bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient screening of pancreatic lipase inhibitors from cod meat hydrolysate through ligand fishing strategy
Authors: Tian Yongqi , Liu Cuicui , Wang Shaoyun , Du Ming , Zhu Beiwei
Published: August 2022

Obesity has become an increasingly serious public health problem. Pancreatic lipase (PL) is identified as a ideal target for the prevention and treatment of obesity. Orlistat, the only approved PL inhibitor (PLI), is a powerful weight loss drug but has many side effects. Therefore, there is an urgent need to discover powerful PLIs with high safety. Protein hydrolysate has been demonstrated to be a treasure trove of PLIs, but recognizing responsible functional peptides from them is like looking for a needle in a haystack. In this work, we synthesized and optimized a PL ligand fishing model (PLLFM) using magnetic nanoparticles (MNPs), then PLLFM was used to quickly fish out potential PLIs from the Cod meat hydrolysate (CMH). Finally, two new PLIs, GSPPPSG and KLEGDLK were identified with IC50 of 0.60 and 1.08 mg/mL, respectively. The Lineweaver-Burk diagram showed that GSPPPSG is a non-competitively dominant mixed-type PLI, whereas KLEGDLK is a competitive inhibitory-type PLI. Moreover, molecular docking suggested that both peptides can stably bind to the key amino acid residues of the PL active site, mainly through hydrogen bonding, hydrophobic, and electrostatic interactions. In general, we not only established a method to rapidly fish out potential PLIs from protein hydrolysate, but also provided safe and efficient lead compounds for the development of novel diet foods or drugs.
Polysaccharide from Hemerocallis citrina Borani by subcritical water with different temperatures and investigation of its physicochemical properties and antioxidant activity
Authors: Ti Yongrui , Zhang Yanli , Ban Yüqian , Wang Xiaoxiao , Hou Yüqing , Song Zihan
Published: August 2022

Hemerocallis citrina Borani as a low-cost vegetable, has various health benefits. However, the industry of H. citrina Borani is in the state of primary processing, with poor economic benefits. This study aimed to investigate the physicochemical properties, and the antioxidant activity of H. citrina Borani polysaccharide (HCBP) using subcritical water extraction (SWE) at different temperatures, to expand the value of H. citrina Borani. HCBP mainly composed of nine monosaccharides (glucose, galactose, rhamnose, fucose, mannose, arabinose, xylose, galacturonic acid, and glucuronic acid), among which the content of neutral sugar was higher and uronic acid was lower. HCBP contained glycosidic bond of β-configurations and trace quantities protein. The molecular weight of HCBP decreased with increasing temperature. Shear thinning occurred in HCBP with the increase of shear rate (0.01–1 s−1), and the apparent viscosity of HCBP decreased at higher temperature (150–160°C) with the increase continuously of shear rate (1–10 s−1), but almost remained constant at lower temperature (130–140°C). Scanning electron microscope showed that HCBP had rough surface, loose structure, obvious particle gap, and irregular shape. In addition, HCBP extracted at 160°C had strong FRAP activity, and HCBP extracted at 130 and 140°C had better ABTS radical scavenging activity. This study suggests that HCBP extracted by SWE could provide a cheap raw material as food thickening agent and natural antioxidants.
Cyclin-dependent kinase inhibitors in malignant hematopoiesis
Authors: Schirripa Alessia , Sexl Veronika , Kollmann Karoline
Published: August 2022

The cell-cycle is a tightly orchestrated process where sequential steps guarantee cellular growth linked to a correct DNA replication. The entire cell division is controlled by cyclin-dependent kinases (CDKs). CDK activation is balanced by the activating cyclins and CDK inhibitors whose correct expression, accumulation and degradation schedule the time-flow through the cell cycle phases. Dysregulation of the cell cycle regulatory proteins causes the loss of a controlled cell division and is inevitably linked to neoplastic transformation. Due to their function as cell-cycle brakes, CDK inhibitors are considered as tumor suppressors. The CDK inhibitors p16INK4a and p15INK4b are among the most frequently altered genes in cancer, including hematopoietic malignancies. Aberrant cell cycle regulation in hematopoietic stem cells (HSCs) bears severe consequences on hematopoiesis and provokes hematological disorders with a broad array of symptoms. In this review, we focus on the importance and prevalence of deregulated CDK inhibitors in hematological malignancies.
Integrated molecular and pharmacological characterization of patient-derived xenografts from bladder and ureteral cancers identifies new potential therapies
Authors: Lang Hervé , Béraud Claire , Cabel Luc , Fontugne Jacqueline , Lassalle Myriam , Krucker Clémentine , Dufour Florent , Groeneveld Clarice S. , Dixon Victoria , Meng Xiangyu , Kamoun Aurélie , Chapeaublanc Elodie , De Reynies Aurélien , Gamé Xavier , Rischmann Pascal , Bieche Ivan , Masliah-Planchon Julien , Beaurepere Romane , Allory Yves , Lindner Véronique , Misseri Yolande , Radvanyi François , Lluel Philippe , Bernard-Pierrot Isabelle , Massfelder Thierry
Published: August 2022

Background

Muscle-invasive bladder cancer (MIBC) and upper urinary tract urothelial carcinoma (UTUC) are molecularly heterogeneous. Despite chemotherapies, immunotherapies, or anti-fibroblast growth factor receptor (FGFR) treatments, these tumors are still of a poor outcome. Our objective was to develop a bank of patient-derived xenografts (PDXs) recapitulating the molecular heterogeneity of MIBC and UTUC, to facilitate the preclinical identification of therapies.

