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The COVID-19 pandemic has introduced new challenges for governments and individuals. Unprecedented efforts at reducing virus transmission launched a novel arena for human face recognition in which faces are partially occluded with masks. Previous studies have shown that masks decrease accuracy of face identity and emotion recognition. The current study focuses on the impact of masks on the speed of processing of these and other important social dimensions. Here we provide a systematic assessment of the impact of COVID-19 masks on facial identity, emotion, gender, and age. Four experiments (N = 116) were conducted in which participants categorized faces on a predefined dimension (e.g., emotion). Both speed and accuracy were measured. The results revealed that masks hindered the perception of virtually all tested facial dimensions (i.e., emotion, gender, age, and identity), interfering with normal speed and accuracy of categorization. We also found that the unwarranted effects of masks were not due to holistic processes, because the Face Inversion Effect (FIE) was generally not larger with unmasked compared with masked faces. Moreover, we found that the impact of masks is not automatic and that under some contexts observers can control at least part of their detrimental effects.

Gossypol, a natural polyphenolic compound, possesses antivirus activity and induces cell death of different types of tumors. However, the efficacy of gossypol on lung carcinoma metastases and epithelial to mesenchymal transition remains unknown. The aim of the present work was to determine the cellular and molecular mechanism of the anti-cancer and anti-metastatic efficacies of gossypol on human lung carcinoma cells. Gossypol showed a marked suppression of the viability, motility, and invasion in H1299 and A549 cells. Zymography assay showed that gossypol was sufficient to suppress the activities of urokinase-type plasminogen activator and matrix metalloproteinase-2. Gossypol reversed TGF-β-induced epithelial to mesenchymal transition. Gossypol reduced vimentin, p-FAK, p-Src and p-paxillin. In vivo studies of gossypol were performed using subcutaneous inoculation and tail vein injection of A549 into immunodeficient BALB/c nude mice and severe combined immunodeficient mice., (© 2024 Wiley Periodicals LLC.)

Background/objectives: Antrodia camphorata , also known as "Niuchangchih" in Taiwan, is a unique medicinal mushroom native to Taiwan. It is used in traditional medicine to treat various health conditions. In this study, we investigated the efficacy of A. camphorata mycelia on alcohol-induced liver damage, both in vitro and in vivo, in a Good Laboratory Practice (GLP) facility., Methods: The experimental groups consisted of a normal control group (G1), a negative control group (G2), an A. camphorata mycelium powder 50 mg/kg/day administration group (G3), a 100 mg/kg/day administration group (G4), a 200 mg/kg/day administration group (G5), and a positive control silymarin 200 mg/kg/day administration group (G6), with 10 Sprague Dawley rats assigned to each treatment group., Results: We found that treatment with A. camphorata mycelium powder significantly reduced alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, cholesterol, adiponectin, triglyceride, and malondialdehyde concentrations. Histopathological analysis also revealed that the inflammation score significantly decreased in the A. camphorata -treated groups., Conclusion: Based on these results, we conclude that repeated oral administration of A. camphorata mycelium powder is effective in improving alcoholic liver disease.

Invasiveness and epithelial-mesenchymal transition (EMT) are main patterns of metastatic disease, which is the major cause cancer-related mortality in human malignant melanoma cells. Tea and its consumption extract are associated with a lower risk of several types of cancer and have anti-inflammatory and antioxidative biological effects. However, the anti-EMT and anti-cancer stemness effect of black tea ethanol extracts (BTEE) in human melanoma remain poorly understood. In this study, the effects of BTEE-reduced invasiveness, EMT, and cancer stemness were evaluated in human A 375 and A2058 melanoma cells. BTEE inhibited the activity of u-PA, migration, and invasiveness by repressing p-FAK signaling pathway. BTEE affected the EMT by downregulating the expression of β-catenin, N-cadherin, fibronectin, vimentin, and Twist-1. BTEE also reduced tumor necrosis factor-alpha (TNF-α)-induced invasiveness and cancer stemness characteristics in vitro. The growth of melanoma in nude mice xenograft model showed that BTEE suppressed A 375 tumor growth in vivo., (© 2024 Wiley Periodicals LLC.)

The relationship between metastasis-associated protein 2 (MTA2) overexpression and tumor growth and metastasis has been extensively studied in a variety of tumor cells but not in human osteosarcoma cells. This study aims to elucidate the clinical significance, underlying molecular mechanisms, and biological functions of MTA2 in human osteosarcoma in vitro and in vivo . Our results show that MTA2 was elevated in osteosarcoma cell lines and osteosarcoma tissues and was associated with tumor stage and overall survival of osteosarcoma patients. Knockdown of MTA2 inhibited osteosarcoma cell migration and invasion by reducing the expression of urokinase-type plasminogen activator (uPA). Bioinformatic analysis demonstrated that high levels of uPA in human osteosarcoma tissues correlated positively with MTA2 expression. Furthermore, treatment with recombinant human uPA (Rh-uPA) caused significant restoration of OS cell migration and invasion in MTA2 knockdown osteosarcoma cells. We found that ERK1/2 depletion increased the expression of uPA, facilitating osteosarcoma cell migration and invasion. Finally, MTA2 depletion significantly reduced tumor metastasis and the formation of lung nodules in vivo . Overall, our study suggests that MTA2 knockdown suppresses osteosarcoma cell metastasis by decreasing uPA expression via ERK signaling. This finding provides new insight into potential treatment strategies against osteosarcoma metastasis by targeting MTA2.

Deoxyshikonin (DSK) is a biological component derived from Lithospermum erythrorhizon. Although DSK possesses potential anticancer activities, whether DSK exerts anticancer effects on cervical cancer cells is incompletely explored. This study was aimed to investigate the anticancer activity of DSK against cervical cancer cells and its molecular mechanisms. Cell viability was evaluated by MTT assay. Level of phosphorylation and protein was determined using Western blot. Involvement of signaling kinases was assessed by specific inhibitors. Our results revealed that DSK reduced viability of human cervical cell in a dose-dependent fashion. Meanwhile, DSK significantly elicited apoptosis of HeLa and SiHa cells. Apoptosis microarray was used to elucidate the involved pathways, and the results showed that DSK dose-dependently diminished cellular inhibitor of apoptosis protein 1 (cIAP1), cIAP2, and XIAP, and induced cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-8/9/3. Furthermore, we observed that DSK significantly triggered activation of ERK, JNK, and p38 MAPK (p38), and only inhibition of p38 diminished the DSK-mediated pro-caspases cleavage. Taken together, our results demonstrate that DSK has anti-cervical cancer effects via the apoptotic cascade elicited by downregulation of IAPs and p38-mediated caspase activation. This suggests that DSK could act as an adjuvant to facilitate cervical cancer management., (© 2024 Wiley Periodicals LLC.)

