bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anastasis: cell recovery mechanisms and potential role in cancer
Authors: Mohammed Rebar N. , Khosravi Mohsen , Rahman Heshu Sulaiman , Adili Ali , Kamali Navid , Soloshenkov Pavel Petrovich , Thangavelu Lakshmi , Saeedi Hossein , Shomali Navid , Tamjidifar Rozita , Isazadeh Alireza , Aslaminabad Ramin , Akbari Morteza 
Published: June 2022

AbstractBalanced cell death and survival are among the most important cell development and homeostasis pathways that can play a critical role in the onset or progress of malignancy steps. Anastasis is a natural cell recovery pathway that rescues cells after removing the apoptosis-inducing agent or brink of death. The cells recuperate and recover to an active and stable state. So far, minimal knowledge is available about the molecular mechanisms of anastasis. Still, several involved pathways have been explained: recovery through mitochondrial outer membrane permeabilization, caspase cascade arrest, repairing DNA damage, apoptotic bodies formation, and phosphatidylserine. Anastasis can facilitate the survival of damaged or tumor cells, promote malignancy, and increase drug resistance and metastasis. Here, we noted recently known mechanisms of the anastasis process and underlying molecular mechanisms. Additionally, we summarize the consequences of anastatic mechanisms in the initiation and progress of malignancy, cancer cell metastasis, and drug resistance.
Bayesian analysis of dynamic phosphoproteomic data identifies protein kinases mediating GPCR responses
Authors: Leo Kirby T. , Chou Chung-Lin , Yang Chin-Rang , Park Euijung , Raghuram Viswanathan , Knepper Mark A. 
Published: June 2022

AbstractBackgroundA major goal in the discovery of cellular signaling networks is to identify regulated phosphorylation sites (“phosphosites”) and map them to the responsible protein kinases. The V2 vasopressin receptor is a G-protein coupled receptor (GPCR) that is responsible for regulation of renal water excretion through control of aquaporin-2-mediated osmotic water transport in kidney collecting duct cells. Genome editing experiments have demonstrated that virtually all vasopressin-triggered phosphorylation changes are dependent on protein kinase A (PKA), but events downstream from PKA are still obscure.MethodsHere, we used: 1) Tandem mass tag-based quantitative phosphoproteomics to experimentally track phosphorylation changes over time in native collecting ducts isolated from rat kidneys; 2) a clustering algorithm to classify time course data based on abundance changes and the amino acid sequences surrounding the phosphosites; and 3) Bayes’ Theorem to integrate the dynamic phosphorylation data with multiple prior “omic” data sets covering expression, subcellular location, known kinase activity, and characteristic surrounding sequences to identify a set of protein kinases that are regulated secondary to PKA activation.ResultsPhosphoproteomic studies revealed 185 phosphosites regulated by vasopressin over 15 min. The resulting groups from the cluster algorithm were integrated with Bayes’ Theorem to produce corresponding ranked lists of kinases likely responsible for each group. The top kinases establish three PKA-dependent protein kinase modules whose regulation mediate the physiological effects of vasopressin at a cellular level. The three modules are 1) a pathway involving several Rho/Rac/Cdc42-dependent protein kinases that control actin cytoskeleton dynamics; 2) mitogen-activated protein kinase and cyclin-dependent kinase pathways that control cell proliferation; and 3) calcium/calmodulin-dependent signaling.ConclusionsOur findings identify a novel set of downstream small GTPase effectors and calcium/calmodulin-dependent kinases with potential roles in the regulation of water permeability through actin cytoskeleton rearrangement and aquaporin-2 trafficking. The proposed signaling network provides a stronger hypothesis for the kinases mediating V2 vasopressin receptor responses, encouraging future targeted examination via reductionist approaches. Furthermore, the Bayesian analysis described here provides a template for investigating signaling via other biological systems and GPCRs.
Single-cell sequencing analysis reveals gastric cancer microenvironment cells respond vastly different to oxidative stress
Authors: Yu Weihua , Chen Guojun , Yan Jiafei , Wang Xianfa , Zhu Yiping , Zhu Linghua 
Published: June 2022