Methods

Fresh tumors were obtained from patients and subcutaneously engrafted into immune-compromised mice. Patient tumors and matched PDXs were compared regarding histopathology, transcriptomic (microarrays), and genomic profiles [targeted Next-Generation Sequencing (NGS)]. Several PDXs were treated with chemotherapy (cisplatin/gemcitabine) or targeted therapies [FGFR and epidermal growth factor (EGFR) inhibitors].

Results

A total of 31 PDXs were established from 1 non-MIBC, 25 MIBC, and 5 upper urinary tract tumors, including 28 urothelial (UC) and 3 squamous cell carcinomas (SCCs). Integrated genomic and transcriptomic profiling identified the PDXs of three different consensus molecular subtypes [basal/squamous (Ba/Sq), luminal papillary, and luminal unstable] and included FGFR3-mutated PDXs. High histological and genomic concordance was found between matched patient tumor/PDX. Discordance in molecular subtypes, such as a Ba/Sq patient tumor giving rise to a luminal papillary PDX, was observed (n=5) at molecular and histological levels. Ten models were treated with cisplatin-based chemotherapy, and we did not observe any association between subtypes and the response. Of the three Ba/Sq models treated with anti-EGFR therapy, two models were sensitive, and one model, of the sarcomatoid variant, was resistant. The treatment of three FGFR3-mutant PDXs with combined FGFR/EGFR inhibitors was more efficient than anti-FGFR3 treatment alone.

Conclusions

We developed preclinical PDX models that recapitulate the molecular heterogeneity of MIBCs and UTUC, including actionable mutations, which will represent an essential tool in therapy development. The pharmacological characterization of the PDXs suggested that the upper urinary tract and MIBCs, not only UC but also SCC, with similar molecular characteristics could benefit from the same treatments including anti-FGFR for FGFR3-mutated tumors and anti-EGFR for basal ones and showed a benefit for combined FGFR/EGFR inhibition in FGFR3-mutant PDXs, compared to FGFR inhibition alone.
Frontiers of ferroptosis research: An analysis from the top 100 most influential articles in the field
Authors: Cheng Kunming , Guo Qiang , Shen Zefeng , Yang Weiguang , Zhou Yan , Sun Zaijie , Yao Xiuhua , Wu Haiyang
Published: August 2022

In recent years, ferroptosis has become a research hotspot in programmed cell death. Since the concept of ferroptosis was proposed, a growing number of articles have been published on this topic. Nevertheless, to our knowledge, these ferroptosis-related publications that have received a great deal of attention have not been quantitatively evaluated. In this study, we analyzed the top 100 most influential articles over the past decade through a bibliometric method to characterize the research status and trends in this field. Web of Science Core Collection was searched to identify relevant studies. After being manually screened, the top 100 most cited studies with original data were identified and analyzed. Bibliometric software including VOSviewer and R-Bibliometrix were used to perform visualization analysis. The citation frequency for the top 100 selected articles ranged from 135 to 3603 (326.6 citations on average). These articles originated from 25 countries/regions, with more than half originating from the United States and China. The most frequently nominated author was Stockwell BR from the Columbia University, and of the top 100 articles, 19 listed his name. Three core journals were Nature, Cell and Proceedings of the National Academy of Sciences of the United States of America. In addition to term of ferroptosis, these terms or phrases including cell death, cancer cell, GPX4, pathway, inhibitor, mechanism, iron, lipid peroxidation, resistance, erastin, sorafenib, P53, reactive oxygen species, necroptosis, apoptosis, glutathione peroxidase, ACSL4, autophagy, and SLC7A11 appeared more frequently in the top 100 articles. Overall, although much progress has been made, the research on ferroptosis is still at an early stage. The current attention in this field mainly focuses on potential regulatory mechanism and pathways including key ferroptosis-related genes/molecules, oxidant and antioxidant system, ferroptosis-inducing agents or nanomedicine for cancer therapy, as well as the role of ferroptosis in non-neoplastic disorders. Meanwhile, combination therapeutic strategies targeting ferroptosis in radiotherapy or immunotherapy also deserve further attention.
Polymorphisms in ERCC4 and ERCC5 and risk of cancers: Systematic research synopsis, meta-analysis, and epidemiological evidence
Authors: Zuo Chunjian , Lv Xiaolong , Liu Tianyu , Yang Lei , Yang Zelin , Yu Cao , Chen Huanwen
Published: August 2022

The variants of DNA repair genes have been widely reported to be associated with cancer risk in the past decades. As were two crucial members of nucleotide excision repair pathway, ERCC4 and ERCC5 polymorphisms are linked with susceptibility to multiple cancers, but the conclusions were controversial. In this updated meta-analysis concerned with ERCC4 and ERCC5 single-nucleotide polymorphisms (SNPs), 160 eligible publications were identified, and we exerted the meta-analysis of correlations between 24 variants and 19 types of cancer. Venice criteria and the false-positive report probability were used to evaluate a cumulative evidence of significant associations. We conducted functional annotations for those strong associations using data from the Encyclopedia of DNA Elements (ENCODE) Project. We obtained 11 polymorphisms significantly related to changed susceptibility to 11 cancers (p < 0.05). Strong evidence was assigned to four variant-related cancer risks in Asians (ERCC4 rs744154 with bladder cancer, ERCC5 rs2296147 with esophageal cancer, ERCC5 rs17655 with laryngeal cancer and uterine cancer, and ERCC5 rs751402 with gastric cancer), moderate to six SNPs with a risk of eight cancers, and weak to nine SNPs with nine cancers. Data from ENCODE and other public databases showed that the loci of these SNPs with strong evidence might fall in putative functional regions. In conclusion, this paper summarizes comprehensive evidence that common variants of ERCC4 and ERCC5 genes are strongly associated with the risk of bladder cancer, esophageal cancer, laryngeal cancer, uterine cancer, and gastric cancer and elucidates the crucial role of the DNA repair genes in the genetic predisposition to human cancers.
The survival benefit of different lymph node yields in radical prostatectomy for pN1M0 prostate cancer patients: Implications from a population-based study
Authors: Hu Jieping , Yu Yue , Liu Wei , Zhong Jialei , Zhou Xiaochen , Xi Haibo
Published: August 2022

