Search

Background: The manipulation of ferroptosis in cancer cells is a possible therapeutic technique that has been investigated for use in the treatment of cancer. Consequently, ferroptosis-inducing medications have recently received increased interest in cancer therapy. In this research, we assessed the anticancer efficacy of 14β-hydroxy- 3β-(β-D-Glucopyranosyloxy)-5α-bufa-20,22-dienolide (HTB50-2), a natural product derived from the plant Helleborus thibetanus Franch, in Triple-Negative Breast Cancer (TNBC). Moreover, we also studied its potential mechanisms., Methods: The biological effects of HTB50-2 in a series of breast cancer cell lines were analyzed using sulforhodamine B (SRB) and other methods. The migration ability was analyzed using three methods: wound healing assay, transwell assay, and Western blot. Meanwhile, the potential therapeutic value of HTB50-2 was evaluated in BALB/c mice by orthotopic transplantation. Transcriptome sequencing was conducted to explore the FOS-like antigen 2 (FOSL2) gene, and its role in ferroptosis was verified by Western blot and immunohistochemistry. The association of FOSL2 and ferroptosis-related genes was analyzed using NetworkAnalyst databases, and a TF-Gene interaction network was constructed., Results: Ferroptosis was found to be induced in TNBC cells by HTB50-2. Furthermore, HTB50-2 inhibited tumor development by inducing ferroptosis in TNBC in vivo. Mechanistically, we demonstrated that a transcription factor FOSL2 mediated ferroptosis by HTB50-2. Additionally, it was found that Forkhead box C1 (FOXC1) was regulated by FOSL2 and correlated with ferroptosis., Conclusion: Our data suggest that HTB50-2 exerts its anti-cancer properties by ferroptosis via FOSL2/FOXC1 signaling pathway. Hence, HTB50-2 has an important application potential in the treatment of TNBC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Postoperative ileus (POI) is a common obstruction of intestinal content passage caused by almost all abdominal operations that seriously strokes the quality of life of patients. Kuanchang-Shu granule (KCSG), a classic modified prescription based on "Da-Cheng-Qi Decoction", has obtained satisfactory efficacy in the clinical therapeutics of POI. However, its material basis and holistic molecular mechanism against POI have not been revealed., Methods: The chemical ingredients of KCSG were first characterized by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Subsequently, an integration strategy of the network pharmacology and molecular docking based on above identified ingredients was performed to unveil the potential targets involved in the treatment of KCSG on POI. Finally, intestinal manipulation induced rat POI model was constructed to verify the efficacy and predicted mechanism of KCSG against POI., Results: In total, 246 ingredients mainly including organic acids, flavonoids, quinones, alkaloids, terpenoids, phenylpropanoids and phenols were identified. 41 essential ingredients, 24 crucial targets as well as 15 relevant signaling pathways were acquired based on network pharmacology analysis. Pharmacodynamic research showed that KCSG treatment could protect intestinal histological damage, promote the recovery of measurement of gastrointestinal transit disorder and inhibit the secretion of myeloperoxidase in the distal ileum tissues. The up-regulated expression of p-AKT and down-regulated expression of p-eNOS and HSP9OAA1 predicted by molecular docking and validated by western blotting showed that AKT/eNOS/HSP90AA1 pathway may be one of the crucial mechanisms that mediates the protective effect of KCSG., (© 2024. The Author(s).)

