Drug repositioning of disulfiram induces endometrioid epithelial ovarian cancer cell death via the both apoptosis and cuproptosis pathways

Various therapeutic strategies have been developed to overcome ovarian cancer.However,the prognoses resulting from these strategies are still unclear.In the present work,we screened 54 small molecule compounds approved by the FDA to identify novel agents that could inhibit the viability of human epithelial ovarian cancer cells.Among these,we identified disulfiram(DSF),an old alcohol-abuse drug,as a potential inducer of cell death in ovarian cancer.Mechanistically,DSF treatment significantly reduced the expression of the anti-apoptosis marker Bcell lymphoma/leukemia-2(Bcl-2)and increase the expression of the apoptotic molecules Bcl2 associated X(Bax)and cleaved caspase-3 to promote human epithelial ovarian cancer cell apoptosis.Furthermore,DSF is a newly identified effective copper ionophore,thus the combination of DSF and copper was used to reduce ovarian cancer viability than DSF single treatment.Combination treatment with DSF and copper also led to the reduced expression of ferredoxin 1 and loss of Fe-S cluster proteins(biomarkers of cuproptosis).In vivo,DSF and copper gluconate significantly decreased the tumor volume and increased the survival rate in a murine ovarian cancer xenograft model.Thus,the role of DSF revealed its potential for used as a viable therapeutic agent for the ovarian cancer.

Operating procedures of traditional Chinese medicine breast massage

Traditional Chinese medicine breast massage,also known as breast Tuina or manual expression of breast milk,is a technique of using certain manipulations to act on specific positions or acupoints of the breast to promote blood and lymphatic circulation of breast and facilitate the discharge of stagnant milk.This technique is widely used in China to treat breastfeeding problems such as breast engorgement,mastitis,and postpartum hypogalactia.In this article,we introduce the definition and standardization process of breast massage,elaborate the operating procedures of breast massage in detail,and summarize and discuss the current situation of its clinical application,so as to provide a reference for its wide application and in‑depth research.

Five-blade scratcher for treating severe rhinophyma:A retrospective study

BACKGROUND Rhinophyma,a late-stage subtype of rosacea,is characterized by excessive sebaceous glands and connective tissue proliferation.Patients may experience respiratory disturbances and psychological distress that significantly affect their quality of life when excessive nasal hyperplasia obstructs the external nasal valves.Surgery is the treatment of choice for rhinophyma.However,excessive bleeding,scarring,pigmentation,and high recurrence rates frequently characterize current surgical methods.AIM To evaluate the clinical effectiveness and recurrence rates after treating severe rhinophyma with the five-blade scratcher.METHODS This study retrospectively analyzed the clinical records of 28 patients with severe rhinophyma rosacea.The Global Flushing Severity Score(GFSS),Clinician Erythema Assessment(CEA),Rhinophyma Severity Index(RHISI),Glasgow Benefit Inventory(GBI),and satisfaction scores were used to assess the recovery of patients at 6 months and 5 years,with the recurrence rate calculated at 5 years postoperatively.In addition,the levels of pro-inflammatory factors(TNF-α,IL-1β,and IL-6)in the serum of patients before and after surgery were detected by ELISA.RESULTS The GFSS,CEA,and RHISI scores at 6 months and 5 years postoperatively were significantly lower than those preoperatively(P<0.001 for both periods).Five-blade scratcher treatment greatly benefits patients as demonstrated by the GBI and patient satisfaction.A small number of patients(7/28,25%)reported recurrence after surgical treatment for rhinophyma in our department that was not more serious than before treatment.The expression of pro-inflammatory factors(TNF-α,IL-1β,and IL-6)in the patient's serum was significantly reduced after surgery of five-blade scratcher.CONCLUSION The five-blade scratcher treatment demonstrates notable advantages,including simplicity,safety,efficacy,and cost-effectiveness,coupled with reduced bleeding,minimized scarring,lower recurrence rates,reduced the level of pro-inflammatory factors and improved patient satisfaction.Consequently,this therapeutic modality exhibits a viable option for individuals afflicted with severe rhinophyma.

Effectiveness and safety of acupoint catgut embedding combined with Chinese herbal medicine in chronic urticaria: A systematic review of randomized controlled trials

Objective:To evaluate the effectiveness and safety of acupoint catgut embedding(ACE)in combination with Chinese herbal medicine(CHM)in treating chronic urticaria(CU).Methods:We thoroughly searched Embase,PubMed,Cochrane Library,Web of Science,China National Knowledge Infrastructure(CNKI),Wangfang database,Chinese Scientific Journal Database(VIP),and Chinese biomedical literature database(SinoMed)for relevant studies from inception until May 2022.Randomized controlled trials(RCTs)on ACE combined with CHM for CU were included.Literature search,data extraction,and risk of bias assessment were independently conducted by two authors.Results:A total of 15 RCTs with 1065 participants were included in this review.Five trials reported that the combined therapy showed a higher total effective rate,and four trials reported that the combined therapy was associated with a lower level of serum immunoglobulin E.Furthermore,two,four,and four trials reported that the combined therapy was more effective in reducing itching degree,size,and number of wheals,respectively.The combined therapy was reported to be associated with a lower recurrence rate in three trials,and with a fewer adverse reaction rate in two trials.Conclusions:ACE in combination with CHM appears to be a safe and effective therapy for patients with CU.Given the relatively low quality of the included trials,these findings should be interpreted cautiously.Further high-quality RCTs are needed to confirm our findings.