Background and objectives

The extent and survival benefits of lymph node dissection (LND) in radical prostatectomy (RP) for pN1M0 prostate cancer (PCa) patients remained unclear and were controversial. This study aimed to determine the survival benefit of different lymph node yields in RP for pN1M0 PCa patients.

Methods

pN1M0 PCa patients who received RP and LND were identified in Surveillance Epidemiology and End Results (SEER) (2010–2015). Patients were divided into two groups in SEER based on the removal of one to three regional lymph nodes (LND1 group) or four or more regional lymph nodes (LND4 group). Kaplan–Meier methods were used to calculate cancer-specific survival (CSS) and overall survival (OS).

Results

In total, 2,200 patients were identified; 264 patients received LND1 and 1,936 patients received LND4. CSS had no significant difference between the LND4 and LND1 groups (101mon vs. 98mon, p = 0.064), and OS was higher in LND4 patients compared with LND1 patients (97mon vs. 93mon, p = 0.024); for patients with Gleason score = 9 or 10 and T3b or T4, 5-year OS was higher in patients undergoing LND4 (80.9%; 95% CI, 79.0–82.8) compared with those undergoing LND1 (67.5%; 95% CI, 60.8–74.2) (p = 0.009).

Conclusion

More lymph node yield provided better survival for patients with Gleason score = 9 or 10 and T3b or T4, but not for other pN1M0 PCa patients. The extent of LND would be determined after a comprehensive evaluation including Gleason score, tumor stage, and the general condition of the patient.
Design and experimental validation of OPERA_MET-A panel for deep methylation analysis by next generation sequencing
Authors: Fabrizio Federico Pio , Castellana Stefano , Centra Flavia , Sparaneo Angelo , Mastroianno Mario , Mazza Tommaso , Coco Michelina , Trombetta Domenico , Cingolani Nicola , Centonza Antonella , Graziano Paolo , Maiello Evaristo , Fazio Vito Michele , Muscarella Lucia Anna
Published: August 2022

DNA methylation is the most recognized epigenetic mark that leads to a massive distortion in cancer cells. It has been observed that a large number of DNA aberrant methylation events occur simultaneously in a group of genes, thus providing a growth advantage to the cell in promoting cell differentiation and neoplastic transformation. Due to this reason, methylation profiles have been suggested as promising cancer biomarkers. Here, we designed and performed a first step of validation of a novel targeted next generation sequencing (NGS) panel for methylation analysis, which can simultaneously evaluate the methylation levels at CpG sites of multiple cancer-related genes. The OPERA_MET-A methylation panel was designed using the Ion AmpliSeq™ technology to amplify 155 regions with 125-175 bp mean length and covers a total of 1107 CpGs of 18 cancer-related genes. The performance of the panel was assessed by running commercially available fully methylated and unmethylated control human genomic DNA (gDNA) samples and a variable mixture of them. The libraries were run on Ion Torrent platform and the sequencing output was analyzed using the “methylation_analysis” plugin. DNA methylation calls on both Watson (W) and Crick (C) strands and methylated:unmethylated ratio for each CpG site were obtained. Cell lines, fresh frozen and formalin-fixed paraffin-embedded (FFPE) lung cancer tissues were tested. The OPERA_MET-A panel allows to run a minimum of 6 samples/530 chip to reach an observed mean target depth ≥2,500X (W and C strands) and an average number of mapped reads >750,000/sample. The conversion efficiency, determined by spiking-in unmethylated Lambda DNA into each sample before the bisulfite conversion process, was >97% for all samples. The observed percentage of global methylation for all CpGs was >95% and <5% for fully methylated and unmethylated gDNA samples, respectively, and the observed results for the variable mixtures were in agreement with what was expected. Methylation-specific NGS analysis represents a feasible method for a fast and multiplexed screening of cancer patients by a high-throughput approach. Moreover, it offers the opportunity to construct a more robust algorithm for disease prediction in cancer patients having a low quantity of biological material available.
Application of artificial intelligence in glioma researches: A bibliometric analysis
Authors: Zhang Dewei , Zhu Weiyi , Guo Jun , Chen Wei , Gu Xin
Published: August 2022

Background

There have been no researches assessing the research trends of the application of artificial intelligence in glioma researches with bibliometric methods.

Purpose

The aim of the study is to assess the research trends of the application of artificial intelligence in glioma researches with bibliometric analysis.

Methods

Documents were retrieved from web of science between 1996 and 2022. The bibliometrix package from Rstudio was applied for data analysis and plotting.

Results

A total of 1081 documents were retrieved from web of science between 1996 and 2022. The annual growth rate was 30.47%. The top 5 most productive countries were the USA, China, Germany, France, and UK. The USA and China have the strongest international cooperative link. Machine learning, deep learning, radiomics, and radiogenomics have been the key words and trend topics. “Neuro-Oncology”, “Frontiers in Oncology”, and “Cancers” have been the top 3 most relevant journals. The top 3 most relevant institutions were University of Pennsylvania, Capital Medical University, and Fudan University.

