Characteristics of and foundation application among Chinese females with sensitive skin.

OBJECTIVE: We conducted a study on women with sensitive skin of various skin tones to analyse their skin characteristics and preferences for foundation shades. METHODS: Volunteers were categorized based on their individual typological angle, and their preferences were assessed using self-perception and software-based mass aesthetic assessment. The Baumann Questionnaire is a valuable tool for identifying patients with sensitive skin and gaining a comprehensive understanding of their skin sensitivity. The skin characteristics of two groups were compared using a more suitable classification method. RESULTS: Individuals diagnosed with sensitive skin typically have skin tones classified as Types I, II and III, with Type I being the most common in sensitive skin cases. The sensitive group exhibited higher levels of transepidermal water loss, lighter skin tone, lower yellowness, increased glossiness, higher haemoglobin content, more acne, fewer blackheads, and fewer pores. Among them, Type I skin is characterized by lower elasticity, increased oiliness, higher hydration levels and fewer visible pores. Type II skin is characterized by lower hydration levels, higher oiliness and increased redness. Type III exhibits more pores, decreased oiliness and enhanced elasticity. Foundations No. 2 and No. 3 are fairer than foundations No. 1 and No. 4. In the self-assessment, Type I and Type II subjects preferred No. 3, while Type III subjects preferred No. 1 and No. 4 because they matched their skin tone. The results of the software evaluation showed that popular aesthetics preferred Type I and Type II to use No. 2, and Type III to use No. 2 and No. 3, as they resulted in a fairer complexion. CONCLUSION: Sensitive skin of different skin tone types confronts different skin problems. The findings also highlight the public's inclination towards lighter foundation shades, despite the common practice of selecting shades that harmonize with one's inherent skin tone.

OBJECTIF: Nous avons mené une étude sur des femmes à la peau sensible de différentes carnations afin d'analyser les caractéristiques de leur peau et leurs préférences en matière de teintes de fond de teint. MÉTHODES: Les volontaires ont été classées en fonction de leur angle typologique individuel et leurs préférences ont été évaluées à l'aide d'une auto­perception et d'une évaluation esthétique de masse basée sur un logiciel. Le questionnaire de Baumann est un outil précieux pour identifier les patients à la peau sensible et obtenir une compréhension globale de leur sensibilité cutanée. Les caractéristiques cutanées de deux groupes ont été comparées à l'aide d'une méthode de classification plus appropriée. RÉSULTATS: Les personnes chez qui l'on a diagnostiqué une peau sensible ont généralement des teintes de peau classées en types I, II et III, le type I étant le plus courant dans les cas de peau sensible. Le groupe sensible présente des niveaux plus élevés de perte d'eau transépidermique, un teint plus clair, une couleur moins jaune, une brillance accrue, une teneur en hémoglobine plus élevée, plus d'acné, moins de points noirs et moins de pores. Parmi eux, la peau de type I se caractérise par une élasticité plus faible, un taux de sébum plus élevé, des niveaux d'hydratation plus élevés et moins de pores visibles. La peau de type II se caractérise par des niveaux d'hydratation plus faibles, un taux de sébum plus élevé et des rougeurs plus importantes. Le type III présente plus de pores, une diminution de l'aspect gras et une meilleure élasticité. Les fonds de teint n° 2 et n° 3 sont plus clairs que les fonds de teint n° 1 et n° 4. Lors de l'auto­évaluation, les sujets des types I et II ont préféré le fond de teint n° 3, tandis que les sujets du type III ont préféré le fond de teint n° 1 et le fond de teint n° 4 parce qu'ils correspondaient à leur carnation. Les résultats de l'évaluation du logiciel ont montré que l'esthétique populaire préférait que les sujets de type I et de type II utilisent le n° 2, et que les sujets de type III utilisent le n° 2 et le n° 3, car ils donnaient un teint plus clair. CONCLUSION: Les peaux sensibles de différents types de carnation sont confrontées à des problèmes cutanés différents. Les résultats mettent également en évidence le penchant du public pour les teintes de fond de teint plus claires, malgré la pratique courante consistant à choisir des teintes qui s'harmonisent avec le teint inhérent à la peau.

New advances in signal amplification strategies for DNA methylation detection in vitro.

