In vitro modulation the Notch pathway by piperine: A therapeutic strategy for docetaxel-resistant and non-resistant prostate cancer.

Docetaxel (DTX) resistance poses a significant challenge in the treatment of prostate cancer (PCa), often leading to chemotherapy failure. This study investigates the ability of piperine, a compound derived from black pepper, to enhance the sensitivity of PCa cells to DTX and elucidates its underlying mechanism. We established a DTX-resistant PCa cell line, DU145/DTX, to conduct our experiments. Through a series of assays, including MTT for cell viability, flow cytometry for apoptosis, Transwell for cell migration and invasion, and western blot for protein expression analysis, we assessed the effects of piperine on these cellular functions and on the Notch signaling pathway components. Our results demonstrated that we successfully established the DTX-resistant PCa cell line DU145/DTX. Piperine effectively decreased the viability of both DU145 and its DTX-resistant counterpart, DU145/DTX, in a concentration and time-dependent manner when used alone and in combination with DTX. Notably, piperine also induced apoptosis and reduced the migration and invasion capabilities of these cells. At the molecular level, piperine down-regulated the Notch pathway by inhibiting Notch1 and Jagged1 signaling, as well as reducing the expression of downstream effectors Hey1 and hes family bHLH transcription factor 1. The study concludes that piperine's ability to modulate the Notch signaling pathway and induce apoptosis highlights its potential as a complementary treatment for DTX-resistant PCa, paving the way for the use of traditional Chinese medicinal compounds in modern oncology treatment strategies.

Crosstalk between cancer-associated fibroblasts and regulated cell death in tumors: insights into apoptosis, autophagy, ferroptosis, and pyroptosis.

Cancer-associated fibroblasts (CAFs), the main stromal component of the tumor microenvironment (TME), play multifaceted roles in cancer progression through paracrine signaling, exosome transfer, and cell interactions. Attractively, recent evidence indicates that CAFs can modulate various forms of regulated cell death (RCD) in adjacent tumor cells, thus involving cancer proliferation, therapy resistance, and immune exclusion. Here, we present a brief introduction to CAFs and basic knowledge of RCD, including apoptosis, autophagy, ferroptosis, and pyroptosis. In addition, we further summarize the different types of RCD in tumors that are mediated by CAFs, as well as the effects of these modes of RCD on CAFs. This review will deepen our understanding of the interactions between CAFs and RCD and might offer novel therapeutic avenues for future cancer treatments.

Transcriptome sequencing reveals novel biomarkers and immune cell infiltration in esophageal tumorigenesis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide, and its development comprises a multistep process from intraepithelial neoplasia (IN) to carcinoma (CA). However, the critical regulators and underlying molecular mechanisms remain largely unknown. AIM: To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention. METHODS: A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide (4NQO) to C57BL/6 mice. Moreover, we established a control group without 4NQO treatment of mice. Then, transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses, including low-grade IN (LGIN), high-grade IN (HGIN), and CA, and controlled normal tissue (NOR) samples. Differentially expressed genes (DEGs) were identified in the LGIN, HGIN, and CA groups, and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The CIBERSORT algorithm was used to detect the pattern of immune cell infiltration. Immunohistochemistry (IHC) was also conducted to validate our results. Finally, the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice. RESULTS: Compared with those in the NOR group, a total of 681541, and 840 DEGs were obtained in the LGIN, HGIN, and CA groups, respectively. Using the intersection of the three sets of DEGs, we identified 86 genes as key genes involved in the development of ESCC. Enrichment analysis revealed that these genes were enriched mainly in the keratinization, epidermal cell differentiation, and interleukin (IL)-17 signaling pathways. CIBERSORT analysis revealed that, compared with those in the NOR group, M0 and M1 macrophages in the 4NQO group showed stronger infiltration, which was validated by IHC. Serum cytokine analysis revealed that, compared with those in the NOR group, IL-1ß and IL-6 were upregulated, while IL-10 was downregulated in the LGIN, HGIN, and CA groups. Moreover, the expression of the representative key genes, such as S100a8 and Krt6b, was verified in external human samples, and the results of immunohistochemical staining were consistent with the findings in mice. CONCLUSION: We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions. In addition, we found that macrophage infiltration and abnormal alterations in the levels of inflammation-associated cytokines, such as IL-1ß, IL-6, and IL-10, in the peripheral blood may be closely associated with the development of ESCC.