Conclusions

With the growth of publications concerning the application of artificial intelligence in glioma researches, bibliometric analysis help researchers to get access to the international academic collaborations and trend topics in the research field.
Gender differences in the experience of interstitial cystitis/bladder pain syndrome
Authors: Windgassen Sula S. , Sutherland Susanna , Finn Michael T. M. , Bonnet Kemberlee R. , Schlundt David G. , Reynolds W. Stuart , Dmochowski Roger R. , McKernan Lindsey C.
Published: August 2022

Aims

This study assessed gender differences in a debilitating urologic pain condition, interstitial cystitis/bladder pain syndrome (IC/BPS). We aimed to (1) evaluate how pain, symptom, and distress profiles of IC/BPS may differ between genders and (2) obtain in-depth firsthand accounts from patients to provide additional insight into their experiences that may explain potential gender differences.

Methods

A mixed methods approach combined validated patient-reported outcome measures with a single timepoint 90-min focus group. Tests of summary score group differences between men and women were assessed across questionnaires measuring urologic symptoms, pain, emotional functioning, and diagnostic timeline. Qualitative analysis applied an inductive-deductive approach to evaluate and compare experiences of living with IC/BPS Group narratives were coded and evaluated thematically by gender using the biopsychosocial model, providing insight into the different context of biopsychosocial domains characterizing the male and female experience of IC/BPS.

Results

Thirty-seven participants [women (n = 27) and men (n = 10)] completed measures and structured focus group interviews across eight group cohorts conducted from 8/2017 to 3/2019. Women reported greater pain intensity (p = 0.043) and extent (p = 0.018), but not significantly greater impairment from pain (p = 0.160). Levels of psychological distress were significantly elevated across both genders. Further, the duration between time of pain symptom onset and time to diagnosis was significantly greater for women than men (p = 0.012). Qualitative findings demonstrated key distinctions in experiences between genders. Men appeared not to recognize or to deter emotional distress while women felt overwhelmed by it. Men emphasized needing more physiological treatment options whilst women emphasized needing more social and emotional support. Interactions with medical providers and the healthcare system differed substantially between genders. While men reported feeling supported and involved in treatment decisions, women reported feeling dismissed and disbelieved.

Conclusion

The findings indicate different pain experiences and treatment needs between genders in persons experiencing urologic pain and urinary symptoms, with potential intervention implications. Results suggest gender health inequality in medical interactions in this urologic population needing further investigation.
Urinary biomarkers for the early prediction of bronchopulmonary dysplasia in preterm infants: A pilot study
Authors: Cui Xuewei , Fu Jianhua
Published: August 2022

Background

This study investigated whether 8-hydroxy-2’-deoxyguanosine (8-OHdG) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations in the urine could predict bronchopulmonary dysplasia (BPD) in preterm infants.

Methods

This prospective cohort study enrolled 165 preterm infants, of whom 70 developed BPD. We measured urinary 8-OHdG and NT-proBNP concentrations from day of life (DOL) 7 to 28. Then, we evaluated the prediction efficiency by receiver operating characteristic curves and assessed correlations between the two biomarkers. Finally, we identified the predictive risk factors for BPD by multivariable logistic regression.

Results

8-OHdG and NT-proBNP levels were significantly higher from DOL 7 to 28 in the BPD group than in the control group (P < 0.05). Additionally, the 8-OHdG level was positively correlated with the NT-proBNP level (r: 0.655–0.789, P < 0.001), and the 8-OHdG and NT-proBNP levels were positively correlated with mechanical ventilation duration and oxygen exposure time (r: 0.175–0.505, P < 0.05) from DOL 7 to 28. Furthermore, the 8-OHdG (DOL 14–28) and NT-proBNP (DOL 7–28) levels were significantly associated with BPD development (P < 0.05).

Conclusion

The urine 8-OHdG concentrations from DOL 14 to 28 and NT-proBNP concentrations from DOL 7 to 28 may be practical non-invasive predictors of BPD development in preterm infants.
An integrative approach to uncover the components, mechanisms, and functions of traditional Chinese medicine prescriptions on male infertility
Authors: Bai Xue , Liu Zhejun , Tang Tian , Yu Shujun , Liu Dan , Liu Guimin , Fan Xiaolei , Tang Yibo , Liu Zhenquan
Published: August 2022

Male infertility is a major and growing health problem with an estimated global prevalence of 4.2%. The current therapy is limited by the unknown etiology of MI, emphasizing the critical requirement forward to a more efficient method or medication. Through thousands of years, Traditional Chinese Medicine (TCM) has been shown to be effective in treating MI effectively. However, the components, mechanisms and functions of TCM prescriptions on MI are still obscure, severely limiting its clinical application. In order to discover the molecular mechanism of TCM against MI, our study presents a comprehensive approach integrated data mining, network pharmacology, molecular docking, UHPLC-Q-Orbitrap HRMS, and experimental validation. Here, we begin to acquire 289 clinical TCM prescriptions for MI from a TCM hospital’s outpatient department. Then, Core Chinese Materia Medica (CCMM) was then retrieved from the TCM Inheritance Support System (TCMISS), which was utilized to discover the underlying rules and connections in clinical prescriptions. After that, 98 CCMM components and 816 MI targets were obtained from ten distinct databases. Additionally, the network pharmacology methods, including network construction, GO and KEGG pathway enrichment, PPI analysis, were utilized to reveal that kaempferol, quercetin, isorhamnetin, and beta-sitosterol are the core components of CCMM in treating MI. The mechanisms and functions of CCMM against MI are hormone regulation, anti-apoptosis, anti-oxidant stress, and anti-inflammatory. Furthermore, the strong connections between four core components and six key targets were verified using a molecular docking method. Following that, the core components of the CCMM extract were identified using UHPLC-Q-Orbitrap HRMS analysis. Finally, in vivo experiments demonstrated that CCMM and four core components could improve the density, motility, viability of sperm, lecithin corpuscle density, decrease the rate of sperm malformation and testis tissue damage, and regulate the protein expressions of AKT1, MAPK3/1, EGFR, and TNF-α in a mouse model of MI. UHPLC-Q-Orbitrap HRMS analysis and in vivo experiments further validated the results of data mining, network pharmacology, and molecular docking. Our study could uncover the components, mechanisms, and functions of TCM prescriptions against MI and develop a new integrative approach to demonstrate TCM’s multi-component, multi-target, and multi-pathway approach to disease treatment.
Lower risk of ischemic stroke among patients with chronic kidney disease using chinese herbal medicine as add-on therapy: A real-world nationwide cohort study
Authors: Shen Hsuan-Shu , Hsu Chung-Yi , Yip Hei-Tung , Lin I-Hsin
Published: August 2022

