bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of MMP2 rs243849 and rs14070 genetic polymorphisms on the ischemic stroke susceptibility in Chinese Shaanxi population
Authors: Li Shilin , Yang Shiyao , Zhang Xiaobo , Zhang Yu , Zhang Jie , Zhang Xiao , Li Weiping , Niu Xiaochen , Shi Wenzhen , Zhang Gejuan , Chang Mingze , Tian Ye
Published: July 2022

Background

Ischemic stroke (IS) is a complex neurological disease affected by genetics and environment. Matrix metalloproteinase-2 (MMP2) is involved in extracellular matrix (ECM) degradation, inflammation and angiogenesis to regulate the development and recovery of IS.

Purposes

The aim of this study was to explore the association of rs1053605, rs243849 and rs14070 in MMP2 with the risk of IS in Chinese Shaanxi population.

Methods

In this study, 677 IS patients and 681 normal controls were recruited. Rs1053605, rs243849 and rs14070 in MMP2 were genotyped. Logistic regression analysis was applied to evaluate the association of rs1053605, rs243849 and rs14070 in MMP2 with IS susceptibility and the association of environmental factors with MMP2 genetic susceptibility to IS.

Results

The results of the overall analysis demonstrated that rs14070 in MMP2 significantly reduced the risk of IS in Chinese Shaanxi population (OR = 0.767, 95% CI = 0.619–0.952, P = 0.016). Subgroup analysis illustrated that rs243849 in MMP2 evidently increased the risk of IS among drinkers, while rs14070 in MMP2 apparently reduced IS susceptibility among females, participants with aged >55, smokers and drinkers.

Conclusions

Collectively, rs243849 and rs14070 in MMP2 were significantly associated with the risk of IS in Chinese Shaanxi population, and the effect of MMP2 to IS may be associated with its genetic susceptibility.
The effect of endovascular baroreflex amplification on central sympathetic nerve circuits and cerebral blood flow in patients with resistant hypertension: A functional MRI study
Authors: Groenland Eline H. , van Kleef Monique E. A. M. , Hendrikse Jeroen , Spiering Wilko , Siero Jeroen C. W.
Published: July 2022

Background

Endovascular baroreflex amplification (EVBA) by implantation of the MobiusHD is hypothesized to lower blood pressure by decreasing sympathetic activity through the mechanism of the baroreflex. In the present exploratory study we investigated the impact of MobiusHD implantation on central sympathetic nerve circuits and cerebral blood flow (CBF) in patients with resistant hypertension.

Materials and methods

In thirteen patients, we performed blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) at rest and during Valsalva maneuvers, before and 3 months after EVBA. Data were analyzed using a whole-brain approach and a brainstem-specific analysis. CBF was assessed using arterial spin labeling MRI.

Results

Resting-state fMRI analysis did not reveal significant differences in functional connectivity at 3 months after EVBA. For the Valsalva maneuver data, the whole-brain fMRI analysis revealed significantly increased activation in the posterior and anterior cingulate, the insular cortex, the precuneus, the left thalamus and the anterior cerebellum. The brainstem-specific fMRI analysis showed a significant increase in BOLD activity in the right midbrain 3 months after EVBA. Mean gray matter CBF (partial volume corrected) decreased significantly from 48.9 (9.9) ml/100 gr/min at baseline to 43.4 (13.0) ml/100 gr/min (p = 0.02) at 3 months.

Conclusions

This first fMRI pilot study in patients with resistant hypertension treated with EVBA showed a significant increase in BOLD activity during the Valsalva maneuver in brain regions related to sympathetic activity. No notable signal intensity changes were observed in brain areas involved in the baroreflex circuit. Future randomized controlled studies are needed to investigate whether the observed changes are directly caused by EVBA.

Clinical trial registration

www.clinicaltrials.gov, identifier: NCT02827032.
A novel perspective of associativity of upper limb motor impairment and cortical excitability in sub-acute and chronic stroke
Authors: Saini Megha , Singh Neha , Kumar Nand , Srivastava M. V. Padma , Mehndiratta Amit
Published: July 2022

Background

The global inclination of stroke onset in earlier years of life and increased lifespan have resulted in an increased chronic post-stroke-related disability. The precise and simplistic approach such as the correlation of Fugl-Meyer Assessment (FMA) with Transcranial Magnetic Stimulation (TMS) parameters, Resting Motor Threshold (RMT) and Motor Evoked Potential (MEP), in patients with stroke might play a critical role, given the prognostic value of MEP, a measure of cortical excitability, and might be the key point in prescribing appropriate therapeutic strategies.

Objective

The study aimed to determine the correlation of FMA-based impairment in the upper extremity function specifically of the wrist and hand with respect to the neurophysiological parameters of corticospinal tract integrity.

Materials and methods

The Institutional Review Board approved the study and 67 (n) patients with stroke were enrolled in the Department of Neurology, AIIMS, New Delhi, India. The motor assessment was performed on patients by the upper extremity subset of Fugl-Meyer Assessment (FMA) and the clinical history was obtained. RMT and MEP of Extensor Digitorum Communis (EDC) muscle were measuredviaTMS.

Results

A significant positive correlation was observed between Fugl-Meyer Assessment Wrist/Hand (FMA W/H) and MEP scores (r= 0.560, <0.001). Also, Fugl-Meyer Assessment Upper Extremity (FMA UE) scores demonstrated a moderate positive association with MEP responsiveness (r= 0.421, <0.001).