AbstractGastric cancer is a common type of gastrointestinal malignant tumor in China. The mechanism of the development and progression of gastric cancer remains the continuing research focus. The tumor microenvironment plays an important role in the development and progression of tumors. The present study used single-cell sequencing data to characterize the microenvironment of gastric cancer, investigate the effects of oxidative stress on gastric cancer microenvironmental cells through the comparison between cancer tissue and normal tissue, and identify the key genes associated with gastric cancer patients’ survival. The results showed that compared with normal gastric tissue, gastric cancer tissue had a decreased oxidative stress response, weaker oxidative detoxification ability, and increased oxidative stress-induced cell death. In the different types of single cells of gastric cancer microenvironment, the oxidative stress response of T cell was increased, the ability of oxidative detoxification was enhanced, and the oxidative stress-induced cell death was exacerbate. Mucous cell showed the same trend as gastric cancer cells: decreased oxidative stress response, weak oxidative detoxification ability, and weakened oxidative stress-induced cell death. Moreover, TRIM62, MET, and HBA1, which were significantly associated with oxidative stress, may be biomarkers for the prognosis of gastric cancer. High expression of TRIM62 indicated a good prognosis, while MET and HBA1 indicated a poor prognosis, which will be confirmed by further clinical studies.
CEST MRI and MALDI imaging reveal metabolic alterations in the cervical lymph nodes of EAE mice
Authors: Thomas Aline M. , Yang Ethan , Smith Matthew D. , Chu Chengyan , Calabresi Peter A. , Glunde Kristine , van Zijl Peter C. M. , Bulte Jeff W. M. 
Published: June 2022

AbstractBackgroundMultiple sclerosis (MS) is a neurodegenerative disease, wherein aberrant immune cells target myelin-ensheathed nerves. Conventional magnetic resonance imaging (MRI) can be performed to monitor damage to the central nervous system that results from previous inflammation; however, these imaging biomarkers are not necessarily indicative of active, progressive stages of the disease. The immune cells responsible for MS are first activated and sensitized to myelin in lymph nodes (LNs). Here, we present a new strategy for monitoring active disease activity in MS, chemical exchange saturation transfer (CEST) MRI of LNs.Methods and resultsWe studied the potential utility of conventional (T2-weighted) and CEST MRI to monitor changes in these LNs during disease progression in an experimental autoimmune encephalomyelitis (EAE) model. We found CEST signal changes corresponded temporally with disease activity. CEST signals at the 3.2 ppm frequency during the active stage of EAE correlated significantly with the cellular (flow cytometry) and metabolic (mass spectrometry imaging) composition of the LNs, as well as immune cell infiltration into brain and spinal cord tissue. Correlating primary metabolites as identified by matrix-assisted laser desorption/ionization (MALDI) imaging included alanine, lactate, leucine, malate, and phenylalanine.ConclusionsTaken together, we demonstrate the utility of CEST MRI signal changes in superficial cervical LNs as a complementary imaging biomarker for monitoring disease activity in MS. CEST MRI biomarkers corresponded to disease activity, correlated with immune activation (surface markers, antigen-stimulated proliferation), and correlated with LN metabolite levels.
DKK3 ameliorates neuropathic pain via inhibiting ASK-1/JNK/p-38-mediated microglia polarization and neuroinflammation
Authors: Zhang Long-Qing , Gao Shao-Jie , Sun Jia , Li Dan-Yang , Wu Jia-Yi , Song Fan-He , Liu Dai-Qiang , Zhou Ya-Qun , Mei Wei 
Published: June 2022

Abstract
Background
Neuropathic pain is a common and severely disabling state that affects millions of people worldwide. Microglial activation in the spinal cord plays a critical role in the pathogenesis of neuropathic pain. However, the mechanisms underlying spinal microglial activation during neuropathic pain remain incompletely understood. Here, we investigated the role of Dickkopf (DKK) 3 and its interplay with microglial activation in the spinal cord in neuropathic pain.

Methods
In this study, we investigated the effects of intrathecal injection of recombinant DKK3 (rDKK3) on mechanical allodynia and microglial activation in the spinal cord after spared nerve injury (SNI) in rats by western blot (WB), immunofluorescence (IF), quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA).

