bluuebunny/crossref_metadata_2025_split huggingface dataset:
MALAT1-related signaling pathways in colorectal cancer
Authors: Xu Wen-Wen , Jin Jin , Wu Xiao-yu , Ren Qing-Ling , Farzaneh Maryam 
Published: March 2022

AbstractColorectal cancer (CRC) is one of the most lethal and prevalent solid malignancies worldwide. There is a great need of accelerating the development and diagnosis of CRC. Long noncoding RNAs (lncRNA) as transcribed RNA molecules play an important role in every level of gene expression. Metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1) is a highly conserved nucleus-restricted lncRNA that regulates genes at the transcriptional and post-transcriptional levels. High expression of MALAT1 is closely related to numerous human cancers. It is generally believed that MALAT1 expression is associated with CRC cell proliferation, tumorigenicity, and metastasis. MALAT1 by targeting multiple signaling pathways and microRNAs (miRNAs) plays a pivotal role in CRC pathogenesis. Therefore, MALAT1 can be a potent gene for cancer prediction and diagnosis. In this review, we will demonstrate signaling pathways associated with MALAT1 in CRC.
Microarray analysis of breast cancer gene expression profiling in response to 2-deoxyglucose, metformin, and glucose starvation
Authors: Aoun Rita , El Hadi Christopher , Tahtouh Roula , El Habre Rita , Hilal George 
Published: March 2022

Abstract
Background
Breast cancer (BC) is the most frequently diagnosed cancer in women. Altering glucose metabolism and its effects on cancer progression and treatment resistance is an emerging interest in BC research. For instance, combining chemotherapy with glucose-lowering drugs (2-deoxyglucose (2-DG), metformin (MET)) or glucose starvation (GS) has shown better outcomes than with chemotherapy alone. However, the genes and molecular mechanisms that govern the action of these glucose deprivation conditions have not been fully elucidated. Here, we investigated the differentially expressed genes in MCF-7 and MDA-MB-231 BC cell lines upon treatment with glucose-lowering drugs (2-DG, MET) and GS using microarray analysis to study the difference in biological functions between the glucose challenges and their effect on the vulnerability of BC cells.

Methods
MDA-MB-231 and MCF-7 cells were treated with 20 mM MET or 4 mM 2-DG for 48 h. GS was performed by gradually decreasing the glucose concentration in the culture medium to 0 g/L, in which the cells remained with fetal bovine serum for one week. Expression profiling was carried out using Affymetrix Human Clariom S microarrays. Differentially expressed genes were obtained from the Transcriptome Analysis Console and enriched using DAVID and R packages.

Results
Our results showed that MDA-MB-231 cells were more responsive to glucose deprivation than MCF-7 cells. Endoplasmic reticulum stress response and cell cycle inhibition were detected after all three glucose deprivations in MDA-MB-231 cells and only under the metformin and GS conditions in MCF-7 cells. Induction of apoptosis and inhibition of DNA replication were observed with all three treatments in MDA-MB-231 cells and metformin-treated MCF-7 cells. Upregulation of cellular response to reactive oxygen species and inhibition of DNA repair mechanisms resulted after metformin and GS administration in MDA-MB-231 cell lines and metformin-treated MCF-7 cells. Autophagy was induced after 2-DG treatment in MDA-MB-231 cells and after metformin in MCF-7 cells. Finally, inhibition of DNA methylation were observed only with GS in MDA-MB-231 cells.

Conclusion
The procedure used to process cancer cells and analyze their expression data distinguishes our study from others. GS had the greatest effect on breast cancer cells compared to 2-DG and MET. Combining MET and GS could restrain both cell lines, making them more vulnerable to conventional chemotherapy.
SLC4A4 promotes prostate cancer progression in vivo and in vitro via AKT-mediated signalling pathway
Authors: Liu Zelin , Wang Qinghua , Zhai Guanzhong , Ke Shuai , Yu Xi , Guo Jia 
Published: March 2022

Abstract
Background
Prostate cancer (PCa) is the second leading cause of cancer-related male deaths worldwide. The purpose of this study was to investigate the effects of homo sapiens solute carrier family 4 member 4 (SLC4A4), which encodes the electrogenic Na+/HCO3− cotransporter isoform 1 (NBCe1), in the development and progression of PCa.

