Eradicating Helicobacter pylori via 13C-urea breath screening to prevent gastric cancer in indigenous communities: a population-based study and development of a family index-case method.

OBJECTIVE: Screening and eradication of Helicobacter pylori help reduce disparities in the incidence of gastric cancer. We aimed to evaluate its acceptability and feasibility in the indigenous communities and develop a family index-case method to roll out this programme. DESIGN: We enrolled residents aged 20-60 years from Taiwanese indigenous communities to receive a course of test, treat, retest and re-treat initial treatment failures with the 13C-urea breath tests and four-drug antibiotic treatments. We also invited the family members of a participant (constituting an index case) to join the programme and evaluated whether the infection rate would be higher in the positive index cases. RESULTS: Between 24 September 2018 and 31 December 2021, 15 057 participants (8852 indigenous and 6205 non-indigenous) were enrolled, with a participation rate of 80.0% (15 057 of 18 821 invitees). The positivity rate was 44.1% (95% CI 43.3% to 44.9%). In the proof-of-concept study with 72 indigenous families (258 participants), family members of a positive index case had 1.98 times (95% CI 1.03 to 3.80) higher prevalence of H. pylori than those of a negative index case. The results were replicated in the mass screening setting (1.95 times, 95% CI 1.61 to 2.36) when 1115 indigenous and 555 non-indigenous families were included (4157 participants). Of the 6643 testing positive, 5493 (82.6%) received treatment. According to intention-to-treat and per-protocol analyses, the eradication rates were 91.7% (89.1% to 94.3%) and 92.1% (89.2% to 95.0%), respectively, after one to two courses of treatment. The rate of adverse effects leading to treatment discontinuation was low at 1.2% (0.9% to 1.5%). CONCLUSION: A high participation rate, a high eradication rate of H. pylori and an efficient rollout method indicate that a primary prevention strategy is acceptable and feasible in indigenous communities. TRIAL REGISTRATION NUMBER: NCT03900910.

Poor prognostic implications of myelodysplasia-related mutations in both older and younger patients with de novo AML.

A set of myelodysplasia-related (MDS-R) gene mutations are incorporated into the 2022 European LeukemiaNet risk classification as adverse genetic factors for acute myeloid leukemia (AML) based on their poor prognostic impact on older patients. The impact of these mutations on younger patients (age < 60 years) remains elusive. In the study of 1213 patients with de novo non-M3 AML, we identified MDS-R mutations in 32.7% of the total cohort, 44.9% of older patients and 23.4% of younger patients. The patients with MDS-R mutations had a significantly lower complete remission rate in both younger and older age groups. With a median follow-up of 9.2 years, the MDS-R group experienced shorter overall survival (P = 0.034 for older and 0.035 for younger patients) and event-free survival (P = 0.004 for older and 0.042 for younger patients). Furthermore, patients with MDS-R mutations more frequently harbored measurable residual disease that was detectable using next generation sequencing at morphological CR than those without MDS-R mutations. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) might ameliorate the negative impact of MDS-R mutations. In summary, AML patients with MDS-R mutations have significantly poorer outcomes regardless of age. More intensive treatment, such as allo-HSCT and/or novel therapies, is warranted for AML patients with MDS-R mutations.

A Case of Delayed Tension Pneumocephalus in a Patient Undergoing Facial Cosmetic Surgery.

There has been a recognizable surge in cosmetic surgery in recent years, partly influenced by social media, and the easy accessibility to such medical procedures. As with all types of surgery, the risks of complications are real, and in this specific setting, they tend to occur in a younger age group. Here, we discuss a rare complication and subsequent presentation of tension pneumocephalus, following an episode of cardiac arrest in a 58 year old female, during elective cosmetic-facial surgery. Typically, pneumocephalus develops when there are skull or facial bone fractures, and presents characteristically with leakage of cerebrospinal fluid from the ears and/or nose. The absence of the typical clinical signs and the lack of a clinical history or radiologically evidence of skull or facial bone fractions, may result in a delayed diagnosis, permanent brain injury and death. Awareness of such an unusual complication is therefore crucial when considering any surgery to the head and face (including cosmetic surgery), or following prolonged resuscitative efforts, which may well develop days after the inciting event.

Niobium carbide (MXene) reduces UHMWPE particle-induced osteolysis.