5-methylcytosine (5 mC) DNA methylation is a prominent epigenetic modification ubiquitous in the genome. It plays a critical role in the regulation of gene expression, maintenance of genome stability, and disease control. The potential of 5 mC DNA methylation for disease detection, prognostic information, and prediction of response to therapy is enormous. However, the quantification of DNA methylation from clinical samples remains a considerable challenge due to its low abundance (only 1% of total bases). To overcome this challenge, scientists have recently developed various signal amplification strategies to enhance the sensitivity of DNA methylation biosensors. These strategies include isothermal nucleic acid amplification and enzyme-assisted target cycling amplification, among others. This review summarizes the applications, advantages, and limitations of these signal amplification strategies over the past six years (2018-2023). Our goal is to provide new insights into the selection and establishment of DNA methylation analysis. We hope that this review will offer valuable insights to researchers in the field and facilitate further advancements in this area.

Design of Novel 2-Phenylquinazolin-4-amines as Selective CYP1B1 Inhibitors for Overcoming Paclitaxel Resistance in A549 Cells.

Cytochrome P450 1B1 (CYP1B1) contributes to the metabolic inactivation of chemotherapeutics when overexpressed in tumor cells. Selective inhibition of CYP1B1 holds promise for reversing drug resistance. In our pursuit of potent CYP1B1 inhibitors, we designed and synthesized a series of 2-phenylquinazolin-4-amines. A substantial proportion of these newly developed inhibitors demonstrated inhibitory activity against CYP1B1, accompanied by improved water solubility. Remarkably, compound 14b exhibited exceptional inhibitory efficacy and selectivity toward CYP1B1. Molecular docking studies suggested that the expansion of the π-system through aromatization, the introduction of an amine group, and iodine atom augmented the binding affinity. Furthermore, inhibitors 14a, 14b, and 14e demonstrated the ability to significantly reduce the resistance in A549 cells to paclitaxel, while also inhibiting the migration and invasion of these cells. Finally, radioiodine labeling experiments shed light on the metabolic pathway of compound 5l in mice, highlighting the potential of 125I-5l as a radioactive probe for future research endeavors.

Design, Synthesis, and Evaluation of 18F-Labeling CYP1B1 PET Tracer Based on 2-Phenylquinazolin.

Cytochrome P450 (CYP)1B1 has been identified to be specifically overexpressed in several solid tumors, thus it's a potential target for the detection of tumors. Based on the 2-Phenylquinazolin CYP1B1 inhibitors, we designed and synthesized several positron emission computed tomography (PET) imaging probes targeting CYP1B1. Through IC50 determinations, most of these probes exhibited good affinity and selectivity to CYP1B1. Considering their affinity, solubility, and their 18F labeling methods, we chose compound 5c as the best candidate. The 18F radiolabeling of [18F] 5c was easy to handle with good radiolabeling yield and radiochemical purity. In vitro and in vivo stability study indicated that probe [18F]5c has good stability. In cell binding assay, [18F]5c could be specifically taken up by tumor cells, especially HCT-116 cells. Although the tumor-blood (T/B) and tumor-muscle (T/M) values and PET imaging results were unsatisfied, it is still possible to develop PET probes targeting CYP1B1 by structural modification on the basis of 5c in the future.

Corrigendum to "Preoperative fibrinogen is associated with the clinical survival of primary liver cancer patients and promotes hepatoma metastasis via the PTEN/AKT/mTOR pathway" [Heliyon 9(6) (June 2023) e16696].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e16696.].

Chloroquine Sensitizes Esophageal Carcinoma EC109 Cells to Paclitaxel by Inhibiting Autophagy.

As an autophagy inhibitor, chloroquine (CQ) showed anti-tumor effect on several types of cancer and paclitaxel (PTX) is widely used in the treatment of esophageal carcinoma patients, but chemoresistance remains a major hurdle for PTX application due to the cytoprotective autophagy. Therefore, the aim of this study was to investigate whether CQ could elevate the anti-tumor effect of PTX on esophageal carcinoma cell line EC109 and explore the potential molecular mechanisms. We confirmed the suppressive effect of PTX on EC109 by MTT, scratch test, transwell and soft agar assay. And, we detected the key proteins in Akt/mTOR pathway, as well as the autophagy marker LC3 and p62 through Western Blot. In addition, GFP-LC3 plasmid was transfected into EC109 cells to monitor the autophagosome after CQ and PTX treatment. Ultimately, we observed the alterations in the proliferation and colony formation abilities of EC109 after knocking down mTOR by shRNA. We confirmed PTX could suppress the proliferation, migration and colony formation (all P < 0.05) abilities of EC109, and CQ could sensitize the inhibition effect of PTX by inhibiting autophagy through Akt/mTOR pathway. Furthermore, inhibiting Akt/mTOR pathway initiated autophagy and enhanced the sensitivity of EC109 to CQ and PTX. In summary, we suggest CQ could be used as a potential chemosensitizer for PTX in esophageal carcinoma treatment.

