bluuebunny/crossref_metadata_2025 huggingface dataset:
Ameliorative Potential of Hot Compress on Sciatic Nerve Pain in Chronic Constriction Injury-Induced Rat Model
Authors: Chan Kwan-Yu , Tsai Wen-Ching , Chiang Chien-Yi , Sheu Meei-Ling , Huang Chih-Yang , Tsai Yi-Ching , Tsai Chia-Yun , Lu Chia-Jung , Ho Zih-Ping , Lai De-Wei
Published: May 2022

Hot compress modalities are used to ameliorate pain despite prevalent confusion about which modality should be used and when. Most recommendations for hot compresses are based on empirical experience, with limited evidence to support its efficacy. To obtain insight into the nerve transmission mechanism of hot compresses and to identify the nerve injury marker proteins specifically associated with sciatic nerve pain, we established a rat model of chronic constriction injury (CCI) and performed mechanical allodynia, electrophysiology, and histopathological analysis. All CCI rats exhibited geometric representation of the affected hind paw, which indicated a hyper-impact on both mechanical gait and asymmetry of gait on day 28. The CCI model after 28 days of surgery significantly reduced compound muscle action potential (CMAP) amplitude, but also significantly reduced latency. Administration of hot compress for 3 weeks (heated at 40–42°C, cycle of 40 min, and rest for 20 min, three cycles each time, three times per week) significantly increased the paw withdrawal thresholds in response to stimulation by Von Frey fibers and reversed the CCI-induced reduced sciatic functional index (SFI) scores. Hot compress treatment in the CCI model improved CMAP amplitude and latency. The S100 protein expression level in the CCI+Hot compression group was 1.5-fold higher than in the CCI group; it dramatically reduced inflammation, such as tumor necrosis factor alpha and CD68 expression in nerve injury sites. Synaptophysin (Syn) expression in the CCI+Hot compression group was less than threefold in the CCI group at both nerve injury sites and brain (somatosensory cortex and hippocampus). This finding indicates that local nerve damage and inflammation cause significant alterations in the sensorimotor strip, and hot compress treatment could significantly ameliorate sciatic nerve pain by attenuating Syn and inflammatory factors from local pathological nerves to the brain. This study determines the potential efficacy and safety of hot compress, and may have important implications for its widespread use in sciatic nerve pain treatment.
Ultrasound-Assisted Extraction of Natural Pigments From Food Processing By-Products: A Review
Authors: Linares Guillermo , Rojas Meliza Lindsay
Published: May 2022

Ultrasound is an emerging technology, which has been highly explored in the food area to improve processes and products. When ultrasound is applied to a product with solid or fluid characteristics, the passage of acoustic waves and acoustic cavitation generates different mechanisms responsible for modifications in the original matrix of the sample. These effects of ultrasound can also be used to take advantage of by-products, for example by extracting compounds of interest, including natural pigments. Natural pigments or colorants are being highly demanded by different industries not only for color purposes but also due to their healthy properties, the greater demands in regulations and new consumer preferences. This review presents an updated critical analysis of the application of ultrasound-assisted extraction (UAE) to obtain natural pigments from food processing by-products. Initially, the ultrasound effects and mechanisms that improve the extraction of natural pigments in a fluid medium, as well as the factors that influence the extraction and the energy consumption of UAE are analyzed and described. Subsequently, the UAE application to obtain pigments belonging to the groups of carotenoids, chlorophyll, anthocyanins and betalains is evaluated. These sections detail the processing conditions, positive and negative effects, as well as possible applications of the extracted pigments. This review presents relevant information that may be useful to expand and explore new applications of ultrasound technology as well as promote the revaluation of by-products to obtain pigments that can be used in food, pharmaceutical or cosmetic industries.
Acute Kidney Injury in Adult Patients With Hepatocellular Carcinoma After TACE or Hepatectomy Treatment
Authors: Mou Zhixiang , Guan Tianjun , Chen Lan
Published: May 2022

Background

Acute kidney injury (AKI) is one of the most common complications in patients with cancer, yet the specific reasons, mechanisms, and the influence of AKI are not clear in hepatocellular carcinoma (HCC) after treatment. This meta-analysis aimed to find out the risk factors and the impact on mortality of AKI in adult patients with HCC after treatment using available published data.

Methods

We performed a systemic literature search using PubMed, Web of Science, and Embase, encompassing publications up until November 30, 2021 (inclusive), with 17 cohort studies involving 11,865 patients that fulfilled the prespecified criteria for inclusion in the meta-analysis. The number of AKI/non-AKI patients identified by risk factors, the number of AKI/non-AKI-related deaths, the incidence rates, the mortality rates, and the irreversible rates of AKI were derived and analyzed using STATA.

Results

Age, diabetes mellitus (DM), and the number of transarterial chemoembolization (TACE) sessions are risk factors for AKI in patients with HCC after TACE. On the other hand, male gender, age, DM, major resection of the liver, and operation-related transfusion are risk factors for AKI in patients with HCC after hepatectomy. The risk of mortality in those with renal failure due to AKI was up to 4.74 times higher than in those without AKI in a short-term observation period after TACE treatment.

