<i>Background</i>. Atopic dermatitis is a common dermatological disease, and mast cell degranulation is believed to be related with the progression of atopic dermatitis. Mas-related G protein-coupled receptor-X2 (MRGPRX2), and calcium release-activated calcium channel protein 1-2 (ORAI-1, ORAI-2) are involved in mast cell degranulation. Celastrol is an active monomer of Tripterygium wilfordii, and it presents an antiatopic role. <i>Methods</i>. 2,4-Dinitrofluorobenzene (DNFB) and compound 48/80 (C 48/80) were used to establish a slow and acute scratching animal model, respectively. Hematoxylin-eosin and toluidine blue staining was used to investigate tissue injury. Inflammatory factor concentration was measured with ELISA. The expression of MRGPRX2, ORAI-1, and ORAI-2 was detected with immunohistochemistry (IHC) staining. Gene expression profiling and microRNA array were performed to investigate gene differential expression. <i>Results</i>. Celastrol greatly inhibited atopic dermatitis-related tissues injury, mast cell production, histamine release, scratching level, inflammatory factor expression, and activation of MRGPRX2/ORAI axis in the DNFB-induced atopic dermatitis model. The influence of Celastrol on atopic dermatitis was remarkably reversed by overexpression of MRGPRX2. <i>Conclusion</i>. We found that the improvements of atopic dermatitis caused by Celastrol were reversed by treatment with MRGPRX2<sup>OE</sup>, indicating that Celastrol might affect atopic dermatitis through MRGPRX2. This study might provide a novel thought for the prevention and treatment of atopic dermatitis by regulating MRGPRX2.

Ciyu Yao

Wenzhen Ye

Mengxue Chen

Inhibition of Mast Cell Degranulation in Atopic Dermatitis by Celastrol through Suppressing MRGPRX2

Gliomas including astrocytomas, oligodendrogliomas, mixed oligoastrocytic, and mixed glioneuronal tumors are an important group of brain tumors. Based on the 2016 WHO classification for tumors in the central nervous system, gliomas were classified into four grades, from I to IV, and brain lower grade glioma (LGG) consists of grade II and grade III. Patients with LGG may undergo recurrence, which makes clinical treatment tough. Stem cell-like features of cancer cells play a key role in tumor’s biological behaviors, including tumorigenesis, development, and clinical prognosis. In this article, we quantified the stemness feature of cancer cells using the mRNA stemness index (mRNAsi) and identified stemness-related key genes based on correlation with mRNAsi. Besides, hallmark gene sets and translate factors (TFs) which were highly related to stemness-related key genes were identified. Therefore, a recurrency-specific network was constructed and a potential regulation pathway was identified. Several online databases, assay for transposase-accessible chromatin using sequencing (ATAC-seq), single-cell sequencing analysis, and immunohistochemistry were utilized to validate the scientific hypothesis. Finally, we proposed that aurora kinase A (AURKA), positively regulated by Non-SMC Condensin I Complex Subunit G (NCAPG), promoted E2F target pathway in LGG, which played an important role in LGG recurrence.

Jin Li

Meng Zhou

Dan Huang

Ruoyi Lin

Xiaomei Cui

Shaofeng Chen

Ying Yao

Shuyuan Xian

Siqiao Wang

Qing Fu

Jiwen Zhu

Xi Yue

Runzhi Huang

Enbo Qi

Zongqiang Huang

The Recurrent-Specific Regulation Network of Prognostic Stemness-Related Signatures in Low-Grade Glioma