Preoperative fibrinogen is associated with the clinical survival of primary liver cancer patients and promotes hepatoma metastasis via the PTEN/AKT/mTOR pathway.

Aim: Hyperfibrinogenemia had been widely observed in various cancer patients, however, whether fibrinogen (FIB) influences the survival outcome of patients with primary liver cancer (PLC) remains unknown. This study was aimed to evaluate the predictive value of preoperative FIB in the survival outcome of PLC patients and explore the possible mechanism. Methods: Retrospective study was performed in PLC patients who underwent hepatectomy. Logistic regression analysis was used to explore the independent risk factors of the overall survival (OS) of PLC patients. The predictive value of FIB for the survival outcome was analyzed by Kaplan-Meier method, receiver operating characteristic curve and Cox proportional hazard model combined with B-splines. Hepatoma cell migration and invasion were detected by wound healing assay and Transwell assay, protein expression was measured by Western blot. mTOR inhibitor and PTEN overexpression plasmid were used to confirm the involvement of the PTEN/AKT/mTOR pathway during FIB treatment. Results: Preoperative FIB was confirmed to be related with the OS in PLC patients, higher FIB (>2.5 g/L) indicated higher hazard ratio. Meanwhile, FIB could promote hepatoma cell migration and invasion through the activation of AKT/mTOR pathway and epithelial-mesenchymal transformation (EMT). Moreover, the promotion of FIB on cell migration and invasion could be inhibited by mTOR inhibitor and PTEN overexpression. Conclusions: Preoperative FIB could be related with the prognosis of PLC patients, the risk of death in PLC patients gradually increases along with the up-regulation of FIB. FIB may promote hepatoma metastasis by inducing EMT via the activation of PTEN/AKT/mTOR pathway.

Post-Traumatic Stress Disorder Is Associated with Elevated Plasma Cholesterol in Female TT Homozygotes of LDLR rs5925.

To explore the mechanism of inconsistent relationships between plasma lipid profiles and post-traumatic stress disorder (PTSD) reported before, we hypothesized that interplays might exist between PTSD and a variation of rs5925 at low-density lipoprotein receptor (LDLR) gene on plasma lipid profiles. To test our hypothesis, we analyzed the plasma lipid profiles of 709 high school pupils with various genotypes of LDLR rs5925 and with or without PTSD. The results demonstrated that PTSD prevalence in the C allele carriers was higher than that in the TT homozygotes regardless of gender. The C allele carriers had higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ratios of TC to high-density lipoprotein cholesterol (TC/HDL-C) and LDL-C/HDL-C than the TT homozygotes in the male controls, and only higher TC in the female controls, but no differences in the male or female PTSD subjects. PTSD increased TC in the female TT homozygotes but not in the female C allele carriers. PTSD increased TC/HDL-C in the male TT homozygotes but not in the C allele carriers. These results suggest interactions between PTSD and LDLR rs5925 on plasma lipid profiles, which may be among the explanations for previously reported inconsistent relationships between LDLR rs5925 or PTSD and plasma lipid profiles, and facilitate the development of precision medicine interferences in hypercholesterolemia in individuals with different genetic backgrounds and psychiatric status. Psychiatric care or drug supplement may particularly be needed by female hypercholesterolemic subjects with the TT genotype of LDLR rs5925 in Chinese adolescents.

A new class of CYP1B1 inhibitors derived from bentranil.

Cytochrome P450 1B1 (CYP1B1) is highly expressed in a variety of tumors and implicated to drug resistance. More and more researches have suggested that CYP1B1 is a new target for cancer prevention and therapy. Various CYP1B1 inhibitors with a rigid polycyclic skeleton have been developed, such as flavonoids, trans-stilbenes, and quinazolines. To obtain a new class of CYP1B1 inhibitors, we designed and synthesized a series of bentranil analogues, moreover, IC50 determinations were performed for CYP1B1 inhibition of five of these compounds and found that 6o and 6q were the best inhibitors, with IC50 values in the nM range. The selectivity index (SI) of CYP1B1 over CYP1A1 and CYP1A2 was 30-fold higher than that of α-naphthoflavone (ANF). The molecular docking results showed that compound 6q fitted better into the CYP1B1 binding site than other compounds, which was consistent with our experimental results. On the basis of 6o and 6q, it is expected to develop CYP1B1 inhibitors with stronger affinity, higher selectivity and better solubility.