Conclusions

Attention should be paid to the risk of AKI in HCC patients with DM. The occurrence of AKI during TACE treatment is especially dangerous and should be considered a strong red flag, obviously with regard to the extremely high risk of death in a short period. Furthermore, studies are needed to detect more associations of AKI in patients with HCC.
From Therapy Resistance to Targeted Therapies in Prostate Cancer
Authors: Moreira-Silva Filipa , Henrique Rui , Jerónimo Carmen
Published: May 2022

Prostate cancer (PCa) is the second most common malignancy among men worldwide. Although early-stage disease is curable, advanced stage PCa is mostly incurable and eventually becomes resistant to standard therapeutic options. Different genetic and epigenetic alterations are associated with the development of therapy resistant PCa, with specific players being particularly involved in this process. Therefore, identification and targeting of these molecules with selective inhibitors might result in anti-tumoral effects. Herein, we describe the mechanisms underlying therapy resistance in PCa, focusing on the most relevant molecules, aiming to enlighten the current state of targeted therapies in PCa. We suggest that selective drug targeting, either alone or in combination with standard treatment options, might improve therapeutic sensitivity of resistant PCa. Moreover, an individualized analysis of tumor biology in each PCa patient might improve treatment selection and therapeutic response, enabling better disease management.
Childhood Acute B-Lineage Lymphoblastic Leukemia With CDKN2A/B Deletion Is a Distinct Entity With Adverse Genetic Features and Poor Clinical Outcomes
Authors: Feng Jing , Guo Ye , Yang Wenyu , Zou Yao , Zhang Li , Chen Yumei , Zhang Yingchi , Zhu Xiaofan , Chen Xiaojuan
Published: May 2022

To further emphasize the clinical–genetic features and prognosis of CDKN2A/B deletions in childhood acute lymphoblastic leukemia (ALL), we retrospectively analyzed 819 consecutive B-ALL patients treated with the Chinese Children’s Cancer Group ALL-2015 (CCCG-ALL-2015) protocol, and fluorescence in situ hybridization (FISH) analysis on CDKN2A/B deletion was available for 599 patients. The prevalence of CDKN2A/B gene deletions was 20.2% (121/599) of B-ALL. CDKN2A/B deletions were significantly associated with older age, higher leukocyte counts, a higher percentage of hepatosplenomegaly, and a higher frequency of BCR-ABL (p < 0.05). Those patients achieved similar minimal residual disease (MRD) clearance and complete remission compared to patients without CDKN2A/B deletion. The CDKN2A/B deletions were correlated with inferior outcomes, including a 3-year event-free survival (EFS) rate (69.8 ± 4.6 vs. 89.2 ± 1.6%, p = 0.000) and a 3-year overall survival (OS) rate (89.4% ± 2.9% vs. 94.7% ± 1.1%, p = 0.037). In multivariable analysis, CDKN2A/B deletion was still an independent prognostic factor for EFS in total cohorts (p < 0.05). We also detected a multiplicative interaction between CDKN2A/B deletions and TP53 deletion on dismal prognosis (p-interaction < 0.05). In conclusion, CDKN2A/B deletion is associated with distinct characteristics and serves as a poor prognostic factor in pediatric ALL, especially in TP53 deletion carriers.
Overall Survival Signature of 5-Methylcytosine Regulators Related Long Non-Coding RNA in Hepatocellular Carcinoma
Authors: Pan Qi , Yi Caiyu , Zhang Yijie
Published: May 2022

Purpose

Studies reported that 5-methylcytosine (m5C) RNA transferase alters tumor progression; however, studies of m5C-related lncRNA remain lacking. This article intends to study the lncRNA modified by m5C RNA transferase in hepatocellular carcinoma using a combination of computational biology and basic experiments.

Method

We identified 13 m5C RNA transferase-related genes and selected long non-coding RNAs with a Pearson correlation coefficient greater than 0.4. Univariate Cox regression analysis was used to screen m5C RNA transferase lncRNA related to survival phenotype. We divided TCGA-LIHC into two types of m5C RNA using non-negative matrix decomposition. According to WGCNA, the co-expression models of two lncRNA regulation modes were constructed to analyze the characteristic biological processes of the two m5C RNA transferase-related lncRNA gene models. Then, a predictive model of m5C RNA transferase lncRNA was using LASSO regression. Finally, we used cell experiments, transwell experiments, and clone formation experiments to test the relationship between SNHG4 and tumor cell proliferation in Hep-G2 and Hep-3b cells line.

Results

We identified 436 m5C RNA transferase-related lncRNAs. Using univariate Cox regression analysis, 43 prognostic-related lncRNAs were determined according to P < 0.001. We divided TCGA-LIHC into two regulation modes of m5C RNA transferase using non-negative matrix factorization. The two regulation modes showed significant differences in overall and disease-free survival. We used LASSO to construct m5c-related lncRNA prognostic signature. Thus, a predictive m5C-lncRNA model was established using four lncRNAs: AC026412.3, AC010969.2, SNHG4, and AP003392.5. The score calculated by the m5C-lncRNA model significantly correlated with the overall survival of hepatocellular carcinoma. The receiver operating characteristic curve and decision curve analysis verified the accuracy of the predictive model. We observed a more robust immune response in the high-risk score group. The transwell experiments and clone formation experiments suggested that m5C RNA transferase-related lncRNA SNHG4 promotes the proliferation and migration of Hep-G2 and Hep-3b cells line.

