for a successful surgery. However, there is a lack of an ideal auxiliary device to facilitate the implantation of intramedullary nail.

Use of CD137 ligand expression in the detection of small B-cell lymphomas involving the bone marrow.

Staging for small B-cell lymphomas is important for prognostic and therapeutic decision making; however, the detection of lymphoid infiltrates in the bone marrow is often hampered by the lack of specific diagnostic markers. We recently described the hematopoietic tissue distribution patterns of CD137 and CD137 ligand (CD137L), which have shown promise as immunotherapeutic targets. CD137 expression was primarily confined to cells in the microenvironment, whereas CD137L was expressed in neoplastic cells in most B-cell lymphomas.

OCILRP2 signaling synergizes with LPS to induce the maturation and differentiation of murine dendritic cells.

Osteoclast Inhibitory Lectin-related Protein 2 (OCILRP2) is a typical type II transmembrane protein and belongs to C-type lectin-related protein family. It is preferentially expressed in dendritic cells (DC), B lymphocytes, and activated T lymphocytes. Upon binding to its ligand, OCILRP2 can promote CD28-mediated co-stimulation and enhance T cell activation.