Results
We found that SNI induced a significant decrease in the levels of DKK3, Kremen-1 and Dishevelled-1 (DVL-1) and up-regulated the expression of phosphorylated apoptosis signal-regulating kinase 1 (p-ASK1), phosphorylated c-JUN N-terminal kinase (p-JNK), phosphorylated p38 (p-p38) in the spinal cord. Moreover, our results showed that exogenous intrathecal administration of rDKK3 inhibited expression of p-ASK1, p-JNK, p-p38, promoted the transformation of microglia from M1 type to M2 type, and decreased the production of pro-inflammatory cytokines compared to the rats of SNI + Vehicle. However, these effects were reversed by intrathecal administration of Kremen-1 siRNA or Dishevelled-1 (DVL-1) siRNA.

Conclusions
These results suggest that DKK3 ameliorates neuropathic pain via inhibiting ASK-1/JNK/p-38-mediated microglia polarization and neuroinflammation, at least partly, by the Kremen-1 and DVL-1 pathways.
Origin and evolution analysis and genetic characteristics of echovirus 9 in China
Authors: Si Fenfen , Ji Tianjiao , Wang Dongyan , Zhang Yong , Zhu Shuangli , Li Junhan , Xu Wenbo , Yan Dongmei 
Published: June 2022

Abstract
Background
Echovirus 9 (E9) is associated with a wide variety of diseases and medical conditions, and the clinical symptoms of sporadic cases caused by E9 often are severe. With a high global prevalence, E9 has caused multiple outbreaks worldwide. However, little is known about the genetic and geographic population dynamics of E9.

Method
A total of 131 VP1 gene sequences, including15 generated in this study and 116 obtained from GenBank, were used to coestimate time-resolved phylogenies to infer viral evolution and transmission in worldwide. Overlapping fragments representing whole genomes were amplified by reverse transcription polymerase chain reaction (RT-PCR) using specific primers. Then, we reported the genetic characteristics of fifteen E9 strains in the Chinese Mainland. Similarity plots and bootscanning analysis were used to determine recombination patterns of E9.

Results
The estimated mean evolutionary rate of global E9 VP1 gene was 4.278 × 10−3 substitutions per site per year (95% confidence interval [CI], 3.822 × 10−3/site/year to 4.710 × 10−3/site/year), and the common ancestor of E9 likely emerged around 1868 (95% CI, 1840 to 1892). The full-length genomic sequences of the fifteen E9 strains showed 76.9–79.6% nucleotide identity and 95.3–95.9% amino acid identity with E9 Barty strain. 11 of 15 E9 whole genome sequence present four recombination patterns, and E9 recombinants have extensive genetic exchanges in the 2C and P3 regions with other Enterovirus B (EV-B) circulated in China. Four of six E9 strains were temperature sensitive, and two were temperature resistant, and a comparative genomics analysis suggested that 411, 865 and 867 amino acid substitution in the P1 region was related to temperature sensitivity.

Conclusion
This study highlights a persistent transmission network of E9 in worldwide, provides valuable information regarding the molecular epidemiology of E9.
Effects of fasudil on blood–brain barrier integrity
Authors: Sato Kei , Nakagawa Shinsuke , Morofuji Yoichi , Matsunaga Yuki , Fujimoto Takashi , Watanabe Daisuke , Izumo Tsuyoshi , Niwa Masami , Walter Fruzsina R. , Vigh Judit P. , Santa-Maria Ana Raquel , Deli Maria A. , Matsuo Takayuki 
Published: June 2022

Abstract
Background
Cerebral infarction accounts for 85% of all stroke cases. Even in an era of rapid and effective recanalization using an intravascular approach, the majority of patients have poor functional outcomes. Thus, there is an urgent need for the development of therapeutic agents to treat acute ischemic stroke. We evaluated the effect of fasudil, a Rho kinase inhibitor, on blood brain barrier (BBB) functions under normoxia or oxygen–glucose deprivation (OGD) conditions using a primary cell-based in vitro BBB model.

Methods
BBB models from rat primary cultures (brain capillary endothelial cells, astrocytes, and pericytes) were subjected to either normoxia or 6 h OGD/24 h reoxygenation. To assess the effects of fasudil on BBB functions, we evaluated real time impedance, transendothelial electrical resistance (TEER), sodium fluorescein permeability, and tight junction protein expression using western blotting. Lastly, to understand the observed protective mechanism on BBB functions by fasudil we examined the role of cyclooxygenase-2 and thromboxane A2 receptor agonist U-46619 in BBB-forming cells.