Joint replacement surgery is one of the orthopedic surgeries with high successful rates; however, wear debris generated from prostheses can ultimately lead to periprosthetic osteolysis and failure of the implant. The implant-derived particulate debris such as ultrahigh molecular weight polyethylene (UHMWPE) can initiate the local immune response and recruit monocytic cells to phagocytose particles for generating reactive oxygen species (ROS). ROS induces osteoclastogenesis and macrophages to secrete cytokines which ultimately promote the development of osteolysis. In this work, we develop the few-layered Nb2C (FNC) as an antioxidant which possesses the feature of decreasing the production of cytokines and inhibiting osteoclastogenesis by its ROS adsorption. Moreover, local injection of FNC attenuates the UHMWPE-induced osteolysis in a mouse calvarial model. In sum, our results suggest that FNC can be used for treating osteolytic bone disease caused by excessive osteoclastogenesis.

Methylene blue prevents osteoarthritis progression and relieves pain in rats via upregulation of Nrf2/PRDX1.

Oxidative stress-related cartilage degeneration, synovitis, and joint pain play vital roles in the progress of osteoarthritis (OA). Anti-oxidative stress agents not only prevent structural damage progression but also relieve OA-related pain. In this study, we investigated the therapeutic effect of methylene blue (MB), a classical and important anti-oxidant with strong neural affinity. Experimental OA was established in rats by radial transection of medial collateral ligament and medial meniscus (MCLT + MMT) of the right knee joint. The OA rats received intra-articular injection of MB (1 mg/kg) every week starting one week after surgery. We showed that MB administration exerted significant cartilage protection, synovitis inhibition as well as pain relief in OA rats. In human chondrocytes and fibroblast-like synoviocytes, MB significantly attenuated tert-butyl hydroperoxide (TBHP)-induced inflammatory response and oxidative stress. We demonstrated that these effects of MB resulted from dual targets of important antioxidant enzymes, Nrf2 and PRDX1, which also mutually reinforcing and participated in an interaction. Furthermore, we found that calcitonin gene-related peptide (CGRP), a neural inflammatory mediator, was accumulated around the vessel in synovium and subchondral bone in OA rats and in TBHP-treated primary cortical neurons; MB administration significantly inhibited CGRP expression through upregulation of Nrf2 and PRDX1. Taken together, these results suggest that MB ameliorates oxidative stress via Nrf2/PRDX1 regulation to prevent progression and relieve pain of OA.

Bone marrow mesenchymal stem cell-derived exosomes inhibit chondrocyte apoptosis and the expression of MMPs by regulating Drp1-mediated mitophagy.

Osteoarthritis (OA) is a joint degenerative disease commonly seen in the elderly. Bone marrow mesenchymal stem cell-exosomes (BMSC-exosomes) are closely associated with the progression of OA. Here, we investigated whether BMSC-exosomes can affect OA development by regulating mitophagy. Primary rat chondrocytes were treated with advanced glycation end products (AGEs) to induce cell damage. The results of flow cytometry showed that AGEs treatment significantly promoted apoptosis of chondrocytes. AGEs treatment also enhanced the expression of matrix metalloproteinases (MMPs), MMP-3 and MMP-13, and dynamin-related protein 1 (Drp1) in chondrocytes. To investigate the impact of BMSC-exosomes on chondrocytes, chondrocytes were treated with BMSC-exosomes. AGEs-mediated increase of apoptosis and up-regulation of MMP-3, MMP-13, and Drp1 in chondrocytes were abrogated by BMSC-exosomes. Western blot analysis of autophagy-related proteins and Mito-Keima assay revealed that BMSC-exosome treatment elevated the expression of autophagy-related proteins, LC3-II/LC3-I and Beclin-1, and promoted mitophagy in the AGEs-treated chondrocytes. Moreover, Drp1 overexpression repressed the expression of LC3-II/LC3-I and Beclin-1, and enhanced apoptosis and the expression of MMP-3 and MMP-13 in AGEs-treated chondrocytes. BMSC-exosomes reversed the impact of Drp1 overexpression on AGEs-treated chondrocytes. In conclusion, this work demonstrates that BMSC-exosomes inhibit chondrocyte apoptosis and the expression of MMPs, which attributes to regulate Drp1-mediated mitophagy. Thus, BMSC-exosomes may be a potential treatment for OA.

Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of Akt.

