International Journal of Molecular Sciences

Jia, Dan;Li, Yingying;Wang, Yingjie;Guo, Yanan;Liu, Junlong;Zhao, Shuaiyang;Wang, Jinming;Guan, Guiquan;Luo, Jianxun;Yin, Hong;Tang, Lijie;Li, Youquan

doi: 10.3390/ijms25010561pmid: 38203732

Despite Bacillus species having been extensively utilized in the food industry and biocontrol as part of probiotic preparations, limited knowledge exists regarding their impact on intestinal disorders. In this study, we investigated the effect of Bacillus licheniformis ZW3 (ZW3), a potential probiotic isolated from camel feces, on dextran sulfate sodium (DSS)-induced colitis. The results showed ZW3 partially mitigated body weight loss, disease activity index (DAI), colon shortening, and suppressed immune response in colitis mice, as evidenced by the reduction in the levels of the inflammatory markers IL-1β, TNF-α, and IL-6 (p < 0.05). ZW3 was found to ameliorate DSS-induced dysfunction of the colonic barrier by enhancing mucin 2 (MUC2), zonula occluden-1 (ZO-1), and occludin. Furthermore, enriched beneficial bacteria Lachnospiraceae_NK4A136_group and decreased harmful bacteria Escherichia-Shigella revealed that ZW3 improved the imbalanced gut microbiota. Abnormally elevated uric acid levels in colitis were further normalized upon ZW3 supplementation. Overall, this study emphasized the protective effects of ZW3 in colitis mice as well as some potential applications in the management of inflammation-related diseases.

Soboska, Kamila;Kusiński, Michał;Pawelczyk, Karol;Migdalska-Sęk, Monika;Brzeziańska-Lasota, Ewa;Czarnecka-Chrebelska, Karolina H.

doi: 10.3390/ijms25010562pmid: 38203733

Thyroid carcinoma is the primary endocrine malignancy worldwide. The preoperative examination of thyroid tissue lesion is often unclear. Approximately 25% of thyroid cancers cannot be diagnosed definitively without post-surgery histopathological examination. The assessment of diagnostic and differential markers of thyroid cancers is needed to improve preoperative diagnosis and reduce unnecessary treatments. Here, we assessed the expression of RASSF1A, DIRAS3, and AKAP9 genes, and the presence of BRAF V600E point mutation in benign and malignant thyroid lesions in a Polish cohort (120 patients). We have also performed a comparative analysis of gene expression using data obtained from the Gene Expression Omnibus (GEO) database (307 samples). The expression of RASSF1A and DIRAS3 was decreased, whereas AKAP9’s was increased in pathologically changed thyroid compared with normal thyroid tissue, and significantly correlated with e.g., histopathological type of lesion papillary thyroid cancer (PTC) vs follicular thyroid cancer (FTC), patient’s age, tumour stage, or its encapsulation. The receiver operating characteristic (ROC) analysis for the more aggressive FTC subtype differential marker suggests value in estimating RASSF1A and AKAP9 expression, with their area under curve (AUC), specificity, and sensitivity at 0.743 (95% CI: 0.548–0.938), 82.2%, and 66.7%; for RASSF1A, and 0.848 (95% CI: 0.698–0.998), 54.8%, and 100%, for AKAP9. Our research gives new insight into the basis of the aggressiveness and progression of thyroid cancers, and provides information on potential differential markers that may improve preoperative diagnosis.

Hu, Xianmei;Liang, Zehui;Sun, Tianxiao;Huang, Ling;Wang, Yanping;Chan, Zhulong;Xiang, Lin

doi: 10.3390/ijms25010563pmid: 38203734

Anthocyanins play a paramount role in color variation and significantly contribute to the economic value of ornamental plants. The conserved activation complex MYB-bHLH-WD40 (MBW; MYB: v-myb avian myeloblastosis viral oncogene homolog; bHLH: basic helix–loop–helix protein; WD40:WD-repeat protein) involved in anthocyanin biosynthesis has been thoroughly researched, but there have been limited investigations into the function of repressor factors. In this study, we characterized TgMYB4, an R2R3-MYB transcriptional repressor which is highly expressed during petal coloration in red petal cultivars. TgMYB4-overexpressing tobaccos exhibited white or light pink petals with less anthocyanin accumulation compared to control plants. TgMYB4 was found to inhibit the transcription of ANTHOCYANIDIN SYNTHASE (TfANS1) and DIHYDRO-FLAVONOL-4-REDUCTASE (AtDFR), although it did not bind to their promoters. Moreover, the TgMYB4 protein was able to compete with the MYB activator to bind to the :bHLHprotein, thereby suppressing the function of the activator MBW complex. These findings demonstrate that TgMYB4 plays a suppressive role in the regulation of anthocyanin synthesis during flower pigmentation.