Preoperative glucose-to-lymphocyte ratio predicts survival in cancer.

Background: Systemic inflammation and glucose metabolism have been closely related to the survival of cancer patients. Therefore, we aimed to evaluate whether preoperative glucose-to-lymphocyte ratio (GLR) can be used to predict the survival of cancer patients. Methods: We retrospectively examined 2172 cancer patients who underwent surgery from January 1, 2014, to December 31, 2016. There were 240 patients with non-small cell lung cancer (NSCLC), 378 patients with colorectal cancer (CRC), 221 patients with breast cancer (BC), 335 patients with gastric cancer (GC), 270 patients with liver cancer, 233 patients with esophageal cancer (EC), 295 patients with renal cancer, and 200 patients with melanoma. The formula for preoperative GLR calculation was as follows: GLR=glucose/lymphocyte count. The overall survival (OS) was estimated using the Kaplan-Meier method. The predictive factors for OS were determined using multivariate analysis. Results: The Kaplan-Meier analysis showed that the median survival time in the high-GLR group was much shorter than that of those in the low-GLR group for different cancers. Cox multivariate regression analysis reveals that preoperative GLR was an independent factor for predicting overall survival in different tumor types. Conclusion: Elevated preoperative GLR was remarkably associated with a poorer prognosis in patients with NSCLC, CRC, breast cancer, gastric cancer, kidney cancer, liver cancer, esophageal cancer, and melanoma. Preoperative GLR promises to be an essential predictor of survival for cancer patients.

Controlled formation of three-dimensional cavities during lateral epitaxial growth.

Epitaxial growth is a fundamental step required to create devices for the semiconductor industry, enabling different materials to be combined in layers with precise control of strain and defect structure. Patterning the growth substrate with a mask before performing epitaxial growth offers additional degrees of freedom to engineer the structure and hence function of the semiconductor device. Here, we demonstrate that conditions exist where such epitaxial lateral overgrowth can produce complex, three-dimensional structures that incorporate cavities of deterministic size. We grow germanium on silicon substrates patterned with a dielectric mask and show that fully-enclosed cavities can be created through an unexpected self-assembly process that is controlled by surface diffusion and surface energy minimization. The result is confined cavities enclosed by single crystalline Ge, with size and position tunable through the initial mask pattern. We present a model to account for the observed cavity symmetry, pinch-off and subsequent evolution, reflecting the dominant role of surface energy. Since dielectric mask patterning and epitaxial growth are compatible with conventional device processing steps, we suggest that this mechanism provides a strategy for developing electronic and photonic functionalities.

Capturing ion trapping and detrapping dynamics in electrochromic thin films.

Ion trapping has been found to be responsible for the performance degradation in electrochromic oxide thin films, and a detrapping procedure was proved to be effective to rejuvenate the degraded films. Despite of the studies on ion trapping and detrapping, its dynamics remain largely unknown. Moreover, coloration mechanisms of electrochromic oxides are also far from clear, limiting the development of superior devices. Here, we visualize ion trapping and detrapping dynamics in a model electrochromic material, amorphous WO3. Specifically, formation of orthorhombic Li2WO4 during long-term cycling accounts for the origin of shallow traps. Deep traps are multiple-step-determined, composed of mixed W4+-Li2WO4, amorphous Li2WO4 and W4+-Li2O. The non-decomposable W4+-Li2WO4 couple is the origin of the irreversible traps. Furthermore, we demonstrate that, besides the typical small polaron hopping between W5+ ↔ W6+ sites, bipolaron hopping between W4+ ↔ W6+ sites gives rise to optical absorption in the short-wavelength region. Overall, we provide a general picture of electrochromism based on polaron hopping. Ion trapping and detrapping were demonstrated to also prevail in other cathodic electrochromic oxides. This work not only provides the ion trapping and detrapping dynamics of WO3, but also open avenues to study other cathodic electrochromic oxides and develop superior electrochromic devices with great durability.

Red blood cell distribution width is associated with sarcopenia risk in early-stage non-small cell lung cancer.

BACKGROUND: Sarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients. METHODS: This study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC. RESULTS: The ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p < 0.001), comorbidities (p = 0.001), histological type (p = 0.002), and cancer stage (p = 0.032) between the high RDW and low RDW groups. Logistic regression analyses revealed that high RDW is an independent risk factor for sarcopenia in early-stage NSCLC. CONCLUSION: RDW is associated with sarcopenia risk in early-stage NSCLC.