Osteosarcoma is a malignant bone tumor affecting adolescents and children. No effective treatment is currently available. Asiatic acid (AA), a triterpenoid compound found in Centella asiatica, possesses anti-tumor, anti-inflammatory, and anti-oxidant properties in various types of tumor cells. This study aims to determine whether AA exerts antitumor effects in human osteosarcoma cells. Our results indicate that AA does not influence the viability, proliferative rate, or cell cycle phase of human osteosarcoma cells under non-toxic conditions. AA suppressed osteosarcoma cell migration and invasion by down-regulating matrix metalloproteinase 1 (MMP1) expression. Data in the TNMplot database suggested MMP1 expression was higher in osteosarcoma than in normal tissues, with associated clinical significance observed in osteosarcoma patients. Overexpression of MMP1 in osteosarcoma cells reversed the AA-induced suppression of cell migration and invasion. AA treatment decreased the expression of specificity protein 1 (Sp1), while Sp1 overexpression abolished the effect of AA on MMP1 expression and cell migration and invasion. AA inhibited AKT phosphorylation, and treatment with a PI3K inhibitor (wortmannin) increased the anti-invasive effect of AA on osteosarcoma cells via the p-AKT/Sp1/MMP1 axis. Thus, AA exhibits the potential for use as an anticancer drug against human osteosarcoma., (© 2024 Wiley Periodicals LLC.)

Background: Chemotherapy and chemoradiation have become essential adjuncts to improve the survival of patients with resectable esophageal squamous cell carcinoma (ESCC) in the perioperative period. Although preoperative treatment plus surgery is commonly used, controversy remains regarding the optimal treatment strategy for patients with locally advanced ESCC., Methods: A retrospective review of clinical stage II and III ESCC patients who underwent esophagectomy at Henan Cancer Hospital between October 2014 and October 2017 was performed. The patients were divided into a neoadjuvant chemotherapy (NAC) group and an adjuvant chemotherapy (AC) group. Propensity score matching (PSM) was used to exclude confounders. Survival was estimated using Kaplan‒Meier analysis and compared by the log-rank test. The Cox proportional hazards regression model was used for both the univariate and multivariate analyses., Results: A total of 684 patients were enrolled, including 365 (53.4%) patients in the NAC group. After PSM, 294 pairs of patients were left. NAC prolonged the OS (not reached versus 57.3 months, P = 0.002) and DFS (57.2 vs. 36.4 months, P = 0.010) and decreased the total rate of recurrence (50.1% vs. 59.2%, P = 0.025) and local recurrence (27.9% vs. 36.7%, P = 0.022) compared with AC. The multivariable analyses showed that NAC plus surgery modality was an independent predictor for improved OS (HR: 0.582, 95% CI: 0.467-0.786, P = 0.001)., Conclusion: NAC plus surgery prolonged OS and DFS, and significantly decreased the total rate of recurrence compared with surgery plus AC in patients with clinical stage II and III ESCC., (© 2023. Society of Surgical Oncology.)

Purpose: The purpose of this retrospective study was to define the pattern of lymph nodal metastases in patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemotherapy (NCT) followed by esophagectomy and to evaluate its influence on prognosis., Methods: A total of 398 patients with clinical stage T3N0 or T1-3N+ ESCC who underwent NCT and radical esophagectomy with two-field lymphadenectomy were included. The distribution and frequency of metastases were counted separately for each lymph node station. The ypN stage, number of positive lymph node stations and lymph node stations with a metastasis rate greater than 5% were analyzed by using univariate Cox regression, followed by separate multivariable Cox regression analyses after adjusting for various clinical factors., Results: Lymph node metastases were most frequently observed in the right upper paratracheal (16.8%) and left gastric artery (13.1%) stations. Multivariable models controlling for clinical factors showed that ypN stage remained a significant independent predictor of survival (N1 vs. N0: hazard ratio [HR], 2.30, 95% confidence interval [CI] 1.38-3.83, P < 0.001; N2 vs. N0: HR, 3.76, 95% CI 2.21-6.38, P < 0.001; N3 vs. N0: HR, 7.14, 95% CI 3.78-13.48, P < 0.001). The model from the multivariable analysis with the highest c-index score, indicating superior discriminatory preference, was ypN stage (c-index, 0.72)., Conclusions: The pattern and influence of lymph node metastases after NCT will provide guidance on the extent of lymphadenectomy. Common positive lymph node stations for thoracic ESCC after NCT include the paratracheal, subcarinal, paraesophageal, paracardial, and left gastric artery stations., (© 2023. Society of Surgical Oncology.)

No adjuvant treatment has been established for patients who remain at high risk of recurrence and incidental pathologic lymph node metastasis for esophageal squamous cell carcinoma (ESCC). In this open-label, multicenter, phase III, randomized controlled trial, ESCC patients who did not achieve pathologic complete response after neoadjuvant chemotherapy plus surgery and clinical T1-2 N0 patients with incidental pathologic lymph node metastasis following initial surgery were randomized at a 2:1 ratio to receive either a sintilimab regimen or observational management (NCT05495152). The primary end point was disease-free survival for all randomized patients. The results of this randomized controlled trial addressed controversy regarding the survival benefits of adjuvant sintilimab treatment for patients with resected locally advanced ESCC. Clinical Trial Registration : NCT05495152 (ClinicalTrials.gov).

Background: The feasibility and safety of en bloc robot-assisted minimally invasive oesophagectomy (RAMIE) need to be verified., Methods: Forty-seven patients who received conventional RAMIE and 31 who received modified en bloc RAMIE at Henan Cancer Hospital were included in the study cohort. We compared the perioperative outcomes of conventional RAMIE and modified en bloc RAMIE., Results: Compared with the conventional RAMIE group, the en bloc RAMIE group yielded a higher total number of lymph nodes (p = 0.001), especially thoracic lymph nodes (p = 0.025) and left recurrent laryngeal nerve (RLN) lymph nodes (p = 0.005). No notable differences were found in the rate of total complications (p = 0.663) or RLN injury (p = 0.891) between the two groups. The preoperative and postoperative serological indicators were comparable between the two groups., Conclusions: Modified en bloc RAMIE was safe and feasible for patients with oesophageal squamous cell carcinoma and improved lymph node dissection, especially thoracic and left RLN lymph node dissection., (© 2023 John Wiley & Sons Ltd.)