Metformin, traditionally regarded as a hypoglycemic drug, has been studied in other various fields including inflammation. The specific mechanism of metformin's effect on immune cells remains unclear. Herein, it is verified that LPS-induced macrophages are characterized by enhanced endogenous fatty acid synthesis and the inhibition of fatty acid synthase (FASN) downregulates proinflammatory responses. We further show that metformin could suppress such elevation of FASN as well as proinflammatory activation in macrophages. In vivo, metformin treatment ameliorates dextran sulfate sodium (DSS)-induced colitis through impairing proinflammatory activation of colonic lamina propria mononuclear cells (LPMCs). The reduction of FASN by metformin hinders Akt palmitoylation, which further disturbs Akt membrane attachment and its phosphorylation. Metformin-mediated suppression of FASN/Akt pathway and its downstream MAPK signaling contributes to its anti-inflammatory role in macrophages. From the perspective of immunometabolism, our work points towards metformin utilization as an effective and potential intervention against macrophages-involved inflammatory diseases.

Exosomal tumor necrosis factor-α from hepatocellular cancer cells (Huh-7) promote osteoclast differentiation.

Bone is the common extra-hepatic site for cancer metastasis. Hepatic cancer is associated with a higher incidence of pathological fracture. However, this important regulatory mechanism remains unexplored. Thus, exosome-mediated cell-cell communication between hepatocellular cancer and bone might be key to osteolytic bone destruction. Huh-7 exosomes were characterized for size and exosome marker expressions (CD63, Alix). Exosome mediated osteoclast differentiation in the RAW 264.7 cells was monitored from day 1 to 6 and multinucleated osteoclast formation and bone resorption activity were analyzed. The osteoclastogenic factor expressions in the exosomes and osteoclast differentiation markers such as tumor necrosis factor receptor 6 (TRAF6), nuclear factor κB (NF-κB), nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), and cathepsin K (CTSK) were analyzed using western blot. Exosomes released by liver cancer cells (Huh-7) promoted osteoclast differentiation in RAW 264.7 cells. Analysis of osteoclastogenic factors in the exosomes showed that exosomes were specifically enriched with tumor necrosis factor α (TNF-α). Huh-7 exosomes promoted osteoclast differentiation by significantly increasing the number of TRAP-positive multi nucleated osteoclasts and resorption pits. Importantly, exosomes upregulated osteoclast markers TRAF6, NF-κB, and CTSK expressions. Further, neutralizing exosomal TNF-α reverted exosome-mediated osteoclast differentiation in RAW 264.7 cells. Collectively, our findings show that cellular communication of exosomal TNF-α from hepatocellular cancer cells (Huh-7) regulates osteoclast differentiation through NF-κB/CTSK/TRAP expressions. Thus, exosomal TNF-α might act as an important therapeutic target to prevent hepatocellular cancer mediated pathological bone disease.

NIR-Activated Multimodal Photothermal/Chemodynamic/Magnetic Resonance Imaging Nanoplatform for Anticancer Therapy by Fe(II) Ions Doped MXenes (Fe-Ti3 C2 ).

2D MXene, Ti3 C2 (TC), has displayed enormous potential in applications in photothermal therapy (PTT), attributing to its biocompatibility and outstanding photothermal conversion capability. However, some tumor ablations are difficult to be realized completely by monotherapy due to the essential defects of monotherapy and intricate tumor microenvironment (TME). In this work, the appropriate doped Fe2+ ions are anchored into the layers of 2D ultrathin TC nanosheets (TC NSs) to synthesize a novel multifunctional nanoshell of Fe(II)-Ti3 C2 (FTC) through interlayer electrostatic adsorption. FTC possesses superior photothermal conversion efficiency (PTCE) than TC NSs, attributing to the enhanced conductivity promoted by interlaminar ferrous ion-channels. Moreover, Fenton reaction based on ferrous ions endows FTC the abilities of reactive oxide species (ROS) releasing and glutathione (GSH) suppression triggered by near-infrared (NIR) laser, featuring splendid biocompatibility and curative effect in hypoxic TME. Meanwhile, magnetic resonance imaging (MRI) responding in FTC reveals the potential as an integrated diagnosis and treatment nanoplatform. FTC could provide new insights into the development of multimoded synergistic nanoplatform for biological applications, especially breaking the shackles of MXenes merely used as a photo-thermal agent (PTA), adopting it to bioimaging sensor and drug loading.