Conclusion

MEP of the EDC muscle was found to be associated with sensorimotor control as measured by FMA. Moreover, FMA W/H score values might be a better prognostic indicator of EDC MEP responsiveness. Interestingly, a novel element comprising the range of FMA UE and FMA W/H components was observed to be a potential indicator of MEP responsiveness and could also indicate establishing FMA as a surrogate for TMS in resource-limited settings for prognostification.
Gut microbes and food reward: From the gut to the brain
Authors: de Wouters d’Oplinter Alice , Huwart Sabrina J. P. , Cani Patrice D. , Everard Amandine
Published: July 2022

Inappropriate food intake behavior is one of the main drivers for fat mass development leading to obesity. Importantly the gut microbiota-mediated signals have emerged as key actors regulating food intake acting mainly on the hypothalamus, and thereby controlling hunger or satiety/satiation feelings. However, food intake is also controlled by the hedonic and reward systems leading to food intake based on pleasure (i.e., non-homeostatic control of food intake). This review focus on both the homeostatic and the non-homeostatic controls of food intake and the implication of the gut microbiota on the control of these systems. The gut-brain axis is involved in the communications between the gut microbes and the brain to modulate host food intake behaviors through systemic and nervous pathways. Therefore, here we describe several mediators of the gut-brain axis including gastrointestinal hormones, neurotransmitters, bioactive lipids as well as bacterial metabolites and compounds. The modulation of gut-brain axis by gut microbes is deeply addressed in the context of host food intake with a specific focus on hedonic feeding. Finally, we also discuss possible gut microbiota-based therapeutic approaches that could lead to potential clinical applications to restore food reward alterations. Therapeutic applications to tackle these dysregulations is of utmost importance since most of the available solutions to treat obesity present low success rate.
Extraction, purification, structural features and biological activities of longan fruit pulp (Longyan) polysaccharides: A review
Authors: Yue Xuan , Chen Zhejie , Zhang Jinming , Huang Chi , Zhao Shiyi , Li Xuebo , Qu Yan , Zhang Chen
Published: July 2022

Dimocarpus longan Lour. (also called as longan) is a subtropical and tropical evergreen tree belonging to the Sapindaceae family and is widely distributed in China, Southeast Asia and South Asia. The pulp of longan fruit is a time-honored traditional medicinal and edible raw material in China and some Asian countries. With the advancement of food therapy in modern medicine, longan fruit pulp as an edible medicinal material is expected to usher in its rapid development as a functional nutrient. As one of the main constituents of longan fruit pulp, longan fruit pulp polysaccharides (LPs) play an indispensable role in longan fruit pulp-based functional utilization. This review aims to outline the extraction and purification methods, structural characteristics and biological activities (such as immunoregulatory, anti-tumor, prebiotic, anti-oxidant, anti-inflammatory and inhibition of AChE activity) of LPs. Besides, the structure-activity relationship, application prospect and patent application of LPs were analyzed and summarized. Through the systematic summary, this review attempts to provide a theoretical basis for further research of LPs, and promote the industrial development of this class of polysaccharides.
Assessment of water consumption during Ramadan intermittent fasting: Result from Indonesian cross-sectional study
Authors: Sunardi Diana , Chandra Dian Novita , Medise Bernie Endyarni , Friska Dewi , Manikam Nurul Ratna Mutu , Lestari Wiji , Insani Putri Novia Choiri , Ayusari Amelya Augusthina , Mayasari Diana , Saftarina Fitria , Sari Dina Keumala , Ulvie Yuliana Noor Setiawati
Published: July 2022

During Ramadan fasting, people are likely to consume water and beverages lower than recommended intake due to the limited time. However, it is necessary to achieve the recommended daily water intake to maintain the hydration status, as well as productivity during fasting. Unfortunately, there is a lack of data on drinking patterns during Ramadan. This study aims to investigate water and beverage intake and drinking patterns to help achieve water requirements during Ramadan among Indonesian adults. This is a cross-sectional study conducted during the Ramadan period from April to May 2021 (Ramadan 1442 Hijri). We used a self-administered questionnaire on drinking habits during Ramadan and utilized a 7-day fluid record (Liq.In 7) to assess water and beverage intake among participants who were managed through online procedure. There were 380 participants from five universities across Indonesia who completed the questionnaire accordingly and then analyzed it. The result shows that total water and beverage intake during Ramadan among participants was below the recommendation [1,670 (1,326–2,034) ml/day]. Among the type of beverages, water is the highest level of consumption [1,262 (983–1,666) ml/day] then followed by sugar-sweetened beverages [200 (91–350) ml/day]. We found a significant difference in water and beverages consumption between time of iftar [474 (375–590) ml/day], nighttime [574 (414–810) ml/day], and suhoor [560 (423–711) ml/day]. From this study, we found that during Ramadan the most common drinking pattern is 2-4-2, but a drinking pattern of 4-2-2 glasses (sequence of four glasses at iftar, two glasses at nighttime, two glasses at suhoor) had a significantly higher chance to adhere with the recommendation of fluid intake compared to other patterns. Therefore, based on this research on water and beverage intake, it is necessary and important to make improvements among Indonesian adults during Ramadan, and the drinking pattern of 4-2-2 glasses may help to achieve the recommended daily water consumption.
Tachysterol2 increases the synthesis of fibroblast growth factor 23 in bone cells
Authors: Ewendt Franz , Kotwan Julia , Ploch Stefan , Feger Martina , Hirche Frank , Föller Michael , Stangl Gabriele I.
Published: July 2022