Our previous studies have shown that the plasminogen activator (PA) and matrix metalloproteinases (MMPs) proteinase systems were highly expressed in highly malignant liver cancer cells and regulated by PKCα. This study investigates whether the PKCα regulation of PA and MMPs systems is conducted through p38 mitogen-activated protein kinase (MAPK) signaling and the pathway is responsible for promoting cell progression. We found that the expressions of p38 MAPK in both highly malignant HA22T/VGH and SK-Hep-1 liver cancer cells were higher than that in other lower malignancy liver cancer cells. Since PKCα activates p38 MAPK in progression of liver cancer, we suspected the PKCα/p38 MAPK signaling pathway to be involved in the regulation of MMPs and PA systems. When SK-Hep-1 cells were treated with SB203580 or DN-p38, only MMP-1 and u-PA mRNA expressions decreased. The p38 MAPK inhibition also decreased the cell migration and invasion. In addition, the mRNA decay assays showed that the higher expressions of MMP-1 and u-PA mRNA in SK-Hep-1 cells were due to the alteration of mRNA stability by p38 MAPK inhibition. Zymography of SK-Hep-1 cells treated with siPKCα vector also showed the decrease of the activity of MMP-1 and u-PA and confirmed changes in mRNA level. Furthermore, only the transfection of MKK6 to the siPKCα-treated SK-Hep-1 stable clone cell restored the attenuation of MMP-1 and u-PA expressions. The treatment of SK-Hep-1 cells with either inhibitor of MMP-1 or u-PA reduced migration, and the reduction was enhanced with both inhibitors. In addition, tumorigenesis was also reduced with both inhibitors. These data suggest a novel finding that MMP-1 and u-PA are critical components in PKCα/MKK6/p38 MAPK signaling pathway which mediates liver cancer cell progression, and that the targeting of both genes may be a viable approach in liver cancer treatment., (© 2023 The Authors. Drug Development Research published by Wiley Periodicals LLC.)

Purpose: To determine whether a deep learning approach using generative adversarial networks (GANs) is beneficial for the classification of retinal conditions with Optical coherence tomography (OCT) images., Methods: Our study utilized 84,452 retinal OCT images obtained from a publicly available dataset (Kermany Dataset). Employing GAN, synthetic OCT images are produced to balance classes of retinal disorders. A deep learning classification model is constructed using pretrained deep neural networks (DNNs), and outcomes are evaluated using 2082 images collected from patients who visited the Department of Ophthalmology and the Department of Endocrinology and Metabolism at the Tri-service General Hospital in Taipei from January 2017 to December 2021., Results: The highest classification accuracies accomplished by deep learning machines trained on the unbalanced dataset for its training set, validation set, fivefold cross validation (CV), Kermany test set, and TSGH test set were 97.73%, 96.51%, 97.14%, 99.59%, and 81.03%, respectively. The highest classification accuracies accomplished by deep learning machines trained on the synthesis-balanced dataset for its training set, validation set, fivefold CV, Kermany test set, and TSGH test set were 98.60%, 98.41%, 98.52%, 99.38%, and 84.92%, respectively. In comparing the highest accuracies, deep learning machines trained on the synthesis-balanced dataset outperformed deep learning machines trained on the unbalanced dataset for the training set, validation set, fivefold CV, and TSGH test set., Conclusions: Overall, deep learning machines on a synthesis-balanced dataset demonstrated to be advantageous over deep learning machines trained on an unbalanced dataset for the classification of retinal conditions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to investigate the survival impact of the number of lymph nodes dissection (LND) in patients receiving neoadjuvant chemotherapy (NCT) for esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed the clinical pathological data and survival of 407 ESCC patients who underwent esophagectomy after NCT between January 2015 and December 2016. The relationship between the number of LNDs and 5-year overall survival (OS) or disease-free survival (DFS) was plotted by using restricted cubic spline analysis. A Cox proportional hazards regression model was used to identify prognostic factors of OS and DFS. We observed an obvious non-linear relationship between LND and the hazard ratios (HRs) for OS (P = 0.0015) and DFS (P < 0.001) of all the patients. In the multivariate analysis of OS and DFS, the number of LNDs (greater than 28 and less than 46) had a significant protective effect on survival (OS: HR: 0.61, 95% CI: 0.42-0.88, P = 0.007; DFS: HR: 0.50, 95% CI: 0.36-0.70, P < 0.001). For patients with nodal metastases, it was also an independent prognostic factor for OS (HR, 0.56, 95% CI, 0.35-0.90, P = 0.017) and DFS (HR, 0.42, 95% CI, 0.28-0.65, P < 0.001). Some degree of lymphadenectomy after NCT was beneficial in improving 5-year OS and DFS for ESCC patients with nodal metastases. For patients with nodal negativity, more extended lymphadenectomy did not improve patient survival., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The error probability of block codes sent under a non-uniform input distribution over the memoryless binary symmetric channel (BSC) and decoded via the maximum a posteriori (MAP) decoding rule is investigated. It is proved that the ratio of the probability of MAP decoder ties to the probability of error grows most linearly in blocklength when no MAP decoding ties occur, thus showing that decoder ties do not affect the code's error exponent. This result generalizes a similar recent result shown for the case of block codes transmitted over the BSC under a uniform input distribution.

Although concurrent chemoradiotherapy is the cornerstone of treatment for locally advanced or recurrent uterine cervical cancer, treatment fails at a high rate. Therefore, the development of novel targeting agents is critical. This study investigated the action of CLEFMA, a potent, synthetic curcumin derivative, on cervical cancer cells and its mechanism of action. We found that CLEFMA negatively regulated the viability of cervical cancer cells, involving induction of cell apoptosis. Cleaved caspase-3, cleaved poly(adenosine diphosphate-ribose) polymerase, cleaved caspase-8, and cleaved caspase-9 expression were increased by treatment with CLEFMA. After U0126 (ERK1/2 inhibitor) and SB203580 (p38 inhibitor) were applied as cotreatment with CLEFMA, the expression of cleaved caspase-8, -9, and -3 was reduced significantly. In conclusion, CLEFMA activates both extrinsic and intrinsic apoptotic pathways through ERK1/2 and p38 signal transduction in cervical cancer cells., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: This study aimed to evaluate the perioperative outcomes of patients undergoing robot-assisted McKeown esophagectomy (RAME) and the learning curves of surgeons performing RAME at a single center., Methods: Perioperative outcomes of RAME and video-assisted McKeown esophagectomy (VAME) were compared after eliminating confounding factors by propensity score matching (PSM). The cumulative sum (CUSUM) method was used to evaluate the learning curves of RAME for a single surgical team., Results: In general, a total of 198 patients with esophageal cancer (RAME: 45 patients, VAME: 153 patients) were included in this study, and 43 pairs of patients receiving RAME or VAME were matched using 1:1 PSM analysis. Those in the RAME group had more lymph nodes dissected in the total lymph nodes (median 29.0 vs. 26.0, P = 0.011) and the upper mediastinum (median 8.0 vs. 6.0, P < 0.001), especially the left recurrent laryngeal nerve (RLN) lymph node (median 4.0 vs. 2.0, P = 0.001). According to the trend of the CUSUM plot, the learning curve was divided into two stages at the 20th RAME procedure. After mastering the learning curve, RAME harvested a significantly higher number of upper mediastinal lymph nodes (median 9.0 vs. 6.0, P = 0.001), left RLN lymph nodes (median 5.0 vs. 3.5, P = 0.003), and right RLN lymph nodes (median 4.0 vs. 2.0, P = 0.002). Meanwhile, the incidence of postoperative pneumonia in the proficiency phase was significantly lower than that in the learning phase (4.0% vs. 25.0%, P = 0.04)., Conclusions: RAME improved left RLN lymph node dissection. Surgeons with extensive VAME experience need at least 20 cases to achieve early proficiency in RAME., (© 2022. The Society for Surgery of the Alimentary Tract.)