Recombinant expression, purification and characterization of human soluble tumor necrosis factor receptor 2.

TNFR2 is aberrantly expressed on various cancer cells and highly immunosuppressive regulatory T cells (Tregs) accumulated in tumor microenvironment. As an oncoprotein and a stimulator of the immune checkpoint Tregs that promote cancer cell survival and tumor growth, TNFR2 is considered to be a prospective target for cancer immunotherapy with the blockers developed to simultaneously inhibit abundant TNFR2+ tumor-associated Tregs and directly kill TNFR2-expressing tumors. The soluble ectodomain of TNFR2 has also been successfully applied in clinical treatment for TNF-related autoimmune diseases. Research practices on these therapeutic strategies need recombinant protein of human soluble TNFR2 (hsTNFR2); however, mass production of such biologics using eukaryotic cells is generally high-cost in culture materials and growth conditions. This study aimed to establish an efficient methodology to prepare bioactive hsTNFR2 through a prokaryotic expression system. Recombinant vector pMCSG7-hsTNFR2 was constructed and the His-tagged fusion protein expressed in E. coli was enriched in inclusion bodies. Recombinant hsTNFR2 was denatured, refolded, and then purified by affinity chromatography, tag removal, ion-exchange chromatography and gel filtration chromatography. A protein yield of 8.4 mg per liter of bacterial culture liquid with a purity of over 97% was obtained. Purified hsTNFR2 exhibited strong affinity to human TNF-α with a KD of 10.5 nM, and inhibited TNF-α-induced cytotoxicity in L929 cells with an EC50 of 0.57 µg/ml. The biological activity assessed in vitro indicated that this soluble protein can be promisingly used in drug discovery for immunotherapy of TNFR2+ cancers and treatment of autoimmune diseases featured by TNF-α overload.

Human antigen R regulates hypoxia-induced mitophagy in renal tubular cells through PARKIN/BNIP3L expressions.

Mitochondrial dysfunction contributes to the pathophysiology of acute kidney injury (AKI). Mitophagy selectively degrades damaged mitochondria and thereby regulates cellular homeostasis. RNA-binding proteins (RBPs) regulate RNA processing at multiple levels and thereby control cellular function. In this study, we aimed to understand the role of human antigen R (HuR) in hypoxia-induced mitophagy process in the renal tubular cells. Mitophagy marker expressions (PARKIN, p-PARKIN, PINK1, BNIP3L, BNIP3, LC3) were determined by western blot analysis. Immunofluorescence studies were performed to analyze mitophagosome, mitolysosome, co-localization of p-PARKIN/TOMM20 and BNIP3L/TOMM20. HuR-mediated regulation of PARKIN/BNIP3L expressions was determined by RNA-immunoprecipitation analysis and RNA stability experiments. Hypoxia induced mitochondrial dysfunction by increased ROS, decline in membrane potential and activated mitophagy through up-regulated PARKIN, PINK1, BNIP3 and BNIP3L expressions. HuR knockdown studies revealed that HuR regulates hypoxia-induced mitophagosome and mitolysosome formation. HuR was significantly bound to PARKIN and BNIP3L mRNA under hypoxia and thereby up-regulated their expressions through mRNA stability. Altogether, our data highlight the importance of HuR in mitophagy regulation through up-regulating PARKIN/BNIP3L expressions in renal tubular cells.

Anti-Inflammatory Activity and Mechanism of Hydrostatin-SN1 From Hydrophis cyanocinctus in Interleukin-10 Knockout Mice.

Biopeptides derived from marine species have garnered significant research interest owing to their anti-inflammatory, antibacterial, and anticancer activities. In our previous study, Hydrostatin-SN1, a bioactive peptide extracted from the Hydrophis cyanocinctus venom gland T7 phage display library, demonstrated anti-inflammatory activity in a dextran sulfate sodium-induced murine colitis model. In this study, we investigated the anti-inflammatory activity and the underlying mechanism of Hydrostatin-SN1 in lipopolysaccharide (LPS)-induced bone marrow-derived macrophage (BMDM) cells and interleukin (IL)-10 knockout mice. The results showed that Hydrostatin-SN1 inhibited phosphorylation of JNK, ERK1/2, and p38 and decreased the mRNA expression of tumor necrosis factor-α (TNF-α), IL-6, and IL-1ß in LPS-stimulated BMDM cells in a dose-dependent manner. In LPS-induced acute shock model, a significant higher survival rate of Hydrostatin-SN1-treated mice was observed. Furthermore, Hydrostatin-SN1 reduced body weight loss, decreased disease activity index, reduced spleen index, prevented histological injury, and inhibited the expression of IL-ß and phosphorylation of JNK, ERK1/2, and p38 in the colon tissue of IL-10 knockout mice. Additionally, the positive expression rate of TNF-α in mice colon was decreased. Overall, our results suggest that Hydrostatin-SN1 has significant anti-inflammatory effects, both in vitro and in vivo.