<i>Objective</i>. Studies aiming at illuminating the complex relationships between cancer, obesity, 25-hydroxy vitamin D (25-OHD) deficiency, and body fat percentage are ongoing. The objective of this study was to investigate the relationships between 25-OHD deficiency, visceral fat tissue, and the Beck Depression Inventory (BDI) in cancer patients. <i>Methods</i>. This study was conducted from 2013 to 2022. Patients’ demographic data, such as age, sex, and body mass index (BMI), and laboratory parameters, including prealbumin, albumin, calcium, phosphorus, parathyroid hormone, 25-OHD, magnesium, hemoglobin, fat percentage, and C-reactive protein, were recorded. The Beck Depression Inventory was used to determine depression levels. <i>Results</i>. A total of 223 colon cancer patients aged 19–84 undergoing chemotherapy at our clinic were included in this prospective study. The male patients’ mean BMI was <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="38.462pt" style="vertical-align:-0.3499298pt" id="M1" height="8.69875pt" version="1.1" viewBox="-0.0498162 -8.34882 38.462 8.69875"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,12.48,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,15.444,0)"><path id="g113-58" d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z"/></g><g transform="matrix(.013,0,0,-0.013,21.685,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g><g transform="matrix(.013,0,0,-0.013,30.831,0)"><path id="g117-37" d="M535 290V340H323V533H265V340H52V290H265V84H323V290H535ZM535 -22V28H52V-22H535Z"/></g></svg><span class="ibiop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.997pt" style="vertical-align:-0.3499298pt" height="8.69875pt" version="1.1" viewBox="41.317183799999995 -8.34882 21.997 8.69875"><g transform="matrix(.013,0,0,-0.013,41.367,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g><g transform="matrix(.013,0,0,-0.013,47.607,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,50.571,0)"><path id="g113-56" d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"/></g><g transform="matrix(.013,0,0,-0.013,56.814,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g></svg></span> kg/m<sup>2</sup>, whereas that of the female patients was <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="38.463pt" style="vertical-align:-0.3499298pt" id="M2" height="8.69875pt" version="1.1" viewBox="-0.0498162 -8.34882 38.463 8.69875"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><path id="g113-55" d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z"/></g><g transform="matrix(.013,0,0,-0.013,12.48,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,15.444,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,21.684,0)"><use xlink:href="#g113-56"/></g><g transform="matrix(.013,0,0,-0.013,30.832,0)"><use xlink:href="#g117-37"/></g></svg><span class="ibiop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.996pt" style="vertical-align:-0.3499298pt" height="8.69875pt" version="1.1" viewBox="41.3181838 -8.34882 21.996 8.69875"><g transform="matrix(.013,0,0,-0.013,41.368,0)"><use xlink:href="#g113-52"/></g><g transform="matrix(.013,0,0,-0.013,47.609,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,50.573,0)"><use xlink:href="#g113-56"/></g><g transform="matrix(.013,0,0,-0.013,56.815,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g></svg></span> kg/m<sup>2</sup>. The difference was statistically significant (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.973pt" style="vertical-align:-3.42938pt" id="M3" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.973 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-113" d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.184pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 28.184 11.7782"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-50"/></g></svg>).</span></span> The mean total Beck Depression Inventory score was <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="23.017pt" style="vertical-align:-0.3499298pt" id="M4" height="8.69875pt" version="1.1" viewBox="-0.0498162 -8.34882 23.017 8.69875"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><use xlink:href="#g113-52"/></g><g transform="matrix(.013,0,0,-0.013,15.386,0)"><use xlink:href="#g117-37"/></g></svg><span class="ibiop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="6.438pt" style="vertical-align:-0.3499298pt" height="8.69875pt" version="1.1" viewBox="25.872183800000002 -8.34882 6.438 8.69875"><g transform="matrix(.013,0,0,-0.013,25.922,0)"><use xlink:href="#g113-58"/></g></svg>.</span></span> In this patient population, 105 (47.09%) patients had minimal depression, 69 (30.94%) had mild depression, 35 (15.70%) had moderate depression, and 14 (6.28%) had severe depression. The Beck Depression Inventory score was negatively and strongly associated with BMI and moderately and negatively associated with albumin levels. <i>Conclusion</i>. This study reveals a significant correlation between 25-OHD levels and the Beck Depression Inventory scores among cancer patients. We believe that 25-OHD levels may be used to determine the presence of depressive symptoms in cancer patients. However, further comprehensive multicentre studies are needed to draw more definitive conclusions.

Savas Tuna

Mehmet Akif Aydin

Muhammet Fatih Aydin

The Four Horsemen of the Apocalypse: Cancer, Depression, Vitamin D Deficiency, and Obesity: An Observational Study