Cervical cancer has a poor prognosis and is the fourth most common cancer among women. Dihydromyricetin (DHM), a flavonoid compound, exhibits several pharmacological activities, including anticancer effects; however, the effects of DHM on cervical cancer have received insufficient research attention. This study examined the antitumor activity and underlying mechanisms of DHM on human cervical cancer. Our results indicated that DHM inhibits migration and invasion in HeLa and SiHa cell lines. Mechanistically, RNA sequencing analysis revealed that DHM suppressed S100A4 mRNA expression in HeLa cells. Moreover, DHM inhibited the protein expressions of β-catenin and GSK3β through the regulated extracellular-signal-regulated kinase (ERK)1/2 signaling pathway. By using the ERK1/2 activator, T-BHQ, reverted β-catenin and S100A4 protein expression and cell migration, which were reduced in response to DHM. In conclusion, our study indicated that DHM inhibited cell migration by reducing the S100A4 expression through the ERK1/2/β-catenin pathway in human cervical cancer cell lines.

Objectives: The histological origin of base of the tongue (BOT) carcinomas is still elusive, and most studies have been focusing on the lingual tonsil. In this study, we sought to identify the existence of the squamous-columnar junction (SCJ) in the human Von Ebner's glandular duct and explored the potential of that in forming squamous cell carcinomas in BOT., Materials and Methods: The specific genomes of BOT carcinoma were acquired and screened out by The Cancer Genome Atlas (TCGA) database analysis. The 4-nitroquinoline-1-oxide (4-NQO)-treated mouse model was used to explore the transformation of SCJ during cancerization. We used immunohistochemistry to confirm the characteristics of SCJ in human Von Ebner's gland, which were further compared with those in the anus and cervix., Results: The SCJ in the human Von Ebner's glandular duct was found to be similar to that of the cervix and anus. The transformation zone in the 4-NQO-treated mouse model had a multilayered epithelium structure similar to that of HPV16-transgenic mice. In human, the transformation zone of Von Ebner's gland is also similar to that of the cervix and anus., Conclusion: It is the first time that the existence of SCJ in the opening of the human Von Ebner's glandular duct was confirmed. The SCJ of Von Ebner's glands may be a significant origin of squamous cell carcinomas in BOT., 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 Chen, Chen, Chen, Luo, Yan, Ruan, Li and Yu.)

The purpose of this research was to evaluate the impact and the underlying molecular mechanism of CLEFMA-induced cell death in human OSCC. The anti-tumour properties of CLEFMA in oral cancer were explored using colony formation, flow cytometry, human apoptosis array, Western blot, and immunohistochemistry assays. The in vivo anti-tumour effect of CLEFMA administered by oral gavage was evaluated using SCC-9-derived xenograft-bearing nude mouse models. CLEFMA significantly suppressed colony formation and elicited cellular apoptosis in oral cancer cells. CLEFMA treatment remarkably increased phosphorylated p38 and HO-1 along with cleavage of poly ADP-ribose polymerase and activation of caspase-8, -9, and -3 in HSC-3 and SCC-9 cells. Administration of HO-1 small interfering RNA significantly protected the cells from CLEFMA-induced caspase-3, -8, and -9 activation. Attenuation of p38 activity by the pharmacologic inhibitor SB203580 dramatically reduced CLEFMA-induced caspase-3, -8, and -9 activation and HO-1 expression in OSCC. The subcutaneous murine xenograft models showed that CLEFMA in vivo suppressed tumour growth in implanted SCC-9 cells. All of these findings indicated that CLEFMA induced apoptosis through the p38-dependent rise in HO-1 signal transduction cascades in OSCC.

Background: The aim of this study was to evaluate the survival benefits of adjuvant chemotherapy in patients with positive lymph nodes after esophagectomy for esophageal squamous cell carcinoma., Methods: Patients who underwent esophagectomy for esophageal cancer in the Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital) in Zhengzhou, China from 2013 to 2017 were selected for this retrospective cohort study. Patients with positive lymph nodes were grouped into the surgery alone group or the adjuvant chemotherapy group. Propensity score matching (1:1) was used to minimize baseline differences., Results: Among the 5118 patients who underwent esophagectomy, 792 patients were enrolled in the study. After matching, 253 (of 476) patients (adjuvant chemotherapy group) and 253 (of 316) patients (surgery alone group) were included. The median overall survival was significantly prolonged in the adjuvant chemotherapy group (54.0 months; 95% CI, 41.1-66.9 months) compared with the surgery alone group (28.0 months; 95% CI, 22.4-33.6 months) (P < .001). A significant difference was also observed in median disease-free survival between the 2 groups (adjuvant chemotherapy group, 33.0 months [95% CI, 20.8-45.2 months] compared with the surgery alone group, 22.0 months [95% CI, 17.0-27.0 months]; P = .007). In a multivariable analysis, receiving adjuvant chemotherapy (P < .001) was significantly associated with a reduced risk of death, and dissection of more than 6 lymph node stations (P = .05) was marginally associated with a reduced risk of death., Conclusions: Postoperative adjuvant chemotherapy improves the overall survival and disease-free survival of patients with resected esophageal squamous cell carcinoma with positive lymph nodes., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Melanoma is a highly aggressive, lethal, and malignant cancer. Once diagnosed early, it can be easily removed and cured with satisfaction. Although many methods such as surgery, chemotherapy, radiotherapy, and immunotherapy have been used to treat this disease at an advanced stage, the outcomes are poor. Terminalia catappa leaves have been shown to have various biological benefits, including antitumor activity. The specific effects and molecular mechanisms of Terminalia catappa leaf in treating A2058 and A375 melanoma cells in vitro need to be clarified. Methods: The A2058 and A375 melanoma cancer cells were treated with Terminalia catappa leaf extracts, and then the effect of Terminalia catappa leaf extracts on migration and invasion was examined. The cell migration/invasion capacities of A2058 and A375 cells were investigated by a modified Boyden chamber assay. Zymography was used to clarify the activities of matrix metalloproteinases-2 and urinary type plasminogen activator. We performed a Western blot to verify the related expression of phospho-Src (Tyr416), phospho-Focal adhesion kinase (Tyr397), Vimentin, and β-catenin. Results: Modified Boyden chamber assays demonstrated that treatment of Terminalia catappa leaf extracts significantly inhibited A2058 and A375 cell migration/invasion capacities. In the zymography results, we showed that Terminalia catappa leaf extracts negatively modulated the activities of matrix metalloproteinases-2 and urinary type plasminogen activator. Western blot indicated that Terminalia catappa leaf extracts reduced the expression of phospho-Src (Tyr416), phospho-Focal adhesion kinase (Tyr397), Vimentin, and β-catenin. Conclusion: Terminalia catappa leaf extracts affected the antimetastasis of the A2058 and A375 melanoma cell lines by inhibiting the Focal adhesion kinase/Src interaction and Wingless-int1/β-catenin pathways in vitro . Terminalia catappa leaf extracts may serve as an effective chemopreventive agent against metastasis of melanoma cancer., 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 Chang, Chu, Huang, Chen and Hsieh.)