Recurrent neural network (RNN) model accelerates the development of antibacterial metronidazole derivatives.

Metronidazole is a specific drug against trichomonas and anaerobic bacteria, and is widely used in the clinic. However, extensive clinical application is often accompanied by extensive side effects, so it is still of great significance to develop metronidazole derivatives with a new skeleton. Compared with other traditional receptor-based drug design methods, the computational model based on a neural network has higher accuracy and reliability. In this work, a Recurrent Neural Network (RNN) model is applied to the discovery of metronidazole drugs with a new skeleton. Firstly, the generation model based on a Gated Recurrent Unit (GRU) is trained to generate an effective Simplified Molecular-Input Line-Entry System (SMILES) string library with high precision. Then, transfer learning is introduced to fine-tune the GRU model, and many molecules with structures similar to known active drugs are generated. After cluster analysis of the structures of the new compounds, 20 small molecular compounds with metronidazole structures of all different categories were selected, of which 19 may not belong to any published patents or applications. Through prediction and personal experience, the difficulty of synthesizing these 20 new structures was analyzed, and compound 0001 was chosen as our synthetic target, and a series of structures (8a-l) similar to compound 0001 were synthesized. Finally, the inhibitory activities of these compounds against bacteria E. coli, P. aeruginosa, B. subtilis and S. aureus were determined. The results showed that compound 8a-l had obvious inhibitory activity against these four bacteria, which proved the accuracy of our compound generation model.

The squeaky wheel gets the grease: Recipients' responses influence children's costly third-party punishment of unfairness.

Third-party punishment promotes cooperation by deterring opportunistic behaviors. Even children are willing to pay a cost to implement third-party punishment of unfair behavior. Whether in judicial practice or in daily third-party punishment, people take recipients' feelings into account out of restorative motives. Restorative motives pay attention to both the offenders and the victims and are committed to best repairing harm. This work examined whether children adopt restorative motives by considering recipients' responses when punishing unfair dividers. Participants (N = 128) were 6-, 8-, and 10-year-old Chinese children. Children were shown allocations proposed among a divider and a recipient with response (positive vs. negative) or without response and were asked to accept or pay a cost to reject the allocation. Two experiments indicated that costly third-party punishment increased with age. Furthermore, children took recipients' responses into consideration, with negative responses prompting children to punish more. These findings show that children adopted a restorative view when implementing costly third-party punishment.

Perioperative Transfusion is Related to the Length of Hospital Stays in Primary Liver Cancer Patients.

PURPOSE: Blood loss may be corrected with red blood cell transfusion, but may ultimately contribute to negative impacts. This study was a retrospective analysis to assess the impact of perioperative blood transfusion on hospital stay days in liver cancer patients. METHODS: We retrospectively examined data from patients with primary liver cancer who underwent curative resection. Patients were divided into perioperative blood transfusion (PBT) and non-PBT groups. Data were given as means and SDs for continuous variables and as counts and percentage for categorical variables. The correlation between blood transfusion and hospital stay days was analyzed by Fisher's exact test. Multivariable logistic regression analyses were used to identify independent predictors of length of hospital stays. RESULTS: Totally 206/1031 patients (20.3%) were given perioperative transfusion. The mean length of hospital stay was 17.8 days in PBT and 13.9 days in non-PBT groups. Our multivariable logistic regression showed transfusion, total bilirubin, indirect bilirubin, and the ratio of albumin to bilirubin were all indicators of the length of hospital stay days. Perioperative transfusion was also associated with prolonged length of hospital stays (95% CI: 0.395-0.811, p = 0.002). Transfusion also affected intrinsic coagulation factors (activated partial thromboplastin time, fibrinogen, platelet), inflammatory index (neutrocyte to lymphocyte ratio, monocyte), albumin and bilirubin levels. CONCLUSION: Perioperative transfusion of blood was associated with a significantly increased length of hospital stays probably via changing intrinsic coagulation and inflammatory factors and bilirubin levels in plasma.

