Molecular Biotechnology

Wang, Jin; Zhang, Yan; Li, Zicai

doi: 10.1007/s12033-023-00838-4pmid: 37661210

Osteosarcoma, the most prevalent primary malignant bone tumor and the third most frequent cancer in children and adolescents worldwide, still poses a significant therapeutic challenge. Even though combined chemotherapy and surgical resection have improved survival rates up to 60%, the prognosis for most patients with metastatic osteosarcoma continues to be dismal. The specific pathogenesis and key regulators of tumor invasion and metastasis remain largely elusive. Circular RNAs (circRNAs), novel endogenous non-coding RNA molecules that form covalently closed continuous loops through splicing, play a crucial role in the development, progression, clinical diagnosis, and treatment of various diseases. Recently, an escalating number of circular structures have been identified in osteosarcoma. Understanding their role in osteosarcoma is advantageous for early detection, diagnosis, and treatment of this disease. The primary function of circRNA involves its unique ability to bind specifically to miRNA, although their biological functions also extend to interacting with proteins, regulating gene transcription, and serving as translation templates. In this review, we explore the mechanisms and clinical applications of circRNAs in the pathogenesis and progression of osteosarcoma, with a particular emphasis on the regulatory mechanisms and functions of circRNAs as miRNA sponges in osteosarcoma development.

Khera, Harvinder Kour; Mishra, Rakesh

doi: 10.1007/s12033-023-00870-4pmid: 37695473

Timely and accurate detection of the causal agent of a disease is crucial to restrict suffering and save lives. Mere symptoms are often not enough to detect the root cause of the disease. Better diagnostics applied for screening at a population level and sensitive detection assays remain the crucial component of disease surveillance which may include clinical, plant, and environmental samples, including wastewater. The recent advances in genome sequencing, nucleic acid amplification, and detection methods have revolutionized nucleic acid-based testing (NABing) and screening assays. A typical NABing assay consists of three modules: isolation of the nucleic acid from the collected sample, identification of the target sequence, and final reading the target with the help of a signal, which may be in the form of color, fluorescence, etc. Here, we review current NABing assays covering the different aspects of all three modules. We also describe the frequently used target amplification or signal amplification procedures along with the variety of applications of this fast-evolving technology and challenges in implementation of NABing in the context of disease management especially in low-resource settings.Graphical Abstract[graphic not available: see fulltext]

Pal, Soumen; Bhattacharya, Manojit; Dash, Snehasish; Lee, Sang-Soo; Chakraborty, Chiranjib

doi: 10.1007/s12033-023-00863-3pmid: 37717248

The review article presents the recent progress in quantum computing and simulation within the field of biological sciences. The article is designed mainly into two portions: quantum computing and quantum simulation. In the first part, significant aspects of quantum computing was illustrated, such as quantum hardware, quantum RAM and big data, modern quantum processors, qubit, superposition effect in quantum computation, quantum interference, quantum entanglement, and quantum logic gates. Simultaneously, in the second part, vital features of the quantum simulation was illustrated, such as the quantum simulator, algorithms used in quantum simulations, and the use of quantum simulation in biological science. Finally, the review provides exceptional views to future researchers about different aspects of quantum simulation in biological science.

Pan, Jiyuan; Dong, Qinglong; Wen, Haibin; Liu, Yang; Wang, Xiaojie; Liu, Yanan; Zhang, Xuemei; Shi, Chengmin; Zhao, Dan; Lu, Xiujun

doi: 10.1007/s12033-023-00794-zpmid: 37523021

In order to determine the underlying mechanism of the senescence occurring in older apple trees, the effects of tree age on the community structure and dominant genus of endophytic rhizosphere bacteria in apple were investigated. The diversity and structure of the bacterial communities and corresponding changes in the dominant genera of endophytic rhizosphere bacteria of apple at different ages (2, 8, 16, 22 years) were compared based on 16S rRNA high-throughput sequencing technology. The results revealed that the longer the tree age, the less the number of ASV in the endophytic bacteria. Moreover, the number of ASV in the endophytic bacteria gradually decreased as the tree age increased, however no significant changes were observed in the alpha diversity. At the phyla level, the relative abundance of Actinobacteria increased, while that of Proteobateria decreased. At the genus level, the relative abundance of Mycobacterium, Chujaibacter, and other genera increased, while the relative abundance of Aquabacterium, Ralstonia, Streptomyces, Asticcacaulis, Hyphomicrobium, Pseudomonas, and Sphingomonas decreased. The reduced relative abundance of endophytic rhizosphere bacteria associated with plant growth and disease resistance may thus be the cause of tree senescence. This work acts as a reference to increases the understanding of plant–microbe interactions.

