Cuproptosis is a regulated form of cell death induced by the accumulation of metal ions and is closely linked to aspects of cellular drug resistance, cellular metabolism, and signalling pathways. Due to its crucial role in regulating physiological and pathological processes, cuproptosis has gained increasing significance as a potential target for anticancer drug development. In this review, we introduce the definition of cuproptosis and provide a comprehensive discussion of the mechanisms of cuproptosis. In addition, the methods for the detection of cuproptosis are summarized, and recent advances in cuproptosis in cancer therapy are reviewed, mainly in terms of elesclomol (ES)-mediated cuproptosis and disulfiram (DSF)-mediated cuproptosis, which provided practical value for applications. Finally, the current challenges and future development of cuproptosis-mediated cancer therapy are discussed. In summary, this review highlights recent progress on cuproptosis in cancer therapy, offering novel ideas and strategies for future research and applications.
Objective To assess the efficacy and safety of endoscopic treatment for foreign body impaction in the esophagus. Methods Demographic and endoscopic data of a total of 78 patients with esophagus foreign body impactions were retrospectively studied, which included foreign body types, number, location and duration of impaction, associated esophageal diseases, endoscopic procedures and complications. The factors which influenced the complications and procedure time were also statistically analyzed. Results Impaction （80. 7% ） and perforation （66. 7% ） most frequently occurred in the upper esophagus. Duration of foreign body impaction exceeded 24 hours in 11 patients （ 14. 1% ） , which was less than 24 hours in 67 others （85.9%）. All of the foreign bodies were successfully removed （2 cases of perforation were transferred to other department for further treatment）, and there was no mortality related to endoscopic management occurred. The common complications included mucosal injury, bleeding, and perforation. Shape of the foreign bodies, duration of impaction and status of perforation were the main influential factors on procedure time and complications （P 〈 0. 05）. Conclusion The endoscopic management for esophageal foreign body impaction is safe and effective. It is the first choice for those whose esophagus is perforated with foreign bodies for less than 24 hours and with no abscesses out of esophageal tract.
Key words:
Impacted esophagus foreign bodies; Endoscopic management
To investigate the differential expression of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4) and their potential role in the pathogenesis of chronic suppurative otitis media and cholesteatoma.Normal canal skin of 30 patients with tympanosclerosis were enrolled as control, 30 cases with chronic suppurative otitis media and 30 patients with cholesteatoma were studied. Real-time PCR, Western blot and Immunohistochemistry were preformed to detect the expression of TLR2/TLR4 in normal canal skin, mucosa and granulation tissue of chronic suppurative otitis media, mucosa, granulation tissue, cholesteatoma epithelium of cholesteatoma, and the differential expression were analyzed.(1) the mRNA and protein expression of TLR2 and TLR4 were detected in all normal canal skin, mucosa and granulation tissue of chronic suppurative otitis media, mucosa, granulation tissue, cholesteatoma epithelium of cholesteatoma. (2) Both mRNA and protein level of TLR2/TLR4 in mucosa of chronic suppurative otitis media and cholesteatoma were higher than those in normal canal skin, but lower in cholesteatoma epithelium, there was no significant difference in mucosa of the two otitis media groups. (3) The mRNA and protein expression of TLR2/TLR4 in granulation tissue of chronic suppurative otitis media and cholesteatoma were significant increased when compared with normal canal skin, and TLR2 expression level was higher in granulation tissue of cholesteatoma than in chronic suppurative otitis media. (4) TLR2/TLR4 positive cells mainly infiltrated in granulations, significantly more than in normal skin, while fewer in the epithelium of cholesteatoma.Differential expression of TLR2 and TLR4 in mucosa suggests middle ear is a TLR2/TLR4 participated functional modulation of the innate immune system and also suggests that they may play a different role in the pathophysiology of chronic otitis media and cholesteatoma.
There remains a common and critical challenge in the preparation of carbon nanotube (CNT) composite materials, i.e., random dispersion of CNTs in the second phase. Here we have reported a general method to prepare perpendicularly aligned CNT/olefin composite films through a conventional slicing technique. The thickness of a composite film can be accurately controlled from about fifty nanometers to fifty micrometers, and the diameter and density of CNTs may be varied in a wide range as required. In particular, due to the generated defect at the end during the slicing process, the separated CNTs from the composite film have been easily unzipped to produce graphenes in the forms of nanoribbons and nanosheets with a yield of almost 100% under ultrasonic treatment.
