Experimental and therapeutic medicine最新文献

Traditional chemotherapy drugs have definite antitumor mechanisms and good therapeutic efficacy; however, their poor water solubility, serious side effects and drug resistance limit their clinical application. To the best of our knowledge, the present study reported for the first time the in vivo and in vitro anticancer effects of procyanidin B1 (PCB1), a compound that is isolated from natural sources such as grape seeds, apples, peanut skin and cranberries. Cell Counting Kit-8 assay showed that PCB1 effectively decreased the number of viable HCT-116 cells compared with cells treated with the small molecule cytotoxic drug doxorubicin. Quantitative PCR and apoptosis analysis, Cell cycle analysis, and WB analysis) of the molecular mechanism showed that PCB1 induced cell apoptosis and cell cycle arrest in S phase by increasing expression of pro-apoptosis protein caspase-3 and BAX and decreasing expression of anti-apoptosis protein Bcl-2. The efficient antitumor activity of PCB1 was demonstrated through in vivo experiments on a xenograft mouse model, demonstrating that PCB1 significantly suppressed tumor growth. The present study suggested that PCB1 represents a novel class of plant-based compounds isolated from natural sources that can be applied as an anticancer drug.

Renal ischemia/reperfusion injury (RIRI) represents the principal factor underlying acute kidney injury (AKI), which primarily stems from cellular injuries and ferroptosis caused by reactive oxygen species (ROS). Salidroside (SA), an antioxidant natural ester, has been attributed with the potential to protect against RIRI. In the present study, rats received daily SA doses (1, 10, or 100 mg/kg) by gavage for 7 consecutive days before surgery. The results revealed aggravated renal injury in the RIRI group, which was effectively prevented by SA pretreatment (10 and 100 mg/kg), with the 1 mg/kg dosage demonstrating lesser efficacy. Additionally, the results indicated that SA pretreatment mitigated the RIRI-related upregulation of antioxidative superoxide dismutase. In vitro studies corroborated SA's ability to maintain hypoxia/reoxygenation-treated NRK cell viability, with the protective effect being observed at SA concentrations ≥1 µM and peaking at 100 µM. Furthermore, the results showed that SA safeguarded renal tubular epithelial cells from oxidative damage, reduced ROS accumulation, and inhibited ferroptosis via activation of the PI3K/AKT signaling pathway. Therefore, the results of the present study highlight the promising therapeutic potential of SA as an effective intervention for RIRI via targeting of PI3K/AKT signaling pathway-mediated anti-oxidative and anti-ferroptotic mechanisms.

Anthracyclic (ANT) drugs are widely used for patients with malignant tumors and can markedly prolong the disease-free survival rate of patients. As its clinical application becomes more common, information regarding serious cardiotoxicity as a result of ANT treatment is becoming understood. However, to the best of our knowledge, delayed-onset cardiotoxicity due to ANT use has not been studied sufficiently. The present report describes a 36-year-old male patient who presented to Guiqian International General Hospital (Guiyang, China) with a complaint of dyspnea in the last 10 days. Substantially elevated B-type natriuretic peptide levels and echocardiography showing enlargement of the entire heart, of the patient suggested that severe heart failure was the cause of his symptoms. However, the cause of this potential heart failure was not apparent until the patient was questioned about his cancer treatment history. Following consultation to evaluate the assessment of end-stage heart failure, currently only anti-heart failure treatment and symptomatic treatment can be provided. The present report describes this case and reviews the existing literature to provide a basis for the diagnosis and treatment of patients with delayed-onset heart failure following ANT treatment.

