Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: The contribution of ectopic lymphoid tissues (eLTs) to local immunoglobulin hyperproduction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. OBJECTIVE: We sought to explore the cellular basis, formation mechanisms, and function of eLTs in patients with CRSwNP. METHODS: We graded lymphoid aggregations in sinonasal mucosa and histologically studied their structures. The expression of lymphorganogenic factors and molecules required for immunoglobulin production was measured by using real-time PCR, and their localization was analyzed by means of immunohistochemistry and immunofluorescence. The phenotype of follicular helper T cells was analyzed by performing flow cytometry. Immunoglobulin levels were quantified by using the Bio-Plex assay or ImmunoCAP system. Nasal tissue explants were challenged ex vivo with Dermatophagoides pteronyssinus group 1 (Der p 1), and the expression of Iε-Cµ and Iε-Cγ circle transcripts was detected by using seminested PCR. RESULTS: Increased formation of eLTs with germinal center-like structures was discovered in patients with eosinophilic (20.69%) and noneosinophilic (17.31%) CRSwNP compared with that in patients with chronic rhinosinusitis without nasal polyps (5.66%) and control subjects (3.70%). The presence of eLTs was associated with increased expression of lymphorganogenic and inflammatory chemokines and cytokines, as well as their receptors. The expression of molecules required for immunoglobulin production, generation of follicular helper T cells, and production of IgE in eosinophilic polyps and IgG and IgA in both eosinophilic and noneosinophilic polyps were predominantly upregulated in patients with eLTs. After Der p 1 challenge ex vivo, Iε-Cµ transcript was detected only in eosinophilic polyps with eLTs but not in polyps without eLTs and noneosinophilic polyps. CONCLUSION: eLTs might support local immunoglobulin production and therefore significantly contribute to the development of CRSwNP.

Curcumin combined with oxaliplatin effectively suppress colorectal carcinoma in vivo through inducing apoptosis.

Studies have shown chemopreventive and/or chemotherapeutic effects of several curcumin-based combinatorial treatments on colorectal cancer cells. However, their in vivo effects remain unclear. This study has demonstrated the therapeutic effect of curcumin and oxaliplatin, alone or in combination, on subcutaneously xenografted LoVo human colorectal cancer cells in immunodeficient (nu/nu) mice in vivo. Combinatorial administration of curcumin and oxaliplatin evidently inhibited the growth of colorectal cancer in nude mice, which was significantly more effective than either agent alone. Curcumin combined with oxaliplatin treatment induced apoptosis, accompanied by ultrastructural changes and cell cycle arrest in S and G2/M phases. Further mechanism analysis indicated that while the number of apoptotic tumor cells and the expression of Bax, caspase-3, and poly (ADP-ribose) polymerase (PARP) increased significantly, the expression of Bcl-2, survivin, HSP70, pro-caspase-3, and pro-PARP were dramatically suppressed in tumor cells after the treatment with combinatorial curcumin and oxaliplatin for 22 days. Taken together, the present study has demonstrated that administration of combined curcumin and oxaliplatin effectively suppressed colorectal carcinoma in vivo through inducing apoptosis and thus may provide an effective treatment for colorectal carcinoma.

Identification, Distribution and Population Dynamics of Francisella-like Endosymbiont in Haemaphysalis doenitzi (Acari: Ixodidae).

Francisella-like endosymbionts (FLEs) with significant homology to Francisella tularensis (γ-proteobacteria) have been characterized in several tick species, whereas knowledge on their distribution and population dynamics in ticks remains meager. Hence, in the current study, we identified a novel Francisella-like endosymbiont (FLEs-Hd) from the tick Haemaphysalis doenitzi and evaluated the putative functions of this symbiont. Results indicated that FLEs-Hd had 100% infection rate and a perfect vertical transmission in H. doenitzi, and that it is distributed in ovaries, malpighian tubules, salivary glands and midguts of the ticks, suggesting that FLEs-Hd presumably is a crucial symbiont of the host without specific tissue tropism. To further explore the function of the symbiont, the population dynamics of FLEs-Hd at each developmental stage of ticks and in tissues at different reproductive statuses were determined by real-time quantitative polymerase chain reaction (real-time qPCR). Results showed that the high density and regular population dynamics of FLEs-Hd appeared in female ovaries, suggesting that the symbiont may provide necessary nutrients or regulators to ensure normal ovary development of ticks.

Microbial communities and symbionts in the hard tick Haemaphysalis longicornis (Acari: Ixodidae) from north China.

BACKGROUND: Close relationships between ticks and microbial communities are important for tick fitness and pathogen colonization and transmission. Haemaphysalis longicornis, distributed widely in China, can carry and transmit various pathogens and pose serious damages to public health and economics. However, little is known about the broader array of microbial communities and symbionts in H. longicornis under natural conditions. In the present study, we investigated the composition of bacterial communities associated with H. longicornis and evaluated the putative symbionts. METHODS: The eubacterial 16S rRNA gene clone libraries of H. longicornis were constructed and analyzed by restriction fragment length polymorphism (RFLP) and DNA sequencing. In addition, diagnostic PCR was performed to assess the prevalence, vertical transmission and infection sites of the symbionts in H. longicornis. RESULTS: Vertically-transmitted symbionts, potential pathogens and allochthonous nonpathogenic bacteria were identified from the field-collected H. longicornis. Three types of symbionts (Coxiella-like, Arsenophonus-like and Rickettsia-like symbionts) were identified in a single host simultaneously. A series of analyses revealed the vertical transmission, prevalence, and infection sites of these symbionts. However, only Coxiella-like bacteria were transmitted stably in the laboratory-reared ticks. In addition, we identified a novel Coxiella-like agent with 95.31% sequence similarity to the taxon described previously. CONCLUSIONS: The present study demonstrated that natural H. longicornis harboured a diverse array of microbial communities. Three types of symbionts were identified in a single host simultaneously. Moreover, high prevalence, vertical transmission and the infection sites supported an obligate symbiotic association between Coxiella symbiont and its host. The role of Coxiella symbiont in the host fitness and the interaction among microbial communities remained to be elucidated. Our investigation of microbial communities in the ticks revealed the complexity of ecological interactions between host and microbe and provided insight for the biological control of ticks.