The functional interplay of lncRNA EGOT and HuR regulates hypoxia-induced autophagy in renal tubular cells.

Autophagy, an important cellular homeostatic mechanism regulates cell survival under stress and protects against acute kidney injury. However, the role of long noncoding RNA (lncRNA) in autophagy regulation in renal tubular cells (HK-2) is unclear. The study was aimed to understand the importance of lncRNA in hypoxia-induced autophagy in HK-2 cells. LncRNA eosinophil granule ontogeny transcript (EGOT) was identified as autophagy-associated lncRNA under hypoxia. The lncRNA EGOT expression was significantly downregulated in renal tubular cells during hypoxia-induced autophagy. Gain- and loss-of-EGOT functional studies revealed that EGOT overexpression reduced autophagy by downregulation of ATG7, ATG16L1, LC3II expressions and LC 3 puncta while EGOT knockdown reversed the suppression of autophagy. Importantly, RNA-binding protein, (ELAVL1)/Hu antigen R (HuR) binds and stabilizes the EGOT expression under normoxia and ATG7/16L1 expressions under hypoxia. Furthermore, HuR mediated stabilization of ATG7/16L1 expressions under hypoxia causes a decline in EGOT levels and thereby promotes autophagy. Altogether, the study first reveals the functional interplay of lncRNA EGOT and HuR on the posttranscriptional regulation of the ATG7/16L1 expressions. Thus, the HuR/EGOT/ATG7/16L1 axis is crucial for hypoxia-induced autophagy in renal tubular cells.

RISK OF AGE-RELATED MACULAR DEGENERATION IN PATIENTS WITH PERIODONTITIS: A Nationwide Population-Based Cohort Study.

PURPOSE: Periodontitis is an inflammatory disease that results in loss of connective tissue and bone support. Evidence shows a possible relationship between periodontitis and age-related macular degeneration (AMD). METHODS: This population-based cohort study was conducted using data from the National Health Insurance Research Database in Taiwan, with a 13-year follow-up, to investigate the risk of AMD in patients with periodontitis. The periodontitis cohort included patients with newly diagnosed periodontitis between 2000 and 2012. The nonperiodontitis cohort was frequency-matched with the periodontitis cohort by age and sex, with a sample size of 41,661 in each cohort. RESULTS: Patients with periodontitis had an increased risk of developing AMD compared with individuals without periodontitis (5.95 vs. 3.41 per 1,000 person-years, adjusted hazard ratio = 1.58 [95% confidence interval, 1.46-1.70]). The risk of developing AMD remained significant after stratification by age (adjusted hazard ratio = 1.48 [1.34-1.64] for age <65 years and 1.76 [1.57-1.97] for age ≥65 years), sex (adjusted hazard ratio = 1.40 [1.26-1.55] for women and 1.82 [1.63-2.04] for men), and presence of comorbidity (adjusted hazard ratio = 1.52 [1.40-1.66] for with comorbidity and 1.92 [1.63-2.26] for without comorbidity). In addition, patients with periodontitis showed an increased incidence for both nonexudative type AMD (5.43 vs. 3.13 per 1,000 person-years) and exudative type AMD (0.52 vs. 0.28 per 1,000 person-years). CONCLUSION: People with periodontitis could be at a greater risk of developing AMD than those without periodontitis. However, we need more evidence to support this association.

The Joint Effect of Interleukin-12B rs3212227 Genotype and Behavioral Factors on Oral Cancer Risk in Taiwanese.

