The elaboration of an effective immune response against pathogenic microbes such as viruses, intracellular bacteria or protozoan parasites relies on the recognition of microbial products called pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs). Ligation of the PRRs leads to synthesis and secretion of pro-inflammatory cytokines and chemokines. Infected cells and other stressed cells also release host-cell derived molecules, called damage-associated molecular patterns (DAMPs, danger signals, or alarmins), which are generic markers for damage. DAMPs are recognized by specific receptors on both immune and nonimmune cells, which, depending on the target cell and the cellular context, can lead to cell differentiation or cell death, and either inflammation or inhibition of inflammation. Recent research has revealed that DAMPs and PAMPs synergize to permit secretion of pro-inflammatory cytokines such as interleukin-1β (IL-1β): PAMPs stimulate synthesis of pro-IL-1β, but not its secretion; while DAMPs can stimulate assembly of an inflammasome containing, usually, a Nod-like receptor (NLR) member, and activation of the protease caspase-1, which cleaves pro-IL-1β into IL-1β, allowing its secretion. Other NLR members do not participate in formation of inflammasomes but play other essential roles in regulation of the innate immune response.

The 7-valent pneumococcal conjugate vaccine (PCV7) is currently being introduced in the vaccine schedule of over 90 countries around the world. After the introduction of the PCV7 vaccine in the United States, a reduction of more than 90% of invasive pneumococcal disease (IPD) was reported in vaccinated children under the age of 5 years. Similar findings were reported from other countries. A reduction in community-acquired pneumonia (CAP) of > 40% has also been reported. In children under the age of 5 years, the number of primary medical visits and antibiotic usage for acute otitis media (AOM) decreased by more than 40%. In adults over 65 years of age a significant reduction of 90% in IPD caused by PCV7 serotypes was reported as well. However, after the introduction of PCV7 there were reports of increase of serotypes not included in the vaccine, such as serotype 19A in various Streptococcus pneumoniae-related diseases such as invasive disease, AOM and pneumonia. In addition, serotypes 1, 5, 7F and 19A were more prevalent in complicated cases of CAP. Recently, new vaccines covering additional serotypes such as the 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) were introduced, and are expected to reduce S. pneumoniae-related diseases furthermore.

Epidermis is composed mainly of keratinocytes and is the ma­jor barrier of human body. The development and maintenance of normal epithelial structures and functions require the transcrip­tion factor p63. The p63 gene encodes proteins with structures simi­lar to that of p53, including an N-terminal transacti­vation (TA) domain, a DNA-binding domain and a car­boxy-oligomerization domain. TAp63 and ΔNp63 (p63 isoforms without TA domain) regulate a wide range of target genes that are important for embryonal development and epithelial integrity. Mutations of p63 gene cause epider­mal abnormalities characterized by ectodermal dysplasia. Recent reports have indicated that p63 plays important role in tumorigenesis as well. However, the relative importance of TAp63 and ΔNp63 in epidermal development and tumorigenesis re­mains mostly unclear and awaits further investigation. In this review, we summarize the current knowledge on the structure and function of p63 and its isoforms.

The efficacy of cancer chemotherapy is often affected by the emergence of resistant can­cer cells. While biochemical and pharmaco­logical mechanisms have been proposed to ex­plain chemo­resistance, the genes involved in this process have not been fully identified. We previ­ously used genomic DNA microarrays and quantitative RT-PCR to identify the genes associ­ated with resistance to chemotherapeutic drugs, particularly to the genotoxic agent cispla­tin. Notably, knockdown of the cisplatin resistance (CPR) genes that we identified was shown to reduce chemoresistance and to suppress the growth of tumor xenographs in cispla­tin-treated mice, indicating that the newly identified CPR genes may represent potential ther­apy candidates to limit chemo­resistance and to improve the efficacy of anticancer drugs. In addi­tion to genetic mutations, re­searchers have found that epigenetic changes and alternative splic­ing of specific genes may also allow cancer cells to become resistant to chemotherapeu­tic drugs. In this article, the au­thors present an overview of the latest findings in this field, includ­ing genetic changes, epige­netic changes and alternative splicing.

