Characterization of genital chlamydia trachomatis infection among women attending infertility and gynecology clinics in Hunan, China.

BACKGROUND: Genital infection with Chlamydia trachomatis (C. trachomatis) is a major public health issue worldwide. It can lead to cervicitis, urethritis, and infertility. This study was conducted to determine the characteristics of genital C. trachomatis infection among women attending to the infertility and gynecology clinics. METHODS: Endocervical swabs were collected from 8,221 women for C. trachomatis nucleotide screening and genotyping, while serum samples were collected for C. trachomatis pgp3 antibody determination using luciferase immunosorbent assays. RESULTS: High C. trachomatis DNA prevalence (3.76%) and seroprevalence (47.46%) rates were found, with genotype E (27.5%) being the most prevalent. C. trachomatis omp1 sense mutation was associated with cervical intraepithelial neoplasia (CIN) (odds ratio [OR] = 6.033, 95% confidence interval [CI] = 1.219-39.185, p = 0.045). No significant differences in C. trachomatis seroprevalence rates were observed between women with detectable C. trachomatis DNA in the infertility and routine physical examination groups (86.67% vs. 95%, p > 0.05); however, among women with negative C. trachomatis DNA, the former group had a markedly higher seroprevalence than the latter group (56.74% vs. 20.17%, p < 0.001). C. trachomatis DNA, but not pgp3 antibody, was significantly associated with CIN (OR = 4.087, 95% CI = 2.284-7.315, p < 0.001). CONCLUSION: Our results revealed a high prevalence, particularly seroprevalence, of C. trachomatis among women with infertility. Furthermore, we found an association between C. trachomatis omp1 sense mutations and CIN. Therefore, C. trachomatis serves as a risk factor for CIN.

C-H activation-initiated spiroannulation reactions and their applications in the synthesis of spirocyclic compounds.

Spirocyclic skeletons are prevalent in natural products, pharmaceuticals and organic functional materials. Meanwhile, transition-metal-catalyzed C-H activation reactions have demonstrated unparalleled advantages such as high efficiency, excellent atom-economy, good chemoselectivity and regioselectivity for the formation of target organic molecules. In recent years, C-H activation reactions have been creatively utilized in the synthesis of spirocyclic compounds. This review summarizes the most recent progress made in C-H activation-initiated spiroannulation reactions and their applications in the construction of structurally diverse and biologically valuable spirocyclic scaffolds by using alkynes, diazo compounds, maleimides, alkenes, quinones and cyclopropenones as the coupling partners.

The dual role of cytokine responses to Chlamydia trachomatis infection in host pathogen crosstalk.

Chlamydia-induced diseases are a significant human health disease. In recent years, a large number of studies have helped to gradually improve our understanding of chlamydia. For example, in the lifestyle of a parasitic host, chlamydia infection stimulates T cell and macrophage-mediated immune responses in the host. Different immune cells produce different cytokines and different immune effects. Th1 cells produce IL-2, IL-12, and IFN-γ, while Th2 cells produce IL-4 and IL-10. The two cytokines produced by T cells play different roles when chlamydia infects the host. In which immune link are these cytokines produced and what role do they play after production? Understanding these mechanisms of action, will help us to develop new strategies against problems caused by chlamydia. Chlamydia trachomatis infection often shows persistence and repeatability due to the lack of bactericidal immunity in humans. The consequences of persistent chlamydia infection can be severe, and can include salpingitis and follicular conjunctival scarring. Recently, many studies have suggested that chlamydia-induced changes in inflammation can affect humans and animals to varying degrees. It is important to study the ways in which these changes can influence the mammalian hosts. Herein, we investigated changes in cytokine expression following chlamydial infection, how this affects disease pathogenesis in chlamydia, and we use this to understand the cause of the high recurrence rate after chlamydial infection. In addition, we summarize the different cytokines produced by other immune cells after chlamydia infection, emphasizing the interaction between various cytokines. Finally, we outline how to deal with the duality of cytokines and reduce their adverse effects after protoplasmic infection.

Lactobacillus Modulates Chlamydia Infectivity and Genital Tract Pathology in vitro and in vivo.