Conclusion

Two lncRNA expression patterns regulated by m5C RNA transferase were identified. The difference between the two expression patterns and the survival phenotype in the biological process was pointed out. A 5-methylcytosine RNA methyltransferases-related lncRNA overall survival signature was constructed. These results provide some understanding of the influence of m5C transferase on hepatocellular carcinoma. The prediction model of m5C transferase lncRNA has potential clinical value in managing hepatocellular carcinoma.
The Roles of FHL3 in Cancer
Authors: Huang Zhenjun , Yu Chengpeng , Yu Liqing , Shu Hongxin , Zhu Xianhua
Published: May 2022

The four and a half LIM domain protein 3, also named the LIM-protein FHL3, belongs to the LIM-only family. Based on the special structure of LIM-only proteins, FHL3 can perform significant functions in muscle proliferation and cardiovascular diseases by regulating cell growth and signal transduction. In recent years, there has been increasing evidence of a relation between FHLs and tumor biology, since FHL3 is often overexpressed or downregulated in different cancers. On the one hand, FHL3 can function as a tumor suppressor and influence the expression of downstream genes. On the other hand, FHL3 can also play a role as an oncoprotein in some cancers to promote tumor progression via phosphorylation. Thus, FHL3 is proposed to have a dual effect on cancer progression, reflecting its complex roles in cancer. This review focuses on the roles of FHL3 in cancer progression and discusses the interaction of FHL3 with other proteins and transcription factors. Finally, the clinical significance of FHL3 for the treatment of cancers is discussed.
A Deep Learning System to Predict the Histopathological Results From Urine Cytopathological Images
Authors: Liu Yixiao , Jin Shen , Shen Qi , Chang Lufan , Fang Shancheng , Fan Yu , Peng Hao , Yu Wei
Published: May 2022

Background

Although deep learning systems (DLSs) have been developed to diagnose urine cytology, more evidence is required to prove if such systems can predict histopathology results as well.

Methods

We retrospectively retrieved urine cytology slides and matched histological results. High-power field panel images were annotated by a certified urological pathologist. A deep learning system was designed with a ResNet101 Faster R-CNN (faster region-based convolutional neural network). It was firstly built to spot cancer cells. Then, it was directly used to predict the likelihood of the presence of tissue malignancy.

Results

We retrieved 441 positive cases and 395 negative cases. The development involved 387 positive cases, accounting for 2,668 labeled cells, to train the DLS to spot cancer cells. The DLS was then used to predict corresponding histopathology results. In an internal test set of 85 cases, the area under the curve (AUC) was 0.90 (95%CI 0.84–0.96), and the kappa score was 0.68 (95%CI 0.52–0.84), indicating substantial agreement. The F1 score was 0.56, sensitivity was 71% (95%CI 52%–85%), and specificity was 94% (95%CI 84%–98%). In an extra test set of 333 cases, the DLS achieved 0.25 false-positive cells per image. The AUC was 0.93 (95%CI 0.90–0.95), and the kappa score was 0.58 (95%CI 0.46–0.70) indicating moderate agreement. The F1 score was 0.66, sensitivity was 67% (95%CI 54%–78%), and specificity was 92% (95%CI 88%–95%).

Conclusions

The deep learning system could predict if there was malignancy using cytocentrifuged urine cytology images. The process was explainable since the prediction of malignancy was directly based on the abnormal cells selected by the model and can be verified by examining those candidate abnormal cells in each image. Thus, this DLS was not just a tool for pathologists in cytology diagnosis. It simultaneously provided novel histopathologic insights for urologists.
Prediction of Tumor Mutation Load in Colorectal Cancer Histopathological Images Based on Deep Learning
Authors: Liu Yongguang , Huang Kaimei , Yang Yachao , Wu Yan , Gao Wei
Published: May 2022

Colorectal cancer (CRC) is one of the most prevalent malignancies, and immunotherapy can be applied to CRC patients of all ages, while its efficacy is uncertain. Tumor mutational burden (TMB) is important for predicting the effect of immunotherapy. Currently, whole-exome sequencing (WES) is a standard method to measure TMB, but it is costly and inefficient. Therefore, it is urgent to explore a method to assess TMB without WES to improve immunotherapy outcomes. In this study, we propose a deep learning method, DeepHE, based on the Residual Network (ResNet) model. On images of tissue, DeepHE can efficiently identify and analyze characteristics of tumor cells in CRC to predict the TMB. In our study, we used ×40 magnification images and grouped them by patients followed by thresholding at the 10th and 20th quantiles, which significantly improves the performance. Also, our model is superior compared with multiple models. In summary, deep learning methods can explore the association between histopathological images and genetic mutations, which will contribute to the precise treatment of CRC patients.
Provider Visual Attention Correlates With the Quality of Pediatric Resuscitation: An Observational Eye-Tracking Study
Authors: Gröpel Peter , Wagner Michael , Bibl Katharina , Schwarz Hannah , Eibensteiner Felix , Berger Angelika , Cardona Francesco S.
Published: May 2022

Background

Eye-tracking devices are an innovative tool to understand providers’ attention during stressful medical tasks. The knowledge about what gaze behaviors improve (or harm) the quality of clinical care can substantially improve medical training. The aim of this study is to identify gaze behaviors that are related to the quality of pediatric resuscitation.

Methods

Forty students and healthcare providers performed a simulated pediatric life support scenario, consisting of a chest compression task and a ventilation task, while wearing eye-tracking glasses. Skill Reporter software measured chest compression (CC) quality and Neo Training software measured ventilation quality. Main eye-tracking parameters were ratio [the number of participants who attended a certain area of interest (AOI)], dwell time (total amount of time a participant attended an AOI), the number of revisits (how often a participant returned his gaze to an AOI), and the number of transitions between AOIs.