Background and Objectives: End-stage renal disease (ESRD) is associated with increased anesthetic risks such as cardiovascular events resulting in higher perioperative mortality rates. This study investigated the perioperative and postoperative outcomes in ESRD patients receiving propofol target-controlled infusion with brachial plexus block during arteriovenous (AV) access surgery. Materials and Methods: We recruited fifty consecutive patients scheduled to receive AV access surgery. While all patients received general anesthesia combined with ultrasound-guided brachial plexus block, the patients were randomly assigned to one of two general anesthesia maintenance groups, with 23 receiving propofol target-controlled infusion (TCI) and 24 receiving sevoflurane inhalation. We measured perioperative mean arterial pressure (MAP), heart rate, and cardiac output and recorded postoperative pain status and adverse events in both groups. Results: ESRD patients receiving propofol TCI had significantly less reduction in blood pressure than those receiving sevoflurane inhalation (p < 0.05) during AV access surgery. Perioperative cardiac output and heart rate were similar in both groups. Both groups reported relatively low postoperative pain score and a low incidence of adverse events. Conclusions: Propofol TCI with brachial plexus block can be used as an effective anesthesia regimen for ESRD patients receiving AV access surgery. It can be used with less blood pressure fluctuation than inhalational anesthesia.

The free generalized endoscopic screening for diagnosis of early esophageal cancer and precancerous lesion could not be satisfactorily implemented in China. At present, the decision to accept endoscopic screening at their own expense may largely depend on the public awareness. This study was aimed to investigate the awareness and other influencing factors associated with the accompanying children of esophageal cancer patients after their hospitalization. In this cross-sectional study, from April to June 2016, 233 children of accompanying patients, who were admitted within the last 1 year due to esophageal cancer in three affiliated hospitals of Zhengzhou University and Anyang Tumor Hospital, were enrolled. In addition, telephone surveys were conducted to investigate their awareness about endoscopic screening. One child was corresponded to an esophageal cancer patient. About half (47.6%, 111/233) of the children were unaware that endoscopic screening could detect early esophageal cancer and precancerous lesion. There was no significant difference in their awareness rates between hospitals with different administration levels. Besides, the males who had a lower family income and lower education level showed a poor awareness rate (P < 0.05). The overall awareness rate among the accompanying children of patients on endoscopic screening was rather low in Henan province (China). Hence, the health education and awareness on the importance of endoscopic screening for early detection of esophageal cancer should be promoted among children accompanying the patients. More attention should be focused towards the subject group, particularly among those male children with lower educational level and family income., (© 2020. American Association for Cancer Education.)

Pulmonary fibrosis is a scarring disease of lung tissue, which seriously threatens human health. Treatment options are currently limited, and effective strategies are still lacking. In the present study, 25 compounds were isolated from the deep-sea fungus Trichoderma sp. MCCC 3A01244. Among them, two β-carboline alkaloids, trichocarbolines A ( 1 ) and C ( 4 ) are new compounds. The chemical structures of these compounds were elucidated based on their HRESIMS, 1D and 2D NMR spectra, optical rotation calculation, and comparisons with data reported in the literature. Trichocarboline B [(+)- and (-)-enantiomers] had previously been synthesized, and this is its first report as a natural product. Their anti-pulmonary fibrosis (PF) activity and cytotoxicity were investigated. Compounds 1 , 11 , and 13 strongly inhibited TGF-β1-induced total collagen accumulation and showed low cytotoxicity against the HFL1 cell line. Further studies revealed compound 1 inhibited extracellular matrix (ECM) deposition by downregulating the expression of protein fibronectin (FN), proliferating cell nuclear antigen (PCNA), and α-smooth muscle actin (α-SMA). Mechanistic study revealed that compound 1 decreased pulmonary fibrosis by inhibiting the TGF-β/Smad signaling pathway. As a newly identified β-carboline alkaloid, compound 1 may be used as a lead compound for developing more efficient anti-pulmonary fibrosis agents., 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 Hao, Chen, Li, Wu, Zhang, Shao, Liu, Ma, Xu, Mahmud and Lan.)

Objective: It has been reported that antroquinonol extracted from Golden- Antrodia camphorate exerts protective effects on liver function both in vitro and in vivo . However, the protective effects of Golden- Antrodia camphorata on liver function have not been fully investigated in human clinical studies. Therefore, the present study aimed to evaluate the beneficial effects of Golden- Antrodia camphorata on hepatic function after alcohol consumption in human subjects. Methods: A total of 80 participants with increased γ-glutamyl transferase levels (60-180 U/L) were enrolled in the current study and were randomly divided into two groups. Participants in the first group were orally administrated with 300 mg/day Golden- Antrodia camphorata (tablets), while those in the second group received placebo tablets for 12 weeks. Biochemical routine blood tests were performed at 6 and 12 weeks following the first administration. Results: At 12 weeks post the first Golden- Antrodia camphorata administration, the serum levels of aspartate aminotransferase (AST; p < 0.0001), alanine aminotransferase (ALT; p = 0.0002) and triglyceride ( p = 0.0158) were notably declined in the Golden- Antrodia camphorata treatment group compared with the placebo group. No clinically significant differences were observed between the Golden- Antrodia camphorata treatment and placebo groups in terms of general safety parameters. Conclusion: A statistically significant difference was obtained in the serum levels of AST, ALT and triglycerides between the Golden- Antrodia camphorata and placebo groups. However, no clinical significance was observed in any of the safety parameters examined. Overall, these findings indicated that treatment with Golden- Antrodia camphorata exerted protective effects on liver function., Competing Interests: Authors TS, HC, W-CW, S-SL, Y-LT, P-NC were employed by the company Golden Biotechnology Corporation. The remaining 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 Yen, Park, Kang, Su, Cheng, Wen, Lin, Tai, Chen and Tsai.)

