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Rare loss-of-function variants in FLNB cause non-syndromic orofacial clefts

Journal of Genetics and Genomics 2024年第2期51卷 222-229页

作者： Wenbin Huang Shiying Zhang Jiuxiang Lin Yi Ding Nan Jiang Jieni Zhang Huaxiang Zhao Feng Chen department of Orthodontics Peking University School and Hospital of StomatologyBeijing100081China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine research College of StomatologyXi’an Jiaotong UniversityXi’anShaanxi710004China Guangdong Provincial High-level Clinical Key Specialty Guangdong Province Engineering Research Center of Oral Disease Diagnosis and TreatmentDepartment of OrthodonticsStomatological CenterPeking University Shenzhen HospitalShenzhen Peking University-The Hong Kong University of Science and Technology Medical CenterShenzhenGuangdong 518036China department of Physiology and pathophysiology School of Basic Medical SciencesXi'an Jiaotong UniversityXi'anShaanxi710049China National Center for Stomatology National Clinical Research Center for Oral DiseasesNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory for Digital StomatologyResearch Center of Engineering and Technology for Computerized Dentistry Ministry of HealthNMPA Key Laboratory for Dental MaterialsBeijing100101China Central Laboratory Peking University School and Hospital of StomatologyBeijing100081China

Orofacial clefts (OFCs) are the most common congenital craniofacial disorders, of which the etiology is closely related to rare coding variants. Filamin B (FLNB) is an actin-binding protein implicated in bone formation. FLNB mutations have been identified in several types of syndromic OFCs and previous studies suggest a role of FLNB in the onset of non-syndromic OFCs (NSOFCs). Here, we report two rare heterozygous variants (p.P441T and p.G565R) in FLNB in two unrelated hereditary families with NSOFCs. Bioinformatics analysis suggests that both variants may disrupt the function of FLNB. In mammalian cells, p.P441T and p.G565R variants are less potent to induce cell stretches than wild type FLNB, suggesting that they are loss-of-function mutations. Immunohistochemistry analysis demonstrates that FLNB is abundantly expressed during palatal development. Importantly, Flnb^(−/−) embryos display cleft palates and previously defined skeletal defects. Taken together, our findings reveal that FLNB is required for development of palates in mice and FLNB is a bona fide causal gene for NSOFCs in humans.

关键词： Or ofacial clefts FLNB Loss-of-function mutati on Cleft palate Filamin B Actin flannent Knockout mouse

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Novel insights into autophagy in gastrointestinal pathologies,mechanisms in metabolic dysfunction-associated fatty liver disease and acute liver failure

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World Journal of Gastroenterology 2024年第27期30卷 3273-3277页

作者： Tsvetelina Velikova Milena Gulinac Medical Faculty Sofia University St Kliment OhridskiSofia 1407Bulgaria department of General and Clinical pathology Medical University of PlovdivPlovdiv 4002Bulgaria

In this editorial,we comment on three articles published in a recent issue of World Journal of *** is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and also novel insights into some liver conditions,such as metabolic dysfunction-associated fatty liver disease(MAFLD)and acute liver failure(ALF).Despite advancements,understanding autophagy's intricate mechanisms and implications in these diseases remains ***,MAFLD's pathogenesis,encompassing hepatic steatosis and metabolic dysregulation,require further ***,the mechanisms underlying ALF,a severe hepatic dysfunction,are poorly *** studies exploring the interplay between autophagy and GI disorders,as well as defined mechanisms of MAFLD and ALF,are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.

关键词： Gastrointestinal diseases Autophagy Metabolic dysfunction-associated fatty liver disease High-normal alanine aminotransferase level Silent information regulator sirtuin 1 Acute liver failure

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Aldo-keto reductases:Role in cancer development and theranostics

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Oncology research 2024年第8期32卷 1287-1308页

作者： SIDDAVARAM NAGINI PRATHAP REDDY KALLAMADI KRANTHI KIRAN KISHORE TANAGALA GEEREDDY BHANUPRAKASH REDDY World Neem Organization Mumbai400101India department of Biochemistry ICMR-National Institute of NutritionHyderabad500007India department of pathology and Cell Biology Columbia University Irving Medical CenterNew York10032USA