Tachysterol2 (T2) is a photoisomer of the previtamin D2 found in UV-B-irradiated foods such as mushrooms or baker’s yeast. Due to its structural similarity to vitamin D, we hypothesized that T2 can affect vitamin D metabolism and in turn, fibroblast growth factor 23 (FGF23), a bone-derived phosphaturic hormone that is transcriptionally regulated by the vitamin D receptor (VDR). Initially, a mouse study was conducted to investigate the bioavailability of T2 and its impact on vitamin D metabolism and Fgf23 expression. UMR106 and IDG-SW3 bone cell lines were used to elucidate the effect of T2 on FGF23 synthesis and the corresponding mechanisms. LC-MS/MS analysis found high concentrations of T2 in tissues and plasma of mice fed 4 vs. 0 mg/kg T2 for 2 weeks, accompanied by a significant decrease in plasma 1,25(OH)2D and increased renal Cyp24a1 mRNA abundance. The Fgf23 mRNA abundance in bones of mice fed T2 was moderately higher than that in control mice. The expression of Fgf23 strongly increased in UMR106 cells treated with T2. After Vdr silencing, the T2 effect on Fgf23 diminished. This effect is presumably mediated by single-hydroxylated T2-derivatives, since siRNA-mediated silencing of Cyp27a1, but not Cyp27b1, resulted in a marked reduction in T2-induced Fgf23 gene expression. To conclude, T2 is a potent regulator of Fgf23 synthesis in bone and activates Vdr. This effect depends, at least in part, on the action of Cyp27a1. The potential of oral T2 to modulate vitamin D metabolism and FGF23 synthesis raises questions about the safety of UV-B-treated foods.
Effect of depression disorder on the efficacy and quality of life of first-line chemotherapy combined with immunotherapy in oncogene-driver negative NSCLC patients
Authors: Li Wen , Bi Ziran , Wu Junxu , Duan Xu , Pang Lulian , Jing Yanyan , Yin Xiangxiang , Cheng Huaidong
Published: July 2022

Objective

The current research was to assess the relevance between depression disorder and first-line chemotherapy combined with immunotherapy, quality of life in patients with oncogene-driver negative non-small cell cancer (NSCLC).

Methods

NSCLC patients (33 with depression disorder and 34 with no depression disorder) who was received first-line chemotherapy combined with immunotherapy performed Zung Self-rating Depression Scale (SDS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).

Results

The Progression-Free Survival (PFS) of depression disorder group survivors were lower than these of no depression disorder group survivors (HR, 0.352; 95% CI, 0.201-0.617; P<0.05). The statistical significant was revealed about the Objective Response Rate (ORR) and Disease Control Rate (DCR) in two groups (P<0.05). The quality of life scores of NSCLC patients in no depression disorder group was significantly higher after chemotherapy combined with immunotherapy, and manifested as 92.7 ± 28 vs. 76.3 ± 23.3 (t=8.317, P<0.05), and had a significant difference.

Conclusion

Depression disorder in oncogene-driver negative NSCLC patients influence the curative effect of chemotherapy combined with immunotherapy, and depression disorder was significantly negatively associated with quality of life following chemotherapy combined with immunotherapy.
A Review of Mathematical and Computational Methods in Cancer Dynamics
Authors: Uthamacumaran Abicumaran , Zenil Hector
Published: July 2022

Cancers are complex adaptive diseases regulated by the nonlinear feedback systems between genetic instabilities, environmental signals, cellular protein flows, and gene regulatory networks. Understanding the cybernetics of cancer requires the integration of information dynamics across multidimensional spatiotemporal scales, including genetic, transcriptional, metabolic, proteomic, epigenetic, and multi-cellular networks. However, the time-series analysis of these complex networks remains vastly absent in cancer research. With longitudinal screening and time-series analysis of cellular dynamics, universally observed causal patterns pertaining to dynamical systems, may self-organize in the signaling or gene expression state-space of cancer triggering processes. A class of these patterns, strange attractors, may be mathematical biomarkers of cancer progression. The emergence of intracellular chaos and chaotic cell population dynamics remains a new paradigm in systems medicine. As such, chaotic and complex dynamics are discussed as mathematical hallmarks of cancer cell fate dynamics herein. Given the assumption that time-resolved single-cell datasets are made available, a survey of interdisciplinary tools and algorithms from complexity theory, are hereby reviewed to investigate critical phenomena and chaotic dynamics in cancer ecosystems. To conclude, the perspective cultivates an intuition for computational systems oncology in terms of nonlinear dynamics, information theory, inverse problems, and complexity. We highlight the limitations we see in the area of statistical machine learning but the opportunity at combining it with the symbolic computational power offered by the mathematical tools explored.
Radionuclide 131I-labeled albumin-indocyanine green nanoparticles for synergistic combined radio-photothermal therapy of anaplastic thyroid cancer
Authors: Zhang Xuemei , Yan Ziyu , Meng Zhaowei , Li Ning , Jia Qiang , Shen Yiming , Ji Yanhui
Published: July 2022

Objectives

Anaplastic thyroid cancer (ATC) cells cannot retain the radionuclide iodine 131 (131I) for treatment due to the inability to uptake iodine. This study investigated the feasibility of combining radionuclides with photothermal agents in the diagnosis and treatment of ATC.

Methods

131I was labeled on human serum albumin (HSA) by the standard chloramine T method. 131I-HSA and indocyanine green (ICG) were non-covalently bound by a simple stirring to obtain 131I-HSA-ICG nanoparticles. Characterizations were performed in vitro. The cytotoxicity and imaging ability were investigated by cell/in vivo experiments. The radio-photothermal therapy efficacy of the nanoparticles was evaluated at the cellular and in vivo levels.

Results

The synthesized nanoparticles had a suitable size (25–45 nm) and objective biosafety. Under the irradiation of near-IR light, the photothermal conversion efficiency of the nanoparticles could reach 24.25%. In vivo fluorescence imaging and single-photon emission CT (SPECT)/CT imaging in small animals confirmed that I-HSA-ICG/131I-HSA-ICG nanoparticles could stay in tumor tissues for 4–6 days. Compared with other control groups, 131I-HSA-ICG nanoparticles had the most significant ablation effect on tumor cells under the irradiation of an 808-nm laser.