The inhibitory effect of muscone on the hyperinflammatory response after myocardial ischemia reperfusion injury (MIRI) was investigated, and the target and signal pathways of muscone were explored. The levels of inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor alpha were detected through qRT-PCR and ELISA. The expression levels of p38 and NF-κB signaling pathway-related proteins were detected through Western blot. TREM-1 siRNA was transfected into macrophages in vitro. The rat model of myocardial ischemia was established and used in studying the inhibitory effect of muscone on the inflammatory response and its protective effect muscone on myocardial apoptosis. The expression of TREM-1 was upregulated during myocardial ischemia. Knocking down TREM-1 decreased the increase in inflammatory cytokines in the supernatant of macrophages induced by rmHMGB1 (1 μg/mL) and rmHSP60 (1 mol/mL). In addition, knocking down TREM-1 decreased p38 and NF-κB signaling activation. Muscone can protect myocardial cells by inhibiting the expression of TREM-1 and the inflammatory response after myocardial infarction. Further study showed that muscone inhibited the production of DAM-triggered (damage-associated molecular pattern trigger) inflammatory cytokines. In addition, muscone inhibited the activation of p38 and NF-κB signals under DAM-induced conditions. Muscone and TREM-1 gene knockout reduced cell apoptosis and provided protection against MIRI by inhibiting p38 and NF-κB signaling activation. Mechanism studies showed that muscone inhibited the production and release of inflammatory cytokines by inhibiting TREM-1, and thereby reducing the inflammatory response and providing protection against MIRI.
Background: Huangqi Guizhi Wuwu Decoction (HGWD) is a traditional and effective Chinese medicine compound decoction for the treatment of rheumatoid arthritis (RA). However, there is few research on the treatment of rheumatoid cardiopulmonary complications. The present study was to study whether HGWD can alleviate the pathological changes caused by rheumatoid arthritis and cardiopulmonary complications. Methods: Five 3-month-old TNF-Tg mice were treated with HGWD (9.1 g/kg) once a day or the same dose of normal saline lasted for 8 weeks, and wild-type littermates of the same age were used as a negative control, and methotrexate (MTX) was intraperitoneally administered as a positive control. After the treatment, pathological staining was performed on the mouse ankle joints, heart, and lungs. Result: It was found that HGWD reduced the inflammation of the ankle joint synovium in TNF-Tg mice, and reduced myocardial hypertrophy, inflammatory infiltration and fibrosis of heart, as well as lung inflammation and fibrosis. Immunohistochemical staining with anti-TNF- α antibody showed that HGWD reduced the expression of TNF- α in the heart of TNF-Tg mice. Conclusion: In conclusion, HGWD alleviates joint inflammation in TNF-Tg mice and reduces the pathological changes of the heart and lungs.
BACKGROUND Acute abdominal pain is one of the most common gastrointestinal symptoms. The etiology of acute abdomen can be challenging for gastroenterologists to establish. Cecal foreign body is a rare cause of cecal perforation. CASE SUMMARY We report a 35-year-old male from China who initially exhibited symptoms suggestive of acute appendicitis. However, during a minimally invasive colonoscopy procedure, the authors found that a wooden toothpick caused the perforation. The patient presented to our emergency department with a 2 days history of right lower abdominal pain and low grade fever. The patient was in good health and had eaten fish 2 days earlier. Physical examination revealed mild pain with positive rebound tenderness in the right lower abdomen. However, computed tomography of the abdomen confirmed a strip of high-density shadows protruding beyond the intestinal cavity outline, with a small amount of peritoneal seepage in the ileocecal area. Combined with the medical history, the possibility of foreign body perforation by a fishbone and peripheral peritonitis were considered. However, the high-density shadow was identified as a wooden toothpick, which was removed via a minimally invasive procedure using a foreign body forceps under colonoscopy. The patient's condition improved significantly within 5 days after treatment. CONCLUSION We emphasize the importance of a detailed patient history, accurate diagnosis and proper treatment in patients with acute abdomen.
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