Aldo-keto reductases(AKRs)are a superfamily of enzymes that play crucial roles in various cellular processes,including the metabolism of xenobiotics,steroids,and carbohydrates.A growing body of evidence has unveiled the involvement of AKRs in the development and progression of various *** are aberrantly expressed in a wide range of malignant *** expression of AKRs enables the acquisition of hallmark traits of cancer by activating oncogenic signaling pathways and contributing to *** have emerged as promising oncotherapeutic targets given their pivotal role in cancer development and *** of aldose reductase(AR),either alone or in combination with chemotherapeutic drugs,has evolved as a pragmatic therapeutic option for *** classes of synthetic aldo-keto reductase(AKR)inhibitors have been developed as potential anticancer agents,some of which have shown promise in clinical *** AKR inhibitors from natural sources also exhibit anticancer *** molecule inhibitors targeting speciﬁc AKR isoforms have shown promise in preclinical *** inhibitors disrupt the activation of oncogenic signaling by modulating transcription factors and kinases and sensitizing cancer cells to *** this review,we discuss the physiological functions of human AKRs,the aberrant expression of AKRs in malignancies,the involvement of AKRs in the acquisition of cancer hallmarks,and the role of AKRs in oncogenic signaling,and drug ***,the potential of aldose reductase inhibitors(ARIs)as anticancer drugs is summarized.

关键词： Aldo-keto reductases(AKRs) Aldo-keto reductase(AKR)inhibitors Cancer Drug-resistance Xenobiotics

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Endoscopic detection and diagnostic strategies for minute gastric cancer:A real-world observational study

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3529-3538页

作者： Xiao-Wei Ji Jie Lin Yan-Ting Wang Jing-Jing Ruan Jing-Hong Xu Kai Song Jian-Shan Mao department of Gastroenterology The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009Zhejiang ProvinceChina department of pathology The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009Zhejiang ProvinceChina

BACKGROUND Minute gastric cancers(MGCs)have a favorable prognosis,but they are too small to be detected by endoscopy,with a maximum diameter≤5 *** To explore endoscopic detection and diagnostic strategies for *** This was a real-world observational *** endoscopic and clinicopathological parameters of 191 MGCs between January 2015 and December 2022 were retrospectively *** discoverable opportunity and typical neoplastic features were emphatically *** All MGCs in our study were of a single pathological type,97.38%(186/191)of which were differentiated-type *** light endoscopy(WLE)detected 84.29%(161/191)of MGCs,and the most common morphology of MGCs found by WLE was ***-band imaging(NBI)secondary observation detected 14.14%(27/191)of MGCs,and the most common morphology of MGCs found by NBI was *** three MGCs were detected by indigo carmine third *** a well-demarcated border lesion exhibited a typical neoplastic color,such as yellowish-red or whitish under WLE and brownish under NBI,MGCs should be *** proportion with high diagnostic confidence by magnifying endoscopy with NBI(ME-NBI)was significantly higher than the proportion with low diagnostic confidence and the only visible groups(94.19%>56.92%>32.50%,P<0.001).CONCLUSION WLE combined with NBI and indigo carmine are helpful for detection of MGCs.A clear demarcation line combined with a typical neoplastic color using nonmagnifying observation is sufficient for diagnosis of *** improves the endoscopic diagnostic confidence of MGCs.

关键词： Minute gastric cancer White light endoscopy Narrow-band imaging endoscopy Indigo carmine Magnifying endoscopy Detection Diagnosis

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miR-125b reverses cisplatin resistance by regulating autophagy via targeting RORA/BNIP3L axis in lung adenocarcinoma

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Oncology research 2024年第4期32卷 643-658页

作者： LEI LIU NA GUO XIANGLING LI QIAN XU RUILONG HE LIMIN CHENG CHUNYAN DANG XINYU BAI YIYING BAI XIN WANG QIANHUI CHEN LI ZHANG department of Immunology Chengde Medical UniversityChengde067000China department of pathology Chengde Medical UniversityChengde067000China department of Oncology The Affiliated Hospital of Chengde Medical UniversityChengde067000China department of Hepatobiliary Surgery The Affiliated Hospital of Chengde Medical UniversityChengde067000China

The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the *** has been shown that microRNAs(miRNAs)play a significant role in tumor *** this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR *** decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival ***-125b decreased the A549/DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of *** addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in *** mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed *** on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.