Results

The most salient AOIs were infant chest and ventilation mask (ratio = 100%). During CC task, 41% of participants also focused on ventilation bag and 59% on study nurse. During ventilation task, the ratio was 61% for ventilation bag and 36% for study nurse. Percentage of correct CC rate was positively correlated with dwell time on infant chest (p = 0.044), while the overall CC quality was negatively correlated with dwelling outside of pre-defined task-relevant AOIs (p = 0.018). Furthermore, more dwell time on infant chest predicted lower leakage (p = 0.042). The number of transitions between AOIs was unrelated to CC parameters, but correlated negatively with mask leak during ventilations (p = 0.014). Participants with high leakage shifted their gaze more often between ventilation bag, ventilation mask, and task-irrelevant environment.

Conclusion

Infant chest and ventilation mask are the most salient AOIs in pediatric basic life support. Especially the infant chest AOI gives beneficial information for the resuscitation provider. In contrast, attention to task-irrelevant environment and frequent gaze shifts seem to harm the quality of care.
Robot-Assisted vs. Open Appendicovesicostomy in Pediatric Urology: A Systematic Review and Single-Center Case Series
Authors: Juul Nikolai , Persad Emma , Willacy Oliver , Thorup Jorgen , Fossum Magdalena , Reinhardt Susanne
Published: May 2022

Introduction

Appendicovesicostomy (APV) is the preferred choice of continent catheterizable channels in pediatric urology. The introduction of robot-assisted laparoscopic techniques has been correlated to superior cosmesis and convalescence and is now increasingly implemented for APV procedures. We aimed to perform a systematic review of the literature comparing open vs. robotic APV regarding possible differences in postoperative outcomes and to evaluate these findings with our own initial experiences with robotic APV compared to our previous open procedures.

Methods

We evaluated the first five patients undergoing robotic APV at our institution and compared 1-year outcomes with a consecutive series of 12 patients undergoing open APV. In a systematic literature review, we screened studies from PubMed, EMBASE, and CENTRAL comparing open and robotic APV in pediatric urology (current to December 2021) and performed meta-analyses on postoperative outcomes comparing the two groups and evaluated the grade of evidence.

Results

We found significantly shortened postoperative length of stay in the robotic group (p = 0.001) and comparable 1-year complication rates in robotic vs. open APV patients. We systematically screened 3,204 studies and ultimately included three non-randomized studies comparing postoperative outcomes of robotic and open APV for quantitative analysis. The open and robotic approaches performed equally well regarding overall postoperative complications, surgical reintervention, and stomal stenosis. Two of the included studies reported comparable stomal continence rates and shortened postoperative length of stay in the robotic group, in agreement with the findings in our own series.

Conclusion

Robotic APV is equally safe to the conventional open approach with additional advantages in postoperative hospitalization length.
Management of Atopic Dermatitis Via Oral and Topical Administration of Herbs in Murine Model: A Systematic Review
Authors: Mohd Kasim Vivi Nur Khalieda , Noble Siti Mahirah , Liew Kong Yen , Tan Ji Wei , Israf Daud Ahmad , Tham Chau Ling
Published: May 2022

Over the past few decades, complementary and alternative medicine (CAM) using herbs, or their active constituents have garnered substantial attention in the management of a chronic and relapsing inflammatory skin disorder called atopic dermatitis (AD), particularly in attenuating disease recurrence and maintaining long-term remission. In Eastern Asian countries including China, Korea and Taiwan, herbal medicine available in both topical and oral preparation plays a significant role in treating skin diseases like AD as they possibly confer high anti-inflammatory properties and immunomodulatory functions. Conventional murine models of AD have been employed in drug discovery to provide scientific evidence for conclusive and specific pharmacological effects elicited by the use of traditional herbs and their active constituents. Coupled with the goal to develop safe and effective novel therapeutic agents for AD, this systematic review consists of a summary of 103 articles on both orally and topically administered herbs and their active constituents in the murine model, whereby articles were screened and selected via a specialized framework known as PICO (Population, Intervention, Comparator and Outcome). The objectives of this review paper were to identify the efficacy of oral and topical administered herbs along with their active constituents in alleviating AD and the underlying mechanism of actions, as well as the animal models and choice of inducer agents used in these studies. The main outcome on the efficacy of the majority of the herbs and their active constituents illustrated suppression of Th2 response as well as improvements in the severity of AD lesions, suppression of Immunoglobulin E (IgE) concentration and mast cell infiltration. The majority of these studies used BALB/c mice followed by NC/Nga mice (commonly used gender–male; commonly used age group – 6–8 weeks). The most used agent in inducing AD was 2, 4-Dinitrochlorobenzene (DNCB), and the average induction period for both oral and topical administered herbs and their active constituents in AD experiments lasted between 3 and 4 weeks. In light of these findings, this review paper could potentially assist researchers in exploring the potential candidate herbs and their active constituents using murine model for the amelioration of AD.
Distinct Gene Expression Patterns of Calcium Channels and Related Signaling Pathways Discovered in Lymphomas
Authors: Stanwood Shawna R. , Chong Lauren C. , Steidl Christian , Jefferies Wilfred A.
Published: May 2022