Inactivation of pathogenic microorganisms in water by electron beam excitation multi-wavelength ultraviolet irradiation: Efficiency, influence factors and mechanism.

Due to the limitations of traditional ultraviolet (UV) in microbial inactivation in water, it is necessary to explore a more suitable and efficient UV disinfection method. In this study, an electron beam excitation multi-wavelength ultraviolet (EBE-MW-UV) system was established and aims to analyze its differential microbial inactivation capabilities in comparison to single-wavelength UV-LEDs in waterborne applications. Furthermore, the inactivation mechanisms of this system on microorganisms were explored. The results showed that EBE-MW-UV had significantly higher inactivation effects on the Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Candida albicans in water compared to UV-LEDs (p＜0.05), and the inactivation effect of EBE-MW-UV on Escherichia coli and Pseudomonas aeruginosa at the same UV dose was 3.8 and 1.9 log higher than that of UV-LEDs, respectively, EBE-MW-UV exhibited better inactivation effects on Gram-negative bacteria. Further research found that, under the majority of irradiation doses, neither EBE-MW-UV nor UV-LEDs were significantly affected by the concentration of suspended solids (5 and 20 mg/L) or humic acids (2 and 5 mg/L) in the water. Mechanism analysis revealed that during the disinfection process of EBE-MW-UV, microbial DNA and proteins were initially damaged, which prevented the occurrence of dark repair and led to bacterial inactivation. In addition, UV irradiation led to the production of additional reactive oxygen species (ROS) inside the cells, increasing cell membrane permeability and exacerbating membrane damage. This was accompanied by a decrease in energy metabolism and depletion of ATP, ultimately resulting in microbial inactivation. Therefore, EBE-MW-UV demonstrated more effective disinfection than single-wavelength UV-LEDs, showing great potential. Our research gives new insights into the characteristics of multiple wavelength ultraviolet, and provides scientific basis for the selection of new light sources in the field of ultraviolet disinfection.

Albumin-bilirubin score predicts trastuzumab resistance in HER2-positive breast cancer.

BACKGROUND: The albumin-bilirubin (ALBI) score is a novel indicator of liver function. Some studies showed that the ALBI score was a predictive marker for the prognosis and efficacy of drug therapy in malignancies. We aimed to assess the predicted role of ALBI score in the sensitivity to therapy with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer (BC). The clinical data of 226 HER2-positive BC patients at the Harbin Medical University Cancer Hospital from January 2017 and December 2018 were retrospectively collected. The ALBI score was calculated with serum albumin and bilirubin before diagnosis. The associations between ALBI score and trastuzumab resistance were analyzed by logistic regression analyses. The patients with trastuzumab resistance had higher ALBI scores compared with the patients without trastuzumab resistance. Moreover, there were weak correlations between the ALBI score and lymph node status (P= 0.093). In addition, multivariate analysis revealed that the ALBI score was an independent prognostic factor for trastuzumab resistance in HER2-positive BC. High ALBI score is associated with trastuzumab resistance in HER2-positive BC. Future studies are needed.

Preoperative small airway dysfunction is associated with skeletal muscle loss in early-stage non-small cell lung cancer.