Background: Compounds that target tumor epigenetic events are likely to constitute a prominent strategy for anticancer treatment. Histone deacetylase inhibitors (HDACis) have been developed as prospective candidates in anticancer drug development, and currently, many of them are under clinical investigation. We assessed the anticancer efficacy of a now hydroxamate-based HDACi, YF-343, in triple-negative breast cancer development and studied its potential mechanisms., Methods: YF-343 was estimated as a novel HDACi by the HDACi drug screening kit. The biological effects of YF-343 in a panel of breast cancer cell lines were analyzed by Western blot and flow cytometry. YF-343 exhibited notable cytotoxicity, promoted apoptosis, and induced cell cycle arrest. Furthermore, it also induced autophagy, which plays a pro-survival role in breast cancer cells., Results: The combination of YF-343 with an autophagy inhibitor chloroquine (CQ) significantly suppressed breast tumor progression as compared to the YF-343 treatment alone both in vitro and in vivo . Mechanistically, the molecular mechanism of YF-343 on autophagy was elucidated by gene chip expression profiles, qPCR analysis, luciferase reporter gene assay, chromatin immunoprecipitation assays, immunohistochemical analysis, and other methods. E2F7, a transcription factor, promoted the expression of ATG2A via binding to the ATG2A promoter region and then induced autophagy in triple-negative breast cancer cells treated with YF-343., Conclusion: Our studies have illustrated the mechanisms for potential action of YF-343 on tumor growth in breast cancer models with pro-survival autophagy. The combination therapy of YF-343 and CQ maybe a promising strategy for breast cancer therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To assess the effect of a novel naturally cultured rice with high resistant starch (RS) on postprandial glycemia in patients with type 2 diabetes compared to ordinary rice., Design: This study is a randomized, double-blinded controlled trial., Methods: Patients with type 2 diabetes were recruited, and postprandial glucose levels were measured at 5-time points after the ingestion of one of two types of cooked rice in random order. Paired t -tests were used to compare postprandial blood glucose changes and increment areas under the blood glucose curve between high-RS rice and ordinary rice., Results: The increments of the postprandial blood glucose levels for high-RS rice were significantly lower than that for ordinary rice, i.e., 2.80 ± 1.38 mmol/L vs. 3.04 ± 1.50 mmol/L ( P = 0.043) and 3.94 ± 2.25 mmol/L vs. 4.25 ± 2.29 mmol/L ( P = 0.036) at 30 min and 60 min, respectively. The incremental areas under the blood glucose curve for high-RS rice were also significantly lower than that for ordinary rice, i.e., 42.04 ± 20.65 [mmol/(L·min)] vs. 45.53 ± 22.45 [mmol/(L·min)] ( P = 0.043), 143.54 ±69.63 [mmol/(L·min)] vs. 155.15 ± 73.53 [mmol/(L·min)] ( P = 0.026), and 354.61 ± 191.96 [mmol/(L·min)] vs. 379.78 ± 195.30 [mmol/(L·min)] ( P = 0.042) at 30, 60, and 120 min, respectively. Repeated-measures ANOVA showed that postprandial glucose levels were not affected by the test order., Conclusion: The novel high-RS rice as a staple food when substituting for widely consumed ordinary rice may provide potential health benefits by lowering blood glucose in patients with type 2 diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tan, Duan, Chen, Mei, Qi and Zhang.)

Background: Citrin deficiency (CD) is an autosomal recessive disease resulting from biallelic mutations of the SLC25A13 gene. This study aimed to investigate the molecular epidemiological features of CD in the Guangdong and Shaanxi provinces of China., Methods: A total of 3,409 peripheral blood samples from Guangdong and 2,746 such samples from Shaanxi province were collected. Four prevalent SLC25A13 mutations NG_012247.2 (NM_014251.3): c.852_855del, c.1638_1660dup, c.615+5G>A, and c.1751-5_1751-4ins(2684) were screened by using the conventional polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism and newly-developed multiplex PCR methods, respectively. The mutated SLC25A13 allele frequencies, carrier frequencies, and CD morbidity rates were calculated and then compared with the Chi-square and Fisher's exact tests., Results: The mutations were detected in 68 out of 6,818 SLC25A13 alleles in Guangdong and 29 out of 5,492 alleles in the Shaanxi population. The carrier frequencies were subsequently calculated to be 1/51 and 1/95, while the CD morbidity rates were 1/10,053 and 1/35,865, in the 2 populations, respectively. When compared with the Shaanxi population, Guangdong exhibited a higher frequency of mutated SLC25A13 allele (68/6,818 vs. 29/5,492, χ 2 =8.570, P=0.003) in general, with higher c.852_855del (54/6,818 vs. 13/5,492, χ 2 =17.328, P=0.000) but lower c.1751-5_1751 -4ins(2684) (2/6,818 vs. 9/5,492, P=0.015) allele frequencies. The distribution of c.615+5G>A and c.1638_1660dup between the 2 provinces, as well as all 4 prevalent mutations among different geographic regions within the 2 provinces, did not differed significantly., Conclusions: Our findings depicted the CD molecular epidemiological features in Guangdong and Shaanxi populations, providing preliminary but significant laboratory evidences for the subsequent CD diagnosis and management in the 2 provinces of mainland China., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp-21-58). The authors have no conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