Conclusions

In summary, 131I-HSA-ICG nanoparticles could successfully perform dual-modality imaging and treatment of ATC, which provides a new direction for the future treatment of iodine-refractory thyroid cancer.
MiR-520a-5p/PPP5C regulation pattern is identified as the key to gemcitabine resistance in pancreatic cancer
Authors: Fu Ruibiao , Shao Qian , Yang Bin , Chen Yan , Ye Qinghuang , Chen Xi , Zhu Jinhui
Published: July 2022

Objective

To explore the effects of the expression level of miR-520-5p/PPP5C in pancreatic cancer cells and exosomes on cell viability, angiogenesis, autophagy, which involved in the mechanism of gemcitabine resistance in pancreatic cancer.

Methods

APSC-1 cell line was treated with gemcitabine, after which its exosomes were extracted for NTA assay. Subsequently, the drug resistance of APSC-1 cells was assayed using CCK8, as well as the activity of HUVEC cells treated with exosomes from each group of APSC-1 cells after drug resistance treatment as well as overexpression treatment. Five groups of HUVEC cells treated with exosomes were subjected to in vitro tubule formation assay. levels of PPP5C in each group of ASPC-1 cells and their exosomes, levels of overexpressed PPP5C, and related exosomal proteins were examined by WB. mRNA expression levels of PPP5C and levels of miR-520a were examined by qPCR The relationship between miR-520a-5p and PPP5C was investigated. After that, the autophagy of PPP5C was detected. Finally, it was analyzed by TCGA database for survival prognosis analysis.

Results

APSC-1 cells had an IC50 value of 227.1 μM for gemcitabine, elevated PPP5C expression, drug resistance, and enhanced HUVEC cell activity; exosomes CD9, CD63, and CD81 were significantly expressed in all groups; meanwhile, enhanced PPP5C expression not only promoted in vitro tubule formation but also increased autophagy levels; meanwhile, its relationship with miR-520-5p and There was a targeted inhibitory relationship between its level and miR-520-5p and PPP5C, and its elevated level also led to a decrease in the survival level of patients over 3-5 years.

Conclusion

PPP5C has a prognostic role in pancreatic cancer by promoting the value-added and invasion of pancreatic cancer cells, and a targeted inhibitory relationship between miR-520-5p and PPP5C was found.
Successful sequential tyrosine kinase inhibitors to overcome a rare compound of EGFR exon 18–18 and EGFR amplification: A case report
Authors: Wang Pascal , Fabre Emmanuelle , Martin Antoine , Chouahnia Kader , Benabadji Ambre , Matton Lise , Duchemann Boris
Published: July 2022

Background

New mutational detection techniques like next-generation sequencing have resulted in an increased number of cases with uncommon mutation and compound mutations [3%–14% of all epidermal growth factor receptor (EGFR) mutations]. In rare exon 18 mutations (3%–6%), G719X and E709X represent the majority, but CMut associating these exon 18 points mutations are even rarer, making the understanding of the impact of epidermal growth factor receptor tyrosine kinase inhibitors still limited. Three generations of EGFR tyrosine kinase inhibitors (TKIs) are available to target EGFR mutations, but according to the types of mutations, the sensitivity to TKI is different. Afatinib, osimertinib, and neratinib have showed some effectiveness in single exon 18, but no report has precisely described their efficiency and acquired mechanism of resistance in a CMut of exon 18–18 (G719A and E709A).

Case presentation

We report a case of a 26-year-old woman with bilateral advanced adenocarcinoma of the lung harboring a compound mutation associating G719A and E709A in exon 18, who developed an EGFR amplification as resistance mechanism to osimertinib. She presented a significant clinical and morphological response under sequential TKIs treatment (afatinib, osimertinib, and then neratinib).

Conclusion

A non-small cell lung cancer (NSCLC) with rare compound mutation exon 18–exon 18 (G719A and E709A) and EGFR amplification can be overcome with adapted sequential second- and third-generation TKIs. This report has potential implications in guiding decisions for the treatment of these rare EGFR mutations.
Stabilization of CCDC102B by Loss of RACK1 Through the CMA Pathway Promotes Breast Cancer Metastasis via Activation of the NF-κB Pathway
Authors: Si Jing , Guo Rong , Xiu Bingqiu , Chi Weiru , Zhang Qi , Hou Jianjing , Su Yonghui , Chen Jiajian , Xue Jingyan , Shao Zhi-Ming , Wu Jiong , Chi Yayun
Published: July 2022

Background

Breast cancer is one of the leading causes of cancer-related death among women, and the pathological status of axillary lymph nodes is an important predictor of prognosis. However, the mechanism involved in this early stage of metastasis remains largely unknown.

Methods

Microarray analysis was used to carry out differential genomics analyses between matched pairs of metastatic sentinel lymph node tissues and breast primary tumors. The CRISPR/Cas9 gene editing system was used for in vivo screening by transplanting a loss-of-function cell pool into immunocompromised mice. MAGeCK was used to analyze the screening results. Survival analysis was performed via the Kaplan–Meier method. Cell proliferation, wound healing, migration and invasion assays were performed to confirm the phenotype. A tail vein model and subcutaneous xenotransplanted tumor model were used for the in vivo study. The relationship between coiled-coil domain containing 102B (CCDC102B) and receptor for activated C kinase 1 (RACK1) was examined using coimmunoprecipitation, mass spectrometry, nuclear protein extraction and immunofluorescence assays. The primary biological functions and pathways related to CCDC102B were enriched by RNA sequencing.