The present study aimed to explore the immune regulatory function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein and related mechanisms. In a series of protein activity experiments, SARS-CoV-2 N protein promoted proliferation of three immune cell lines: mouse Raw264.7, human Jurkat and human Raji in a dose-dependent manner. A total of 10 µg/ml N protein could significantly change cell cycle progression of the aforementioned three immune cell lines and could promote quick entry of Raw264.7 cells into G₂/M phase from S phase to achieve rapid growth. Additionally, the N protein could also stimulate Raw264.7 cells to secrete a number of proinflammatory factors such as TNF-α, IL-6 and IL-10. RNA sequencing analysis indicated that the N protein changed the expression of certain genes involved in immune-related functions and four important signaling pathways, including JAK-STAT, TNF, NF-κB and MAPK signaling pathways, which suggested that the N protein may not only regulate the expression of genes involved in the process of resisting viral infection in macrophages of the immune system, but also change cellular signal processing.

Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of inherited DEB. In the present study, whole-exome sequencing was conducted on 12 individuals from the same affected family and a rare heterozygous variation was identified in the collagen type VII, α1 (COL7A1) gene, namely c.6859G>A (p.Gly2287Arg). Subsequently, this heterozygous variant was confirmed using Sanger sequencing of individual plasma cell-free DNA (cfDNA) and it was demonstrated for the first time, to the best of our knowledge, that COL7A1 exons can be amplified from plasma cfDNA. Within the large pedigree examined, 14 out of 18 individuals carried the variant, 3 carried the wild type, and one exceptional case, III-9, showed no disease symptoms despite carrying the disease variant. A general association between genotype and phenotype was established. Of note, the mutation landscape indicated that this G2287R variant is primarily reported in Asian countries. In silico structure prediction suggested that the residue resulting from the mutation may affect collagen protein stability. In conclusion, the present study provides evidence for the involvement of the COL7A1 G2287R gene variant in the development of DEB-Pr and highlights the potential utility of cfDNA in genetic disease diagnosis.

Tetracaine hydrochloride (TTC) is a long-lasting local anesthetic commonly used for topical anesthesia. Inappropriate dosage or allergic reactions to TTC can lead to local anesthetic toxicity. TTC exerts cytotoxic effects on certain cell types by inducing apoptosis and necrosis; however, the effects of TTC on macrophages are currently unclear. In the present study, the RAW 264.7 and BV2 cell lines, and murine peritoneal macrophages, were used to evaluate the cytotoxicity of TTC. The present study demonstrated that TTC caused a decrease in cell viability according to a Cell Counting Kit-8 assay, increased lactate dehydrogenase and IL-1β secretion according to ELISA, and induced morphological changes characteristic of pyroptosis according to western blotting. Moreover, TTC-induced macrophage pyroptosis was mediated by gasdermin (GSDM)D, and the cleavage of GSDMD was modulated by both caspase-1 and caspase-11. These results were experimentally validated using caspase-1 and caspase-11 inhibitors. Furthermore, it was observed that TTC and lipopolysaccharide (LPS) exerted similar effects on macrophages. However, the mechanism of induction of pyroptosis by TTC was different from that of LPS. The present study demonstrated that TTC alone could induce macrophage pyroptosis mediated by canonical and non-canonical inflammatory caspases. Therapies targeting pyroptosis may potentially provide a promising future strategy for the prevention and treatment of local anesthetic toxicity induced by TTC.

Laryngocele is a rare clinical condition characterized by an abnormal dilation of the laryngeal saccule. The present study focused on two separate cases of diagnosed patients. The first patient suffered from internal laryngocele and complained of hoarseness for almost 1 year. Plasma was used to treat the internal laryngocele and the outcomes were satisfying. The patient did not undergo any tracheostomy due to previous endoscopic surgery. The second patient included in the present study was diagnosed with mixed laryngocele and complained of swelling on the left side of the upper aspect of the neck with considerable pain for >1 month. The patient was prepped for excision by an external transcervical technique under general anesthesia. None of the two patients had any recurrence or other changes during follow-up. The purpose of reporting these two cases of laryngocele was to increase awareness of this condition. Surgery is still the first-line treatment for diagnosed cases, but with the advent of new microscopic techniques, the use of plasma in an inter-pharynx setting has become more common. The results observed after using plasma to treat one internal laryngocele may be relevant to better understanding the application of this method and confirm that it may be a new suitable approach to treat this condition.