Cell surface calcium (Ca2+) channels permit Ca2+ ion influx, with Ca2+ taking part in cellular functions such as proliferation, survival, and activation. The expression of voltage-dependent Ca2+ (CaV) channels may modulate the growth of hematologic cancers. Profile analysis of Ca2+ channels, with a focus on the Ca2+ release-activated Ca2+ (CRAC) and L-type CaV channels, was performed on RNA sequencing data from lymphoma cell lines and samples derived from patients with diffuse large B cell lymphoma (DLBCL). CaV1.2 expression was found to be elevated in classical Hodgkin lymphoma (CHL) cell lines when compared to other B cell lymphoma cell lines. In contrast, CHL exhibited reduced expression of ORAI2 and STIM2. In our differential expression analysis comparing activated B cell-like DLBCL (ABC-DLBCL) and germinal centre B cell-like DLBCL (GCB-DLBCL) patient samples, ABC-DLBCL revealed stronger expression of CaV1.3, whereas CaV1.1, CaV1.2, and CaV1.4 showed greater expression levels in GCB-DLBCL. Interestingly, no differences in ORAI/STIM expression were noted in the patient samples. As Ca2+ is known to bind to calmodulin, leading to calcineurin activation and the passage of nuclear factor of activated T cells (NFAT) to the cell nucleus, pathways for calcineurin, calmodulin, NFAT, and Ca2+ signaling were also analyzed by gene set enrichment analysis. The NFAT and Ca2+ signaling pathways were found to be upregulated in the CHL cell lines relative to other B cell lymphoma cell lines. Furthermore, the calmodulin and Ca2+ signaling pathways were shown to be downregulated in the ABC-DLBCL patient samples. The findings of this study suggest that L-type CaV channels and Ca2+-related pathways could serve as differentiating components for biologic therapies in targeted lymphoma treatments.
Plasma Metabolomics Identifies the Dysregulated Metabolic Profile of Primary Immune Thrombocytopenia (ITP) Based on GC-MS
Authors: Zhang Ziyan , Wu Xiaojin , Zhou Meng , Qi Jiaqian , Zhang Rui , Li Xueqian , Wang Chang , Ruan Changgeng , Han Yue
Published: May 2022

ITP is a common autoimmune bleeding disorder with elusive pathogenesis. Our study was implemented to profile the plasma metabolic alterations of patients diagnosed with ITP, aiming at exploring the potential novel biomarkers and partial mechanism of ITP. The metabolomic analysis of plasma samples was conducted using GC-MS on 98 ITP patients and 30 healthy controls (HCs). Age and gender matched samples were selected to enter the training set or test set respectively. OPLS-DA, t-test with FDR correction and ROC analyses were employed to screen out and evaluate the differential metabolites. Possible pathways were enriched based on metabolomics pathway analysis (MetPA). A total of 85 metabolites were investigated in our study and 17 differential metabolites with diagnostic potential were identified between ITP patients and HCs. MetPA showed that the metabolic disorders of ITP patients were mainly related to phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and glyoxylate and dicarboxylate metabolism. Additionally, we discriminated 6 differential metabolites and 5 enriched pathways in predicting the resistance to glucocorticoids in chronic ITP patients. The distinct metabolites discovered in our study could become novel biomarkers for the auxiliary diagnosis and prognosis prediction of ITP. Besides, the dysregulated pathways might contribute to the development of ITP.
Curcumin and Related Compounds in Cancer Cells: New Avenues for Old Molecules
Authors: Costantino Matteo , Corno Cristina , Colombo Diego , Perego Paola
Published: May 2022

Curcumin and related compounds are known for the large spectrum of activities. The chemical features of these compounds are important for their biological effects with a key role for the thiol-reactiveα−βunsaturated carbonyl groups. Curcumin derivatives may overcome the limitation of the bioavailability of the parent compound, while maintaining the key chemical features responsible for biological activities. Curcumin and related compounds show anti-viral, anti-fungal, anti-microbial and anti-tumor activities. The therapeutic effects of curcumin, used as a supplement in cancer therapy, have been documented in various cancer types, in which inhibition of cell growth and survival pathways, induction of apoptosis and other cell death pathways have been reported. Curcumin-induced apoptosis has been linked both to the intrinsic and extrinsic apoptotic pathways. Necroptosis has also been involved in curcumin-induced toxicity. Among curcumin-induced effects, ferroptosis has also been described. The mechanism of curcumin toxicity can be triggered by reactive oxygen species-mediated endoplasmic reticulum stress. Curcumin targets have been identified in the context of the ubiquitin-proteasome system with evidence of inhibition of the proteasome proteolytic activities and cellular deubiquitinases. Curcumin has recently been shown to act on the tumor microenvironment with effects on cancer-associated fibroblasts and immune cells. The related product caffeic acid phenethyl ester has shown promising preclinical results with an effect on the inflammatory microenvironment. Here, we review the mechanisms underlying curcumin and derivatives toxicity towards cancer cells with particular emphasis on cell death pathways and the ubiquitin-proteasome system.
BK Channel in the Physiology and in the Cancer of Pancreatic Duct: Impact and Reliability of BK Openers
Authors: Zuccolini Paolo , Gavazzo Paola , Pusch Michael
Published: May 2022

BK (KCa 1.1, Slo-1) is a K+ channel characterized by an allosteric regulation of the gating mechanism by Ca2+ binding and voltage, and a high unitary conductance. The channel is expressed in many different tissues, where it is involved in the regulation or the fine-tuning of many physiological processes. Among other organs, BK is expressed in the pancreatic duct, a part of the gland important for the correct ionic composition of the pancreatic juice. Unfortunately, the pancreatic duct is also the site where one of the deadliest cancer types, the pancreatic duct adenocarcinoma (PDAC), develops. In the past years, it has been reported that continuous exposure of cancer cells to BK openers can have a significant impact on cell viability as well as on the ability to proliferate and migrate. Here, we first summarize the main BK channel properties and its roles in pancreatic duct physiology. Then we focus on the potential role of BK as a pharmacological target in PDAC. Moreover, we discuss how results obtained when employing BK activators on cancer cells can, in some cases, be misleading.
1-Mesityl-3-(3-Sulfonatopropyl) Imidazolium Protects Against Oxidative Stress and Delays Proteotoxicity in C. elegans
Authors: Andersen Natalia , Veuthey Tania , Blanco María Gabriela , Silbestri Gustavo Fabian , Rayes Diego , De Rosa María José
Published: May 2022