Diabetic cardiovascular autonomic neuropathy (DCAN) is a common complication of diabetes mellitus which brings about high mortality, high morbidity, and large economic burden to the society. Compensatory tachycardia after myocardial ischemia caused by DCAN can increase myocardial injury and result in more damage to the cardiac function. The inflammation induced by hyperglycemia can increase P2X7 receptor expression in the superior cervical ganglion (SCG), resulting in nerve damage. It is proved that inhibiting the expression of P2X7 receptor at the superior cervical ganglion can ameliorate the nociceptive signaling dysregulation induced by DCAN. However, the effective drug used for decreasing P2X7 receptor expression has not been found. Schisandrin B is a traditional Chinese medicine, which has anti-inflammatory and antioxidant effects. Whether Schisandrin B can decrease the expression of P2X7 receptor in diabetic rats to protect the cardiovascular system was investigated in this study. After diabetic model rats were made, Schisandrin B and shRNA of P2X7 receptor were given to different groups to verify the impact of Schisandrin B on the expression of P2X7 receptor. Pathological blood pressure, heart rate, heart rate variability, and sympathetic nerve discharge were ameliorated after administration of Schisandrin B. Moreover, the upregulated protein level of P2X7 receptor, NLRP3 inflammasomes, and interleukin-1<i>β</i> in diabetic rats were decreased after treatment, which indicates that Schisandrin B can alleviate the chronic inflammation caused by diabetes and decrease the expression levels of P2X7 via NLRP3. These findings suggest that Schisandrin B can be a potential therapeutical agent for DCAN.

Zhihua Zhang

Hongmin Guo

Zihui Hu

Congfa Zhou

Qixing Hu

Hao Peng

Gan Tang

Zehao Xiao

Lingzhi Pi

Guilin Li

Schisandrin B Alleviates Diabetic Cardiac Autonomic neuropathy Induced by P2X7 Receptor in Superior Cervical Ganglion via NLRP3

<i>Background</i>. Systemic lupus erythematosus (SLE) is an autoimmune disease with strong heterogeneity, leading to variable clinical symptoms, which makes diagnosis and activity evaluation difficult. <i>Methods</i>. The original dataset of GSE88884 was analyzed to screen differentially expressed genes (DEGs) of SLE and the correlation between DEGs and clinical parameters (SLEDAI, anti-dsDNA, C3, and C4). The result was validated by microarray GSE121239 and SLE patients with RT-qPCR. Next, receiver operator characteristic (ROC) analysis, correlation analysis, and ordinal logistic regression were applied, respectively, to evaluate the capability of diagnosis and prediction of the candidate biomarker. Subsequently, the biological functions of the candidate biomarker were investigated through KEGG and GO enrichment, protein–protein interaction network, and the correlation matrix. <i>Results</i>. A total of 283 DEGs were screened, and seven of them were overlapped with SLE-related genes. DDX60 was identified as the candidate biomarker. Analyses of GSE88884, GSE121239, and SLE patients with RT-qPCR indicated that DDX60 expression level is significantly higher in patients with high disease activity. ROC analysis and the area under the ROC curve (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="37.804pt" style="vertical-align:-0.2324905pt" id="M1" height="8.98583pt" version="1.1" viewBox="-0.0498162 -8.75334 37.804 8.98583"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g190-66" d="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z"/></g><g transform="matrix(.013,0,0,-0.013,8.226,0)"><path id="g190-86" d="M716 650H478V622C549 617 570 605 575 566C579 535 582 493 582 401V326C582 161 537 40 393 40C269 40 205 133 205 294V521C205 611 213 617 291 622V650H33V622C111 615 120 611 120 521V272C120 154 148 80 208 34C252 0 309 -14 368 -14C434 -14 501 7 548 55C605 116 623 201 623 319V401C623 493 626 536 629 563C633 605 656 618 716 622V650Z"/></g><g transform="matrix(.013,0,0,-0.013,17.794,0)"><path id="g190-68" d="M614 175C564 76 510 21 408 21C256 21 146 149 146 336C146 488 235 629 402 629C510 629 570 586 597 480L626 488C620 541 614 582 606 638C578 643 510 665 429 665C206 665 44 527 44 316C44 157 153 -15 402 -15C474 -15 558 5 586 11C604 45 629 119 643 165L614 175Z"/></g><g transform="matrix(.013,0,0,-0.013,30.173,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="34.42pt" style="vertical-align:-0.2324905pt" height="8.98583pt" version="1.1" viewBox="41.3861838 -8.75334 34.42 8.98583"><g transform="matrix(.013,0,0,-0.013,41.436,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,47.676,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,50.64,0)"><path id="g113-57" d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"/></g><g transform="matrix(.013,0,0,-0.013,56.88,0)"><use xlink:href="#g113-57"/></g><g transform="matrix(.013,0,0,-0.013,63.12,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g><g transform="matrix(.013,0,0,-0.013,69.36,0)"><use xlink:href="#g113-57"/></g></svg>)</span></span> suggested that DDX60 has good diagnostic performance. DDX60 expression level was positively correlated with SLEDAI scores (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="16.751pt" style="vertical-align:-0.2063904pt" id="M2" height="8.55521pt" version="1.1" viewBox="-0.0498162 -8.34882 16.751 8.55521"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-115" d="M393 379C402 394 400 411 393 422C384 437 365 448 348 448C301 448 237 372 186 285H182L193 335C210 408 205 448 178 448C150 448 80 402 29 344L45 321C80 355 114 373 122 373C128 373 130 365 124 330C106 228 76 98 50 -5L57 -12C82 -5 112 3 132 6L172 203C196 256 234 304 254 329C275 355 293 367 306 367C318 367 330 360 342 348C347 343 355 343 365 350S386 367 393 379Z"/></g><g transform="matrix(.013,0,0,-0.013,9.12,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.912pt" style="vertical-align:-0.2063904pt" height="8.55521pt" version="1.1" viewBox="20.3331838 -8.34882 21.912 8.55521"><g transform="matrix(.013,0,0,-0.013,20.383,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,26.623,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,29.587,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g><g transform="matrix(.013,0,0,-0.013,35.827,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g></svg>).</span></span> For every 1-unit increase in DDX60 expression value, the odds of a higher stage of activity of SLE disease are multiplied by 1.47. The function of DDX60 mainly focuses on IFN-I-induced antiviral activities, RIG-I signaling, and innate immune. Moreover, DDX60 plays a synergistic role with DDX58, IFIH1, OASL, IFIT1, and other related genes in the SLE pathogenesis<i>. Conclusions</i>. DDX60 is differently expressed in SLE, and it is significantly related to both serological indicators and the disease activity of SLE. We suggested that DDX60 might be a potential biomarker for SLE diagnosis and management.