Cancer metastasis is the major cause of the high mortality risk of patients with osteosarcoma. Cinnamaldehyde has been shown to exhibit multiple tumour-suppressing activities, but its role in human osteosarcoma is not yet completely defined. In this study, the antimetastatic effect of cinnamaldehyde on highly metastatic human osteosarcoma cells was observed in vitro and in vivo using Saos-2 and 143B cells. Cinnamaldehyde reduced the activity and protein level of urokinase-type plasminogen activator (u-PA) and suppressed the invasion ability of osteosarcoma cells by inhibiting the phosphorylation of focal adhesion kinase. In addition, cinnamaldehyde reduced cell movement, cell-matrix adhesion, and the expression of the mesenchymal markers of epithelial-to-mesenchymal transition, namely, fibronectin and N -cadherin. Importantly, the oral administration of cinnamaldehyde remarkably suppressed the pulmonary metastasis of osteosarcoma in mice. Results indicated that cinnamaldehyde has therapeutic potential for inhibiting osteosarcoma metastasis.

Cinnamomum cassia possesses antioxidative activity and induces the apoptotic properties of various cancer types. However, its effect on osteosarcoma invasion and cancer stemness remains ambiguous. Here, we examined the molecular evidence of the anti-invasive effects of ethanoic C. cassia extracts (CCE). Invasion and migration were obviously suppressed after the expression of urokinase-type plasminogen activator and matrix metalloprotein 2 in human osteosarcoma 143B cells were downregulated. CCE reversed epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor β1 and downregulated mesenchymal markers, such as snail-1 and RhoA. CCE suppressed self-renewal property and the expression of stemness genes (aldehyde dehydrogenase, Nanog, and CD44) in the 143B cells. CCE suppressed cell viability, reduced the colony formation of osteosarcoma cancer cells, and induced apoptotic cell death in the 143B cells, as indicated by caspase-9 activation. The xenograft tumor model of immunodeficient BALB/c nude mice showed that CCE administered in vivo through oral gavage inhibited the growth of implanted 143B cells. These findings indicated that CCE inhibited the invasion, migration, and cancer stemness of the 143B cells. CCE reduced proliferation of 143B cell possibly because of the activation of caspase-9 and the consequent apoptosis, suggesting that CCE is a potential anticancer supplement for osteosarcoma., (© 2022 Wiley Periodicals LLC.)

Background: Recent studies on acute mountain sickness (AMS) have used fixed-location and fixed-time measurements of environmental and physiological variable to determine the influence of AMS-associated factors in the human body. This study aims to measure, in real time, environmental conditions and physiological variables of participants in high-altitude regions to develop an AMS risk evaluation model to forecast prospective development of AMS so its onset can be prevented., Results: Thirty-two participants were recruited, namely 25 men and 7 women, and they hiked from Cuifeng Mountain Forest Park parking lot (altitude: 2300 m) to Wuling (altitude: 3275 m). Regression and classification machine learning analyses were performed on physiological and environmental data, and Lake Louise Acute Mountain Sickness Scores (LLS) to establish an algorithm for AMS risk analysis. The individual R 2 coefficients of determination between the LLS and the measured altitude, ambient temperature, atmospheric pressure, relative humidity, climbing speed, heart rate, blood oxygen saturation (SpO 2 ), heart rate variability (HRV), were 0.1, 0.23, 0, 0.24, 0, 0.24, 0.27, and 0.35 respectively; incorporating all aforementioned variables, the R 2 coefficient is 0.62. The bagged trees classifier achieved favorable classification results, yielding a model sensitivity, specificity, accuracy, and area under receiver operating characteristic curve of 0.999, 0.994, 0.998, and 1, respectively., Conclusion: The experiment results indicate the use of machine learning multivariate analysis have higher AMS prediction accuracies than analyses utilizing single varieties. The developed AMS evaluation model can serve as a reference for the future development of wearable devices capable of providing timely warnings of AMS risks to hikers., (© 2022. The Author(s).)

Background: Lumbar disc herniation (LDH) is a common and frequently occurring disease in clinics. Low back pain and sciatica are the presenting symptoms of LDH. To some extent, it can be considered that measures with the capability to improve low back pain or sciatica have the potential to treat LDH. Ma's bamboo-based medicinal moxibustion therapy can effectively reduce the degree of low back pain and has been widely used. Studies of small sample size have seen significant improvement on pain relief. The aim of this trial is to evaluate the clinical efficacy and safety of Ma's bamboo-based medicinal moxibustion therapy in the treatment of LDH low back pain., Methods/design: The trial is a multicenter, randomized, parallel-group, non-inferiority study. Three hundred and twelve patients will be randomly assigned to a Ma's bamboo-based medicinal moxibustion group (n=156) and an acupuncture group (n=156). Patients in each group will receive treatment every day, 6 times a week, 12 times in total. Follow-up will be conducted 14 days after treatment. The primary outcome will be the visual analog scale(VAS) at baseline, after 6 times of treatment, end of treatment, and follow-up. The secondary outcomes will include Oswestry disability indexes (ODI), modified Japanese Orthopaedic Association low back pain (M-JOA) score, serum β-endorphin (β-EP), and serum substance P (SP). β-EP and SP, as well as safety evaluation indexes (routine blood, liver, and kidney function and electrocardiogram), will be measure at baseline and after the end of treatment. The number, nature, and severity of adverse events will be recorded., Discussion: The results of the trial will compare the efficacy of low back pain in LDH between Ma's bamboo-based medicinal moxibustion group and the acupuncture group and will be expected to make a systematic and objective evaluation of the clinical efficacy and safety of Ma's bamboo-based medicinal moxibustion therapy., Trial Registration: ChiCTR2000038725 . Registered on 29 September 2020., (© 2022. The Author(s).)