Due to the increase in life expectancy worldwide, age-related disorders such as neurodegenerative diseases (NDs) have become more prevalent. Conventional treatments comprise drugs that only attenuate some of the symptoms, but fail to arrest or delay neuronal proteotoxicity that characterizes these diseases. Due to their diverse biological activities, imidazole rings are intensively explored as powerful scaffolds for the development of new bioactive molecules. By using C. elegans, our work aims to explore novel biological roles for these compounds. To this end, we have tested the in vivo anti-proteotoxic effects of imidazolium salts. Since NDs have been largely linked to impaired antioxidant defense mechanisms, we focused on 1-Mesityl-3-(3-sulfonatopropyl) imidazolium (MSI), one of the imidazolium salts that we identified as capable of improving iron-induced oxidative stress resistance in wild-type animals. By combining mutant and gene expression analysis we have determined that this protective effect depends on the activation of the Heat Shock Transcription Factor (HSF-1), whereas it is independent of other canonical cytoprotective molecules such as abnormal Dauer Formation-16 (DAF-16/FOXO) and Skinhead-1 (SKN-1/Nrf2). To delve deeper into the biological roles of MSI, we analyzed the impact of this compound on previously established C. elegans models of protein aggregation. We found that MSI ameliorates β-amyloid-induced paralysis in worms expressing the pathological protein involved in Alzheimer’s Disease. Moreover, this compound also delays age-related locomotion decline in other proteotoxic C. elegans models, suggesting a broad protective effect. Taken together, our results point to MSI as a promising anti-proteotoxic compound and provide proof of concept of the potential of imidazole derivatives in the development of novel therapies to retard age-related proteotoxic diseases.
Recommendations for Off-Label Drug Use in Ophthalmology in China: A Clinical Practice Guideline
Authors: Li Guangyao , Wang Ningli , Zhang Yu , Wei Wenbin , Lu Hai , Zhai Suodi , Zhang Chao
Published: May 2022

Off-label drugs use is widespread in ophthalmology due to the delay in drug approvals and package inserts update. It has been found to vary among different medical institutions in China, leading to safety problems since inappropriate use. Guidance is urgently needed regarding how best to use the drugs for unapproved indications and routes of administration. We aimed to develop an evidence-based guideline to guide off-label drugs used in ophthalmology in China. The practice guideline was developed by the Hospital Pharmacy Professional Committee, Chinese Pharmaceutical Association, following the WHO handbook for guideline development. The guideline was initially registered in the International Practice Guidelines Registry Platform (IPGRP-2021CN096). The clinical questions included in the guideline were identified through a three-round Delphi vote. Databases search was performed in PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, and WanFang Database from their inception to 31 March 2021. Systematic reviews and meta-analyses for each clinical question were conducted individually to synthesize available scientific evidence. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence and grade the recommendations’ strengths. The multidisciplinary guideline groups were set up, including ophthalmologists, pharmacists, methodology experts, pharmacologists, pharmacoeconomists, and lawyers. The guideline identified 25 clinical questions included. A total of 32 systematic reviews, including 24 conducted by the systematic review group and eight high-relevance published within 2 years, were referred to address these questions. Finally, the guideline presented 32 recommendations addressing 25 clinical questions, involving five strong recommendations and 27 weak recommendations for the treatment of ocular fundus, corneal disease, glaucoma, and endophthalmitis. Current evidence from clinical studies supports the off-label drugs used in ophthalmology. We developed an evidence-based guideline using a rigorous multidisciplinary approach to guide these usages in route clinical practice.
Melatonin Improved the Survival of Multi-Territory Perforator Flaps by Promoting Angiogenesis and Inhibiting Apoptosis via the NRF2/FUNDC1 Axis
Authors: Huang Chengxiong , Qing Liming , Pang Xiaoyang , Fu Jinfei , Xiao Yu , Tang Juyu , Wu Panfeng
Published: May 2022

Background: Multi-territory perforator flaps are a reconstructive measure for repairing large soft tissue defects caused by tumors or trauma. However, the use of these flaps in clinical practice has been restricted due to the uncertain blood supply. Therefore, promoting the survival of the multi-territory perforator flap is critical for clinical repair and reconstruction. In our study, we explored the effects of melatonin (MLT) on multi-territory perforator flaps and the possible molecular mechanisms.

Materials and Methods: Seventy-two Sprague–Dawley rats (250–300 g) were randomly divided into 3 groups (n = 24): Control, MLT and MLT + ML385 groups. First, we assessed the survival area of the flap, followed by the micro-vessel density and CD31-positive vessel expression. Apoptosis of the skin flap under immunofluorescence and expression of the apoptosis-related proteins Bcl-2, Bax and Caspase3 were measured. Additionally, angiogenesis of the skin flaps was shown by angiography, and NRF2 and FUNDC1 mRNA and protein expression was detected by real-time PCR and western blotting.