Wu Chen

Zhi-Yu Li

Lin Huang

Dong-Hai Zhou

Wen-Qing Luo

Xu-Feng Zhang

Lin Li

Cheng-Ping Wen

Qiao Wang

Integrative Bioinformatics Analysis Identifies DDX60 as a Potential Biomarker for Systemic Lupus Erythematosus

<i>Background</i>. Currently, how to successfully control refractory and metastatic diseases remains a fundamental goal for clinicians to improve therapeutic effects for patients with non-small cell lung cancer (NSCLC). Several studies have discovered that TRIM58, a member of tripartite motif protein family, shows antitumor effect in multiple types of cancer. In this study, we aimed to further clarify the molecular regulatory network of TRIM58 and corresponding targets for NSCLC patients. <i>Methods</i>. TRIM58 expression in clinical tumor tissue samples and cancer cell lines was examined. Functional experiments including cellular invasion, cell metastasis, chemoresistance assay, and ubiquitination evaluation experiments were conducted to investigate the interaction between TRIM58 and ZEB1, which is a prime element of transcription factor network that controls epithelial-to-mesenchymal transition. <i>Results</i>. TRIM58 expression was characteristically decreased in NSCLC tumor tissues and cancer cell lines. Functional experiments demonstrated that TRIM58 suppression enhanced malignant biological behaviors including cellular survivability, migration, and invasion, as well as stem-like cellular phenotype of tumor cells. TRIM58 silencing also significantly enhanced the chemoresistance of NSCLC cells to chemoagents. TRIM58-ZEB1 interaction accelerated degradation of ZEB1 protein, thus further leading to the augment of tumor behaviors. Further detailed molecular experiments revealed that the interaction between TRIM58 and ZEB1 was mediated <i>via</i> ubiquitin-proteasome pathway (UPP). <i>Conclusion</i>. TRIM58 suppressed NSCLC through interacting with ZEB1 and promoting ZEB1 protein degradation <i>via</i> UPP. The present research sheds light on the interaction between TRIM58 and ZEB1, and TRIM58/ZEB1 axis might be the potential therapeutic targets of NSCLC.

Rongxin Shang

Jiakuan Chen

Yang Gao

Jijun Chen

Guoliang Han

TRIM58 Interacts with ZEB1 to Suppress NSCLC Tumor Malignancy by Promoting ZEB1 Protein Degradation via UPP

About this journal

<p><em>Disease Markers</em> publishes papers related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.</p>


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<p>Chief Editor Paola Gazzaniga is an Associate Professor in the Department of Molecular Medicine at Sapienza University of Rome, Italy. Her core research focuses on liquid biopsies in patients with solid tumors.</p>


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title

Disease Markers publishes papers related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.

Disease Markers