BACKGROUND: Postoperative skeletal muscle loss (SM loss) was reported to be associated with a poor prognosis in early-stage non-small cell lung cancer (NSCLC). Small airway dysfunction (SAD) is a common but neglected respiratory abnormality. Little information is known about the association between preoperative SAD and postoperative SM loss in early-stage NSCLC. Therefore, this study aimed to investigate the correlation between preoperative SAD and SM loss after surgery in early-stage NSCLC patients. METHODS: There were 348 NSCLC patients with stages I-IIIA in this study from January 2017 to December 2020. All CT images were contrast-enhanced scans, and the skeletal muscle index (SMI) was measured using CT images. A 10.0% decrease in SMI over 12 months was determined as the cut-off value to define excessive SM loss. Logistic regression analyses were used to examine the relationship between SAD and SM loss. RESULTS: This study included 348 subjects who underwent pulmonary operation (159 males and 189 females; mean age: 57.5 ± 8.8 years). 152 (43.7%) patients were identified as having SAD before surgery, and 179 patients (51.4%) were identified as having SM loss after 1 year. Moreover, a higher incidence of SAD was found in the SM loss group compared with that in the non-SM loss group (52.0% vs. 34.9%, p = 0.001). The patients with SAD were older, had larger tumor size, and had lower albumin levels. Furthermore, there were significant correlations between the lung function parameters manifesting SAD and the percentage change in SMI (for the forced expiratory flow when 75% of forced vital capacity has been exhaled (FEF75%), Pearson r=-0.107, p = 0.046; for FEF50%, r = -0.142, p = 0.008; and for FEF25-75%, r=-0.124, p = 0.021; respectively). However, no significant correlations were found between SMI and the lung function parameters reflecting proximal airway obstruction (p > 0.05). Logistic regression analysis revealed that preoperative SAD (HR, 2.465; 95% CI, 1.256-4.838; p = 0.009) was independent risk factor for postoperative SM loss in early-stage NSCLC. In addition, multivariable analysis revealed that SAD (HR, 1.816; 95% CI, 1.025-3.216, P = 0.041) were associated with postoperative complications. CONCLUSION: Preoperative SAD is significantly associated with postoperative complications and SM loss in early NSCLC patients. Our results suggest that preoperative assessment of SAD may be useful for risk stratification of surgical candidates with potential for targeted interventions.

Lower subcutaneous fat index predicts bone metastasis in breast cancer.

BACKGROUND: Bone metastases affect 50% to 70% of breast cancer (BC) patients and have a high mortality rate. Adipose tissue loss plays a pivotal role in the progression of cancer. OBJECTIVE: This study aims to evaluate the prognostic value of adipose tissue for bone metastasis in BC patients. METHODS: 517 BC patients were studied retrospectively. Patients' characteristics before the surgery were collected. Quantitative measurements of the subcutaneous fat index (SFI) were performed at the level of the eleventh thoracic vertebra. In order to adjust for the heterogeneity between the low SFI and high SFI groups, propensity score matching (PSM) was used. The Kaplan-Meier method was used to estimate the 5-year bone metastatic incidence. The prognostic analysis was performed with the Cox regression models. RESULTS: Compared with the patients without bone metastasis, the patients with bone metastasis had reduced SFI levels. In addition, Kaplan-Meier analysis revealed that patients with low SFI were more likely to develop bone metastases. The independent predictive value of SFI for bone metastases was confirmed by Cox regression analysis. The survival analysis was repeated after PSM with a 1:1 ratio, yielding similar results (P< 0.05). CONCLUSIONS: SFI is an independent predictor of bone metastasis in BC patients.

The role of mammalian Sirtuin 6 in cardiovascular diseases and diabetes mellitus.

Cardiovascular diseases are severe diseases posing threat to human health because of their high morbidity and mortality worldwide. The incidence of diabetes mellitus is also increasing rapidly. Various signaling molecules are involved in the pathogenesis of cardiovascular diseases and diabetes. Sirtuin 6 (Sirt6), which is a class III histone deacetylase, has attracted numerous attentions since its discovery. Sirt6 enjoys a unique structure, important biological functions, and is involved in multiple cellular processes such as stress response, mitochondrial biogenesis, transcription, insulin resistance, inflammatory response, chromatin silencing, and apoptosis. Sirt6 also plays significant roles in regulating several cardiovascular diseases including atherosclerosis, coronary heart disease, as well as cardiac remodeling, bringing Sirt6 into the focus of clinical interests. In this review, we examine the recent advances in understanding the mechanistic working through which Sirt6 alters the course of lethal cardiovascular diseases and diabetes mellitus.

Stress granule activation attenuates lipopolysaccharide-induced cardiomyocyte dysfunction.