Methods
The expression levels of SLC4A4 in PCa and normal prostate tissues were evaluated by immunohistochemistry. The SLC4A4 knockdown cell model was structured by lentiviral infection, and the knockdown efficiency was validated by RT-qPCR and Western blotting. The effects of SLC4A4 knockdown on cell proliferation, apoptosis and cycle, migration, and invasion were detected by Celigo cell counting assay and CCK-8 assay, flow cytometry analysis, wound-healing, and Transwell assay, respectively. Tumor growth in nude mice was surveyed by in vivo imaging and Ki-67 staining. Furthermore, underlying mechanism of SLC4A4 silence induced inhibition of PCa progression was explored by human phospho-kinase array.

Results
Our results revealed that SLC4A4 expression was up-regulated in PCa tissues and human PCa cell lines. High expression of SLC4A4 in tumor specimens was significantly correlated with disease progression. SLC4A4 knockdown inhibited cell proliferation, migration and invasion, while facilitated apoptosis, which was also confirmed in vivo. Moreover, SLC4A4 promoted PCa progression through the AKT-mediated signalling pathway.

Conclusion
The results of this study indicated that SLC4A4 overexpression was closely associated with the progression of PCa; SLC4A4 knockdown suppressed PCa development in vitro and in vivo. SLC4A4 acts as a tumor promotor in PCa by regulating key components of the AKT pathway and may therefore act as a potential therapeutic target for PCa treatment.
The effect of the polycystic ovary syndrome and hypothyroidism on the risk of fibrocystic breast changes: a meta-analysis
Authors: Kohnepoushi Parisa , Dehghanbanadaki Hojat , Mohammadzedeh Pardis , Nikouei Maziar , Moradi Yousef 
Published: March 2022

AbstractThis meta-analysis aimed to determine the pooled association between polycystic ovary syndrome (PCOS), hypothyroidism, and fibrocystic breast changes. We searched important databases, including PubMed (Medline), Scopus, Web of Science, and Embase to retrieve all relevant studies published from 1990 to April 2021. The bias risk of selected articles was assessed based on the JBI checklist. Our search strategy yielded a total of 487 articles from the international databases. After screening their full-texts, 6 articles met the inclusion criteria and were considered for meta-analysis. The effect of PCOS on the incidence of fibrocystic breast changes was 2.49 (95% CI 1.85–3.34). Also, the effect of hypothyroidism on the incidence of fibrocystic breast changes was 1.90 (95% CI 0.92–3.93). The results showed that women with PCOS were at higher risks to develop fibrocystic breast changes.
Durability of three types of dual active ingredient long-lasting insecticidal net compared to a pyrethroid-only LLIN in Tanzania: methodology for a prospective cohort study nested in a cluster randomized controlled trial
Authors: Martin Jackline L. , Messenger Louisa A. , Mosha Franklin W. , Lukole Eliud , Mosha Jacklin F. , Kulkarni Manisha , Churcher Thomas S. , Sherrard-Smith Ellie , Manjurano Alphaxard , Protopopoff Natacha , Rowland Mark 
Published: March 2022

Abstract
Background
Progress achieved by long-lasting insecticidal nets (LLINs) against malaria is threatened by widespread selection of pyrethroid resistance among vector populations. LLINs with non-pyrethroid insecticides are urgently needed. This study aims to assess the insecticide and textile durability of three classes of dual-active ingredient (A.I.) LLINs using techniques derived from established WHO LLIN testing methods to set new standards of evaluation.

Methods
A WHO Phase 3 active ingredients and textile durability study will be carried out within a cluster randomized controlled trial in 40 clusters in Misungwi district, Tanzania. The following treatments will be evaluated: (1) Interceptor®G2 combining chlorfenapyr and the pyrethroid alpha-cypermethrin, (2) Royal Guard® treated with pyriproxyfen and alpha-cypermethrin, (3) Olyset™ Plus which incorporates a synergist piperonyl butoxide and the pyrethroid permethrin, and (4) a reference standard alpha-cypermethrin only LLIN (Interceptor®). 750 nets will be followed in 5 clusters per intervention arm at 6, 12, 24 and 36 months post distribution for survivorship and hole index assessment. A second cohort of 1950 nets per net type will be identified in 10 clusters, of which 30 LLINs will be withdrawn for bio-efficacy and chemical analysis every 6 months up to 36 months and another 30 collected for experimental hut trials every year. Bio-efficacy will be assessed using cone bioassays and tunnel tests against susceptible and resistant laboratory strains of Anopheles gambiae sensu stricto. Efficacy of field-collected nets will be compared in six experimental huts. The main outcomes will be Anopheles mortality up to 72 h post exposure, blood feeding and egg maturation using ovary dissection to assess impact on fecundity.