While genetic alterations in several regulators of the cell cycle have a significant impact on the gastric carcinogenesis process, the prognostic role of them remains to be further elucidated. The TCGA-STAD training set were downloaded and the mRNA expression matrix of cell cycle genes was extracted and corrected for further analysis after taking the intersection with GSE84437 dataset. Differentially expressed mRNAs were identified between tumor and normal tissue samples in TCGA-STAD. Univariate Cox regression analysis and lasso Cox regression model established a novel seven-gene cell cycle signature (including GADD45B, TFDP1, CDC6, CDC25A, CDC7, SMC1A and MCM3) for GC prognosis prediction. Patients in the high-risk group shown significantly poorer survival than patients in the low-risk group. The signature was found to be an independent prognostic factor for GC survival. Nomogram including the signature shown some clinical net benefit for overall survival prediction. The signature was further validated in the GSE84437 dataset. In tissue microarray, CDC6 and MCM3 protein expression were significant differences by the immunohistochemistry-based H-score between tumor tissues and adjacent tissues, and CDC6 is an independent prognostic factor for GC. Interestingly, our GSEA revealed that low-risk patients were more related to cell cycle pathways and might benefit more from therapies targeting cell cycle. Our study identified a novel robust seven-gene cell cycle signature for GC prognosis prediction that may serve as a beneficial complement to clinicopathological staging. The signature might provide potential biomarkers for the application of cell cycle regulators to therapies and treatment response prediction.

Aims: Angelol-A (Ang-A), a kind of coumarins, is isolated from the roots of Angelica pubescens f. biserrata. However, AA exerts antitumor effects and molecular mechanism on cervical cancer cells is unknown., Main Methods: Cell viability was determined using the MTT assay, and the cell cycle phase was assessed by PI staining with flow cytometry. Ang-A-treated cells with/without Antago-miR-29a-3p (miR-29a-3p inhibitor) or U0126 (MEK inhibitor) were assessed for the expression of miR-29a-3p, in vitro migration/invasion, and angiogenesis using qRT-PCR, a chemotaxis assay, and tube formation assay, respectively. The expression of mitogen-activated protein kinases/MMP2/MMP9/VEGFA was determined by western blot analysis with applicable antibodies., Key Findings: Ang-A significantly inhibited MMP2 and VEGFA expression, cell migration, and invasive motility in human cervical cancer cells. Conditioned medium inhibited tube formation in HUVECs. Ang-A principally inhibited invasive motility and angiogenesis by upregulating the expression of miR-29a-3p that targets the VEGFA-3' UTR. The role of miR-29a-3p was confirmed using Antago-miR-29a-3p, which reversed the Ang-A-inhibited expression of MMP2 and VEGFA, invasive motility, and angiogenesis in human cervical cancer cells. The ERK pathway was implicated in mediating the metastatic and angiogenic action of Ang-A. Combined treatment with Ang-A treated and U0126 exerted a synergistic inhibitory effect on the expression of MMP2 and VEGFA and the metastatic and angiogenic properties of human cervical cancer cells., Significance: These findings are the first to indicate that in human cervical cancer cells, Ang-A exerts anti-metastatic and anti-angiogenic effects via targeting the miR-29a-3p/MMP2/VEGFA axis, mediated through the ERK pathway., (Copyright © 2022. Published by Elsevier Inc.)

Southern River Terrapin, Batagur affinis , is a freshwater turtle listed as critically endangered on the IUCN Red List since 2000. Many studies suggest that faecal DNA metabarcoding can shield light on the host-associated microbial communities that play important roles in host health. Thus, this study aimed to characterise and compare the faecal bacterial community between captive and wild B. affinis using metabarcoding approaches. A total of seven faeces samples were collected from captive ( N = 5) and wild ( N = 2) adult B. affinis aseptically, crossing the East and West coast of peninsular Malaysia. The DNA was extracted from the faeces samples, and the 16S rRNA gene (V3-V4 region) was amplified using polymerase chain reaction (PCR). The amplicon was further analysed using SILVA and DADA2 pipelines. In total, 297 bacterial communities taxonomic profile (phylum to genus) were determined. Three phyla were found in high abundance in all faeces samples, namely Firmicutes (38.69%), Bacteroidetes (24.52%), and Fusobacteria (6.95%). Proteobacteria were detected in all faeces samples (39.63%), except the wild sample, KBW3. Under genus level, Cetobacterium was found as the most abundant genus (67.79%), followed by Bacteroides (24.56%) and Parabacteroides (21.78%). The uncultured genus had the highest abundance (88.51%) even though not detected in the BK31 and KBW2 samples. The potential probiotic genera (75.00%) were discovered to be more dominant in B. affinis faeces samples. Results demonstrated that the captive B. affinis faeces samples have a greater bacterial variety and richness than wild B. affinis faeces samples. This study has established a starting point for future investigation of the gut microbiota of B. affinis ., Competing Interests: The authors declare there are no competing interests., (©2022 Mohd Salleh et al.)

Background: Comorbidities and stages may influence the prognosis of melanoma patients in Taiwan and need to be determined., Methods: We performed a retrospective cohort study by using the national health insurance research database in Taiwan. Patients with a primary diagnosis of melanoma by the Taiwan Cancer Registry from 2009 to 2017 were recruited as the study population. The comparison group was never diagnosed with melanoma from 2000 to 2018. The Charlson comorbidity index was conducted to calculate the subjects' disease severity. The Cox proportional hazards model analysis was used to estimate the hazard ratio of death., Results: We selected 476 patients, 55.5% of whom had comorbidity. A higher prevalence of comorbidity was associated with a more advanced cancer stage. The mortality rate increased with an increasing level of comorbidity in both cohorts and was higher among melanoma patients. The interaction between melanoma and comorbidity resulted in an increased mortality rate., Conclusion: An association between poorer survival and comorbidity was verified in this study. We found that the level of comorbidity was strongly associated with mortality. A higher risk of mortality was found in patients who had localized tumors, regional metastases, or distant metastases with more comorbidity scores. Advanced stage of melanoma patients with more comorbidities was significantly associated with the higher risk of mortality rate., 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 Chang, Hsieh, Chen, Chu, Huang, Wang and Wei.)

Arctiin, a lignan glycoside, is isolated from Arctium lappa L. The anticancer effects of arctiin have been demonstrated in several studies. However, no research has been conducted on the anti-migration effect of arctiin in cervical cancer cells. The present study examined the effects of arctiin on cervical cancer cells and investigated the possible molecular mechanism. We demonstrated that arctiin exhibited low cytotoxicity and significantly inhibited cell migration and invasion in human cervical cancer cells. The S100A4 protein expression and mRNA levels were significantly reduced in HeLa and SiHa cells with arctiin treatment. Furthermore, silencing S100A4 by using small interfering RNA reduced cell migration, while overexpression of S100A4 mitigated the migration inhibition imposed by arctiin in cervical cancer cells. Western blotting revealed that arctiin significantly reduced phosphoinositide 3-kinase (PI3K) and phosphorylation of Akt in cervical cancer cells. Moreover, selective Akt induction by an Akt activator, SC-79, reverted cervical cancer cell migration and S100A4 protein expression, which were reduced in response to arctiin. Taken together, these results suggest that arctiin inhibits cervical cancer cell migration and invasion through suppression of S100A4 and the PI3K/Akt pathway.