Results

We identified CCDC102B through screening and found that it was significantly upregulated in metastatic lesions in lymph nodes compared to matched primary tumors. Increased expression of CCDC102B promoted breast cancer metastasis in vitro and in vivo. Additionally, high expression of CCDC102B was correlated with poor clinical outcomes in breast cancer patients. We further identified that CCDC102B was stabilized by the loss of RACK1, a protein negatively correlated with breast cancer metastasis. Mechanistically, we found that RACK1 promoted CCDC102B lysosomal degradation by mediating chaperone-mediated autophagy (CMA). The aggressive behavior of CCDC102B in breast cancer cells could be reversed by the expression of RACK1. Moreover, CCDC102B was correlated with the significant enrichment of NF-κB pathway components. Overexpressing CCDC102B led to less interaction between RACK1 and IKKa. Thus, CCDC102B positively regulates the NF−κB pathway by interacting with RACK1.

Conclusion

Taken together, our findings uncover a novel role of CCDC102B in breast cancer metastasis. CCDC102B serves as a potential metastasis promoter by regulating the activation of the NF-κB pathway and can be degraded by RACK1 via CMA.
Cyclooxygenase-2 Upregulated by Temozolomide in Glioblastoma Cells Is Shuttled In Extracellular Vesicles Modifying Recipient Cell Phenotype
Authors: Lombardi Francesca , Augello Francesca Rosaria , Artone Serena , Ayroldi Emira , Giusti Ilaria , Dolo Vincenza , Cifone Maria Grazia , Cinque Benedetta , Palumbo Paola
Published: July 2022

Temozolomide (TMZ) resistance is frequent in patients with glioblastoma (GBM), a tumor characterized by a marked inflammatory microenvironment. Recently, we reported that cyclooxygenase-2 (COX-2) is upregulated in TMZ-resistant GBM cells treated with high TMZ concentrations. Moreover, COX-2 activity inhibition significantly counteracted TMZ-resistance of GBM cells. Extracellular vesicles (EV) are considered crucial mediators in orchestrating GBM drug resistance by modulating the tumor microenvironment (TME) and affecting the surrounding recipient cell phenotype and behavior. This work aimed to verify whether TMZ, at low and clinically relevant doses (5-20 µM), could induce COX-2 overexpression in GBM cells (T98G and U87MG) and explore if secreted EV shuttled COX-2 to recipient cells. The effect of COX-2 inhibitors (COXIB), Celecoxib (CXB), or NS398, alone or TMZ-combined, was also investigated. Our results indicated that TMZ at clinically relevant doses upregulated COX-2 in GBM cells. COXIB treatment significantly counteracted TMZ-induced COX-2 expression, confirming the crucial role of the COX-2/PGE2 system in TMZ-resistance. The COXIB specificity was verified on U251MG, COX-2 null GBM cells. Western blotting of GBM-EV cells showed the COX-2 presence, with the same intracellular trend, increasing in EV derived from TMZ-treated cells and decreasing in those derived from COXIB+TMZ-treated cells. We then evaluated the effect of EV secreted by TMZ-treated cells on U937 and U251MG, used as recipient cells. In human macrophage cell line U937, the internalization of EV derived by TMZ-T98G cells led to a shift versus a pro-tumor M2-like phenotype. On the other hand, EV from TMZ-T98G induced a significant decrease in TMZ sensitivity in U251MG cells. Overall, our results, in confirming the crucial role played by COX-2 in TMZ-resistance, provide the first evidence of the presence and effective functional transfer of this enzyme through EV derived from GBM cells, with multiple potential consequences at the level of TME.
Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma
Authors: Xing Jiahua , Jia Ziqi , Li Yan , Han Yan
Published: July 2022

Background

Cutaneous melanoma (CM), a kind of skin cancer with a high rate of advanced mortality, exhibits a wide variety of driver and transmitter gene alterations in the immunological tumor microenvironment (TME) associated with tumor cell survival and proliferation.

Methods

We analyzed the immunological infiltration of TME cells in normal and malignant tissues using 469 CM and 556 normal skin samples. We used a single sample gene set enrichment assay (ssGSEA) to quantify the relative abundance of 28 cells, then used the LASSO COX regression model to develop a riskScore prognostic model, followed by a small molecule drug screening and molecular docking validation, which was then validated using qRT-PCR and IHC.

Results

We developed a prognosis model around seven essential protective genes for the first time, dramatically elevated in tumor tissues, as did immune cell infiltration. Multivariate Cox regression results indicated that riskScore is an independent and robust prognostic indicator, and its predictive value in immunotherapy was verified. Additionally, we identified Gabapentin as a possible small molecule therapeutic for CM.

Conclusions

A riskScore model was developed in this work to analyze patient prognosis, TME cell infiltration features, and treatment responsiveness. The development of this model not only aids in predicting patient response to immunotherapy but also has significant implications for the development of novel immunotherapeutic agents and the promotion of tailored treatment regimens.
New functions of DDR1 collagen receptor in tumor dormancy, immune exclusion and therapeutic resistance
Authors: Sirvent Audrey , Espie Kevin , Papadopoulou Evangelia , Naim Dana , Roche Serge
Published: July 2022