BACKGROUND We investigated the epidemiology of patients admitted to the Burn Center of West China Hospital during 2011-2016, to provide measures for burn prevention. MATERIAL AND METHODS We conducted a retrospective review of patients admitted to the Burn Center of West China Hospital during 2011-2016. We collected information on patient demographics, burn etiology, burn extent, place of injury, education level, and burn knowledge of patients. RESULTS A total of 1323 patients (1033 males and 290 females), mean age 35.4 years (range 10 days to 91 years), were admitted to our burn center. Among all patients, 214 were children aged 0-14 years, 998 were adults aged 15-59 years, and 111 were elderly adults over age 60 years. Scalds were the predominant cause of pediatric burns; however, flame burns were most common among adults and elderly patients. The injury location varied by age, with most burns occurring at work among adults; however, most children and elderly patients were burned at home. Educational levels were lower among adults from rural areas than those from urban areas, but both groups had little first aid knowledge. Furthermore, rural patients had received less vocational education and training than urban patients. CONCLUSIONS There has been a decrease in burn incidence in Sichuan Province. Flame injury should be a focus of attention in all age groups. Prevention programs for adults in the workplace are imperative. Burn prevention programs should continue to improve living conditions, especially for elderly people.

Background: Myocardial infarction (MI) is often accompanied by cardiomyocyte apoptosis, which decreases heart function and leads to an increased risk of heart failure. The aim of this study was to examine the effects of transforming growth factor-β receptor III (TGFβR3) on cardiomyocyte apoptosis during MI., Methods and Results: An MI mouse model was established by left anterior descending coronary artery ligation. Cell viability, apoptosis, TGFβR3, and mitogen-activated protein kinase signaling were assessed by methylthiazolyldiphenyl-tetrazolium bromide assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunofluorescence, electron microscopy, and Western blotting. Our results demonstrated that TGFβR3 expression in the border region of the heart was dynamically changed during MI. After stimulation with H 2 O 2 , TGFβR3 overexpression in cardiomyocytes led to increased cell apoptosis and activation of p38 signaling, whereas TGFβR3 knockdown had the opposite effect. ERK1/2 and JNK1/2 signaling was not altered by TGFβR3 modulation, and p38 inhibitor (SB203580) reduced the effect of TGFβR3 on apoptosis, suggesting that p38 has a nonredundant function in activating apoptosis. Consistent with the in vitro observations, cardiac TGFβR3 transgenic mice showed augmented cardiomyocyte apoptosis, enlarged infarct size, increased injury, and enhanced p38 signaling upon MI. Conversely, cardiac loss of function of TGFβR3 by adeno-associated viral vector serotype 9-TGFβR3 short hairpin RNA attenuated the effects of MI in mice., Conclusions: TGFβR3 promotes apoptosis of cardiomyocytes via a p38 pathway-associated mechanism, and loss of TGFβR3 reduces MI injury, which suggests that TGFβR3 may serve as a novel therapeutic target for MI., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objectives: The combination of transumbilical single-site laparoscopic inguinal hernia inversion and ligation is a new approach for girls. We have done 13 cases in our hospital since May 2013., Materials and Methods: Thirteen girls with inguinal hernia, from 6 months to 10 years of age, were treated with transumbilical single-site laparoscopy., Results: None of the patients underwent conversion from single-site laparoscopy to the open approach or conventional laparoscopic surgery. The average operation time was 35.15±6.68 minutes. Four cases were found to have a contralateral inguinal hernia. The patients were discharged the day after operation. Follow-up of 7 months to a year with all cases showed no recurrence and no incision complication., Conclusions: The combination of transumbilical single-site laparoscopic inguinal hernia inversion and ligation is a reliable, safe, and cosmetic herniorrhaphy for girls with inguinal hernia.