Background: The incidence of ischemic stroke (IS) is much higher among patients with chronic kidney disease (CKD) compared to the general population. Few studies have evaluated the association between the risk of IS and the use of Chinese herbal medicine (CHM) in patients with CKD. We aimed to investigate the risk of IS among patients with CKD using CHM as add-on therapy.

Methods: We conducted a retrospective cohort study based on Taiwan’s National Health Insurance Research Database to assess 21,641 patients with newly diagnosed CKD between 2003 and 2012. Patients were classified as either the CHM (n = 3,149) or the non-CHM group (n = 3,149) based on whether they used CHM after first diagnosis of CKD. We used the proportional subdistribution hazards model of Fine and Gray to examine the hazard ratio (HR) of IS in propensity-score matched samples at a ratio of 1:1 for two groups.

Results: The risk of IS was significantly reduced in the CHM group (adjusted HR [aHR]: 0.58, 95% confidence interval [CI]: 0.48–0.70) compared with the non-CHM group. Those who used CHM for >180 days had an even lower risk of IS than those in the non-CHM group (aHR: 0.51, 95% CI: 0.41–0.63). Additionally, frequently prescribed formulae, such as Ji-Sheng-Shen-Qi-Wan, Liu-Wei-Di-Huang-Wan, and Zhen-Wu-Tang were associated with a 30%–50% reduced risk of IS.

Conclusion: Our results suggest that patients with CKD who used CHM as add-on therapy had a lower hazard of IS than those in the non-CHM group, especially for patients taking CHM for >180 days. Further experimental studies are required to clarify the causal relationship.
Cinnamomum cassia (L.) J.Presl Alleviates Allergic Responses in Asthmatic Mice via Suppression of MAPKs and MMP-9
Authors: Lim Je-Oh , Kim Yun Hee , Lee Ik Soo , Kim Woong-Il , Lee Se-Jin , Pak So-Won , Shin In-Sik , Kim Taesoo
Published: August 2022

The prevalence of asthma is gradually increasing, and endangers human health. Many therapeutic agents have been developed to address this concern. Cinnamomum cassia (L.) J.Presl is a traditional herbal remedy in China, Japan, and Korea and used mainly to control common cold, cough, pneumonitis and fever in Donguibogam, a medical encyclopedia of Korea. Therefore, we investigated whether C. cassia (L.) J.Presl extract (CCE) confers protective effects on asthma model induced by ovalbumin (OVA). The animals were received intraperitoneal administration of OVA on day 1 and 14, and then subjected to OVA inhalation from day 21–23. They were orally treated CCE (30 and 100 mg/kg) from day 18–23. CCE administration decreased allergic responses, including airway hyperresponsiveness, eosinophilia, inflammatory cytokine production, and immunoglobulin E in OVA-exposed mice, along with the decline in inflammatory cell count and mucus secretion in respiratory tract. Additionally, CCE suppressed MAPK phosphorylation and MMP-9 expression in OVA-exposed mice. Overall, CCE treatment attenuated allergic responses induced by OVA exposure, which may be connected to the suppression of MAPK phosphorylation.
Enhanced healing of oral chemical burn by inhibiting inflammatory factors with an oral administration of shengFu oil
Authors: Yin Xin , Hong Jing , Tang He-Bin , Liu Min , Li Yu-Sang
Published: August 2022

ShengFu oil is a compounded Chinese medicinal prescription, and provides antibacterial, anti-inflammatory, and analgesic effects, favoring burn wound repair. In this study, we aimed at investigating the effects of topical applications of ShengFu oil and its active ingredients in oral chemical burns and elucidating its regulatory effects on β-catenin, COX-2, and MMP-9 expression caused by exposure to acid or alkaline agents. ShengFu oil contains 16 components, such as Frankincense, Radix Scutellariae and Radix Rehmanniae, and the main active ingredients from Frankincense are α-pinene, linalool, and n-octanol. Mouse models of oral chemical burns were induced by using glacial acetic acid or sodium hydroxide. Hematoxylin and eosin staining and immunohistochemical staining were used to detect the protein expressions of β-catenin, COX-2, and MMP-9 in wound tissues. They were further quantified by multispectral imaging analysis to clarify the effective mechanism of ShengFu oil for intervening inflammatory factors and active components. Our results indicated that the application of ShengFu oil on oral chemical burns effectively stopped the oral burn bleeding and reduced the inflammatory reaction in the damaged tissues, demonstrating that ShengFu oil can promote wound tissue repair in burns caused by heat, acids, and alkalis. The immunohistochemical staining results illustrated that ShengFu oil and its active ingredients significantly reversed the abnormal changes in inflammation-related proteins in mouse tongue tissues that were caused by chemical burns. Regarding long-term toxic effects of ShengFu oil on the gastrointestinal tract, liver, and kidney system, the results of hematoxylin and eosin staining experiments depicted that ShengFu oil was safe and effective for liver, kidney, intestine, esophagus, and tongue. All of these demonstrated that ShengFu oil and its active ingredients are effective and safe in preventing and treating oral chemical burns by interfering with the inflammatory microenvironment.
Distinct alterations of fecal microbiota refer to the efficacy of adalimumab in Crohn’s disease
Authors: Chen Liang , Lu Zhanjun , Kang Dengfeng , Feng Zhongsheng , Li Gengfeng , Sun Mingming , Liu Zhanju , Wu Wei , Fang Leilei
Published: August 2022