BACKGROUND/AIM: Oral cancer is of the highest incidence worldwide in Taiwan, and a better marker for personalized therapeutic strategies such as immunotherapies is urgently needed. Interleukin-12 (IL12) is a cytokine that has been reported to exhibit potent tumoricidal effects, however, its genotypic contribution to oral cancer is still largely unknown. The current study aimed at investigating whether IL12B rs3212227 genotype is associated with oral cancer in Taiwan. MATERIALS AND METHODS: Genotypic characteristics of IL12B rs3212227 were determined among 958 oral cancer cases and age- and gender-matched individuals via typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The AA, AC and CC genotypes of IL12B rs3212227 were 38.2, 38.9 and 22.9% in the case group and 36.2, 41.5 and 22.3% in the control group (p=0.5189), respectively. CONCLUSION: IL12B rs3212227 genotype was associated with oral cancer risk only in betel quid chewers.

Association of Caspase-8 Genotypes With Oral Cancer Risk in Taiwan.

BACKGROUND/AIM: Recently, mounting evidence has shown that caspase-8 (CASP8) rs3834129 (-652, 6N insertion/deletion) polymorphism may serve as a genetic biomarker for personal risk of various cancer types. The contribution of CASP8 rs3834129 polymorphism has been investigated in several oral cancer populations, but not in Taiwan. This study investigated the role of CASP8 rs3834129 polymorphism on oral risk in Taiwan. MATERIALS AND METHODS: CASP8 rs3834129 polymorphic genotypes were determined and their associations with oral cancer risk were investigated among 788 patients with oral cancer and 956 age- and gender-matched healthy controls via polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) methodology. In addition, the interaction of CASP8 rs3834129 genotype with personal behavior and clinicopathological features were also examined. RESULTS: The frequencies of II, ID and DD genotypes for CASP8 rs3834129 were 57.5, 36.5 and 6.0% in the patient group and 54.0, 39.0 and 7.0% in the healthy control group, respectively (p for trend=0.3052), genotypes were not significantly differentially distributed between the two groups. The comparisons in allelic frequency distribution also supported the findings that the D variant allele may not serve as a determinant of risk for oral cancer. There was no interaction of CASP8 rs3834129 genotype with age, gender, smoking, alcohol or betel quid consumption in regard to oral cancer risk. CONCLUSION: Our results indicate that the caspase-8 genotype does not appear to play a direct role in personal susceptibility to oral cancer in Taiwan.

Effects of mineral trioxide aggregate and bioceramics on macrophage differentiation and polarization in vitro.

BACKGROUND/PURPOSE: Mineral trioxide aggregate (Pro-Root MTA, PR-MTA) and bioceramics (iRoot® SP Injectable Root Canal Sealer, iR-BC) are used for making apical plugs used in apexification, repairing root perforations during root canal therapy, and treating internal root resorption. The purpose of the present in vitro study was to compare the biological effects of PR-MTA- and iR-BC-based dental sealers in the mouse macrophage cell line RAW 264.7. METHODS: Cytotoxicity and cell proliferation were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell hemocytometer, respectively. Protein expression of biomarkers of cell proliferation, autophagy, and osteoclast differentiation was determined by western blotting. Pro-inflammatory gene expression was examined using quantitative reverse transcription-PCR. RESULTS: PR-MTA induced cytotoxicity in RAW 264.7 cells in a dose-dependent manner, and iR-BC was more cytotoxic than PR-MTA. Low-dose and short-term treatments of both PR-MTA and iR-BC induced RAW 264.7 cell proliferation. PR-MTA induced autophagy, whereas iR-BC did not. Neither PR-MTA nor iR-BC induced osteoclastogenesis. Pro-inflammatory genes were activated by both materials. However, the expression of inducible nitric oxide synthase (iNOS) mRNA was upregulated by iR-BC treatment, but not by PR-MTA treatment. CONCLUSION: Overall, dental PR-MTA and iR-BC induced pro-inflammatory genes but did not induce osteoclastogenesis in macrophages. PR-MTA and iR-BC induced M2 and M1 polarization, respectively, of RAW 264.7 cells.

Contribution of MMP2 Promoter Genotypes to Oral Cancer Susceptibility, Recurrence and Metastasis in Taiwan.