关键词： Lung adenocarcinoma miRNAs Cisplatin Resistance Autophagy

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Stable diffusion gradients in microfluidic conduits bounded by fluid walls

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Microsystems & Nanoengineering 2024年第3期10卷 357-367页

作者： Federico Nebuloni Cyril Deroy Peter R.Cook Edmond J.Walsh department of Engineering Science Osney Thermo-Fluids InstituteUniversity of OxfordOxford OX20ESUK Sir William Dunn School of pathology University of OxfordOxford OX13REUK

Assays mimicking in vitro the concentration gradients triggering biological responses like those involved in fighting infections and blood clotting are essential for biomedical *** assays prove especially attractive as they allow precise control of gradient shape allied to a reduction in *** microfluidic devices are fabricated using solid plastics that prevent direct access to responding ***-walled microfluidics allows the manufacture of circuits on standard Petri dishes in seconds,coupled to simple operating methods;cell-culture medium sitting in a standard dish is confined to circuits by fluid walls made of an immiscible *** develop and experimentally validate an analytical model of diffusion between two or more aqueous streams flowing at different rates into a fluid-walled conduit with the cross-section of a circular *** solid walls,fluid walls morph during flows as pressures fall,with wall shape changing down the *** model is validated experimentally for Fourier numbers<0.1 using fluorescein diffusing between laminar *** enables a priori prediction of concentration gradients throughout a conduit,so allowing rapid circuit design as well as providing bioscientists with an accurate way of predicting local concentrations of bioactive molecules around responsive and nonresponsive cells.

关键词： walls diffusion attractive

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Identification of Proteins and Genes Associated with Hedgehog Signaling Pathway Involved in Neoplasm Formation Using Text-Mining Approach

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Big Data Mining and Analytics 2024年第1期7卷 107-130页

作者： Nadezhda Yu.Biziukova Sergey M.Ivanov Oga A.Tarasova department of Bioinformatics Institute of Biomedical ChemistryMoscow 119121Russia department of Bioinformatics Pirogov Russian National Research Medical UniversityMoscow 117997Russia

Analysis of molecular mechanisms that lead to the development of various types of tumors is essential for biology and medicine,because it may help to find new therapeutic opportunities for cancer treatment and cure including personalized treatment *** of the pathways known to be important for the development of neoplastic diseases and pathological processes is the Hedgehog signaling pathway that normally controls human embryonic *** accumulation of various types of biological data,including interactions between proteins,regulation of genes transcription,proteomics,and metabolomics experiments results,allows the application of computational analysis of these big data for identification of key molecular mechanisms of certain diseases and pathologies and promising therapeutic *** aim of this study is to develop a computational approach for revealing associations between human proteins and genes interacting with the Hedgehog pathway components,as well as for identifying their roles in the development of various types of *** automatically collect sets of abstract texts from the NCBI PubMed bibliographic *** recognition of the Hedgehog pathway proteins and genes and neoplastic diseases we use a dictionary-based named entity recognition approach,while for all other proteins and genes machine learning method is *** association extraction,we develop a set of semantic *** complete the results of the text analysis with the gene set enrichment *** identified key pathways that may influence the Hedgehog pathway and their roles in tumor development are then verified using the information in the literature.

关键词： text-mining data mining Hedgehog pathway neoplastic processes enrichment analysis pathology molecularmechanisms

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Mex-3 RNA binding family member A(MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2091-2103页

作者： Ri-Xin Chen Shui-Dan Xu Min-Hua Deng Shi-Hui Hao Jie-Wei Chen Xiao-Dan Ma Wei-Tao Zhuang Jing-Hua Cao Yong-Rui Lv Jin-Long Lin Si-Yu Li Gui-Bin Qiao Dan Xie Feng-Wei Wang department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China Medical research Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China department of pathology Sun Yat-sen University Cancer CenterGuangzhou 510060China