BACKGROUND: Sepsis is the leading cause of death in intensive care units. Sepsis-induced myocardial dysfunction, one of the most serious complications of sepsis, is associated with higher mortality rates. As the pathogenesis of sepsis-induced cardiomyopathy has not been fully elucidated, there is no specific therapeutic approach. Stress granules (SG) are cytoplasmic membrane-less compartments that form in response to cellular stress and play important roles in various cell signaling pathways. The role of SG in sepsis-induced myocardial dysfunction has not been determined. Therefore, this study aimed to determine the effects of SG activation in septic cardiomyocytes (CMs). METHODS: Neonatal CMs were treated with lipopolysaccharide (LPS). SG activation was visualized by immunofluorescence staining to detect the co-localization of GTPase-activating protein SH3 domain binding protein 1 (G3BP1) and T cell-restricted intracellular antigen 1 (TIA-1). Eukaryotic translation initiation factor alpha (eIF2α) phosphorylation, an indicator of SG formation, was assessed by western blotting. Tumor necrosis factor alpha (TNF-α) production was assessed by PCR and enzyme-linked immunosorbent assays. CMs function was evaluated by intracellular cyclic adenosine monophosphate (cAMP) levels in response to dobutamine. Pharmacological inhibition (ISRIB), a G3BP1 CRISPR activation plasmid, and a G3BP1 KO plasmid were employed to modulate SG activation. The fluorescence intensity of JC-1 was used to evaluate mitochondrial membrane potential. RESULTS: LPS challenge in CMs induced SG activation and resulted in eIF2α phosphorylation, increased TNF-α production, and decreased intracellular cAMP in response to dobutamine. The pharmacological inhibition of SG (ISRIB) increased TNF-α expression and decreased intracellular cAMP levels in CMs treated with LPS. The overexpression of G3BP1 increased SG activation, attenuated the LPS-induced increase in TNF-α expression, and improved CMs contractility (as evidenced by increased intracellular cAMP). Furthermore, SG prevented LPS-induced mitochondrial membrane potential dissipation in CMs. CONCLUSION: SG formation plays a protective role in CMs function in sepsis and is a candidate therapeutic target.

Treatment of Netherton Syndrome With Abrocitinib.

This case report describes a 28-year-old woman with Netherton syndrome who had large erythematous migratory patches with serpiginous double-edged scales on her face, neck, trunk, and extremities.

Ligamentum teres hepatis as a graft for portal and/or superior mesenteric vein reconstruction: From bench to bedside.

BACKGROUND: Pancreaticoduodenectomy combined with portal vein (PV) and/or superior mesenteric vein (SMV) resection in patients with pancreaticobiliary malignancy has become a common surgical procedure. There are various grafts currently used for PV and/or SMV reconstruction, but each of these grafts have certain limitations. Therefore, it is necessary to explore novel grafts that have an extensive resource pool, are low cost with good clinical application, and are without immune response rejection or additional damage to patients. AIM: To observe the anatomical and histological characteristics of the ligamentum teres hepatis (LTH) and evaluate PV/SMV reconstruction using an autologous LTH graft in pancreaticobiliary malignancy patients. METHODS: In 107 patients, the post-dilated length and diameter in resected LTH specimens were measured. The general structure of the LTH specimens was observed by hematoxylin and eosin (HE) staining. Collagen fibers (CFs), elastic fibers (EFs), and smooth muscle (SM) were visualized by Verhoeff-Van Gieson staining, and the expression of CD34, factor VIII-related antigen (FVIIIAg), endothelial nitric oxide synthase (eNOS), and tissue type plasminogen activator (t-PA) were detected using immunohistochemistry in LTH and PV (control) endothelial cells. PV and/or SMV reconstruction using the autologous LTH was conducted in 26 patients with pancreaticobiliary malignancies, and the outcomes were retrospectively analyzed. RESULTS: The post-dilated length of LTH was 9.67 ± 1.43 cm, and the diameter at a pressure of 30 cm H2O was 12.82 ± 1.32 mm at the cranial end and 7.06 ± 1.88 mm at the caudal end. Residual cavities with smooth tunica intima covered by endothelial cells were found in HE-stained LTH specimens. The relative amounts of EFs, CFs and SM in the LTH were similar to those in the PV [EF (%): 11.23 ± 3.40 vs 11.57 ± 2.80, P = 0.62; CF (%): 33.51 ± 7.71 vs 32.11 ± 4.82, P = 0.33; SM (%): 15.61 ± 5.26 vs 16.74 ± 4.83, P = 0.32]. CD34, FVIIIAg, eNOS, and t-PA were expressed in both LTH and PV endothelial cells. The PV and/or SMV reconstructions were successfully completed in all patients. The overall morbidity and mortality rates were 38.46% and 7.69%, respectively. There were no graft-related complications. The postoperative vein stenosis rates at 2 wk, 1 mo, 3 mo and 1 year were 7.69%, 11.54%, 15.38% and 19.23%, respectively. In all 5 patients affected, the degree of vascular stenosis was less than half of the reconstructed vein lumen diameter (mild stenosis), and the vessels remained patent. CONCLUSION: The anatomical and histological characteristics of LTH were similar to the PV and SMV. As such, the LTH can be used as an autologous graft for PV and/or SMV reconstruction in pancreaticobiliary malignancy patients who require PV and/or SMV resection.