Stem cell characteristics of early colon cancer tissue and their relationship with cell proliferation and invasion

Objective:To study the stem cell characteristics of early colon cancer tissue and their relationship with cell proliferation and invasion.Methods: Colon cancer tissues and adjacent tissues surgically removed in Dongguan People's Hospital between January 2010 and October 2017 were selected as the clinical samples of this study, the protein was extracted to determine the protein expression of tumor stem cell genes USP22, Nanog, Lgr5 and CD44, and RNA was extracted to determine the mRNA expression of cell proliferation genes and cell invasion genes.Results:USP22, Nanog, Lgr5 and CD44 protein expression as well as Rab5A, TBX2, MDM2, TGF-β1, Smad2/3, Vimentin, Rac1 and VEGF mRNA expression in colon cancer tissues were significantly higher than those in adjacent tissues while Bad, Bax and Fas mRNA expression were significantly lower than those in adjacent tissues;USP22, Nanog, Lgr5 and CD44 protein expression in colon cancer tissues were positively correlated with Rab5A, TBX2, MDM2, TGF-β1, Smad2/3, Vimentin, Rac1 and VEGF mRNA expression, and negatively correlated with Bad, Bax and Fas mRNA expression.Conclusion: The activation of stem cell characteristics in early colon cancer can promote the proliferation and invasion of cancer cells.

Technical operation specification for pricking-cupping therapy

Pricking-cupping therapy is a Traditional Chinese Medicine(TCM)nursing technology that can adjust the viscera of the human body,make the meridians smooth,and Yin and Yang balanced mainly by means of relieving heat and detoxification,harmonizing Qi and blood,promoting blood circulation and removing blood stasis,dredging meridians and activating collaterals,reducing swelling and pain,purging heat and calming shock,clearing heat,and opening orifices.Pricking-cupping therapy has a long history and wide application.After thousands of years of development,it has made great progress.They are widely used to treat lumbar disc herniation,herpes zoster,acute arthritis,migraine,and other diseases in China.Through the clinical practice and theoretical exploration of physicians of past dynasties,the therapeutic mechanism and application scope of pricking-cupping therapy have been greatly enriched.Modern TCM practitioners have conducted in-depth researches on the operation norms of the therapy on the basis of the ancients,hoping to grasp the essence of the disease more accurately and make the rational use of the operation technology of the therapy.

Combined treatment with valproic acid and estrogen has neuroprotective effects in ovariectomized mice with Alzheimer’s disease

Postmenopausal women with Alzheimer’s disease exhibit dramatically reduced sensitivity to estrogen replacement therapy,which is though to be related to an estrogen receptor(ER)α/ERβratio imbalance arising from a significantly decreased level of ERs of the brain.The aim of our study was to investigate whether valproic acid(VPA)can enhance the beneficial effects of estrogen on cognitive function through restoration of ERαand ERβexpression in the brain.We removed the ovaries of female APP/PS1 mice to simulate the low estrogen levels present in postmenopausal women and then administered VPA(30 mg/kg,intraperitoneal injection,once daily),17β-estradiol(E2)(2.4μg,intraperitoneal injection,once daily),liquiritigenin(LG)(50μg/kg,intragastric infusion,once daily),VPA+E2,or VPA+LG for 4 successive weeks.Compared with treatment with a single drug,treatment with VPA+E2 or VPA+LG significantly increased the level of glycogen synthase kinase 3β,increased the expression of estrogen receptorα,reduced the expression of small ubiquitin-like modifiers,and increased the level of estrogen receptorβ.This resulted in enhanced sensitivity to estrogen therapy,reduced amyloidβaggregation,reduced abnormal phosphorylation of the tau protein,reduced neuronal loss,increased dendritic spine and postsynaptic density,and significantly alleviated memory loss and learning impairment in Alzheimer’s disease.This study was approved by the Chongqing Medical University Animal Protection and Ethics Committee,China on March 6,2013.

Entinostat,a classⅠselective histone deacetylase inhibitor,plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer:A multicenter,randomized,double-blind,placebo-controlled,phase 3 trial

Entinostat plus exemestane in hormone receptor-positive(HR+)advanced breast cancer(ABC)previously showed encouraging outcomes.This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR+ABC that relapsed/progressed after≥1 endocrine therapy.Patients were randomized(2:1)to oral exemestane 25 mg/day plus entinostat(n=235)or placebo(n=119)5 mg/week in 28-day cycles.The primary endpoint was the independent radiographic committee(IRC)-assessed progression-free survival(PFS).The median age was 52(range,28—75)years and 222(62.7%)patients were postmenopausal.CDK4/6 inhibitors and fulvestrant were previously used in 23(6.5%)and 92(26.0%)patients,respectively.The baseline characteristics were comparable between the entinostat and placebo groups.The median PFS was 6.32(95%CI,5.30—9.11)and 3.72(95%CI,1.91—5.49)months in the entinostat and placebo groups(HR,0.76;95%CI,0.58—0.98;P=0.046),respectively.Grade≥3 adverse events(AEs)occurred in 154(65.5%)patients in the entinostat group versus 23(19.3%)in the placebo group,and the most common grade≥3 treatment-related AEs were neutropenia[103(43.8%)],thrombocytopenia[20(8.5%)],and leucopenia[15(6.4%)].Entinostat plus exemestane significantly improved PFS compared with exemestane,with generally manageable toxicities in HR+ABC(ClinicalTrials.gov#NCT03538171).