Background and Aims: Anti-tumor necrosis factor mAb (i.e., adalimumab, ADA) is currently used in the treatment of patients with Crohn’s disease (CD). However, its regulation on fecal microbiota is still not fully understood.

Methods: A retrospective analysis was conducted on 115 patients with CD who received treatment with ADA for 12 weeks at the Inflammatory Bowel Disease Center in Shanghai Tenth People’s Hospital and Department of Gastroenterology in Shanghai General Hospital. The Crohn’s disease activity index (CDAI) evaluation was applied to patients before ADA therapy at week 0, 4, 8, and 12. Clinical remission (CR) was defined as the CDAI < 150. All patients underwent ileocolonoscopy or enteroscopy at baseline (week 0) and week 12. Crohn’s Disease Endoscopic Index of Severity (CDEIS) scores were calculated by two experienced physicians to assess endoscopic activity. Mucosal healing (MH) was assigned a CDEIS score between 0 and 3. Fecal samples were collected from eight CD patients at baseline and week 12, and the microbiota was analyzed by using 16S RNA sequencing.

Results: At week 12, CR was achieved in 70.6% (72/102) of the patients with active CD. A total of 47.1% (48/102) of the patients with active CD attained MH, among which, 56.6% (30/53) of the patients with mildly active CD (3 ≤ CDEIS <9) and 48.0% (12/25) of the moderately active CD patients (9 ≤ CDEIS <12) attained MH, but only 25.0% (6/24) achieved MH in severely active CD patients (CDEIS ≥12). The efficacy of ADA was not associated with lesion locations (χ2 = 0.409, p = 0.815). Unexpectedly, we found an increase in protective microbiota at the genus level (e.g., Barnesiella, Anaerostipes, Tyzzerella, Lachnoclostridium, and Lachnospiraceae_unclassified) but a decrease in pathogenic bacteria (Escherichia–Shigella) in fecal samples of the ADA-responsive group (ADA-R) when compared with those in the ADA-nonresponsive group (ADA-NR). Notably, the gene bglX coding β-glucosidase and gph encoding phosphoglycolate phosphatase were enriched in fecal samples of ADA-R. Conversely, the abundance of genes coding ATP-binding cassette (ABC) transporter system proteins was significantly enriched in fecal samples of ADA-NR when compared with that of the ADA-R.

Conclusion: This study reveals that ADA markedly improves clinical remission and induces MH in mildly to moderately active CD patients and that distinct changes in the gut microbiota can be used to predict the efficacy of ADA.
Kuoxin Decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysis
Authors: Peng Longping , Ma Mengjiao , Dong Yidan , Wu Qiong , An Shiying , Cao Min , Wang Yi , Zhou Chang , Zhou Maolin , Wang Xu , Liang Qianqian , Wang Youhua
Published: August 2022

Background: Inadequate lymphangiogenesis is closely related to the occurrence of many kinds of diseases, and one of the important treatments is to promote lymphangiogenesis. Kuoxin Decoction (KXF) is an herbal formula from traditional Chinese medicine used to treat dilated cardiomyopathy (DCM), which is associated with lymphangiogenesis deficiency. In this study, we comprehensively verified whether KXF promotes lymphangiogenesis in zebrafish and in vitro based on network analysis.

Methods: We performed virtual screening of the active compounds of KXF and potential targets regarding DCM based on network analysis. Tg (Flila: EGFP; Gata1: DsRed) transgenic zebrafish embryos were treated with different concentrations of KXF for 48 h with or without the pretreatment of MAZ51 for 6 h, followed by morphological observation of the lymphatic vessels and an assessment of lymphopoiesis. RT-qPCR was employed to identify VEGF-C, VEGF-A, PROX1, and LYVE-1 mRNA expression levels in different groups. After the treatment of lymphatic endothelial cells (LECs) with different concentrations of salvianolic acid B (SAB, the active ingredient of KXF), their proliferation, migration, and protein expression of VEGF-C and VEGFR-3 were compared by CCK-8 assay, wound healing assay, and western blot.

Results: A total of 106 active compounds were identified constituting KXF, and 58 target genes of KXF for DCM were identified. There were 132 pathways generated from KEGG enrichment, including 5 signaling pathways related to lymphangiogenesis. Zebrafish experiments confirmed that KXF promoted lymphangiogenesis and increased VEGF-C and VEGF-A mRNA expression levels in zebrafish with or without MAZ51-induced thoracic duct injury. In LECs, SAB promoted proliferation and migration, and it could upregulate the protein expression of VEGF-C and VEGFR-3 in LECs after injury.