Keloid is regarded as a fibroproliferative disorder with excessive accumulation of extracellular matrix. However, the molecular mechanism of keloid formation is not well understood and no treatment modality is consistently effective. Heat shock protein 47 (HSP47) is known as a collagen-specific molecular chaperone which plays a critical role in collagen biosynthesis. Results of our previous in vitro experiments demonstrated that HSP47 might be an important reason for excessive collagen accumulation in regard to keloid formation. Our objective is to investigate whether HSP47 has an influence on collagen metabolism in animal keloid models. The constructed plasmids, carrying HSP47-small hairpin RNA (shRNA), were transfected into animal keloid models, in comparison with the control groups. After transfection, the mRNA and protein expression of HSP47 and collage type I were detected by quantitative real-time PCR and Western blot. Both the mRNA and protein levels of HSP47 in animal keloid models were decreased dramatically after transfection of the HSP47- shRNA plasmid, in comparison with the control group. Following the down-regulation of HSP47, we found that the volume of animal keloid models and the major collagen expression were reduced correspondingly. Combining the results of our previous in vitro experiment results, we suggest that overexpression of HSP47 in keloid fibroblast cells could induce excessive collagen accumulation by enhancing collagen synthesis, which not only presents a possible mechanism of keloid formation, but also offers a therapeutic potential of RNA interference to HSP47 for the treatment of keloids and other fibroproliferative disorders.

Recently it was shown that financial time series are not completely random process but exhibit long-term or short-term dependences, which offer promises for predictability. However, we do not clearly understand the potential relationship between serial structure and predictability. This paper proposed a framework to magnify the correlations and regularities contained in financial time series through constructing accumulative return series. This method can help us distinguish the real world financial time series from random-walk process effectively by examining the change patterns of volatility, Hurst exponent, and approximate entropy. Furthermore, we have found that the predictable degree increases continually with the increasing length of accumulative return. Our results suggest that financial time series are predictable to some extent and approximate entropy is a good indicator to characterize the predictable degree of financial time series if we take the influence of their volatility into account.

Fairness plays a key role in explaining the emergence and maintenance of cooperation. Opponent-oriented social utility models were often proposed to explain the origins of fairness preferences in which agents take into account not only their own outcomes but are also concerned with the outcomes of their opponents. Here, we propose a payoff-oriented mechanism in which agents update their beliefs only based on the payoff signals of the previous ultimatum game, regardless of the behaviors and outcomes of the opponents themselves. Employing adaptive ultimatum game, we show that (1) fairness behaviors can emerge out even under such minimalist assumptions, provided that agents are capable of responding to their payoff signals, (2) the average game payoff per agent per round decreases with the increasing discrepancy rate between the average giving rate and the average asking rate, and (3) the belief update process will lead to 50%-50% fair split provided that there is no mutation in the evolutionary dynamics.

The present study was to investigate chemical components of polysaccharides isolated from Golden needle (GNP) mushroom using high performance liquid chromatography (HPLC) and nuclear magnetic resonance spectroscopy (NMR). Then, anti-inflammatory effect of the polysaccharides was also evaluated. Results indicated that GNP was composed of the three monosaccharides (glucose, mannose and xylose) with a molar ratio of 3.5:0.8:1.4. GNP could significantly decreased CD4+ CD8+, ICAM-1, and MPO in serum and colon of normal and burned rats. It could be concluded that GNP possessed strong anti-inflammatory activity in burned rats., (Copyright 2009 Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of connective tissue growth factor (CTGF) on angiogenensis of random skin flaps in rats., Methods: Thirty-two SD rats were randomly divided into three CTGF groups (rCTGF 120 ng, rCTGF 160 ng, rCTGF 200 ng) and one control group. Ischemic random dorsal skin flaps (2 cm x 8 cm) were constructed on the backs of the rats. In the CTGF groups, connective tissue growth factor (CTGF) was injected subcutaneously to the rats in the skin flaps at the time of surgery. The same volume of 0.9% NaCl solution was injected to the rats in the control group. Ten days later, the amount of viable tissues within the flaps were examined by planimetry. Specimens from the random skin flaps were harvested for immunohistological and HE staining to examine the microvascular growth., Results: The immunohistochemical staining and HE staining revealed that the three CTGF groups had more vessels than the control group (21.00 +/- 3.423, 27.38 +/- 3.114 and 37.38 +/- 3.583 vs. 13.88 +/- 1.959, P < 0.05). Similar results were found in the middle parts of the skin flaps (15.50 +/- 2.777, 24.63 +/- 3.335 and 28.63 +/- 4.984 vs. 9.50 +/- 1.927, P < 0.05)., Conclusion: CTGF may enhance the survival of skin flaps in a dose-dependent manner, which is associated with an increase in angiogenesis of skin flaps.