Metal transducer-assisted acoustic deformation potential characterization via coherent acoustic phonon dynamics.

Acoustic deformation potential (ADP) plays a significant role in quantifying carrier-acoustic phonon interactions in semiconductors. In this work, we report a novel ultrafast spectroscopy method to extract the ADP coupling constant of a semiconductor by jointly analyzing the coherent acoustic phonon signals with and without a metal transducer. By applying this method to GaAs, the ADP coupling constant corresponding to the band gap was extracted using a pump photon energy near the band gap, which agrees well with literature values. With a larger pump photon energy, the ADP coupling constant deviates from the one for the band gap, which is attributed to contributions from the carrier dynamics in multiple energy and wavevector states.

Serum Exosome-Derived piRNAs Could Be Promising Biomarkers for HCC Diagnosis.

Background: Serum exosome-based liquid biopsy has significant advantages for screening and diagnosing hepatocellular carcinoma (HCC). P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are novel small silencing RNAs that have been identified to function in cancer-related signalling pathways. However, studies on the presence of piRNAs in serum exosomes from HCC patients and their diagnostic values in HCC are not well reported. Our aim is to validate serum exosome-derived piRNAs as the valuable component of liquid biopsy for diagnosing HCC. Methods: We used small RNA (sRNA) sequencing to profile piRNAs from serum exosomes and describe the base distribution characteristics of serum exosome-derived piRNAs. Serum exosomes from 125 HCC patients and 44 nontumor donors were included in this study. Results: We found that piRNAs were components of serum exosomes from HCC patients. A total of 253 differentially expressed serum exosome-derived piRNAs were screened from HCC compared with the piRNAs from nontumor donors. Serum exosome-derived piRNAs from HCC displayed a distinctive base distribution. To further confirm the potential diagnostic value of serum exosome-derived piRNAs in HCC, we detected the levels of the top 5 upregulated piRNAs in our Chinese cohort. The training set and validation set both showed that all 5 piRNAs were dramatically increased in the serum exosomes from HCC compared with the piRNAs from non-tumour donors. The piRNAs could strongly identify HCC patients from non-tumour donors according to the area under the receiver operating characteristic (AUROC) model. Additionally, the piRNAs could also present significant values for the diagnosis of HCC with low tumour burden. Conclusion: piRNAs enriched the components of serum exosomes from HCC and could serve as promising biomarkers for HCC diagnosis.

Targeting pyroptosis in breast cancer: biological functions and therapeutic potentials on It.

Pyroptosis is a lytic and inflammatory type of programmed cell death that is mediated by Gasdermin proteins (GSDMs). Attractively, recent evidence indicates that pyroptosis involves in the development of tumors and can serve as a new strategy for cancer treatment. Here, we present a basic knowledge of pyroptosis, and an overview of the expression patterns and roles of GSDMs in breast cancer. In addition, we further summarize the available evidence of pyroptosis in breast cancer progression and give insight into the clinical potential of applying pyroptosis in anticancer strategies for breast cancer. This review will deepen our understanding of the relationship between pyroptosis and breast cancer, and provide a novel potential therapeutic avenue for breast cancer.

Megastigmane sesquiterpenoids from Saussurea medusa and their anti-inflammatory activities.

Objectives: An ethanol extract of the whole plants of Saussurea medusa had been investigated to find novel anti-inflammatory sesquiterpenoids. Methods: Extensive spectroscopic data and chemical methods were applied to elucidate the structures of the compounds. Results: One new megastigmane sesquiterpenoid (1), along with 11 known analogues (2-12), were obtained from S. medusa. All isolates, except compounds 3 and 6, were mentioned from the studied plant for the first time. Compounds 1, 2, 4, 5, 7, 8 and 12 were firstly isolated from the genus Saussurea. Compounds 2, 9 and 10 were found to inhibit the lipopolysaccharide (LPS)-induced release of NO by RAW264.7 cells with IC50 values ranging from 21.1 ± 1.7 to 46.7 ± 1.9 µM. Furthermore, iNOS expression experiment was performed to examine the interactions between the active compounds and the iNOS enzyme.