Class IIa HDAC Downregulation Contributes to Surgery-Induced Cognitive Impairment Through HMGB1-Mediated Inflammatory Response in the Hippocampi of Aged Mice.

OBJECTIVE: Perioperative neurocognitive disorders (PND) are a common complication in the elderly. Histone deacetylases (HDACs) are a class of enzymes that control the acetylation status of intracellular proteins. Thus, we explored whether HDACs trigger the release of high mobility group box 1 (HMGB1) through altering the acetylation status in the hippocampi of aged mice. MATERIALS AND METHODS: The effect of the Class IIa HDAC in PND was explored using an in vivo form of splenectomy. Sixteen-month-old healthy male C57BL/6J mice were randomly divided into five groups: control, anesthesia plus sham surgery, anesthesia plus splenectomy, LMK235 treatment, and PBS treatment. The hippocampi were harvested on either first, third, or seventh postoperative day. Cognitive function was assessed via a Morris water maze (MWM) test. Quantitative RT-PCR, Western blots and ELISAs were carried out to assess the targeted gene expression at transcriptional and translational levels. RESULTS: Splenectomy led to a significant deficiency in spatial memory acquisition, marked decreases in mRNA and protein levels of HDAC4 and HDAC5 in the hippocampus, and increases in the levels of total HMGB1 and acetylated HMGB1. In a similar fashion to splenectomy, treatment with the HDAC4/5 inhibitor LMK235 produced impaired spatial memory and an increase in the expression of HMGB1 and its acetylated counterpart in the hippocampus. CONCLUSION: These results suggest that surgery leads to PND through class IIa HDAC downregulation-triggered HMGB1 release in hippocampus of aged mice. HDACs may be a potential therapeutic target for postoperative cognitive dysfunction.

Improving visual perspective-taking performance in children with autism spectrum conditions: Effects of embodied self-rotation and object-based mental rotation strategies.

LAY ABSTRACT: When answering how the same object might appear to others in different locations, people can provide answers by mentally putting themselves into another person's location using the embodied self-rotation strategy or by rotating the target object toward themselves using the object-based mental rotation strategy. In this study, after learning the embodied self-rotation or object-based mental rotation strategies, autistic children improved their visual perspective-taking performance, which is believed to be impaired or delayed in autistic individuals. We recruited 34 autistic children and an equal number of ability-matched typical children and examined their visual perspective-taking performance at baseline and after learning the embodied self-rotation and object-based mental rotation strategies. As previous visual perspective-taking and other social cognition interventions for autistic individuals have primarily focused on the embodied self-rotation strategy, showing moderate effectiveness and limited generalizability, we explored the effects of both embodied self-rotation and object-based mental rotation strategies for improving perspective-taking performance and discussed their implications in this study. The results showed that autistic children had a lower performance at baseline compared with typical children; however, they were still sensitive to both embodied self-rotation and object-based mental rotation strategies. Unlike typical children, who gained more from the embodied self-rotation strategy, autistic children benefited similarly from the two strategies. This suggests that there are multiple ways to helping autistic children overcome their difficulty in perspective-taking tasks. Future interventions for autistic children could consider combining various strategies that better suit their autistic traits.

Extracellular ubiquitin promotes hepatoma metastasis by mediating M2 macrophage polarization via the activation of the CXCR4/ERK signaling pathway.

BACKGROUND: Stored red blood cell (RBC) transfusion has been shown to enhance the risk of cancer recurrence. However, the underlying mechanism remains unknown. At our lab, we have demonstrated that the extracellular ubiquitin (eUb) released by aged RBCs could promote tumor metastasis in a melanoma mouse model. This study aimed to confirm the pro-tumor effect of eUb on hepatocellular carcinoma (HCC) and explore the related immunoregulatory mechanisms. METHODS: Forty HCC tissue specimens and the corresponding adjacent nontumor and normal liver tissues were collected. Two human hepatoma cell lines (MHCC-97H and HepG2.2.15), one murine hepatoma cell line (Hepa1-6), and one human monocyte cell line (THP-1) were adopted in this study. The coculture of hepatoma cells with macrophages was initiated with Transwell inserts. Cell migration in vitro was detected by Transwell and wound-healing assays, while in vivo tumor metastasis was measured by luciferase assay and H&E staining. Macrophage polarization was measured by flow cytometry, immunofluorescence, ELISA, qPCR, and Western blot. Protein expression was detected by Western blot, and immunoprecipitation was used to confirm the interaction between Ub and CXCR4 (CXC chemokine receptor type 4). RESULTS: Ub and CXCR4 were significantly upregulated in HCC tissues, and a positive correlation existed between them. In vitro, the migration of hepatoma cells was not affected by eUb directly, but their metastatic abilities were enhanced after coculture with the macrophages pretreated with eUb. Meanwhile, eUb promoted hepatoma cell metastasis in the lung in vivo and increased the ratio of M2 macrophages in the lung tissues and peripheral blood of tumor-bearing mice. Furthermore, the eUb-induced M2 macrophage polarization was related to the activation of the CXCR4/ERK (extracellular regulated protein kinase) signaling pathway. CONCLUSIONS: Extracellular ubiquitin promoted hepatoma metastasis through M2 macrophage polarization via the activation of the CXCR4/ERK signaling pathway, indicating that a personalized transfusion strategy is needed for the treatment of HCC patients. Neutralizing Ub in stored RBC units could lessen the detrimental clinical outcomes induced by the transfusion of stored RBCs.