Conclusions
Study findings will help develop bio-efficacy and physical durability criteria for partner A.I., in relation to the cRCT epidemiological and entomological outcomes, and refine preferred product characteristics of each class of LLIN. If suitable, the bioassay and hut outcomes will be fitted to transmission models to estimate correlation with cRCT outcomes.
Trial registration number: NCT03554616.
Effect of two types of shoulder prosthesis on the muscle forces using a generic multibody model for different arm motions
Authors: Weisse Bernhard , Lama Susan , Piskoty Gabor , Affolter Christian , Aiyangar Ameet K. 
Published: March 2022

Abstract
Background
This study aims to analyze the effects of a novel dual-bearing shoulder prosthesis and a conventional reverse shoulder prosthesis on the deltoid and rotator cuff muscle forces for four different arm motions. The dual-bearing prosthesis is a glenoid-sparing joint replacement with a moving center of rotation. It has been developed to treat rotator cuff arthropathy, providing an increased post-operative functionality.

Methods
A three-dimensional musculoskeletal OpenSim® model of an upper body, incorporating a natural gleno-humeral joint and a scapula-thoracic joint developed by Blana et al. (J Biomech 41: 1714-1721, 2008), was used as a reference for the natural shoulder. It was modified by integrating first a novel dual-bearing prosthesis, and second, a reverse shoulder prosthesis into the shoulder joint complex. Four different arm motions, namely abduction, scaption, internal and external rotation, were simulated using an inverse kinematics approach. For each of the three models, shoulder muscle forces and joint reaction forces were calculated with a 2 kg weight in the hand.

Results
In general, the maximal shoulder muscle force and joint reaction force values were in a similar range for both prosthesis models during all four motions. The maximal deltoid muscle forces in the model with the dual-bearing prosthesis were 18% lower for abduction and 3% higher for scaption compared to the natural shoulder. The maximal rotator cuff muscle forces in the model with the dual-bearing prosthesis were 36% lower for abduction and 1% higher for scaption compared to the natural shoulder. Although the maximal deltoid muscle forces in the model with the dual-bearing prosthesis in internal and external rotation were 52% and 64% higher, respectively, compared to the natural shoulder, the maximal rotator cuff muscle forces were 27% lower in both motions.

Conclusion
The study shows that the dual-bearing shoulder prosthesis is a feasible option for patients with rotator cuff tear and has a strong potential to be used as secondary as well as primary joint replacement. The study also demonstrates that computer simulations can help to guide the continued optimization of this particular design concept for successful clinical outcomes.
Near-roadway air pollution, immune cells and adipokines among obese young adults
Authors: Rahman Md Mostafijur , Liu Fei Fei , Eckel Sandrah P. , Sankaranarayanan Ishwarya , Shafiei-Jahani Pedram , Howard Emily , Baronikian Lilit , Sattler Fred , Lurmann Frederick W. , Allayee Hooman , Akbari Omid , McConnell Rob 
Published: March 2022