Results
We found that treatment with 0.3–30 µM of fasudil increased cellular impedance. Fasudil enhanced barrier properties in a concentration-dependent manner, as measured by an increased (TEER) and decreased permeability. Fasudil also increased the expression of tight junction protein claudin-5. Reductions in TEER and increased permeability were observed after OGD/reoxygenation exposure in mono- and co-culture models. The improvement in BBB integrity by fasudil was confirmed in both of the models, but was significantly higher in the co-culture than in the monoculture model. Treatment with U-46619 did not show significant changes in TEER in the monoculture model, whereas it showed a significant reduction in TEER in the co-culture model. Fasudil significantly improved the U-46619-induced TEER reduction in the co-culture models. Pericytes and astrocytes have opposite effects on endothelial cells and may contribute to endothelial injury in hyperacute ischemic stroke. Overall, fasudil protects the integrity of BBB both by a direct protective effect on endothelial cells and by a pathway mediated via pericytes and astrocytes.

Conclusions
Our findings suggest that fasudil is a BBB-protective agent against acute ischemic stroke.
Claudin-5a is essential for the functional formation of both zebrafish blood-brain barrier and blood-cerebrospinal fluid barrier
Authors: Li Yanyu , Wang Chunchun , Zhang Liang , Chen Bing , Mo Yuqian , Zhang Jingjing 
Published: June 2022

Abstract
Background
Mammalian Claudin-5 is the main endothelial tight junction component maintaining blood-brain barrier (BBB) permeability, while Claudin-1 and -3 seal the paracellular space of choroid plexus (CP) epithelial cells contributing to the blood-cerebrospinal fluid barrier (BCSFB). In zebrafish, two paralogs of claudin-5a and -5b are expressed while their roles in the formation of BBB and BCSFB are unclear.

Methods
The expression patterns of Claudin-5a and -5b in zebrafish brains were systematically analyzed by immunofluorescence (IF) assay. The developmental functions of Claudin-5a and -5b were characterized by generating of claudin-5a and -5b mutants respectively. Meanwhile, the cerebral inflammation and cell apoptosis in claudin-5a-/- were assessed by live imaging of transgenic zebrafish, RT-qPCR, IF, and TUNEL assay. The integrity of BBB and BCSFB was evaluated by in vivo angiographic and dye permeation assay. Finally, RT-qPCR, whole-mount RNA in situ hybridization (WISH), and transmission electron microscopy (TEM) analyses were performed to investigate the development of cerebral vessels and choroid plexus.

Results
We showed that Claudin-5a and -5b are both expressed in zebrafish cerebrovascular endothelial cells (ECs). In addition, Claudin-5a was strongly expressed in CP epithelial cells. Loss of Claudin-5b showed no effect on zebrafish vasculogenesis or BBB function. In contrast, the knockout of claudin-5a caused a lethal phenotype of severe whole-brain oedema, ventricular dilatation, and cerebral hernia in zebrafish larvae, although the cerebral vasculogenesis and the development of CP were not altered. In claudin-5a-/- , although ultrastructural analysis of CP and cerebral capillary showed intact integrity of epithelial and endothelial tight junctions, permeability assay indicated a disruption of both BBB and BCSFB functions. On the molecular level, it was found that ZO-1 was upregulated in the CP epithelium of claudin-5a-/-, while the notch and shh pathway responsible for CP development was not affected due to loss of Claudin-5a.

Conclusions
Our findings verified a non-functional role of zebrafish Claudin-5b in the BBB and identified Claudin-5a as the ortholog of mammalian Claudin-5, contributing to the development and the functional maintenance of both BBB and BCSFB.
The influence of minimally invasive esophagectomy versus open esophagectomy on postoperative pulmonary function in esophageal cancer patients: a meta-analysis
Authors: Su Jingwen , Li Shuang , Sui Qiyu , Wang Gongchao 
Published: June 2022

Abstract
Objective
To compare the influence of minimally invasive esophagectomy (MIE) and open esophagectomy (OE) on postoperative pulmonary function in patients with esophageal cancer.

Methods
Studies about the influence of MIE and OE on postoperative pulmonary function in esophageal cancer patients were searched from PubMed, EMBASE, the Cochrane Library, CNKI, Chinese Science and Technology Journal Database, CBM, and Wanfang Data from inception to March 18, 2021. Meta-analysis was performed using the RevMan 5.3.