The tumor microenvironment facilitates cancer progression and therapeutic resistance. Tumor collagens and their architecture play an essential role in this process. However, little is known about the mechanisms by which tumor cells sense and respond to this extracellular matrix environment. Recently, the Discoidin Domain Receptor 1 (DDR1), a collagen receptor and tyrosine kinase has emerged as an important player in this malignant process, although the underlying signaling mechanisms remain unclear. Here, we review new DDR1 functions in tumor dormancy following dissemination, immune exclusion and therapeutic resistance induced by stromal collagens deposition. We also discuss the signaling mechanisms behind these tumor activities and the therapeutic strategies aiming at targeting these collagens-dependent tumor responses.
An Apriori Algorithm-Based Association Analysis of Analgesic Drugs in Chinese Medicine Prescriptions Recorded From Patients With Rheumatoid Arthritis Pain
Authors: Lai Wei-dong , Li Dian-ming , Yu Jie , Huang Lin , Zheng Ming-zhi , Jiang Yue-peng , Wang Song , Wen Jun-jun , Chen Si-jia , Wen Cheng-ping , Jin Yan
Published: July 2022

Chronic pain, a common symptom of people with rheumatoid arthritis, usually behaves as persistent polyarthralgia pain and causes serious damage to patients' physical and mental health. Opioid analgesics can lead to a series of side effects like drug tolerance and addiction. Thus, seeking an alternative therapy and screening out the corresponding analgesic drugs is the key to solving the current dilemma. Traditional Chinese Medicine (TCM) therapy has been recognized internationally for its unique guiding theory and definite curative effect. In this study, we used the Apriori Algorithm to screen out potential analgesics from 311 cases that were treated with compounded medication prescription and collected from “Second Affiliated Hospital of Zhejiang Chinese Medical University” in Hangzhou, China. Data on 18 kinds of clinical symptoms and 16 kinds of Chinese herbs were extracted based on this data mining. We also found 17 association rules and screened out four potential analgesic drugs—“Jinyinhua,” “Wugong,” “Yiyiren,” and “Qingfengteng,” which were promised to help in the clinical treatment. Besides, combined with System Cluster Analysis, we provided several different herbal combinations for clinical references.
Expression and Possible Role of Silent Mating Type Information Regulation 2 Homolog 1 in Post-necrotizing Enterocolitis Stricture in vivo and in vitro
Authors: Chen Rui , Lv Chengjie , Zhao Yun , Gu Weizhong , Zhang Luyin , Shi Bo , Tou Jingfa
Published: July 2022

Purpose

To investigate the expression and possible role of Sirtuin1 or Silent mating–type information regulation 2 homolog-1 (SIRT1) in post-necrotizing enterocolitis stricture.

Materials and Methods

The expression characteristics of SIRT1 and TGF-β1 in post-necrotizing enterocolitis stricture were detected by immunohistochemistry. The siRNA-SIRT1 was used to inhibit the expression of SIRT1 in intestinal epithelial cells-6 (IEC-6), and qRT-PCR, WB, and ELISA were utilized to detect the changes of Transforming growth factor-β1 (TGF-β1), nuclear factor (NF)-κB, tumor necrosis factor-α (TNF-α), tight junction protein-1 (ZO-1), and vascular endothelial growth factor (VEGF) expressions. The IEC-6 cell proliferation and migration ability were tested via CCK8 kit and Transwell test. The expression of E-cadherin and Vimentin in cells was detected by immunofluorescence.

Results

The CRP, IL-6, IL-10, and IFN-γ in the serum of Necrotizing enterocolitis (NEC) intestinal stenosis patients were significantly higher than the reference values. The SIRT1 protein was under-expressed and the TGF-β1 protein was overexpressed in NEC intestinal stenosis tissue. And the expression of SIRT1 was negatively correlated with TGF-β1. At the time of diagnosis of NEC, the expression of SIRT1 decreased in children with respiratory distress syndrome and CRP level increased. After inhibiting the expression of SIRT1 in IEC6 cells, the expression levels of TGF-β1, Smad3, and NF-κB were decreased, and the expression of ZO-1 was also decreased. The proliferation and migration ability of IEC6 cells was decreased significantly, and the expression of E-cadherin and Vimentin proteins in IEC6 cells did not change significantly.

Conclusion

Promotion of intestinal fibrosis by inflammation may be the mechanism of post-necrotizing enterocolitis stricture. SIRT1 may be a protective protein of NEC. The probable mechanism is that SIRT1 can regulate intestinal fibrosis and can protect the intestinal mucosal barrier function to participate in the process of post-necrotizing enterocolitis stricture.
Case report: Is exchange transfusion a possible treatment for metabolic decompensation in neonates with methylmalonic aciduria in the setting of limited resources?
Authors: Cui Xiaoyu , Li Na , Xue Hong , Zhang Fang , Shu Jianbo , Liu Yang
Published: July 2022

Hyperammonemia is a serious complication of methylmalonic acidemia, with high mortality and permanent neurological sequelae in survivors. Primary hospitals are often the first admission hospitals for these children but are limited by their experience and facilities to provide rapid and effective treatment, increasing the risk of death in children with methylmalonic acidemia's metabolic crisis. In this report, we reported a case of a 7-day-old male neonate with decompensated methylmalonic acidemia, who underwent automatic peripheral arteriovenous exchange transfusion. The serum ammonia level of the boy decreased significantly post exchange transfusion. Therefore, we put forward the suggestion of exchange transfusion for hyperammonemia, in combination with medical therapy, in children with inborn errors of metabolism as an initial treatment option in primary hospitals if a rapid transfer to a center with dialysis facilities is not possible.
Buddhist-like opposite diminishing and non-judging during ketamine infusion are associated with antidepressant response: an open-label personalized-dosing study
Authors: Stocker Kurt , Hartmann Matthias , Reissmann Steffen , Kist Andreas , Liechti Matthias E.
Published: July 2022

Background: Cognition that is not dominated by thinking in terms of opposites (opposite diminishing) or by making judgments (non-judging) can be found both in Buddhist/mindfulness contexts and in mental states that are fostered by dissociative psychedelics (N-methyl-D-aspartate antagonists) such as ketamine. Especially for the Buddhist/mindfulness case, both opposite diminishing and non-judging have been proposed to relate to mental well-being. Whether ketamine-occasioned opposite diminishing and/or non-judging relate to increased mental well-being in the form of antidepressant response is unknown, and was investigated in the present study.

