Expression of programmed death 1 ligand 1 on periodontal tissue cells as a possible protective feedback mechanism against periodontal tissue destruction.

Programmed death 1 ligand 1 (PD‑L1) is a negative co‑stimulatory molecule in immune responses. Previous reports have indicated that inflammatory cytokines can upregulate the expression of PD‑L1 in tumor cells, which in turn suppresses host immune responses. Periodontitis is characterized by persistent inflammation of the periodontium, which is initiated by infection with oral bacteria and results in damage to cells and the matrices of the periodontal connective tissues.

Which subtype of functional dyspepsia patients responses better to acupuncture? A retrospective analysis of a randomized controlled trial.

Background: Whether subgroups of functional dyspepsia (FD) should be treated with different approaches is controversially discussed in research. As our previous study has demonstrated the effect of acupuncture in FD treatment, we now further analyze the therapeutic effect of acupuncture in the treatment of postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS).

Methods: A retrospective analysis was conducted in 465 eligible PDS patients and 241 EPS patients.

Replication stress by Py-Im polyamides induces a non-canonical ATR-dependent checkpoint response.

Pyrrole-imidazole polyamides targeted to the androgen response element were cytotoxic in multiple cell lines, independent of intact androgen receptor signaling. Polyamide treatment induced accumulation of S-phase cells and of PCNA replication/repair foci. Activation of a cell cycle checkpoint response was evidenced by autophosphorylation of ATR, the S-phase checkpoint kinase, and by recruitment of ATR and the ATR activators RPA, 9-1-1, and Rad17 to chromatin.

Animal toxicity of hairpin pyrrole-imidazole polyamides varies with the turn unit.

A hairpin pyrrole-imidazole polyamide (1) targeted to the androgen receptor consensus half-site was found to exert antitumor effects against prostate cancer xenografts. A previous animal study showed that 1, which has a chiral amine at the α-position of the γ-aminobutyric acid turn (γ-turn), did not exhibit toxicity at doses less than 10 mg/kg. In the same study, a polyamide with an acetamide at the β-position of the γ-turn resulted in animal morbidity at 2.

Biosynthesis of the sesquiterpene botrydial in Botrytis cinerea. Mechanism and stereochemistry of the enzymatic formation of presilphiperfolan-8beta-ol.

Presilphiperfolan-8beta-ol synthase, encoded by the BcBOT2 gene from the necrotrophic plant pathogen Botrytis cinerea, catalyzes the multistep cyclization of farnesyl diphosphate (2) to the tricyclic sesquiterpene alcohol presilphiperfolan-8beta-ol (3), the preursor of the phytotoxin botrydial, a strain-dependent fungal virulence factor. Incubation of (1R)-[1-(2)H]farnesyl diphosphate (2b) with recombinant presilphiperfolan-8beta-ol synthase gave exclusively (5R)-[5alpha-(2)H]-3b, while complementary incubation of (1S)-[1-(2)H]FPP (2c) gave (5S)-[5beta-(2)H]-3c. These results established that cyclization of farnesyl diphosphate involves displacement of the diphosphate group from C-1 with net inversion of configuration and ruled out the proposed intermediacy of the cisoid conformer of nerolidyl diphosphate (9) in the cyclization.

Sesquiterpene synthase from the botrydial biosynthetic gene cluster of the phytopathogen Botrytis cinerea.

The fungus Botrytis cinerea is the causal agent of the economically important gray mold disease that affects more than 200 ornamental and agriculturally important plant species. B. cinerea is a necrotrophic plant pathogen that secretes nonspecific phytotoxins, including the sesquiterpene botrydial and the polyketide botcinic acid.

Biochemistry and molecular genetics of the biosynthesis of the earthy odorant methylisoborneol in Streptomyces coelicolor.

Methylisoborneol (2) is a volatile organic compound produced by a wide variety of Actinomycete soil organisms, myxobacteria, and cyanobacteria. It has an unusually low odor threshold and, together with geosmin, is responsible for the characteristic smell of moist soil as well as unpleasant taste and odor episodes associated with public water supplies and contamination of various foodstuffs, including fish, wine, and beer. Despite considerable interest in detection and remediation of methylisoborneol, the biosynthesis of this methylated monoterpene has been obscure.