AIM: Metalloproteinase 2 (MMP2) is a multi-functional protein which has been shown to be up-regulated in patients with oral cancer, especially those with lymph node metastasis. However, the association of MMP2 genotype with oral cancer risk or metastatic behavior is unknown. This study aimed to evaluate the role of MMP2 promoter 1306 and -735 genotypes in the risk of oral cancer and metastasis. MATERIALS AND METHODS: In this case-control study, MMP2 promoter 1306 (rs243865) and -735 (rs2285053) genotypes and their interaction with consumption of areca, cigarettes, and alcohol in determining oral cancer risk were investigated among 788 patients with oral cancer and 956 gender-matched healthy controls. In addition, their role in oral cancer metastasis were also examined. RESULTS: The distribution of CC, CT and TT for MMP2 promoter 1306 genotype was 79.0, 20.1 and 0.9% in the oral cancer group and 68.7, 29.2 and 2.1% in the non-cancer control group, respectively (p for trend=4.3E-6). The allelic frequency distributions showed that the variant T allele of MMP2 promoter 1306 conferred lower oral cancer susceptibility than the wild-type C allele (odds ratio=0.61, 95% confidence interval=0.50-0.75, p=1.1E-6). As for the MMP2 -735 genotypes, there was no differential distribution in genotypic or allelic frequencies. The variant CT and TT genotypes were also associated with lower metastasis rates within 5 years among the patients with oral cancer (odds ratio=0.34, 95% confidence interval=0.15-0.80, p=0.0102). CONCLUSION: The CT and TT genotypes of MMP2 promoter 1306 may have a protective effect on oral cancer susceptibility and metastasis risk within 5 years for Taiwanese. They may serve as predictive markers for oral cancer in precise medical practice.

Expression of Livin and PlGF in human osteosarcoma is associated with tumor progression and clinical outcome.

Baculoviral IAP repeat containing 7 (BIRC7/Livin/ML-IAP/KIAP; referred to as Livin throughout the present study) and placental growth factor (PlGF) are not detectable in the majority of normal differentiated tissues, but are present in a number of types of cancer, including hepatocellular carcinoma, ovarian cancer and renal cell carcinoma. The aim of the present study was to assess the expression levels of Livin and PlGF in human osteosarcoma specimens and cell lines, and to analyze the functions of Livin and PIGF in the prognosis of osteosarcoma. The expression levels of Livin and PlGF in 48 osteosarcoma specimens and three osteosarcoma cells were determined using immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. The positivity rates of Livin and PlGF in osteosarcoma specimens were 58.3 and 60.4%, respectively, but were 0% in normal bone tissues. The expression levels of Livin and PlGF were increased in MG-63 cells, compared with those in the other cell lines evaluated in the present study. In addition, the expression levels of Livin and PlGF were significantly associated with tumor diameter and Enneking staging, but were independent of tumor site, age and sex of patients. The expression level of Livin was not associated with PlGF. Furthermore, the 5-year overall survival rate was decreased in the Livin or PlGF expression group, compared with that in the non-expression group (P=0.034 and P=0.012, respectively). The expression levels of Livin and PlGF were independent prognostic factors for patients with osteosarcoma. The results of the present study demonstrated that Livin and PlGF may participate in the pathogenesis of osteosarcoma. Therefore, pharmacological inhibition of Livin or PlGF may provide a novel strategy for osteosarcoma treatment.

Compression neuropathy of common peroneal nerve caused by a popliteal cyst: A case report.

RATIONALE: Popliteal cyst developing in the sheath of a peripheral nerve or joint capsule may cause compression neuropathy. Although popliteal cyst is very common lesion, it seldom causes serious complications. Common peroneal nerve compression is rarely caused by an extraneural popliteal cyst. PATIENT CONCERNS: We presented the case of a 52-year-old female with common peroneal nerve compression caused by an extraneural popliteal cyst. DIAGNOSES: Electromyography showed the damage of common peroneal nerve. MRI magnetic resonance imaging showed the lump to be a popliteal cyst. She was diagnosed as peroneal nerve injury and popliteal cyst. INTERVENTIONS: The patient was performed peroneal nerve decompression and popliteal cyst excision surgery. We excised the cyst completely and soluted the common peroneal nerve thoroughly. The cyst was filled with thick mucinous material. OUTCOMES: The pathological report showed that the excised mass was a popliteal cyst. There were no postoperative complications. Pain and hypoesthesia resolved 6 months after surgery. LESSONS: In this case, compression of the common peroneal nerve was due to an extraneural popliteal cyst, a situation rarely encountered. MRI can show in better detail their size and internal contents as well as their relation with surrounding anatomic structures. Patients with nerve entrapment caused by enlarged or ruptured cysts must be microsurgically excised if symptomatic.