RNA-binding proteins(RBPs)-RNA networks have contributed to cancer *** RNAs(circRNAs)are considered as protein recruiters;nevertheless,the patterns of circRNA-protein interactions in colorectal cancer(CRC)are still *** bodies(PBs)formed through liquid-liquid phase separation(LLPS)are membrane-less organelles(MLOs)consisting of RBPs and *** evidence suggests a connection between PBs dynamics and cancer *** the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs,there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in ***,we identify that MEX-3 RNA binding family member A(MEX3A),frequently upregulated in CRC tissues,predicts poorer patient *** MEX3A accelerates malignance and inhibits autophagy of CRC ***,MEX3A undergoes intrinsically disordered regions(IDRs)-dependent LLPS in the ***,circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs *** MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A(PDE5A)mRNA degradation,consequently leading to the aggressive properties of CRC ***,CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall *** findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation,which provides prognostic markers and/or therapeutic targets for CRC.

关键词： colorectal inhibiting MPP

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Capsosiphon fulvescens suppresses LPS-stimulated inflammatory responses by suppressing TLR4/NF-κB activation in RAW264.7 murine macrophages

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Asian Pacific Journal of Tropical Biomedicine 2024年第3期14卷 115-126页

作者： Seon Yeong Ji EunJin Bang Hyun Hwangbo Min Yeong Kim Da Hye Kim Su Hyun Hong Shin-Hyung Park Chang-Young Kwon Gi-Young Kim You-Jin Jeon Suengmok Cho Yung Hyun Choi department of Biochemistry Dong-eui University College of Korean MedicineBusan 47227Republic of Korea Basic research Laboratory for the Regulation of Microplastic-Mediated Diseases and Anti-Aging research Center Dong-eui UniversityBusan 47227Republic of Korea department of pathology Dong-eui University College of Korean MedicineBusan 47227Republic of Korea department of Oriental Neuropsychiatry Dong-eui University College of Korean MedicineBusan 47227Republic of Korea department of Marine Life Science Jeju National UniversityJeju 63243Republic of Korea department of Food Science and Technology/Institute of Food Science Pukyong National UniversityBusan 48513Republic of Korea

Objective:To evaluate the effects of Capsosiphon fulvescens(***)ethanolic extract on inflammation in lipopolysaccharide(LPS)-induced RAW296.7 ***:The protective effects of *** ethanolic extract on LPS-induced inflammation in RAW264.7 macrophages were assessed using biochemical analysis,including enzyme-linked immunosorbent assay,quantitative reverse transcription-polymerase chain reaction,and Western blot *** examine reactive oxygen species(ROS)production,flow cytometry analysis,and immunofluorescence staining were ***,the modulatory effect of *** ethanolic extract on NF-κB activation was ***:*** ethanolic extract significantly attenuated LPS-induced levels of pro-inflammatory cytokines and notably reduced the secretion and mRNA levels of LPS-mediated matrix *** addition,*** ethanolic extract decreased ROS production and suppressed the TLR4/NF-κB signaling ***:*** ethanolic extract alleviates inflammation as well as oxidative stress by modulating the TLR4/NF-κB signaling in LPS-induced RAW264.7 *** can be used as a potential therapeutic agent to suppress inflammation and oxidative stress-associated diseases.

关键词： Capsosiphon fulvescens Inflammation Oxidative stress NF-κB Nrf2 TLR4

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Transient receptor potential channels as predictive marker and potential indicator of chemoresistance in colon cancer

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Oncology research 2024年第1期32卷 227-239页

作者： WEI HU THOMAS WARTMANN MARCO STRECKER ARISTOTELIS PERRAKIS ROLAND CRONER ARPAD SZALLASI WENJIE SHI ULF D.KAHLERT The Fourth Clinical Medical College of Yangzhou University Nantong Rich HospitalNantongChina Molecular and Experimental Surgery Clinic for General-Visceral-Vascular and Transplant SurgeryFaculty of Medicine and University Hospital MagdeburgOtto-von-Guericke UniversityMagdeburgGermany department of pathology and Experimental Cancer research Semmelweis UniversityBudapestHungary

Transient receptor potential(TRP)channels are strongly associated with colon cancer development and *** study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient ***-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,***,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional *** support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy *** findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD *** of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk ***-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression ***,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of ***,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data a

关键词： Colon cancer Transient receptor potential channels Prognostic signature Chemotherapy efficiency TRPM5

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