The PI3K/mTOR dual inhibitor NVP-BEZ235 stimulates mutant p53 degradation to exert anti-tumor effects on triple-negative breast cancer cells.

Nearly half of human cancers harbor p53 mutations, and mutant p53 (mutp53) promotes carcinogenesis, metastasis, tumor recurrence and chemoresistance. mutp53 is observed in 30% of breast carcinomas, including triple-negative breast cancer (TNBC), and thus mutp53 is a promising target for treatment of TNBC. In this study, we investigated the effect of a phosphatidylinositide 3 kinase/mammalian target of rapamycin dual inhibitor, NVP-BEZ235 (BEZ235), on two TNBC cell lines with mutp53: MDA-MB-231 and MDA-MB-468. Cell growth, migration and colony-formation abilities were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, scratch assay, transwell and soft agar assay, revealing that BEZ235 can inhibit the growth, migration and colony-formation abilities of TNBC cells. In addition, BEZ235 caused degradation of mutp53 in these cells. We investigated the underlying mechanism by inhibiting proteasome function using MG132 and inhibiting autophagy using 3-methyladenine and shRNAs. We observed that BEZ235 may induce autophagy through repression of the Akt/mammalian target of rapamycin signaling pathway. The observed interplay between mutp53 and autophagy in TNBC cells was examined further by knockdown of ATG5 and ATG7, revealing that degradation of mutp53 induced by BEZ235 may be independent of the ubiquitin-proteasome pathway and autophagy mediated by ATG5 and ATG7. Moreover, we found evidence of positive feedback between mutp53 and autophagy in TNBC cells. In conclusion, BEZ235 may exert antitumor effects against TNBC cells by targeting mutp53, and this may have implications for the development of future therapies.

Extracellular ubiquitin inhibits the apoptosis of hepatoma cells via the involvement of macrophages.

BACKGROUND: Blood transfusion is a vital treatment for cancer patients, but some studies have proved that there is an association between transfusion and the risk of cancer recurrence. Storage time influences the quality of red blood cells (RBCs), and the transfusion of aged RBCs can result in hepatocellular carcinoma (HCC) recurrence, which could be related to the ubiquitin (Ub) released by aged RBCs. In this study, we explored the effect of eUb on the biological characteristics of hepatoma cells. METHODS: We checked the proliferation and apoptosis of hepatoma cells (MHCC-97H and HepG2.2.15) by CCK-8, colony formation assay, flow cytometry and Western blot. THP-1-derived macrophages were used in this study, and the co-culturing of hepatoma cells with macrophages was initiated with Transwell inserts. We also measured the secretion of macrophages through ELISA. RESULTS: eUb did not directly influence the proliferation and apoptosis of hepatoma cells. However, the Akt/mTOR signaling pathway in hepatoma cells was activated, and the apoptosis of hepatoma cells was inhibited significantly after they were co-cultured with the macrophages pretreated with eUb. In addition, we confirmed that eUb modulated the phenotype and secretion function of macrophages. CONCLUSIONS: Extracellular Ub repressed the apoptosis of hepatoma cells via the involvement of macrophages, which might affect the local tumor microenvironment and display pro-tumor effect.

Surgery-induced downregulation of hippocampal sirtuin-1 contributes to cognitive dysfunction by inhibiting autophagy and activating apoptosis in aged mice.