The aim of the study was to determine the risk of distant metastases in patients with gynecologic cancers after surgery, including cervical, uterine and ovarian cancers. This is a retrospective study evaluating gynecologic cancer from 2009 to 2014 using population-based administrative datasets from the Health and Welfare Data Science Center (HWDC) and from The National Health Informatics Project (NHIP). A total of 1,464 gynecologic cancer patients, including 321 cervical cancer patients, 724 uterine cancer patients and 419 ovarian cancer patients, were analyzed retrospectively from 2009 to 2014. Among the cervical cancer patients, 173 (53.89%) received surgery only and 148 (46.11%) received surgery with radiotherapy /chemotherapy. Among the uterus cancer patients, 425(58.70%) received surgery only and 299 (41.3%) received surgery with radiotherapy /chemotherapy. Among the ovarian cancer patients, 81 (19.33%) received surgery only and 338 (80.67%) received surgery with radiotherapy/chemotherapy. Among patients with brain, liver or lung metastasis, cervical cancer patients have more cumulative metastasis-free survival than those ovarian cancer (p=0.0041). In analyzing liver metastasis based on primary cancer sites, cervical cancer patients and uterine cancer cases have more cumulative metastasis- free survival than those ovarian cancer (p<0.0001). In conclusion, ovarian cancer patients have higher risk of liver metastasis than cervical or uterine cancer. There were significantly different of pathological stage for cumulative metastasis-free survival among gynecologic cancer patients with brain or liver or lung metastasis. Pathological T stage remains the main predictive for distant metastasis of gynecologic cancer.

Proliferative vitreoretinopathy (PVR) involves retinal pigment epithelium (RPE) cell proliferation and migration and leads to tractional retinal detachment. Demethoxycurcumin (DMC), a curcuminoid, has anti-inflammatory and anti-tumour properties. However, whether DMC affects the migration of RPE cells and the molecular mechanism of human PVR remains unclear. The aim of the current study was to investigate the effects of DMC on the inhibition of migration and proteinase expression of human ARPE-19 cells. Herein, we provided molecular evidence associated with PVR prevention through DMC by inhibiting ARPE-19 cell migration. We performed gelatin zymography, Western blot and RT-PCR and respectively found that DMC is sufficient to reduce matrix metalloproteinase-2 (MMP-2) activity, protein level and mRNA expression. DMC suppressed the nuclear levels of transcriptional factors specificity protein 1 and c-Fos, which are involved in the modulation of the transcriptional activation of the MMP-2 gene. DMC also inhibited STAT-3 phosphorylation in ARPE-19 cells. Selective STAT-3 induction by a STAT-3 activator, colivelin, reverted MMP activity and protein expression and cell migration, which were reduced in response to DMC. The results proved the inhibitory effect of DMC on RPE cell migration and MMP-2 expression by the down-regulation of the STAT-3 signalling pathway., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Glioblastoma multiforme (GBM) is one of the most aggressive and common types of brain tumor. Due to its high proliferation ability, a high lethality rate has been observed with this malignant glial tumor. Terminalia catappa L. ( T . catappa ) is currently known to have anti-inflammatory and anti-carcinogenesis effects. However, few studies have examined the mechanisms of the leaf extracts of T . catappa (TCE) on GBM cells. In the current study, we demonstrated that TCE can significantly inhibit the migration and invasion capabilities of GBM cell lines without showing biotoxic effects. Matrix metalloproteinases-2 (MMP-2) activity and protein expression were attenuated by reducing the p38 phosphorylation involved in the mitogen-activated protein kinase (MAPK) pathway. By treating with TCE and/or p38 inhibitor (SB203580), we confirmed that p38 MAPK is involved in the inhibition of cell migration. In conclusion, our results demonstrated that TCE inhibits human GBM cell migration and MMP-2 expression by regulating the p38 pathway. These results reveal that TCE contains potent therapeutic compounds which could be applied for treating GBM brain tumors.

Shikonin mitigated tumor cell proliferation by elevating reactive oxygen species (ROS) levels. Herein, we investigated the effects of shikonin on renal cancer cell (RCC) cell proliferation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that shikonin dose-dependently reduced the proliferation of Caki-1 and ACHN cells. Shikonin remarkably triggered necrosis and apoptosis in Caki-1 and ACHN cells in proportion to its concentration. Moreover, necrostatin-1 recovered cell viability in the presence of shikonin. Elevated ROS levels and mitochondrial dysfunction were also found in shikonin treatment groups. Pretreatment with N-acetyl cysteine remarkably mitigated shikonin-induced cell death and ROS generation. Western blot analysis revealed that shikonin reduced pro-PARP, pro-caspase-3, and Bcl-2 expression and increased cleavage PARP expression. Enhanced autophagy was also found in the shikonin-treated group as evidenced by acridine orange staining. Moreover, light chain 3B (LC3B)-II accumulation and enhanced p62 expression indicated that autophagy occurred in the shikonin-treated group. LC3B knockdown considerably recovered cell viability in the presence of shikonin. Shikonin treatment elevated p38 activity in a dose-dependent manner. In conclusion, our results revealed that shikonin triggered programmed cell death via the elevation of ROS level and p38 activity in different types of RCC cells. These findings suggested that shikonin may be a potential anti-RCC agent.

Background: Doctors can detect symptoms of diabetic retinopathy (DR) early by using retinal ophthalmoscopy, and they can improve diagnostic efficiency with the assistance of deep learning to select treatments and support personnel workflow. Conventionally, most deep learning methods for DR diagnosis categorize retinal ophthalmoscopy images into training and validation data sets according to the 80/20 rule, and they use the synthetic minority oversampling technique (SMOTE) in data processing (e.g., rotating, scaling, and translating training images) to increase the number of training samples. Oversampling training may lead to overfitting of the training model. Therefore, untrained or unverified images can yield erroneous predictions. Although the accuracy of prediction results is 90%-99%, this overfitting of training data may distort training module variables., Results: This study uses a 2-stage training method to solve the overfitting problem. In the training phase, to build the model, the Learning module 1 used to identify the DR and no-DR. The Learning module 2 on SMOTE synthetic datasets to identify the mild-NPDR, moderate NPDR, severe NPDR and proliferative DR classification. These two modules also used early stopping and data dividing methods to reduce overfitting by oversampling. In the test phase, we use the DIARETDB0, DIARETDB1, eOphtha, MESSIDOR, and DRIVE datasets to evaluate the performance of the training network. The prediction accuracy achieved to 85.38%, 84.27%, 85.75%, 86.73%, and 92.5%., Conclusions: Based on the experiment, a general deep learning model for detecting DR was developed, and it could be used with all DR databases. We provided a simple method of addressing the imbalance of DR databases, and this method can be used with other medical images., (© 2021. The Author(s).)