AbstractBackgroundAir pollution has been associated with metabolic disease and obesity. Adipokines are potential mediators of these effects, but studies of air pollution-adipokine relationships are inconclusive. Macrophage and T cells in adipose tissue (AT) and blood modulate inflammation; however, the role of immune cells in air pollution-induced dysregulation of adipokines has not been studied. We examined the association between air pollution exposure and circulating and AT adipokine concentrations, and whether these relationships were modified by macrophage and T cell numbers in the blood and AT.MethodsFasting blood and abdominal subcutaneous AT biopsies were collected from 30 overweight/obese 18–26 year-old volunteers. Flow cytometry was used to quantify T effector (Teff, inflammatory) and regulatory (Treg, anti-inflammatory) lymphocytes and M1 [inflammatory] and M2 [anti-inflammatory]) macrophage cell number. Serum and AT leptin and adiponectin were measured using enzyme-linked immunosorbent assay (ELISA). Exposure to near-roadway air pollution (NRAP) from freeway and non-freeway vehicular sources and to regional particulate matter, nitrogen dioxide and ozone were estimated for the year prior to biopsy, based on participants’ residential addresses. Linear regression models were used to examine the association between air pollution exposures and adipokines and to evaluate effect modification by immune cell counts.ResultsAn interquartile increase in non-freeway NRAP exposure during 1 year prior to biopsy was associated with higher leptin levels in both serum [31.7% (95% CI: 10.4, 52.9%)] and AT [19.4% (2.2, 36.6%)]. Non-freeway NRAP exposure effect estimates were greater among participants with greater than median Teff/Treg ratio and M1/M2 ratio in blood, and with greater M1 counts in AT. No adipokine associations with regional air pollutants were found.DiscussionOur results suggest that NRAP may increase serum leptin levels in obese young adults, and this association may be promoted in a pro-inflammatory immune cell environment in blood and AT.
Novel multifunctional NIR-II aggregation-induced emission nanoparticles-assisted intraoperative identification and elimination of residual tumor
Authors: Qu Qiaojun , Zhang Zeyu , Guo Xiaoyong , Yang Junying , Cao Caiguang , Li Changjian , Zhang Hui , Xu Pengfei , Hu Zhenhua , Tian Jie 
Published: March 2022

AbstractIncomplete tumor resection is the direct cause of the tumor recurrence and metastasis after surgery. Intraoperative accurate detection and elimination of microscopic residual cancer improve surgery outcomes. In this study, a powerful D1–π–A–D2–R type phototheranostic based on aggregation-induced emission (AIE)-active the second near-infrared window (NIR-II) fluorophore is designed and constructed. The prepared theranostic agent, A1 nanoparticles (NPs), simultaneously shows high absolute quantum yield (1.23%), excellent photothermal conversion efficiency (55.3%), high molar absorption coefficient and moderate singlet oxygen generation performance. In vivo experiments indicate that NIR-II fluorescence imaging of A1 NPs precisely detect microscopic residual tumor (2 mm in diameter) in the tumor bed and metastatic lymph nodes. More notably, a novel integrated strategy that achieves complete tumor eradication (no local recurrence and metastasis after surgery) is proposed. In summary, A1 NPs possess superior imaging and treatment performance, and can detect and eliminate residual tumor lesions intraoperatively. This work provides a promising technique for future clinical applications achieving improved surgical outcomes.
Graphic Abstract
PINK1/TAX1BP1-directed mitophagy attenuates vascular endothelial injury induced by copper oxide nanoparticles
Authors: Fan Yinzhen , Cheng Zhenli , Mao Lejiao , Xu Ge , Li Na , Zhang Mengling , Weng Ping , Zheng Lijun , Dong Xiaomei , Hu Siyao , Wang Bin , Qin Xia , Jiang Xuejun , Chen Chengzhi , Zhang Jun , Zou Zhen 
Published: March 2022

AbstractCopper oxide nanoparticles (CuONPs) are widely used metal oxide NPs owing to their excellent physical–chemical properties. Circulation translocation of CuONPs after inhalation leads to vascular endothelial injury. Mitochondria, an important regulatory hub for maintaining cell functions, are signaling organelles in responses to NPs-induced injury. However, how mitochondrial dynamics (fission and fusion) and mitophagy (an autophagy process to degrade damaged mitochondria) are elaborately orchestrated to maintain mitochondrial homeostasis in CuONPs-induced vascular endothelial injury is still unclear. In this study, we demonstrated that CuONPs exposure disturbed mitochondrial dynamics through oxidative stress-dependent manner in vascular endothelial cells, as evidenced by the increase of mitochondrial fission and the accumulation of fragmented mitochondria. Inhibition of mitochondrial fission with Mdivi-1 aggravated CuONPs-induced mtROS production and cell death. Furthermore, we found that mitochondrial fission led to the activation of PINK1-mediated mitophagy, and pharmacological inhibition with wortmannin, chloroquine or genetical inhibition with siRNA-mediated knockdown of PINK1 profoundly repressed mitophagy, suggesting that the protective role of mitochondrial fission and PINK1-mediated mitophagy in CuONPs-induced toxicity. Intriguingly, we identified that TAX1BP1 was the primary receptor to link the ubiquitinated mitochondria with autophagosomes, since TAX1BP1 knockdown elevated mtROS production, decreased mitochondrial clearance and aggravated CuONPs-induced cells death. More importantly, we verified that urolithin A, a mitophagy activator, promoted mtROS clearance and the removal of damaged mitochondria induced by CuONPs exposure both in vitro and in vivo. Overall, our findings indicated that modulating mitophagy may be a therapeutic strategy for pathological vascular endothelial injury caused by NPs exposure.
Graphical Abstract
GSK-3β suppression upregulates Gli1 to alleviate osteogenesis inhibition in titanium nanoparticle-induced osteolysis
Authors: Wang Qing , Zhang Wei , Peng Xiaole , Tao Yunxia , Gu Ye , Li Wenming , Liang Xiaolong , Wang Liangliang , Wu Zerui , Wang Tianhao , Zhang Haifeng , Liu Xin , Xu Yaozeng , Liu Yu , Zhou Jun , Geng Dechun 
Published: March 2022