Results
This analysis included eight studies, enrolling 264 patients who underwent MIE and 257 patients who underwent OE. The meta-analysis results showed that the MIE group had a higher outcome regarding the percent predicted vital capacity (%VC), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximum voluntary ventilation (MVV) 1 month after surgery than the OE group. In addition, those who underwent MIE had lower ΔVC%, ΔFVC, and ΔFEV1 between pre-operation and 1 month after surgery than those who underwent OE. There is no statistical difference between the two groups in ΔMVV.

Conclusion
Compared with OE, MIE has a more protective effect on postoperative pulmonary function. However, due to the small number of included literature and all cohort studies, this finding needs to be validated with larger samples and higher quality RCT studies.
Surgical treatment of type A acute aortic dissection with cerebral malperfusion: a systematic review
Authors: Wang Changtian , Zhang Lei , Li Tao , Xi Zhilong , Wu Haiwei , Li Demin 
Published: June 2022

Abstract
Objectives
Type A acute aortic dissection (TAAAD) complicated with cerebral malperfusion (CM) is a life-threatening condition associated with high mortality, poor outcomes, and the optimal surgical management remains controversial. The aim of this review was to report the current results of surgical interventions of these patients.

Methods
A systematic review was performed using PubMed and MEDLINE search for cases underwent surgical repair for TAAAD with CM. Demographics, neurological symptom, the time from onset of symptoms to operation, operation data, mortality, neurological outcome, and follow-up were reviewed.

Results
A total of 363 patients with mean age of 65.7 ± 13 years underwent surgical repair for TAAAD with CM were identified in 12 retrospective studies. In-hospital mortality was 20.1%. Mean duration of follow-up was 40.1 ± 37.6 months. The involved supra-aortic branch vessels were RCCA (n = 99), LCCA (n = 25), B-CCA (n = 52), CCA (n = 131), IA (n = 19), and LSA (n = 8). Time from onset of neurological symptoms to surgery was 13.3 h. Antegrade and/or retrograde cerebral perfusion were applied. Postoperatively, improved, unchanged and worsened neurological status was occurred in 54.3%, 27.1%, and 8.5%, respectively in 199 patients.

Conclusion
The outcomes of surgical treatment of TAAAD complicated with CM indicate acceptable early mortality and morbidity. It is reasonable to perform lifesaving surgery on these patients. Early central surgical repair and reperfusion of brain may improve the outcomes.
Impact of sleep debt, social jetlag, and insomnia symptoms on presenteeism and psychological distress of workers in Japan: a cross-sectional study
Authors: Takano Yuta , Ibata Rui , Nakano Norihito , Sakano Yuji 
Published: June 2022

Abstract
Background
Presenteeism is an indicator of productivity loss and the risk of absence from work due to mental health problems. The purpose of this study was to determine the impact of sleep debt, social jetlag, and insomnia symptoms on presenteeism and psychological distress.

Methods
The participants were 351 Japanese workers (271 males, 79 females, and one of other gender, with a mean age of 49 ± 9.49 years). The eligibility criteria for this study were full-time employment, working eight hours per day, five days per week, and no night shifts. The participants answered questionnaires measuring sleep debt, social jetlag, insomnia symptoms, presenteeism, and psychological distress.

Results
Insomnia symptoms had the greatest impact on presenteeism and psychological distress when compared with sleep debt and social jetlag (adjusted odds ratio (OR) = 5.61, 95% confidence interval (CI) = 2.88–10.91; adjusted OR = 7.29, 95%CI = 3.06–17.35). Sleep debt had a greater impact on presenteeism and psychological distress than did social jetlag (adjusted OR = 1.61, 95%CI = 1.14–2.27; adjusted OR = 1.68, 95%CI = 1.11–2.54), which had no impact on these variables (adjusted OR = 1.04, 95%CI = 0.91–1.20; adjusted OR = 0.96, 95%CI = 0.76–1.22).

Conclusions
The findings of this study indicated that insomnia symptoms had a more significant impact on presenteeism and psychological distress than social jetlag and sleep debt. Although sleep debt might have an independent impact on presenteeism and psychological distress, social jetlag did not.