Conclusion: The results of network analysis showed that KXF could regulate lymphangiogenesis through VEGF-C and VEGF-A, and experiments with zebrafish confirmed that KXF could promote lymphangiogenesis. Cell experiments confirmed that SAB could promote the proliferation and migration of LECs and upregulate the protein expression of VEGF-C and VEGFR-3. These results suggest that KXF promotes lymphangiogenesis by a mechanism related to the upregulation of VEGF-C/VEGFR-3, and the main component exerting this effect may be SAB.
Ruthenium complexes show potent inhibition of AKR1C1, AKR1C2, and AKR1C3 enzymes and anti-proliferative action against chemoresistant ovarian cancer cell line
Authors: Kljun Jakob , Pavlič Renata , Hafner Eva , Lipec Tanja , Moreno-Da Silva Sara , Tič Primož , Turel Iztok , Büdefeld Tomaž , Stojan Jure , Rižner Tea Lanišnik
Published: August 2022

In this study, we present the synthesis, kinetic studies of inhibitory activity toward aldo-keto reductase 1C (AKR1C) enzymes, and anticancer potential toward chemoresistant ovarian cancer of 10 organoruthenium compounds bearing diketonate (1–6) and hydroxyquinolinate (7–10) chelating ligands with the general formula [(η6-p-cymene)Ru(chel)(X)]n+ where chel represents the chelating ligand and X the chlorido or pta ligand. Our studies show that these compounds are potent inhibitors of the AKR enzymes with an uncommon inhibitory mechanism, where two inhibitor molecules bind to the enzyme in a first fast and reversible step and a second slower and irreversible step. The binding potency of each step is dependent on the chemical structure of the monodentate ligands in the metalloinhibitors with the chlorido complexes generally acting as reversible inhibitors and pta complexes as irreversible inhibitors. Our study also shows that compounds 1–9 have a moderate yet better anti-proliferative and anti-migration action on the chemoresistant ovarian cancer cell line COV362 compared to carboplatin and similar effects to cisplatin.
Case Report: Clinical complete response of advanced renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion by treated by camrelizumab and axitinib: A rare case report
Authors: Zhao Juping , Dai Kun , Xie Jialing , Fang Chen , Chen Na , Dai Jun , Xu Danfeng
Published: August 2022

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusions is a rare subtype of renal tumor. This entity predominantly occurs in juveniles, but rarely in adults. Xp11.2 translocation RCC (tRCC) patients with lymph node or organ metastasis are associated with poor prognosis, and the strategy remains controversial. Herein, we presented our experience with the diagnosis and treatment of an adult case of Xp11.2 tRCC. In our clinical practice, a 32-year-old male manifested fever and right flank paroxysmal blunt pain, and computed tomography showed an inhomogeneous mass, 6 cm in diameter, in the right kidney. Then right partial nephrectomy (PN) and renal hilar lymph node dissection by laparoscopic surgery were performed. Pathology revealed that the tumor cells were positive for TFE3 immunohistologically and positive for TFE3 break-apart fluorescence in situ hybridization assay. A splice site mutation c.1544-1G>T of protein tyrosine phosphatase receptor delta (PTPRD) was detected by next-generation sequencing and weak PTPRD expression was confirmed in tumor tissues compared to tumor periphery. This patient was diagnosed with stage III RCC and received immune checkpoint inhibitor (camrelizumab) in combination with tyrosine kinase inhibitor (axitinib) treatment for 1 year. He achieved a clinical complete response with no sign of recurrence or metastasis. PTPRD mutation might be a favorable indicator for Xp11.2 tRCC patients managed by PN and followed by the adjuvant therapy of immune checkpoint inhibitor and tyrosine kinase inhibitor.
Roles of exosomes and exosome-derived miRNAs in pulmonary fibrosis
Authors: Yang Yongfeng , Huang Hong , Li Yi
Published: August 2022

Pulmonary fibrosis is a chronic, progressive fibrosing interstitial lung disease of unknown etiology that leads rapidly to death. It is characterized by the replacement of healthy tissue through an altered extracellular matrix and damage to the alveolar structure. New pharmacological treatments and biomarkers are needed for pulmonary fibrosis to ensure better outcomes and earlier diagnosis of patients. Exosomes are nanoscale vesicles released by nearly all cell types that play a central role as mediators of cell-to-cell communication. Moreover, exosomes are emerging as a crucial factor in antigen presentation, immune response, immunomodulation, inflammation, and cellular phenotypic transformation and have also shown promising therapeutic potential in pulmonary fibrosis. This review summarizes current knowledge of exosomes that may promote pulmonary fibrosis and be utilized for diagnostics and prognostics. In addition, the utilization of exosomes and their cargo miRNAs as novel therapeutics and their potential mechanisms are also discussed. This review aims to elucidate the role of exosomes in the pathogenesis of pulmonary fibrosis and paves the way for developing novel therapeutics for pulmonary fibrosis. Further in-depth research and clinical trials on this topic are encouraged in the future.
Curcuma longa and Boswellia serrata Extracts Modulate Different and Complementary Pathways on Human Chondrocytes In Vitro: Deciphering of a Transcriptomic Study
Authors: Sanchez Christelle , Zappia Jérémie , Lambert Cécile , Foguenne Jacques , Dierckxsens Yvan , Dubuc Jean-Emile , Delcour Jean-Pierre , Gothot André , Henrotin Yves
Published: August 2022

Objectives:Curcuma longa (CL) and Boswellia serrata (BS) extracts are used to relieve osteoarthritis symptoms. The aim of this in vitro study was to investigate their mechanisms of action at therapeutic plasmatic concentrations on primary human osteoarthritic (OA) chondrocytes.