Wang, Shijie;Wei, Wenwen;Yuan, Yuncang;Guo, Jing;Liang, Dandan;Zhao, Xudong

doi: 10.3390/ijms25010564pmid: 38203736

Lung cancer is one of the most common and intractable malignancies. It is associated with low survival rates despite existing treatments, indicating that new and more effective therapies are urgently needed such as the chimeric antigen receptor-T (CAR-T) cell immunotherapy. The cell-surface glucose-regulated protein 78 (csGRP78) is expressed in various hematological malignancies and solid tumor cells including lung cancer in response to cancer-related endoplasmic reticulum stress, while GRP78 is restricted to inside the normal cells. Here, we detected the prominent expression of csGRP78 in both lung cancer cell lines, A549 and H1299, as well as cancer stemlike cells derived from A549 by immunofluorescence. Next, a csGRP78-targeted CAR was constructed, and the transduced CAR-T cells were tested for their potency to kill the two lung cancer cell lines and derived stemlike cells, which was correlated with specific interferon γ release in vitro. Finally, we found that csGRP78 CAR-T cells also efficiently killed both lung cancer cells and cancer stemlike cells, resulting into the elimination of tumor xenografts in vivo, neither with any evidence of relapse after 63 days of tumor clearance nor any detrimental impact on other body organs we examined. Our study reveals the capacity of csGRP78 as a therapeutic target and offers valuable insight into the development of csGRP78 CAR-T cells as potential therapy for lung cancer.

Michel, Piotr;Olszewska, Monika Anna

doi: 10.3390/ijms25010565pmid: 38203735

Gaultheria procumbens L. is a medicinal plant whose aerial parts (leaves, stems, and fruits) and methyl salicylate-rich essential oil (wintergreen oil) are used in phytotherapy to treat inflammation, muscular pain, and infection-related disorders. This overview summarises the current knowledge about ethnobotany, phytochemistry, pharmacology, molecular mechanisms, biocompatibility, and traditional use of G. procumbens and the wintergreen oil distilled from different plant organs. Over 70 hydrophilic compounds, including methyl salicylate glycosides, flavonoids, procyanidins, free catechins, caffeoylquinic acids, and simple phenolic acids, have been identified in G. procumbens plant parts. Moreover, aliphatic compounds, triterpene acids, and sterols have been revealed in lipophilic fractions. Furthermore, over 130 volatile compounds have been detected in wintergreen oil with dominating methyl salicylate (96.9–100%). The accumulated research indicates that mainly hydrophilic non-volatiles are responsible for the pharmacological effects of G. procumbens, primarily its potent anti-inflammatory, antioxidant, and photoprotective activity, with mechanisms verified in vitro and ex vivo in cellular and cell-free assays. The biological effectiveness of the dominant methyl salicylate glycoside—gaultherin—has also been confirmed in animals. Wintergreen oil is reported as a potent anti-inflammatory agent exhibiting moderate antioxidant and antimicrobial activity in vitro and significant insecticidal and larvicidal capacity. Together, G. procumbens accumulate a diverse fraction of polyphenols, triterpenes, and volatiles with validated in vitro and ex vivo biological activity but with the absence of in vivo studies, especially clinical trials concerning effective dose determination and toxicological verification and technological research, including drug formulation.

Qian, Zhihao;Shi, Dexi;Zhang, Hongxia;Li, Zhenzhen;Huang, Li;Yan, Xiufeng;Lin, Sue

doi: 10.3390/ijms25010566pmid: 38203741

Male gametophyte development in plants relies on the functions of numerous genes, whose expression is regulated by transcription factors (TFs), non-coding RNAs, hormones, and diverse environmental stresses. Several excellent reviews are available that address the genes and enzymes associated with male gametophyte development, especially pollen wall formation. Growing evidence from genetic studies, transcriptome analysis, and gene-by-gene studies suggests that TFs coordinate with epigenetic machinery to regulate the expression of these genes and enzymes for the sequential male gametophyte development. However, very little summarization has been performed to comprehensively review their intricate regulatory roles and discuss their downstream targets and upstream regulators in this unique process. In the present review, we highlight the research progress on the regulatory roles of TF families in the male gametophyte development of flowering plants. The transcriptional regulation, epigenetic control, and other regulators of TFs involved in male gametophyte development are also addressed.

Brīvība, Monta;Silamiķele, Laila;Birzniece, Līga;Ansone, Laura;Megnis, Kaspars;Silamiķelis, Ivars;Pelcmane, Līva;Borisova, Daniella;Rozenberga, Maija;Jagare, Lauma;Elbere, Ilze;Kloviņš, Jānis