Liu, Xueqi; Zhao, Yunyan; Liang, Xiaoshan; Ding, Yuewen; Hu, Jiao; Deng, Ning; Zhao, Yiting; Huang, Ping; Xie, Wei

doi: 10.1007/s12033-023-00851-7pmid: 37608078

Saikosaponin-a (SSa) exhibits antiepileptic effects. However, its poor water solubility and inability to pass through the blood–brain barrier greatly limit its clinical development and application. In this study, SSa-loaded Methoxy poly (ethylene glycol)-poly(ε-caprolactone) (MePEG-SSa-PCL) NPs were successfully prepared and characterized. Our objective was to further investigate the effect of this composite on acute seizure in mice. First, we confirmed the particle size and surface potential of the composite (51.00 ± 0.25 nm and − 33.77 ± 2.04 mV, respectively). Further, we compared the effects of various MePEG-SSa-PCL doses (low, medium, and high) with those of free SSa, valproic acid (VPA - positive control), and saline only (model group) on acute seizure using three different acute epilepsy mouse models. We observed that compared with the model group, the three MePEG-SSa-PCL treatments showed significantly lowered seizure frequency in mice belonging to the maximum electroconvulsive model group. In the pentylenetetrazol and kainic acid (KA) acute epilepsy models, MePEG-SSa-PCL increased both clonic and convulsion latency periods and shortened convulsion duration more effectively than equivalent SSa-only doses. Furthermore, hematoxylin–eosin and Nissl staining revealed considerably less neuronal damage in the hippocampal CA3 area of KA mice in the SSa, VPA, and three MePEG-SSa-PCL groups relative to mice in the model group. Hippocampal gamma-aminobutyric acid-A (GABA-A) receptor and cleaved caspase-3 expression levels in KA mice were significantly higher and lower, respectively, in the three MePEG-SSa-PCL treatment groups than in the model group. Thus, MePEG-SSa-PCL exhibited a more potent antiepileptic effect than SSa in acute mouse epilepsy models and could alleviate neuronal damage in the hippocampus following epileptic seizures, possibly via GABA-A receptor expression upregulation.

Zhang, Meng; Wang, Xiang; Zhao, Jianfeng; Yan, Jizhou; He, Xiaodan; Qin, Danxia; Liang, Fang; Tong, Kai; Wang, Jianjian

doi: 10.1007/s12033-023-00812-0pmid: 37608076

Osteogenic sarcoma (OS), one of the mesenchymal tumors with a high degree of malignancy, mainly occurs in the metaphysis of the long bones and around the knee joints in children and adolescents. The poor diagnosis in patients with OS can be attributed to the lack of early clinical symptoms, although the growth of tumor mass gradually results in severe pain and systemic symptoms. The mechanisms underlying the pathogenesis of OS are not fully understood. Thus, identifying early diagnostic biomarkers and novel targets involved in the progression of OS is of critical significance in the management of OS. CircRNA is a class of non-coding RNAs characterized by the close-loop structure and increased stability, which are implicated in the regulation of cell proliferation, differentiation, migration, and apoptosis. Moreover, circRNAs also play significant roles in aging and chronic disorders, such as cancer and cardiovascular diseases. Accordingly, we reported the upregulation of circRNA-CIRH1A in OS tissues and cell lines. Silencing circRNA-CIRH1A in OS cell lines (U2OS, HOS, Saos-2, and MG-63) could inhibit the cell proliferation, invasion, migration, and apoptosis, which was also validated in xenograft tumorigenesis mouse model. We further demonstrated that circRNA-CIRH1A sponged miR-1276, which subsequently disrupted the effect of miR-1276 on PI3K/AKT and JAK2/STAT3 signaling pathways. Together, our study revealed the oncogenic role of circRNA-CIRH1A in OS, and identified miR-1276/ PI3K-AKT and JAK2-STAT3 signaling axis as the key downstream mediators of circRNA-CIRH1A.

Yu, Mengsi; Yang, Changcheng; Wang, Song; Shi, Ying; Wang, Jialu; Meng, Cunren; Xue, Li; Chen, Zhaoyun

doi: 10.1007/s12033-023-00855-3pmid: 37608077

This study aimed to explore the role of plasma methylated SEPT9 (mSEPT9) in predicting liver metastasis (LM) in colorectal cancer (CRC) patients. The clinicopathological information of 115 consecutive CRC patients were collected. The differences of clinical characteristics and several biomarkers between CRC patients with LM and those with non-liver metastasis (NM) were analyzed. Multivariate logistic regression analysis was used to identify the risk factors for predicting LM in CRC patients. Receiver operating characteristic curve (ROC) analysis was applied to investigate the sensitivity and specificity of potential biomarkers in indicating the presence of LM in CRC. Compared with the CRC without LM, the levels of plasma mSEPT9 and carcinoembryonic antigen (CEA) were significantly increased in CRC with LM. Multivariate logistic regression analysis showed that plasma mSEPT9 was an independent risk factor for predicting LM in CRC. ROC curves showed that mSEPT9 and CEA could efficiently distinguish LM from NM in CRC. The area under the curve (AUC) of mSEPT9 was 0.850, which was slightly higher than that of CEA (0.842). The optimal cut-off value of mSEPT9 was 35.09 with a sensitivity of 81.82% and a specificity of 73.33%, both similar with that of CEA (sensitivity 87.27% and specificity 75.00%). In addition, the combination of mSEPT9 and CEA had a higher specificity than CEA alone (81.70% Vs 75.00%). Our findings suggest, for the first time, that plasma mSEPT9 might serve as a potential biomarker to predict LM in CRC, which deserves further in-depth study.