OBJECTIVES: Elderly patients often suffer from cognitive dysfunction following surgery. However, the mechanisms underlying this phenomenon still remain unclear. This study investigated the critical part of Sirtuin-1 (SIRT1)-mediated autophagy and apoptosis in surgery-induced cognitive impairment. METHODS: The aged (16-month-old) male C57BL/6 mice underwent anesthesia and surgery. Some mice received intraperitoneal injections of resveratrol, which is an activator of SIRT1, prior to exposure to splenectomy. To examine learning and memory behavior in different sets, the study performed a Morris water maze. Tissues from the hippocampus were harvested 1, 3 and 7 days after surgery. Western blotting and immunofluorescence analysis determined the expression of autophagy- and apoptosis- associated protein. RESULTS: This article demonstrated surgery but not anesthesia considerably affected memory behavior and downregulated SIRT1 expression in the aged mice. Interestingly, rescue of hippocampal SIRT1 expression ameliorated the cognitive impairment in the elderly mice under splenectomy. In addition, surgical trauma decreased Beclin-1 protein levels and the LC3-II/LC3-I ratio, while expression of p62, Bax and cleaved caspase-3 in hippocampal neurons increased. However, rescue of hippocampal SIRT1 expression considerably attenuated the surgery-induced downregulation of Beclin-1, increased the ratio of LC3-II/LC3-I, and decreased expression of p62, Bax, and cleaved caspase-3. CONCLUSION: These findings suggest that surgery-induced downregulation of hippocampal SIRT1 participates in cognitive impairment after surgery by inhibiting the autophagy process and activating apoptosis.

The Role Of PD-1/PD-L1 Axis In Treg Development And Function: Implications For Cancer Immunotherapy.

During the past decade, immunotherapy targeting immune checkpoints has become an important component of the treatment paradigm for numerous malignancies, especially PD-1/PD-L1 blockade which was demonstrated to rejuvenate disabled T cells in cancer patients to achieve long-term remissions. However, the clinical outcome of PD-1/PD-L1 targeted monotherapy against solid malignancies is not satisfactory which may be related with the intricate tumor microenvironment. As a vital suppressive immunocyte in tumor microenvironment, Tregs are characterized by PD-1 and PD-L1 and demonstrated to contribute to the tumor progression. The latest studies have suggested that Tregs might be involved in the treatment of PD-1/PD-L1 blockade and PD-1/PD-L1 axis could influence Treg differentiation and function. However, the complicated relationship between PD-1/PD-L1 pathway and Tregs has not been fully clarified. Here, we explored the role of PD-1/PD-L1 axis in Treg development and function, as well as the potential mechanisms of PD-1/PD-L1 blockade resistance related with Tregs. Meanwhile, we discussed the combination therapy aimed at targeting PD-1/PD-L1 axis and Tregs, hoping to provide novel insights for the future cancer treatment.

Dihydroartemisinin inhibits HepG2.2.15 proliferation by inducing cellular senescence and autophagy.

Dihydroartemisinin (DHA) has been reported to possess anti-cancer activity against many cancers. However, the pharmacologic effect of DHA on HBV-positive hepatocellular carcinoma (HCC) remains unknown. Thus, the objective of the present study was to determine whether DHA could inhibit the proliferation of HepG2.2.15 cells and uncover the underlying mechanisms involved in the effect of DHA on HepG2.2.15 cells. We found that DHA effectively inhibited HepG2.2.15 HCC cell proliferation both in vivo and in vitro. DHA also reduced the migration and tumorigenicity capacity of HepG2.2.15 cells. Regarding the underlying mechanisms, results showed that DHA induced cellular senescence by up-regulating expression levels of proteins such as p-ATM, p-ATR, γ-H2AX, P53, and P21 involved in DNA damage response. DHA also induced autophagy (green LC3 puncta gathered together and LC3II/LC3I ratio increased through AKT-mTOR pathway suppression). Results also revealed that DHA-induced autophagy was not linked to senescence or cell death. TPP1 (telomere shelterin) overexpression could not rescue DHA-induced anticancer activity (cell proliferation). Moreover, DHA down-regulated TPP1 expression. Gene knockdown of TPP1 caused similar phenotypes and mechanisms as DHA induced phenotypes and mechanisms in HepG2.2.15 cells. These results demonstrate that DHA might inhibit HepG2.2.15 cells proliferation through inducing cellular senescence and autophagy. [BMB Reports 2019; 52(8): 520-524].