Results: The results showed that MLT increased the survival area of the multi-territory perforator flap, which was related to increased angiogenesis and decreased apoptosis. We also found that mRNA and protein of NRF2 and FUNDC1 levels were significantly increased after MLT treatment, and an NRF2 inhibitor reversed the ability of MLT to enhance multi-territory perforator flap survival, promote angiogenesis and inhibit apoptosis and reduced FUNDC1 protein expression.

Conclusion: MLT promoted angiogenesis and inhibited apoptosis to promote the survival of multi-territory perforator flaps, which may be regulated via the NRF2/FUNDC1 axis.
Robust and Broadband Graphene Surface Plasmon Waveguide Coupler via Quantum Control
Authors: Chen Yun , Huang Wei , Ooi Kelvin J. A. , Zhang Wentao
Published: May 2022

In this article, a novel graphene subwavelength waveguide coupler is designed based on the quantum control theory. Compared with metal surface plasmon polaritons (SPPs), graphene surface plasmon polaritons (GSPPs) have a smaller SPP wavelength and tunable properties. The dielectric load graphene plasmon waveguide (DLGPW) is used for designing to avoid the influence of the edge shape of the graphene nanoribbons on the waveguide mode. The coupling coefficient between the waveguides is calculated by using the coupled-mode theory (CMT). Due to the subwavelength properties of the graphene surface plasmons (GSP) and the robustness of the quantum control technique, our device is more compact and robust against perturbations of geometrical parameters under the premise of high transmission efficiency. The device we designed also has broadband characteristics, ranging from 30 THz to 40 THz, with high transmission efficiency when considering the transmission loss. We believe that our device will significantly contribute to integrated optics and photo-communication.
Glucocorticoid Receptor Maintains Vasopressin Responses in Kidney Collecting Duct Cells
Authors: Yang Hsiu-Hui , Su Shih-Han , Ho Cheng-Hsuan , Yeh Ai-Hsin , Lin Yi-Jiun , Yu Ming-Jiun
Published: May 2022

Water permeability of the kidney collecting ducts is regulated in part by the amount of the molecular water channel protein aquaporin-2 (AQP2), whose expression, in turn, is regulated by the pituitary peptide hormone vasopressin. We previously showed that stable glucocorticoid receptor knockdown diminished the vasopressin-induced Aqp2 gene expression in the collecting duct cell model mpkCCD. Here, we investigated the pathways regulated by the glucocorticoid receptor by comparing transcriptomes of the mpkCCD cells with or without stable glucocorticoid receptor knockdown. Glucocorticoid receptor knockdown downregulated 5,394 transcripts associated with 55 KEGG pathways including “vasopressin-regulated water reabsorption,” indicative of positive regulatory roles of these pathways in the vasopressin-induced Aqp2 gene expression. Quantitative RT-PCR confirmed the downregulation of the vasopressin V2 receptor transcript upon glucocorticoid receptor knockdown. Glucocorticoid receptor knockdown upregulated 3,785 transcripts associated with 42 KEGG pathways including the “TNF signaling pathway” and “TGFβ signaling pathway,” suggesting the negative regulatory roles of these pathways in the vasopressin-induced Aqp2 gene expression. Quantitative RT-PCR confirmed the upregulation of TNF and TGFβ receptor transcripts upon glucocorticoid receptor knockdown. TNF or TGFβ inhibitor alone, in the absence of vasopressin, did not induce Aqp2 gene transcription. However, TNF or TGFβ blunted the vasopressin-induced Aqp2 gene expression. In particular, TGFβ reduced vasopressin-induced increases in Akt phosphorylation without inducing epithelial-to-mesenchymal transition or interfering with vasopressin-induced apical AQP2 trafficking. In summary, our RNA-seq transcriptomic comparison revealed positive and negative regulatory pathways maintained by the glucocorticoid receptor for the vasopressin-induced Aqp2 gene expression.
Chronic and Binge Alcohol Ingestion Increases Truncated Oxidized Phosphatidylcholines in Mice Lungs Due to Increased Oxidative Stress
Authors: Appolonia Corynn N. , Wolf Kaelin M. , Zawatsky Charles N. , Cinar Resat
Published: May 2022

Heavy alcohol drinking has negative health effects in multiple organs. It predisposes lungs to inflammatory conditions associated with acute lung injury and increased incidence of pneumonia and sepsis, which may lead to death due to acute respiratory distress syndrome in some individuals with alcohol use disorder (AUD). In general, rodent models of alcohol exposure either do not recapitulate multiple organ injuries as seen in humans or require longer duration to establish tissue injury and inflammation. The recently introduced NIAAA model of alcohol-induced liver injury, characterized by a marked increase in steatosis and liver damage with 10 days of a liquid diet containing 5% ethanol followed by a single ethanol binge (5 g/kg). Therefore, we employed this model to explore the status of surfactant phospholipids, oxidative stress, tissue injury markers and inflammatory cytokines in lungs. In lungs of C57BL/6J mice, the alcohol feeding significantly increased levels of the surfactant phospholipid dipalmitoyl phosphatidylcholine (DPPC) as well as the truncated oxidized phosphatidylcholines palmitoyl oxovaleryl phosphatidyl-choline (POVPC), palmitoyl glutaryl phosphatidyl-choline (PGPC), palmitoyl oxo-nonanoyl phosphatidyl-choline (ALDO-PC), and palmitoyl azelaoyl phosphatidyl-choline (PAzePC) at 9 h post-binge. Additionally, gene expression of the enzymes catalyzing lipid oxidation, such as arachidonate 15-lipoxygenase (Alox15), prostaglandin synthase 2 (Ptgs2), Cytochrome P450 2E1 (Cyp2E1) and NADPH oxidase 1 (Nox1) were significantly increased. Furthermore, ethanol increased levels of the inflammatory cytokine Interleukin-17 in bronchoalveolar lavage fluid. In conclusion, the NIAAA alcohol feeding model might be suitable to study alcohol-induced lung injury and inflammation.
Acinetobacter calcoaceticus is Well Adapted to Withstand Intestinal Stressors and Modulate the Gut Epithelium
Authors: Glover Janiece S. , Browning Brittney D. , Ticer Taylor D. , Engevik Amy C. , Engevik Melinda A.
Published: May 2022