Methods: In this open-label outpatient study, the dose level and frequency for the ketamine infusions were adjusted individually in close consultation with the patients suffering from depression with the overall goal to maximize antidepressant benefits—a novel dose regimen that we term personalized antidepressant dosing. In general, treatment started with an initial series of ketamine infusions with a dosage of 0.5 mg/kg body weight and was then adjusted (usually increased). A possible relationship between ketamine-induced antidepressant benefits and retrospectively reported peri-infusion experiences of opposite diminishing and non-judging was assessed based on a total of 45 ketamine-infusion treatment sessions from 11 different patients suffering from depression. Opposite diminishing and non-judging were measured with the two items from the Altered States of Consciousness Inventory (ASCI) that measure these concepts. Depression was measured with the Beck Depression Inventory (BDI-II).

Results: Peri-infusion experiences of both opposite diminishing and non-judging were associated with antidepressant responses confirming our hypothesis. Furthermore, opposite diminishing and non-judging were closely related to one another while relating to antidepressant response in distinguishable ways.

Conclusion: Future controlled randomized trials with dissociative and other psychedelics and with a larger number of participants are needed to establish the possible link of psychedelically induced opposite diminishing and non-judging with an antidepressant response more firmly.
Activation of liver X receptors protects oligodendrocytes in CA3 of stress-induced mice
Authors: Zhu Peilin , Tang Jing , Liang Xin , Luo Yanmin , Wang Jin , Li Yue , Xiao Kai , Li Jing , Deng Yuhui , Jiang Lin , Xiao Qian , Qi Yingqiang , Xie Yuhan , Yang Hao , Zhu Lin , Tang Yong , Huang Chunxia
Published: July 2022

Depression is a complex disorder that is associated with various structural abnormalities. Oligodendrocyte (OL) dysfunction is associated with the pathogenesis of depression and the promotion of hippocampal oligodendrocyte maturation and myelination could be a novel therapeutic strategy for ameliorating depressive behaviors. Recent studies have shown that activation of liver X receptors (LXRs) by GW3965 improves depressive phenotypes, but the effects of GW3965 on OL function and myelination in the hippocampus of depression remain relatively unclear. To address this issue, we investigated the effects of GW3965 on mature OL in the hippocampus and on the myelin sheaths of mice subjected to chronic unpredictable stress (CUS). Behavioral tests were performed to assess depressive behaviors. Then, the number of mature OLs (CC1+) in each hippocampal subregion was precisely quantified with immunohistochemical and stereological methods, and the density of newborn mature OLs (BrdU+/Olig2+/CC1+ cells) in each hippocampal subregion was quantified with immunofluorescence. In addition, myelin basic protein (MBP) staining intensity in the cornu ammonis 3 (CA3) region was assessed by using immunofluorescence. We found that both the number of CC1+ OLs and the density of BrdU+/Olig2+/CC1+ cells were obviously decreased in each hippocampal subregion of mice subjected to CUS, and 4 weeks of GW3965 treatment reversed these effects only in the CA3 region. Furthermore, the decreased MBP expression in the CA3 region of mice subjected to CUS was ameliorated by GW3965 treatment. Collectively, these results suggested that improvement of OL maturation and enhancement of myelination may be structural mechanisms underlying the antidepressant effects of LXR agonists.
Double-Pass Multiple-Plate Continuum for High-Temporal-Contrast Nonlinear Pulse Compression
Authors: Chen Bo-Han , Su Jia-Xuan , Guo Jhan-Yu , Chen Kai , Chu Shi-Wei , Lu Hsuan-Hao , Lu Chih-Hsuan , Yang Shang-Da
Published: July 2022

We propose a new architecture, double-pass multiple-plate continuum (DPMPC), for nonlinear pulse compression. In addition to having a smaller footprint, a double-pass configuration is designed to achieve substantial bandwidth broadening without incurring noticeable higher-order dispersion, thus improving the temporal contrast over those of the traditional single-pass geometry when only the quadratic spectral phase can be compensated. In our proof-of-concept experiment, 187 μJ, 190-fs Yb-based laser pulse is compressed to 20 fs with high throughput (75%), high Strehl ratio (0.76), and excellent beam homogeneity by using DPMPC. The subsequently generated octave-spanning spectrum exhibits a significantly raised blue tail compared with that driven by pulses from a single-pass counterpart.
Biochemical, biophysical, and functional characterisation of the E3 ubiquitin ligase APC/C regulator CDC20 from Arabidopsis thaliana
Authors: Cosma Maria-Alexa , Curtis Natalie L. , Pain Charlotte , Kriechbaumer Verena , Bolanos-Garcia Victor M.
Published: July 2022