Li, Congcong; Zhao, Wanxia; Zhou, Huijie; Wu, Jiao; Huo, Yong; Jiang, Dongfeng; Ji, Xiangbo; Liu, Kun; Xu, Qiuliang; Li, Wantao

doi: 10.1007/s12033-023-00857-1pmid: 37624482

Limited research has been conducted on porcine miR-155 promoters, and previous study from our group have identified two haplotypes (TT and CC) in different pig breeds, each associated with five fully linked mutation sites within or near the miR-155 gene (Li et al. Dev Comp Immunol 39(1):110–116, 2013). In this study, the promoter region of porcine miR-155 was screened, and two important transcription factors, Foxp3 and RelA, were identified. The binding ability of Foxp3 protein was found to be affected by the first mutation site (A/C) using EMSA analysis. In vitro experiments revealed that the expression level of miR-155 was significantly higher in the C haplotype compared to the T haplotype. Additionally, northern blotting assays indicated that both the first mutation site (A/C) and the fourth mutation site (G/T) had a significant impact on miR-155 expression levels. These findings provide further insights into the transcriptional regulation of porcine miR-155 and identify crucial mutation sites that influence miR-155 expression. This knowledge can serve as a basis for identifying potential molecular markers associated with disease resistance in swine.

Yue, Jianning; Wang, Qi; Zhao, Wenxing; Wu, Baishan; Ni, Jiaxiang

doi: 10.1007/s12033-023-00847-3pmid: 37632673

We investigated the function and molecular mechanism of long non-coding RNA (lncRNA) small nucleolar RNA host gene 16 (Snhg16) in modifying ozone treatment for neuropathic pain (NP) in a mouse model of chronic constriction injury (CCI). Pain-related behavioral responses were evaluated using paw withdrawal threshold (PWT), paw lifting number (PLN), and paw withdrawal latency (PWL) tests. Interleukin (IL)-1β, IL-10, IL-6, and tumor necrosis factor-alpha (TNF-α) were measured by ELISA and qRT-PCR to evaluate neuroinflammation. qRT-PCR was performed to detect expressions of Snhg16, microRNA (miR)-719, sodium voltage-gated channel alpha subunit 1 (SCN1A), and inflammatory factors. Bioinformatics, dual-luciferase reporter assay, and RNA pull-down verified the underlying molecular mechanisms. Snhg16 expression increased in CCI mice. Snhg16 overexpression retarded the curative effect of ozone and induced NP. miR-719 was sponged by Snhg16. SCN1A was a target of miR-719. Inhibition of miR-719 markedly reversed the effects of Snhg16 on pain-related behavioral responses and neuroinflammation. Upregulation of SCN1A partly abrogated the effects of elevated miR-719 levels on the occurrence of NP. The findings demonstrate that lncRNA Snhg16 promotes NP progression in CCI mice by binding to miR-719 to increase SCN1A expression. The Snhg16/miR-719/SCN1A axis may influence the curative effects of ozone therapy in treating NP.

Sun, Heyan; Li, Zhenwei; Liu, Nannan; Xu, Tao; Hu, Kongzu; Shao, Yubao; Chen, Xiaoyu

doi: 10.1007/s12033-023-00856-2pmid: 37632672

This study aims to explore the molecular mechanism of LncRNA SNHG7 in Osteoarthritis (OA). Cartilage tissues of OA patients or patients with trauma or amputation were collected. Compared to normal cartilage tissues, SNHG7 was downregulated while miR-324-3p was upregulated in cartilage tissues of OA patients. IL-1β was used to induce damage to chondrocytes and treatment with IL-1β reduced SNHG7 expression in OA chondrocytes. In IL-1β-treated OA chondrocytes, SNHG7 overexpression reduced the levels of TNF-α and IL-6, inhibited cell apoptosis, and increased cell viability. Additionally, the luciferase reporter assay proved that SNHG7 upregulated dual-specificity phosphatase 1 (DUSP1) by sponging miR-324-3p, thereby inactivating the p38 MAPK signaling pathway by regulating the miR-324-3p/DUSP1 axis. Anisomycin (a p38 MAPK activator) enhanced OA chondrocytes inflammation, promoted cell apoptosis, and reduced cell viability; however, this was reversed by SNHG7 overexpression. This study demonstrates that the SNHG7/miR-324-3p/DUSP1 axis suppresses OA chondrocytes inflammation and apoptosis by inhibiting the p38 MAPK signaling pathway. Thus, this study indicates that SNHG7 is a novel target for OA treatment.