Background: The gastrointestinal tract has been speculated to serve as a reservoir for Acinetobacter, however little is known about the ecological fitness of Acinetobacter strains in the gut. Likewise, not much is known about the ability of Acinetobacter to consume dietary, or host derived nutrients or their capacity to modulate host gene expression. Given the increasing prevalence of Acinetobacter in the clinical setting, we sought to characterize how A. calcoaceticus responds to gut-related stressors and identify potential microbe-host interactions.

Materials and Methods: To accomplish these aims, we grew clinical isolates and commercially available strains of A. calcoaceticus in minimal media with different levels of pH, osmolarity, ethanol and hydrogen peroxide. Utilization of nutrients was examined using Biolog phenotypic microarrays. To examine the interactions of A. calcoaceticus with the host, inverted murine organoids where the apical membrane is exposed to bacteria, were incubated with live A. calcoaceticus, and gene expression was examined by qPCR.

Results: All strains grew modestly at pH 6, 5 and 4; indicating that these strains could tolerate passage through the gastrointestinal tract. All strains had robust growth in 0.1 and 0.5 M NaCl concentrations which mirror the small intestine, but differences were observed between strains in response to 1 M NaCl. Additionally, all strains tolerated up to 5% ethanol and 0.1% hydrogen peroxide. Biolog phenotypic microarrays revealed that A. calcoaceticus strains could use a range of nutrient sources, including monosaccharides, disaccharides, polymers, glycosides, acids, and amino acids. Interestingly, the commercially available A. calcoaceticus strains and one clinical isolate stimulated the pro-inflammatory cytokines Tnf, Kc, and Mcp-1 while all strains suppressed Muc13 and Muc2.

Conclusion: Collectively, these data demonstrate that A. calcoaceticus is well adapted to dealing with environmental stressors of the gastrointestinal system. This data also points to the potential for Acinetobacter to influence the gut epithelium.
Anion Transport Across Human Gallbladder Organoids and Monolayers
Authors: Zarei Keyan , Thornell Ian M. , Stoltz David A.
Published: May 2022

Fluid and anion secretion are important functions of the biliary tract. It has been established that cAMP regulates Na+ absorption through NHE3. However, mechanisms of gallbladder anion transport are less defined. We created organoids and organoid-derived monolayers from human gallbladder tissue to measure organoid swelling and transepithelial electrophysiology. In our in vitro models, forskolin-stimulation caused organoid swelling and increased transepithelial anion transport. Full organoid swelling required Cl−while changes in short-circuit current were HCO3−-dependent. Organoids and monolayers from an individual homozygous for the cystic fibrosis-causing ΔF508 CFTR mutation had no apical expression of CFTR and minimal changes in transepithelial current and conductance with forskolin treatment. However, organoid swelling remained intact. Dilution potential studies revealed that forskolin treatment increased the paracellular permeability to anions relative to cations. These data suggest a novel paracellular contribution to forskolin-stimulated fluid transport across the gallbladder epithelium.
Adapting Grapevine Productivity and Fitness to Water Deficit by Means of Naturalized Rootstocks
Authors: Villalobos-Soublett Emilio , Verdugo-Vásquez Nicolás , Díaz Irina , Zurita-Silva Andrés
Published: May 2022

Climate change effects are unbalanced in all regions and cultivars linked to the wine industry. However, the impact of extreme weather events, such as drought and rising global temperatures, highlight the potential vulnerability in plant productivity, phenology, and crop water requirements that affect quality and harvests. Among adaptative measures for grapevine cultivars in existing or new winegrowing areas, the use of tolerant rootstocks to abiotic stress has been regarded as a mid-term strategy to face emerging constrains. The aim of this study was to compare naturalized or autochthonous rootstocks influence over grapevine cultivar performance and to characterize their response to deficit irrigation conditions. Data was collected from Cabernet Sauvignon and Syrah grafted plants for over 3 growing seasons (2018–2021) from a hyper-arid experimental field in Vicuña, Chile. Morpho-physiological parameters were determined throughout seasons and combinations where significant effects from rootstocks, irrigation treatment, and cultivar were observed over An and gs, thus modifying CO2 assimilation and intrinsic Water Use Efficiency (WUEi). Primary productivity and yield were also modified by rootstock depending upon cultivar hydric behavior. Interestingly, cluster and berry traits were unaffected despite how water productivity and integral water stress were modulated by rootstock. In both cultivars, it was observed that trait responses varied according to the irrigation conditions, rootstocks, and their respective interactions, thus highlighting a relative influence of the rootstocks in the processes of adaptation to the water deficit. Moreover, harvest date and acidity were modified by deficit irrigation treatment, and rootstocks did not modify phenological stages. Adaptation of grapevines to expected lower water availability might be improved by using suitable tolerant rootstocks, and maturity index can be modified through irrigation management.