Background: Tendon-bone tunnel healing is crucial for long term success in anterior cruciate liga­ment (ACL) reconstruction. The periosteum contains osteochondral progenitor cells that can differenti­ate into osteoblasts and chondroblasts during tendon-bone healing. We developed a scaf­fold-free method using polymerized fibrin-coated dishes to make functional periosteal progenitor cell (PPC) sheets. Bioengineered PPC sheets for enhancing tendon-bone healing were evaluated in an extra-articular bone tunnel model in rabbit. Methods: PPC derived from rabbit tibia periosteum, cultivated on polymerized fi­brin-coated dishes and harvested as PPC sheet. A confocal microscopy assay was used to evaluate the morphology of PPC sheets. PPC sheets as a periosteum to wrap around hamstring tendon grafts were pulled into a 3-mm diameter bone tunnel of tibia, and compared with a tendon graft without PPC sheets treatment. Rabbits were sacrificed at 4 and 8 weeks postoperatively for biochemical as­say and histological assay to demonstrate the enhancement of PPC sheets in tendon-bone healing. Results: PPC spread deposit on fibrin on the dish surface with continuous monolayer PPC was ob­served. Histological staining revealed that PPC sheets enhance collagen and glycosaminoglycans deposi­tion with fibrocartilage formation in the tendon-bone junction at 4 weeks. Collagen fiber with fibrocartilage formation at tendon-bone junction was also found at 8 weeks. Matured fibrocartilage and dense collagen fiber were formed at the tendon-bone interface at 8 weeks by Masson trichrome and Safranin-O staining Conclusions: Periosteal progenitor cell monolayer maintains the differentiated capacity and osteochon­dral potential in order to promote fibrocartilage formation in tendon-bone junction. Bioengi­neered PPC sheets can offer a new feasible therapeutic strategy of a novel approach to en­hance tendon-bone junction healing.

Background: This study analyzed the long-term outcomes of extracorporeal shockwave therapy (ESWT) and core decompression for early osteonecrosis of the femoral head (ONFH) with 8- to 9-year follow-up. Methods: The study cohort consisted of 48 patients with 57 hips including 23 patients with 29 hips in the ESWT group and 25 patients with 28 hips in the surgical group. Patients in ESWT group received shockwave therapy to the affected hip. Patients in surgical group underwent core decompression and autogenous cancellous bone and allogenous fibular graft. The average length of follow-up was 103.5 ΁3.4 (ranged 93-106) months and 104.5΁4.3 (ranged 95-108) months for the ESWT and the surgical group, respectively. The evaluations included clinical assessment for pain and function, X-ray and MRI of the affected hips. Results: The overall clinical results were 76% good or fair and 24% poor for the ESWT group; and 21% good or fair and 79% poor for the surgical group. THA was performed in 3% and 21% at one year, 10% and 32% at 2 years and 24% and 64% at 8-9 years for ESWT and the surgical group respectively. Significant differences in pain and Harris hip scores were observed at different time intervals favoring the ESWT group. There was a trend of decrease in the size of the lesion in the ESWT group when compared with the surgical group. Conclusion: ESWT appears to be more effective than core decompression and bone grafting for early ONFH with 8- to 9-year long-term follow-up.

Background: Phyllodes tumors (PT) are rare. We evaluated the expression status of ER, Bcl2, p53, and MIB-1 protein in these tumors. Methods: One hundred and ninety-three tumors were examined using immunohistochemistry on tissue microarray. Results: ERβ (p <0.001), and p53 (p=0.006) in the stromal component were associated with tumor size. p53 expression was significantly associated with both epithelial and stro­mal components of malignant PTs (p<0.05). In PT, the decreased expressions of p53 and MIB-1 were significantly different with positive Bcl2 protein expression in epi­thelial component (p=0.000). Besides, MIB-1 was also found to be associated with ERα and ERβ in stromal component (p=0.000). Conclusion: The expression of p53 with tumor size and histological grade in PTs may increase risk for malignancy.

Background: Human tear film plays an important role in protecting the ocular surface against vari­ous pathogens. Dry eye, the major ocular complication of peripheral blood stem cell trans­plantation (PBSCT), may predispose bacterial colonization to the conjunctiva, and increase the risk of infectious keratitis. The aim of this study is to investigate the con­junctival bacterial flora in patients receiving PBSCT and to stratify the severity of dry eye for comparison. Methods: This cross-sectional study encompassed patients who received PBSCT from 2002 to 2008 in our hospital. At least 1 year after PBSCT, patients were re-evaluated for ocu­lar surface status, and bacterial culture of the conjunctival sac was performed. The eyes of patients were divided into three groups in accordance to the result of the Schirmer Ia test. In the control group, we enrolled dry-eye patients with underlying dis­ease other than hematopoietic stem cell transplantation of which the age range was simi­lar to the study group. Results: Thirty-six patients with 72 eyes were included in our study. The first group (n=36) was defined as having Schirmer Ia test result of 0-5 mm, and the culture of conjuncti­val sac were positive in 8 eyes (22%). The second group (n=20) was defined as having Schirmer Ia result between 6 and 9 mm, and 4 of which were positive for bacterial cul­ture (20%). In the third group (n=16) with Schirmer Ia result of ≧10mm, flora in pa­tients receiving PBSCT were coagulase-negative Staphylococci, Staphylococcus au­reus and Corynebacterium sp. The bacterial colonization rate in the post-PBSCT group was not higher than the control group (22.2% vs. 30.8%), and coagulase-nega­tive Staphylococci was the most common flora in the control group. Conclusion: Despite not having statistical significance, there seems to be a positive correlation be­tween the colonization rate and the severity of dry eye. However, bacterial profile iso­lated in post-PBSCT patients is not significantly different from other dry eye patients.