Ultrasound technology has been applied in the biomedical field,particularly in drug delivery and cell processing.In this study,the effects of different ultrasound power levels(40 W to 100 W)and time durations(1 min,5 min,or 5 min discontinuously)on the morphology of human red blood cells(hRBCs)membranes were systematically investigated using cryo-electron tomography(Cryo-ET).The hRBCs membranes were firstly subjected to ultrasound at power levels of 40 W and 60 W for 5 min each.Cryo-ET observations revealed minimal morphological changes in the hRBCs membranes following the 40 W treatment,with the membrane structure remaining relatively intact and only minor undulations appearing on the membrane surface.These undulations might result from the mild mechanical stress induced by ultrasound,which was insufficient to disrupt the overall membrane structure.At power of 60 W,the hRBCs membranes largely preserved their structural integrity.When the ultrasonic power was increased to 80 W,the structural damage to the hRBCs membranes became more severe.Cryo-ET images showed irregular ruptures and larger pores on the membrane surface,indicating a significant compromise in membrane integrity.At ultrasound power of 100 W,the hRBCs membranes were completely disrupted,resulting in the formation of numerous membrane fragments,and a complete loss of membrane continuity.To further explore the effects of ultrasound duration on erythrocyte membrane morphology,the ultrasonic power was fixed at 100 W and the impacts of varying treatment durations(1 min,5 min,and intermittent ultrasound)on the membrane structure were systematically investigated.After 1 min of ultrasonic treatment,Cryo-ET images showed minimal changes in erythrocyte membrane morphology.Although some small pores and undulations appeared on the membrane surface,the overall structure remained relatively intact.As the ultrasound duration extended to 5 min,the degree of membrane damage increased significantly.Cryo-ET images revealed extensive rupture and detachment of the membrane,with continuity being severely compromised.As to treatment alternating 1 min of ultrasound with 1 min of rest,for a total of 5 min of ultrasound exposure,Cryo-ET observations showed the integrity of the membrane-cytoskeleton attachment remained.Under intermittent ultrasound treatment,although some pores and ruptures were observed on the membrane surface,the overall structure remained more intact compared to continuous ultrasonic treatment.This preservation might be due to the intermittent treatment providing buffer periods for the membrane,allowing partial recovery after mechanical stress,thereby reducing the cumulative damage caused by continuous ultrasound.This work provided experimental basis for further understanding of mechanism of ultrasound induced change of cell membrane and cytoskeleton.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Prostate cancer(PCa) is a common malignant tumor among elderly men, with high incidence and mortality rates worldwide, posing a serious threat to human health. Traditional treatments face limitations, highlighting the urgent need for novel therapeutic strategies. Recent studies on the regulatory mechanisms of micro ribonucleic acid(microRNA, miRNA) in tumor development has identified miRNA as new targets for PCa diagnosis and treatment. Traditional Chinese medicine(TCM), with its multi-mechanism, multi-target, and multi-pathway regulatory properties, shows promising potential in miRNA-based PCa therapy. This review summarized recent findings on miRNA' roles in PCa and research progress of TCM intervention and found that a variety of miRNA played important regulatory roles in cell differentiation, proliferation, apoptosis, invasion, metastasis, immune microenvironment, and drug resistance, and their potential as biomarkers for PCa diagnosis, prognosis, and therapy, indicating the potential to be a biomarker for the diagnosis, prognosis evaluation, and treatment of PCa. The review concluded that the active components of TCM(terpenoids, flavonoids, alkaloids, and others) and compounds(Yishen Tonglong Decoction, Shenhu Decoction, Zhoushi Qiling Decoction, Fuzheng Yiliu Decoction, and Qilan Formula) could regulate the expression of their downstream target genes by acting on specific miRNA and affect the above biological behaviors of PCa cells, thus playing a role in the treatment of PCa. This review aims to provide a theoretical basis for miRNA as potential biomarkers and therapeutic targets for PCa and suggest new avenues for further development of targeted therapy strategies against miRNA.
Humans ; MicroRNAs/metabolism* ; Prostatic Neoplasms/metabolism* ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Animals ; Gene Expression Regulation, Neoplastic/drug effects*

OBJECTIVE: To explore the co-morbid influencing factors of postmenopausal osteoporosis(PMOP) and dyslipidemia, and to provide evidence-based basis for clinical co-morbidity management. METHODS: Based on the 2017 to 2018 Beijing community cross-sectional survey data, PMOP patients were included and divided into the dyslipidemia group and the uncomplicated dyslipidemia group according to whether they were comorbid with dyslipidemia. Demographic characteristics, living habits and disease history were collected through questionnaires, and bone mineral density and bone metabolism biomarkers (osteocalcin, blood calcium, serum typeⅠprocollagen N-terminal prepeptide, etc.) were detected on site. Co-morbidity risk factors were analyzed using binary logistic regression. RESULTS: Three hundred and twenty patients with PMOP were included, including the comorbid group (75 patients) and the uncomplicated group (245 patients). The results showed that history of cardiovascular disease [OR=1.801, 95%CI(1.003, 3.236), P=0.049], history of cerebrovascular disease [OR=2.923, 95%CI(1.460, 5.854), P=0.002], frying and cooking methods[OR=5.388, 95%CI(1.632, 17.793), P=0.006], OST results[OR=0.910, 95%CI(0.843, 0.983), P=0.016], and blood Ca results [OR=60.249, 95%CI(1.862, 1 949.926), P=0.021] were the influencing factors of PMOP complicated with dyslipidemia. CONCLUSION Focus should be placed on the influencing factors of PMOP and dyslipidemia co-morbidities, with emphasis on multidimensional assessment, combining lifestyle interventions with bone metabolism marker monitoring to optimize co-morbidity management.
Humans ; Dyslipidemias/epidemiology* ; Female ; Middle Aged ; Osteoporosis, Postmenopausal/metabolism* ; Aged ; Cross-Sectional Studies ; Risk Factors ; Bone Density