doi: 10.3390/ijms25010567pmid: 38203738

The gut microbiome plays a pivotal role in the modulation of host responses during viral infections, and recent studies have underscored its significance in the context of coronavirus disease 2019 (COVID-19). We aimed to investigate the dynamics and compositional changes in the gut microbiome of COVID-19 patients, addressing both the acute phase and the recovery process, with a particular focus on the emergence of post-COVID-19 conditions. Involving 146 COVID-19 patients and 110 healthy controls, this study employed a shotgun metagenomics approach for cross-sectional and longitudinal analyses with one- and three-month follow-ups. We observed a decline in taxonomic diversity among hospitalized COVID-19 patients compared to healthy controls, while a subsequent increase in alpha diversity was shown during the recovery process. A notable contribution of Enterococcus faecium was identified in the acute phase of the infection, accompanied by an increasing abundance of butyrate-producing bacteria (e.g., Roseburia, Lachnospiraceae_unclassified) during the recovery period. We highlighted a protective role of the Prevotella genus in the long-term recovery process and suggested a potential significance of population-specificity in the early gut microbiome markers of post-acute COVID-19 syndrome. Our study represents distinctive gut microbiome signatures in COVID-19, with potential diagnostic and prognostic implications, pinpointing potential modulators of the disease progression.

Chen, Claire C.;Benavente, Claudia A.

doi: 10.3390/ijms25010568pmid: 38203737

Osteosarcoma (OS) is a primary malignant bone tumor with high metastasis. Poor prognosis highlights a clinical need for novel therapeutic strategies. Exosomes, also known as extracellular vesicles, have been identified as essential players in the modulation of cancer. Recent studies have suggested that OS-derived exosomes can drive pro-tumorigenic or anti-tumorigenic phenotypes by transferring specific cargos, including proteins, nucleic acids, and metabolites, to neighboring cells, significantly impacting the regulation of cellular processes. This review discusses the advancement of exosomes and their cargos in OS. We examine how these exosomes contribute to the modulation of cellular phenotypes associated with tumor progression and metastasis. Furthermore, we explore the potential of exosomes as valuable biomarkers for diagnostics and prognostic purposes and their role in shaping innovative therapeutic strategies in OS treatment development.

Yan, Peng;Wang, Yisi;Yu, Cailin;Piao, Jingmei;Li, Shuying;Liu, Yinggao;Li, Shujiang

doi: 10.3390/ijms25010569pmid: 38203739

Arthrinium phaeospermum is the major pathogen responsible for the significant stem disease “blight” in B. pervariabilis × D. grandis. The interacting proteins of the key pathogenic factor ApCtf1β, BDUbc and BDSKL1, have previously been obtained by two-hybrid, BiFC, GST pull-down yeast assays. However, the functions of these interacting proteins remain unknown. This study successfully obtained transgenic plants overexpressing BDUbc, BDSKL1, and BDUbc + BDSKL1 via Agrobacterium-mediated gene overexpression. qRT-PCR analysis revealed significantly increased expression levels of BDUbc and BDSKL1 in the transgenic plants. After infection with the pathogenic spore suspension, the disease incidence and severity index significantly decreased across all three transgenic plants, accompanied by a marked increase in defense enzyme levels. Notably, the co-transformed plant, OE-BDUbc + BDSKL1, demonstrated the lowest disease incidence and severity index among the transgenic variants. These results not only indicate that BDUbc and BDSKL1 are disease-resistant genes, but also that these two genes may exhibit a synergistic enhancement effect, which further improves the resistance to blight in Bambusa pervariabilis × Dendrocalamopsis grandis.

Raimondi, Lavinia;De Luca, Angela;Gallo, Alessia;Perna, Fabrizio;Cuscino, Nicola;Cordaro, Aurora;Costa, Viviana;Bellavia, Daniele;Faldini, Cesare;Scilabra, Simone Dario;Giavaresi, Gianluca;Toscano, Angelo

doi: 10.3390/ijms25010570pmid: 38203740

Adolescent Idiopathic Scoliosis (AIS) is the most common form of three-dimensional spinal disorder in adolescents between the ages of 10 and 18 years of age, most commonly diagnosed in young women when severe disease occurs. Patients with AIS are characterized by abnormal skeletal growth and reduced bone mineral density. The etiology of AIS is thought to be multifactorial, involving both environmental and genetic factors, but to date, it is still unknown. Therefore, it is crucial to further investigate the molecular pathogenesis of AIS and to identify biomarkers useful for predicting curve progression. In this perspective, the relative abundance of a panel of microRNAs (miRNAs) was analyzed in the plasma of 20 AIS patients and 10 healthy controls (HC). The data revealed a significant group of circulating miRNAs dysregulated in AIS patients compared to HC. Further bioinformatic analyses evidenced a more restricted expression of some miRNAs exclusively in severe AIS females. These include some members of the miR-30 family, which are considered promising regulators for treating bone diseases. We demonstrated circulating extracellular vesicles (EVs) from severe AIS females contained miR-30 family members and decreased the osteogenic differentiation of mesenchymal stem cells. Proteomic analysis of EVs highlighted the expression of proteins associated with orthopedic disease. This study provides preliminary evidence of a miRNAs signature potentially associated with severe female AIS and suggests the corresponding vesicular component may affect cellular mechanisms crucial in AIS, opening the scenario for in-depth studies on prognostic differences related to gender and grade.