Methods: BS (10–50 μg/ml) and CL (0.4–2 μg/ml corresponding to 1–5 µM of curcumin) were evaluated separately or in combination on primary chondrocytes isolated from 17 OA patients and cultured in alginate beads. Ten patients were used for RNA-sequencing analysis. Proteomic confirmation was performed either by immunoassays in the culture supernatant or by flow cytometry for cell surface markers after 72 h of treatment.

Results: Significant gene expression modifications were already observed after 6 h of treatment at the highest dose of CL (2 μg/ml) while BS was significantly effective only after 24 h of treatment irrespective of the concentration tested. The most over-expressed genes by CL were anti-oxidative, detoxifying, and cytoprotective genes involved in the Nrf2 pathway. Down-regulated genes were principally pro-inflammatory cytokines and chemokines. Inversely, BS anti-oxidant/detoxifying activities were related to the activation of Nrf1 and PPARα pathways. BS anti-inflammatory effects were associated with the increase in GDF15, decrease in cholesterol cell intake and fatty acid metabolism-involved genes, and down-regulation of Toll-like receptors (TLRs) activation. Similar to CL, BS down-regulated ADAMTS1, 5, and MMP3, 13 genes expression. The combination of both CL and BS was significantly more effective than CL or BS alone on many genes such as IL-6, CCL2, ADAMTS1, and 5.

Conclusion: BS and CL have anti-oxidative, anti-inflammatory, and anti-catabolic activities, suggesting a protective effect of these extracts on cartilage. Even if they share some mechanism of action, the two extracts act mainly on distinct pathways, and with different time courses, justifying their association to treat osteoarthritis.
Astragaloside IV promotes pharmacological effect of Descurainia sophia seeds on isoproterenol-induced cardiomyopathy in rats by synergistically modulating the myosin motor
Authors: Liu Xingkai , Chen Qian , Ji Xuming , Yu Wanchen , Wang Tong , Han Juanjuan , Li Shumu , Liu Jianan , Zeng Fangang , Zhao Yao , Zhang Yanyan , Luo Qun , Wang Shijun , Wang Fuyi
Published: August 2022

Descurainia sophia seeds (DS), Astragalus mongholicus (AM), and their formulas are widely used to treat heart failure caused by various cardiac diseases in traditional Chinese medicine practice. However, the molecular mechanism of action of DS and AM has not been completely understood. Herein, we first used mass spectrometry coupled to UPLC to characterize the chemical components of DS and AM decoctions, then applied MS-based quantitative proteomic analysis to profile protein expression in the heart of rats with isoproterenol-induced cardiomyopathy (ISO-iCM) before and after treated with DS alone or combined with AM, astragaloside IV (AS4), calycosin-7-glucoside (C7G), and Astragalus polysaccharides (APS) from AM. We demonstrated for the first time that DS decoction alone could reverse the most of differentially expressed proteins in the heart of the rats with ISO-iCM, including the commonly recognized biomarkers natriuretic peptides (NPPA) of cardiomyopathy and sarcomeric myosin light chain 4 (MYL4), relieving ISO-iCM in rats, but AM did not pronouncedly improve the pharmacological efficiency of DS. Significantly, we revealed that AS4 remarkably promoted the pharmacological potency of DS by complementarily reversing myosin motor MYH6/7, and further downregulating NPPA and MYL4. In contrast, APS reduced the efficiency of DS due to upregulating NPPA and MYL4. These findings not only provide novel insights to better understanding in the combination principle of traditional Chinese medicine but also highlight the power of mass spectrometric proteomics strategy combined with conventional pathological approaches for the traditional medicine research.
Melatonin promotes sirtuin 1 expression and inhibits IRE1α–XBP1S–CHOP to reduce endoplasmic reticulum stress–mediated apoptosis in chondrocytes
Authors: Qin Kunpeng , Tang Hao , Ren Yi , Yang Di , Li Yetian , Huang Wei , Wu Yunfeng , Yin Zongsheng
Published: August 2022

Osteoarthritis (OA) is the most common chronic disease characterized by a loss of chondrocytes and the degeneration of cartilage. Inflammation plays an important role in the pathogenesis and progression of OA via the activation of the endoplasmic reticulum (ER) stress signaling pathway. In this study, we stimulated human primary chondrocytes with lipopolysaccharide (LPS) to reduce cell viability and induce chondrocyte apoptosis. LPS–stimulated human primary chondrocytes induced ER stress and significantly upregulated the ER chaperone glucose–regulated protein 78 (GRP78) and increased the expression level of C/EBP–homologous protein (CHOP), a key mediator of ER stress––induced apoptosis. Interestingly, melatonin treatment attenuated ER stress–mediated chondrocyte apoptosis. Melatonin inhibited the expression of cleaved caspase-3, cleaved caspase-10, Bax, CHOP, GRP78, cleaved caspase-4, phospho–inositol–requiring enzyme 1α (P-IRE1α), and spliced X-box-binding protein 1 (XBP1S). In an anterior cruciate ligament transection mouse model of OA, melatonin (50 and 150 mg/kg) dose–dependently relieved joint cartilage degeneration and inhibitied of chondrocyte apoptosis. Immunohistochemical analysis indicated that melatonin could promote SIRT1 the expression and inhibit CHOP and cleaved caspase-3 expression in OA mice. In conclusion, our findings demonstrate for the first time that melatonin inhibits the IRE1α-XBP1S-CHOP signaling pathway by promoting the expression of SIRT1 in LPS-treated human chondrocytes and delaying OA progression in vivo.