Synthesis and positive inotropic activity evaluation of liguzinediol metabolites.

2,5-Dihydroxymethyl-3,6-dimethylpyrazine (liguzinediol) has been recently discovered as a potential agent for treatment of heart failure with low safety risk. In the present study, four main metabolites of liguzinediol were synthesized and their positive inotropic activities were evaluated. Synthetic compounds were identical with the isolated metabolites of liguzinediol. Pharmacological examinations showed that the four major metabolites were not observed positive inotropic activity, and revealed that the positive inotropic activity of liguzinediol was essentially attributed to the parent agent.

Synthesis and biological evaluation of liguzinediol mono- and dual ester prodrugs as promising inotropic agents.

The potent positive inotropic effect, together with the relatively low safety risk of liguzinediol (LZDO), relative to currently available inotropic drugs, has prompted us to intensively research and develop LZDO as a potent positive inotropic agent. In this study, to obtain LZDO alternatives for oral chronic administration, a series of long-chain fatty carboxylic mono- and dual-esters of LZDO were synthesized, and preliminarily evaluated for physicochemical properties and bioconversion. Enhanced lipophilic properties and decreased solubility of the prodrugs were observed as the side chain length increased. All esters showed conspicuous chemical stability in phosphate buffer (pH 7.4). Moreover, the enzymatic hydrolysis of esters in human plasma and human liver microsomes confirmed that the majority of esters were converted to LZDO, with release profiles that varied due to the size and structure of the side chain. In vivo pharmacokinetic studies following oral administration of monopivaloyl (M5), monodecyl (M10) and monododecyl (M12) esters demonstrated the evidently extended half-lives relative to LZDO dosed alone. In particular the monopivaloyl ester M5 exhibited an optimal pharmacokinetic profile with appropriate physiochemical characteristics.

Extraovarian Brenner tumor in the uterus: a case report and review of literature.

BACKGROUND: Extraovarian Brenner tumors (EOBTs) are extremely rare and can be observed incidentally in both female and male patients, raising concerns regarding the origin of Brenner tumors. CASE PRESENTATION: A 53-year-old postmenopausal woman presented with a nodular lesion in the left side of the corpus uteri, which was found at a routine health check. Macroscopically, the lesion appeared as a solid nodule with a yellowish-gray cut surface, approximately 6 cm in greatest diameter. Microscopically, the lesion consisted of well-defined epithelial nests and spindled stromal cells. Parenchymal cells expressed CK7, GATA3, CK5/6, 34ßE12, and p63. A single layer of cavity-lined cells with umbrella-like shape showed apical Uroplakin III positivity. Stromal cells were positive for SMA, ER, and PR. The final diagnosis was EOBT and the patient was followed for 2 months with no recurrence. CONCLUSIONS: We report here the third case of EOBTs in the uterus. The combination of morphologic and immunohistochemical results supported the involvement of urothelial metaplasia in the development of EOBTs. The similarities between EOBTs and Walthard nests made Müllerian epithelium an attractive candidate as the cellular origin. Changes of tissue structure or sex hormones imbalance may lead to the translocation of Müllerian remnants to distant organs, explaining the pathogenesis of EOBTs.

The changes of the peripheral CD4+ lymphocytes and inflammatory cytokines in Patients with COVID-19.

To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. The results show that the lymphocytopenia in patients with COVID-19 was mainly manifested by decreases in the CD4+ T lymphocyte number and the CD4+/CD8+ ratio. The decreased number of CD4+ T lymphocytes and the elevated levels of TNF-α and IL-6 were correlated with the severity of COVID-19 disease.

Effects of perfluorooctane on the retina as a short-term and small amounts remnant in rabbits.

AIM: To investigate changes in the rabbit retina after short-term and small amounts tamponade of perfluorooctane (PFO). METHODS: New Zealand rabbits were used, and 48 eyes were randomly and evenly assigned into four different groups. The PFO groups received a residue of 0.1 mL of PFO for ophthalmic surgery or 0.1 mL of F-Octane at the end of surgery; eyes from the pars plana vitrectomy (PPV) group were filled with balanced salt solution and those having not received surgical intervention served as controls. Eyes were collected at 1, 4 and 12wk and studied. RESULTS: Under a microscope, nuclear counts of the inner nuclear layer (INL) and outer nuclear layer (ONL) did not differ among the four groups at all time points; however, slight disarrangement of the ONL and occasional vacuolization of the INL were found in the inferior retina only at 12wk in two PFO groups. Four of the groups had similar results of Caspase-3 and TNF-α staining at all time points. Alternatively, IL-8 was increased in PFOa and PPV control groups at 4wk and in all three PPV groups at 12wk; also, the apoptotic index (%) was similarly increased in all three PPV groups at 4 and 12wk. CONCLUSION: Both PFOs are well tolerated in rabbit eyes for up to 12wk, which suggests that they can be used safely as intraoperative tools or for short-term and small amounts tamponade after surgery.

Prediction of a new BeC monolayer with perfectly planar tetracoordinate carbons.

Recently, there has been a growing interest in exploring planar hypercoordinate carbons in two-dimensional nanostructures. However, atomic monolayers with ideal planar hypercoordinate carbon are quite rare due to the challenge in stabilizing the exotic motifs. We predicted a global minimum two-dimensional BeC monolayer using the global particle-swarm optimization method. Each carbon binds peripheral four atoms in the same plane, forming a perfectly planar tetracoordinate carbon moiety. The cohesive energy, phonon-spectrum and mechanical stability criteria confirm the stability of monolayer BeC. In addition, the BeC monolayer has a large in-plane stiffness (145.54 N m-1) and thermo-dynamical stability (up to 2000 K). Furthermore, BeC is an indirect semiconductor with a band gap of 1.01 eV and possesses exceptionally high carrier mobilities (∼104 cm2 V-1 s-1), rendering it suitable for application in electronics and photoelectronics.