Exploring m6A-linked aging genes in osteoarthritis and broad cancer spectrum: Prospects for diagnostic and therapeutic advancements.

Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly impacts individuals and healthcare systems worldwide. However, the exploration of N6-methyladenosine (m6A)-related aging genes in OA pathogenesis remains largely underexplored. This study aimed to elucidate the role of m6A-related aging genes in OA and to develop a robust diagnostic model based on their expression profiles. Leveraging publicly available gene expression datasets, we conducted consensus clustering to categorize OA into distinct subtypes, guided by the expression patterns of m6A-related aging genes. Utilizing XGBoost, a cutting-edge machine learning approach, we identified key diagnostic genes and constructed a predictive model. Our investigation extended to the immune functions of these genes, shedding light on potential therapeutic targets and underlying regulatory mechanisms. Our analysis unveiled specific OA subtypes, each marked by unique expression profiles of m6A-related aging genes. We pinpointed a set of pivotal diagnostic genes, offering potential therapeutic avenues. The developed diagnostic model exhibited exceptional capability in distinguishing OA patients from healthy controls. To corroborate our computational findings, we performed quantitative real-time polymerase chain reaction analyses on two cell lines: HC-OA (representing adult osteoarthritis cells) and C-28/I2 (representative of normal human chondrocytes). The gene expression patterns observed were consistent with our bioinformatics predictions, further validating our initial results. In conclusion, this study underscores the significance of m6A-related aging genes as promising biomarkers for diagnosis and prognosis, as well as potential therapeutic targets in OA. Although these findings are encouraging, further validation and functional analyses are crucial for their clinical application.

Synthesis of dibenzocyclohepten-5-ones by electrophilic iodocyclization of 1-([1,1'-biphenyl]-2-yl)alkynones.

A synthesis of iodo-substituted dibenzocyclohepten-5-ones by the iodine monochloride (or iodine)-induced intramolecular 7-endo-dig cyclization of 1-([1,1'-biphenyl]-2-yl)alkynones is reported. Detailed investigations on the substituent effects during the electrophilic iodocyclization of the alkynones show that they play a crucial role in determining the reaction pathways of the cyclization. By modifying the substitution pattern on the alkynone substrates, the cyclization takes place regioselectively, leading to either dibenzocyclohepten-5-ones, via a 7-endo-dig cyclization, or spiroconjugated compounds, via a 6-endo-dig cyclization.

ICl-induced intramolecular electrophilic cyclization of 1-[4'-methoxy(1,1'-biphenyl)2-yl]alkynones--a facile approach to spiroconjugated molecules.

Spiro compounds: An iodine monochloride-induced intramolecular cyclization of 1-[4'-methoxy(1,1'-biphenyl)2-yl]alkynones has been developed (see scheme). An electrophilic iodocyclization selectively takes place at the ipso position (versus the ortho electrophilic aromatic substitution) to afford 4'H-spiro(cyclohexa[2,5]diene-1,1'-naphthalene)-4,4'-diones, a new group of spiroconjugated compounds.

Management of patients with coronary stents in elective thoracic surgery.

PURPOSE: Interruption of oral antiplatelet agents for noncardiac surgery places patients who have received coronary stent implantation at high risk of coronary events, including stent thrombosis. We investigated retrospectively perioperative management for patients with coronary stents undergoing thoracic surgery. METHODS: We investigated 38 patients (age, 38-83 years; 33 men and 5 women) who underwent thoracic surgery (35 lung cancer resections and 3 other procedures) after coronary stent implantation at our hospital between January 2006 and August 2010. Data on implanted stents, perioperative medications, and cardiac and hemorrhagic complications were analyzed. RESULTS: Sirolimus-eluting stents (n = 18) and bare-metal stents (n = 20) were implanted. Regarding oral antiplatelet agents, 21 patients received aspirin, 16 received thienopyridine derivative and aspirin, and 1 received no oral antiplatelet agents. Oral antiplatelet agents were stopped 3-7 days before surgery. Perioperative heparinization was performed in 16 patients. Oral antiplatelet agents were restarted after confirmation of hemostasis and the lack of need for further invasive procedures (median, 4 days after surgery). No major cardiac events including stent thrombosis developed. There were no excessive intraoperative bleeding events related to oral antiplatelet agents or heparin. CONCLUSIONS: In our patients, no coronary events occurred with the short-term stopping of oral antiplatelet agents for thoracic surgery.

Non-surgical closure of post-pneumonectomy empyema with bronchopleural fistula after open window thoracotomy using basic fibroblast growth factor.

Empyema with bronchopleural fistula (BPF) is one of the severest complications following pneumonectomy. Many papers have reported that it is difficult to cure, with a high rate of associated mortality. Closure of the fistula and an appropriate choice of obliteration materials are crucial for successful treatment. However, obliteration is sometimes impractical because of a lack of suitable materials, excessive surgical risk, or lack of patient willingness to undergo the procedure. We report a case of post-pneumonectomy empyema with BPF that was treated by non-surgical closure after open-window thoracotomy (OWT) with the use of basic fibroblast growth factor (bFGF), which was sprayed into the unepithelialized empyema cavity transiting from epidermis and surrounding the fistula. After spraying, the orifice of the OWT was covered by a film dressing. This procedure yielded successful results after two months.

Synthesis and biological evaluation of N-heterocyclic indolyl glyoxylamides as orally active anticancer agents.

A series of N-heterocyclic indolyl glyoxylamides were synthesized and evaluated for in vitro and in vivo anticancer activities. They exhibited a broad spectrum of anticancer activity not only in murine leukemic cancer cells but also in human gastric, breast, and uterus cancer cells as well as their multidrug resistant sublines with a wide range of IC(50) values. They also induced apoptosis and caused DNA fragmentation in human gastric cancer cells. Among the compounds studied, 7 showed the most potent activity of growth inhibition (IC(50) = 17-1711 nM) in several human cancer cells. Given orally, compounds 7 and 13 dose-dependently prolonged the survival of animals inoculated with P388 leukemic cancer cells. N-Heterocyclic indolyl glyoxylamides may be useful as orally active chemotherapeutic agents against cancer and refractory cancerous diseases of multidrug resistance phenotype.