AbstractWear particle-induced periprosthetic osteolysis (PPO) have become a major reason of joint arthroplasty failure and secondary surgery following joint arthroplasty and thus pose a severe threat to global public health. Therefore, determining how to effectively suppress particle-induced PPO has become an urgent problem. The pathological mechanism involved in the PPO signaling cascade is still unclear. Recently, the interaction between osteogenic inhibition and wear particles at the implant biological interface, which has received increasing attention, has been revealed as an important factor in pathological process. Additionally, Hedgehog (Hh)-Gli1 is a crucial signaling cascade which was regulated by multiple factors in numerous physiological and pathological process. It was revealed to exert a crucial part during embryonic bone development and metabolism. However, whether Hh-Gli1 is involved in wear particle-induced osteogenic inhibition in PPO remains unknown. Our present study explored the mechanism by which the Hh-Gli1 signaling cascade regulates titanium (Ti) nanoparticle-induced osteolysis. We found that Hh-Gli1 signaling was dramatically downregulated upon Ti particle treatment. Mechanistically, glycogen synthesis kinase 3β (GSK-3β) activation was significantly increased in Ti particle-induced osteogenic inhibition via changes in GSK-3β phosphorylation level and was found to participate in the posttranslational modification and degradation of the key transcription factor Gli1, thus decreasing the accumulation of Gli1 and its translocation from the cytoplasm to the nucleus. Collectively, these findings suggest that the Hh-Gli1 signaling cascade utilizes a GSK3β-mediated mechanism and may serve as a rational new therapeutic target against nanoparticle-induced PPO.Graphical Abstract
GelMA/PEGDA microneedles patch loaded with HUVECs-derived exosomes and Tazarotene promote diabetic wound healing
Authors: Yuan Meng , Liu Kun , Jiang Tao , Li Shengbo , Chen Jing , Wu Zihan , Li Wenqing , Tan Rongzhi , Wei Wenying , Yang Xiaofan , Dai Honglian , Chen Zhenbing 
Published: March 2022

AbstractClinical work and research on diabetic wound repair remain challenging globally. Although various conventional wound dressings have been continuously developed, the efficacy is unsatisfactory. The effect of drug delivery is limited by the depth of penetration. The sustained release of biomolecules from biological wound dressings is a promising treatment approach to wound healing. An assortment of cell-derived exosomes (exos) have been proved to be instrumental in tissue regeneration, and researchers are dedicated to developing biomolecules carriers with unique properties. Herein, we reported a methacrylate gelatin (GelMA) microneedles (MNs) patch to achieve transdermal and controlled release of exos and tazarotene. Our MNs patch comprising GelMA/PEGDA hydrogel has distinctive biological features that maintain the biological activity of exos and drugs in vitro. Additionally, its unique physical structure prevents it from being tightly attached to the skin of the wound, it promotes cell migration, angiogenesis by slowly releasing exos and tazarotene in the deep layer of the skin. The full-thickness cutaneous wound on a diabetic mouse model was carried out to demonstrate the therapeutic effects of GelMA/PEGDA@T + exos MNs patch. As a result, our GelMA/PEGDA@T + exos MNs patch presents a potentially valuable method for repairing diabetic wound in clinical applications.
Graphic Abstract