Substantial studies have demonstrated that the initiation and progression of cervical cancer were closely associated with human papillomavirus (HPV) E6 and E7 oncogenes. The therapeutic strategy with ribozyme or antisense oligonucleotides to inhibit the expression of HPV E6 or E7 oncogenes showed effect to some degree, but problems such as low efficiency, short-period maintenance, and high cost still remain. The aim of this study was to investigate in vitro and in vivo the effect of HPV 16 E6 small interfering RNA (HPV 16 E6 siRNA) on cervical cancer cell line CaSki cells. The specific siRNA of HPV 16 E6 was synthesized and transfected into CaSki cells by liposome. The number of apoptotic cells, HPV 16 E6 messenger RNA (mRNA) level, and E6 protein expression were measured before and after the transfection by flow cytometry, reverse transcriptase-polymerase chain reaction, and Western blot, respectively. Cervical cancer in nude mice was established, and siRNA was injected directly into the nude mice peritoneal cavity or subcutaneous tumor. The efficiency of siRNA was evaluated by tumor volume change, HPV 16 E6 protein expression, and apoptosis of tumor cells. Apoptosis rate of CaSki cells at days 1, 2, 5, and 9 after siRNA transfection were 7.7%, 11.8%, 37.4%, and 12.6%, respectively. The mRNA level of HPV 16 E6 at the same time points were reduced by 77%, 83%, 59%, and 41%, respectively. But the mRNA level of beta-actin, as an internal control, showed no significant change. The inhibition rates of E6 protein synthesis at days 1, 2, 5, and 9 after the transfection were 79.7%, 80.4%, 71.3%, and 57.4%, respectively, whereas the protein levels of Lamin A/C, as internal control, had no change. In vivo, E6 siRNA administration groups showed a dramatic effect in inhibiting tumor growth, suppressing expression of E6 protein, and inducing tumor necrosis and apoptosis as compared with the control group. Direct injection of siRNA into subcutaneous tumor resulted in tumor suppression effect similar to that via the peritoneal cavity, and with additional injection better results could be achieved in cervical cancer CaSki cells. RNA interference exists, and the interference to HPV 16 E6 is specific and highly efficient both in vitro and in vivo.

Objective: The efficiency of HPV16 E6 gene silenced by RNA interference in vitro and in vivo was assessed., Methods: The specific siRNA of HPV16 E6 was designed and transfected into CaSki cells by liposome. Cell apoptotic rates and the changes in HPV16 E6 mRNA and protein before and after transfection were measured. Cervical cancer nude mice models were set up, siRNA was injected directly into subcutaneous tumor. The function of siRNA was evaluated by the changes in tumor volume, HPV16 E6 protein expression and apoptosis of tumor cells., Results: In vitro research, the cell apoptotic rates were 7.7%, 11.8%, 37.4% and 12.6% respectively at 24 h, 48 h, 5th day and 9th day after transfection. The HPV16 E6 mRNA was reduced by 77%, 83%, 59% and 41% at 24 h, 48 h, 5th day and 9th day after transfection. The inhibition rates of E6 protein measured by Flow cytometry were 79.7%, 80.4%, 71.3% and 57.4% at 24 h, 48 h, 5th day and 9th day after transfection, which were confirmed by the results of Western blot. In vivo research, E6 siRNA administration groups had great power in inhibiting tumor growth, restraining E6 protein expression, increasing tumor necrosis and apoptosis. The result of repeated injections of siRNA was better than that of single injection., Conclusion: RNA interference with HPV16 E6 is specific and highly efficient in vitro and in vivo.

Objective: To analyze the complications induced by polyacrylamide hydrogel injection for augmentation mammaplasty, explore the reason of the complication., Methods: Twenty three patients with complications after polyacrylamide hydrogel injection were classified by signs and symptoms, ultrasound and pathologic examinations were made., Results: The main complications were pain, hard nodule, asymmetry and breast deformation. The injected material was distributed diffusely behind gland, in gland, in muscles subcutaneous, even out of breast, caused some pathologic changes and it's hard to be cleaned completely from normal tissue., Conclusions: The complications were caused mainly by incorrect manipulation during operation, others might be relative to the injected material. The reliability of this injection method for augmentation should be cautiously observed.