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

This study was aimed at preliminarily assessing the prevalence of latent tuberculosis infection(LTBI)among cattle farming and slaughterhouse workers across Wuxue,Xianning,and Yichang Cities in Hubei Province,and exploring associated risk factors.Data on cattle farming and slaughterhouse workers were gathered via a questionnaire.LTBI detection was performed with a tu-berculin skin test and interferon-gamma release assay,and influencing factors were subsequently analyzed.The LTBI prevalence among cattle farming and slaughterhouse personnel in the three cities was 30.50%,and a higher rate was observed in slaughterhouse workers(39.01%)than cattle farmers(21.63%)(P<0.01).Multifactor analysis indicated that working in slaughterhouses(95%CI:1.582-3.878),having a history of tuberculosis(95%CI:1.377-25.057)or BCG vaccination(95%CI:1.229-3.285),and having a college education or above(95%CI:0.303-0.859)were significant factors influencing LTBI positivity in these personnel.Having more than 30 years of work experience(95%CI:1.303-18.782)was a risk factor for personnel at cattle breeding farms.Among slaugh-terhouse personnel,having a college education or above(95%CI:0.164-0.894),11-20 years of work experience(95%CI:0.122-0.994),or a history of tuberculosis(95%CI:1.661-64.397);performing logistics work(95%CI:3.234-126.424);and working in slaughter-related positions(95%CI:1.209-19.639)were associated with LTBI positivity.Therefore,the slaughterhouse workers in the three cities had higher LTBI rates than the cattle farming workers,thus underscoring the need for increased attention to personnel in logistics and slaughter-related positions.

This study was aimed at preliminarily assessing the prevalence of latent tuberculosis infection(LTBI)among cattle farming and slaughterhouse workers across Wuxue,Xianning,and Yichang Cities in Hubei Province,and exploring associated risk factors.Data on cattle farming and slaughterhouse workers were gathered via a questionnaire.LTBI detection was performed with a tu-berculin skin test and interferon-gamma release assay,and influencing factors were subsequently analyzed.The LTBI prevalence among cattle farming and slaughterhouse personnel in the three cities was 30.50%,and a higher rate was observed in slaughterhouse workers(39.01%)than cattle farmers(21.63%)(P<0.01).Multifactor analysis indicated that working in slaughterhouses(95%CI:1.582-3.878),having a history of tuberculosis(95%CI:1.377-25.057)or BCG vaccination(95%CI:1.229-3.285),and having a college education or above(95%CI:0.303-0.859)were significant factors influencing LTBI positivity in these personnel.Having more than 30 years of work experience(95%CI:1.303-18.782)was a risk factor for personnel at cattle breeding farms.Among slaugh-terhouse personnel,having a college education or above(95%CI:0.164-0.894),11-20 years of work experience(95%CI:0.122-0.994),or a history of tuberculosis(95%CI:1.661-64.397);performing logistics work(95%CI:3.234-126.424);and working in slaughter-related positions(95%CI:1.209-19.639)were associated with LTBI positivity.Therefore,the slaughterhouse workers in the three cities had higher LTBI rates than the cattle farming workers,thus underscoring the need for increased attention to personnel in logistics and slaughter-related positions.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective To explore the effect of scutellarin on lipopolysaccharide(LPS)induced neuroinflammation in BV-2 microglia cells.Methods BV-2 microglia were cultured and randomly divided into 6 groups:control group(Ctrl),cyclic GMP-AMP synthetase(cGAS)inhibitor RU320521 group(RU.521 group),LPS group,LPS+RU.521 group,LPS+scutellarin pretreatment group(LPS+S)and LPS+S+RU.521 group.The expressions of cGAS,stimulator of interferon gene(STING),nuclear factor kappa B(NF-κB),phosphorylated NF-κB(p-NF-κB),neuroinflammatory factors PYD domains-containing protein 3(NLRP3)and tumor necrosis factor α(TNF-α)in BV-2 microglia were detected by Western blotting and immunofluorescent double staining(n= 3).Results Western blotting and immunofluorescent double staining showed that compared with the control group,the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in BV-2 microglia increased significantly after LPS induction(P<0.05),while the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in LPS+S group were significantly lower than those in LPS group(P<0.05).Treatment with cGAS pathway inhibitor RU.521 showed similar effects as the pre-treatment group with scutellarin.In addition,the change of NF-κB in each group was not statistically significant(P>0.05).Conclusion Scutellarin inhibits the neuroinflammation mediated by BV-2 microglia cells,which may be related to cGAS-STING signaling pathway.