Since we previously reported that women infected with chlamydia had a significant overall reduction in Lactobacillus in the vagina microbiota as compared to those uninfected individuals; the interactions between the altered Lactobacillus and Chlamydia trachomatis, on the other hand, need to be elucidated. Here, we employed both in vitro and in vivo models to evaluate the effects of this changed Lactobacillus on Chlamydia infection. We found that L. iners, L. crispatus, L. jensenii, L. salivarius, L. gasseri, L. mucosae, and L. reuteri all significantly reduced C. trachomatis infection in a dose- and time-dependent manner. The strongest anti-Chlamydia effects were found in L. crispatus (90 percent reduction), whereas the poorest was found in L. iners (50 percent reduction). D (-) lactic acid was the key component in Lactobacillus cell-free supernatants (CFS) to inactivate Chlamydia EBs, showing a positive correlation with the anti-Chlamydia activity. The effects of D (-) lactic acid were substantially attenuated by neutralizing the pH value to 7.0. In vivo, mice intravaginally inoculated with Lactobacillus mixtures (L. crispatus, L. reuteri, and L. iners at a ratio of 1:1:1), but not single Lactobacillus, after genital Chlamydia infection, significantly attenuated the levels of Chlamydia live organism shedding in both the lower genital tract and the intestinal tract, reduced cytokines production (TNF-α, IFN-γ, and IL-1ß) in the vagina, and lessened upper genital tract inflammation and pathogenicity. Taken together, these data demonstrate that Lactobacillus inhibits Chlamydia infectivity both in vivo and in vitro, providing useful information for the development of Lactobacillus as adjunctive treatment in Chlamydia infection.

Synthesis of Spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]s via [4+1+1] Annulation of N-Aryl Amidines with Diazo Homophthalimides and O2.

Synthesis of spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]s through a unique [4+1+1] annulation of N-aryl amidines with diazo homophthalimides and O2 is presented. This unprecedented spirocyclization reaction features readily obtainable substrates, structurally and pharmaceutically attractive products, a cost-free and clean oxygen source, sustainable reaction medium, tolerance of a broad spectrum of functional groups, and an interesting reaction mechanism based on sequential C(sp2)-H/C(sp3)-H bond cleavage and oxygen insertion.

Direct α-Alkenylation of Cyclic Amines with Maleimides through Fe(III)-Catalyzed C(sp3)-H/C(sp2)-H Cross Dehydrogenative Coupling.

Presented herein is a novel and efficient α-C(sp3)-H alkenylation of cyclic amines with maleimides. Mechanistically, this C(sp3)-H/C(sp2)-H cross dehydrogenative coupling (CDC) reaction involves a cascade procedure including oxidative α-amino radical formation from the cyclic amine substrate and nucleophilic addition of the in situ formed α-amino radical onto the electron-deficient carbon-carbon double bond of maleimide followed by oxidation and ß-elimination. Notably, this direct α-functionalization provides an effective alternative to the conventional ionic reaction mode, in which an imine or iminium intermediate is formed to react with electron-rich coupling partners other than electron-deficient ones. In general, this method features readily available and structurally diverse substrates, a green and economical catalyst, a unique reaction pathway, mild reaction conditions, high efficiency, and excellent atom economy. This new reaction enriches the application of Fe(III)-catalyzed C(sp3)-H activation and functionalization.

Synthesis of 1,3-Benzodiazepines through [5 + 2] Annulation of N-Aryl Amidines with Propargylic Esters.

In this paper, an efficient synthesis of functionalized 1,3-benzodiazepines through an unprecedented [5 + 2] annulation of N-aryl amidines with propargylic esters is presented. The reactions proceed through Rh(III)-catalyzed C(sp2)-H alkenylation followed by annulation and deacetoxylation along with cascade C-H/N-H/C-O bond cleavage and C-C/C-N bond formation. Furthermore, the cytotoxicity of selected products against several human cancer cell lines was tested, which demonstrated their good potential for pharmaceutical applications.

Synthesis of α-Amidoketones through the Cascade Reaction of Carboxylic Acids with Vinyl Azides under Catalyst-Free Conditions.

An efficient synthesis of α-amidoketone derivatives through the cascade reactions of carboxylic acids with vinyl azides is presented. Compared with literature protocols, notable features of this new method include catalyst-free conditions, broad substrate scope, good tolerance of a wide range of functional groups, and high efficiency. In addition, the synthetic potential of this method as a tool for late-stage modification was convincingly manifested by its application in the structural elaborations of a number of carboxylic acid drug molecules.