The Anaphase Promoting Complex (APC/C), a large cullin-RING E3-type ubiquitin ligase, constitutes the ultimate target of the Spindle Assembly Checkpoint (SAC), an intricate regulatory circuit that ensures the high fidelity of chromosome segregation in eukaryotic organisms by delaying the onset of anaphase until each chromosome is properly bi-oriented on the mitotic spindle. Cell-division cycle protein 20 homologue (CDC20) is a key regulator of APC/C function in mitosis. The formation of the APC/CCDC20 complex is required for the ubiquitination and degradation of select substrates, which is necessary to maintain the mitotic state. In contrast to the roles of CDC20 in animal species, little is known about CDC20 roles in the regulation of chromosome segregation in plants. Here we address this gap in knowledge and report the expression in insect cells; the biochemical and biophysical characterisation of Arabidopsis thaliana (AtCDC20) WD40 domain; and the nuclear and cytoplasmic distribution of full-length AtCDC20 when transiently expressed in tobacco plants. We also show that most AtCDC20 degrons share a high sequence similarity to other eukaryotes, arguing in favour of conserved degron functions in AtCDC20. However, important exceptions were noted such as the lack of a canonical MAD1 binding motif; a fully conserved RRY-box in all six AtCDC20 isoforms instead of a CRY-box motif, and low conservation of key residues known to be phosphorylated by BUB1 and PLK1 in other species to ensure a robust SAC response. Taken together, our studies provide insights into AtCDC20 structure and function and the evolution of SAC signalling in plants.
Multi-Locus Genome-Wide Association Studies to Characterize Fusarium Head Blight (FHB) Resistance in Hard Winter Wheat
Authors: Zhang Jinfeng , Gill Harsimardeep S. , Halder Jyotirmoy , Brar Navreet K. , Ali Shaukat , Bernardo Amy , Amand Paul St. , Bai Guihua , Turnipseed Brent , Sehgal Sunish K.
Published: July 2022

Fusarium head blight (FHB), caused by the fungus Fusarium graminearum Schwabe is an important disease of wheat that causes severe yield losses along with serious quality concerns. Incorporating the host resistance from either wild relatives, landraces, or exotic materials remains challenging and has shown limited success. Therefore, a better understanding of the genetic basis of native FHB resistance in hard winter wheat (HWW) and combining it with major quantitative trait loci (QTLs) can facilitate the development of FHB-resistant cultivars. In this study, we evaluated a set of 257 breeding lines from the South Dakota State University (SDSU) breeding program to uncover the genetic basis of native FHB resistance in the US hard winter wheat. We conducted a multi-locus genome-wide association study (ML-GWAS) with 9,321 high-quality single-nucleotide polymorphisms (SNPs). A total of six distinct marker-trait associations (MTAs) were identified for the FHB disease index (DIS) on five different chromosomes including 2A, 2B, 3B, 4B, and 7A. Further, eight MTAs were identified for Fusarium-damaged kernels (FDK) on six chromosomes including 3B, 5A, 6B, 6D, 7A, and 7B. Out of the 14 significant MTAs, 10 were found in the proximity of previously reported regions for FHB resistance in different wheat classes and were validated in HWW, while four MTAs represent likely novel loci for FHB resistance. Accumulation of favorable alleles of reported MTAs resulted in significantly lower mean DIS and FDK score, demonstrating the additive effect of FHB resistance alleles. Candidate gene analysis for two important MTAs identified several genes with putative proteins of interest; however, further investigation of these regions is needed to identify genes conferring FHB resistance. The current study sheds light on the genetic basis of native FHB resistance in the US HWW germplasm and the resistant lines and MTAs identified in this study will be useful resources for FHB resistance breeding via marker-assisted selection.
Full-length transcriptome sequencing analysis and characterization, development and validation of microsatellite markers in Kengyilia melanthera
Authors: Xiong Yanli , Yang Jian , Xiong Yi , Zhao Junming , Liu Lin , Liu Wei , Sha Lina , Zhou Jiqiong , You Minghong , Li Daxu , Lei Xiong , Bai Shiqie , Ma Xiao
Published: July 2022

As a typical psammophyte of the Triticeae, Kengyilia melanthera possesses high feeding potential and great utilization values in desertification control in the Qinghai-Tibet Plateau. However, few gene function and genetic studies have been performed in K. melanthera. In this study, single-molecule real-time sequencing technology was used to obtain the full-length transcriptome sequence of K. melanthera, following the functional annotation of transcripts and prediction of coding sequences (CDSs), transcription factors (TFs), and long noncoding RNA (lncRNA) sequences. Meanwhile, a total of 42,433 SSR loci were detected, with 5′-UTRs having the most SSR loci and trinucleotide being the most abundant type. In total, 108,399 SSR markers were designed, and 300 SSR markers were randomly selected for diversity verification of K. melanthera. A total of 49 polymorphic SSR markers were used to construct the genetic relationships of 56 K. melanthera accessions, among which 21 SSR markers showed good cross-species transferability among the related species. In conclusion, the full-length transcriptome sequence of the K. melanthera will assist gene prediction and promote molecular biology and genomics research, and the polymorphic SSR markers will promote molecular-assisted breeding and related research of K. melanthera and its relatives.
Toward a smart skin: Harnessing cuticle biosynthesis for crop adaptation to drought, salinity, temperature, and ultraviolet stress
Authors: Liu Lang , Wang Xiaoyu , Chang Cheng
Published: July 2022

Drought, salinity, extreme temperatures, and ultraviolet (UV) radiation are major environmental factors that adversely affect plant growth and crop production. As a protective shield covering the outer epidermal cell wall of plant aerial organs, the cuticle is mainly composed of cutin matrix impregnated and sealed with cuticular waxes, and greatly contributes to the plant adaption to environmental stresses. Past decades have seen considerable progress in uncovering the molecular mechanism of plant cutin and cuticular wax biosynthesis, as well as their important roles in plant stress adaptation, which provides a new direction to drive strategies for stress-resilient crop breeding. In this review, we highlighted the recent advances in cuticle biosynthesis in plant adaptation to drought, salinity, extreme temperatures, and UV radiation stress, and discussed the current status and future directions in harnessing cuticle biosynthesis for crop improvement.