PeerJ:Cell Biologyhttps://peerj.com/articles/index.atom?journal=peerj&subject=800Cell Biology articles published in PeerJAnti-ENO1 antibody combined with metformin against tumor resistance: a novel antibody-based platformhttps://peerj.com/articles/168172024-03-182024-03-18Xiong ShuHui Wen ZhangShi Ya LiuLi Xin SunTao ZhangYu Liang Ran
Background
Antibody-based platforms (i.e., ADC) have emerged as one of the most encouraging tools for the cancer resistance caused by cancer stem cells (CSCs) enrichment. Our study might provide a promising therapeutic direction against drug resistance and serve as a potential precursor platform for screening ADC.
Methods
The cell migration, invasion, drug resistance, and self-renewal were assessed by the cell invasion and migration assay, wound healing assay, CCK-8 assay, colony formation assay, and sphere formation assay, respectively. The expression profiles of CSCs (ALDH+ and CD44+) subpopulations were screened by flow cytometry. The western blot and cell immunofluorescence assay were used to evaluate pathway-related protein expression in both anti-ENO1 antibody, MET combined with DPP/CTX-treated CSCs.
Results
In the present study, western blot and flow cytometry verified that anti-ENO1 antibody target the CD44+ subpopulation by inhibiting the PI3K/AKT pathway, while metformin might target the ALDH+ subpopulation through activation of the AMPK pathway and thus reverse drug resistance to varying degrees. Subsequently, in vitro investigation indicated that anti-ENO1 antibody, metformin combined with cisplatin/cetuximab could simultaneously target ALDH+ and CD44+ subpopulations. The combination also inhibited the CSCs proliferation, migration, invasion, and sphere formation; which may result in overcoming the drug resistance. Then, molecular mechanism exploration verified that the anti-ENO1 antibody, metformin combined with cisplatin/cetuximab inhibited the Wnt/β-catenin signaling.
Conclusions
The study preliminarily revealed anti-ENO1 antibody combined with metformin could overcome drug resistance against CSCs by inhibiting the Wnt//β-catenin pathway and might serve as a potential precursor platform for screening ADC. More importantly, it is reasonably believed that antibody-based drug combination therapy might function as an encouraging tool for oncotherapy.
Background
Antibody-based platforms (i.e., ADC) have emerged as one of the most encouraging tools for the cancer resistance caused by cancer stem cells (CSCs) enrichment. Our study might provide a promising therapeutic direction against drug resistance and serve as a potential precursor platform for screening ADC.
Methods
The cell migration, invasion, drug resistance, and self-renewal were assessed by the cell invasion and migration assay, wound healing assay, CCK-8 assay, colony formation assay, and sphere formation assay, respectively. The expression profiles of CSCs (ALDH+ and CD44+) subpopulations were screened by flow cytometry. The western blot and cell immunofluorescence assay were used to evaluate pathway-related protein expression in both anti-ENO1 antibody, MET combined with DPP/CTX-treated CSCs.
Results
In the present study, western blot and flow cytometry verified that anti-ENO1 antibody target the CD44+ subpopulation by inhibiting the PI3K/AKT pathway, while metformin might target the ALDH+ subpopulation through activation of the AMPK pathway and thus reverse drug resistance to varying degrees. Subsequently, in vitro investigation indicated that anti-ENO1 antibody, metformin combined with cisplatin/cetuximab could simultaneously target ALDH+ and CD44+ subpopulations. The combination also inhibited the CSCs proliferation, migration, invasion, and sphere formation; which may result in overcoming the drug resistance. Then, molecular mechanism exploration verified that the anti-ENO1 antibody, metformin combined with cisplatin/cetuximab inhibited the Wnt/β-catenin signaling.
Conclusions
The study preliminarily revealed anti-ENO1 antibody combined with metformin could overcome drug resistance against CSCs by inhibiting the Wnt//β-catenin pathway and might serve as a potential precursor platform for screening ADC. More importantly, it is reasonably believed that antibody-based drug combination therapy might function as an encouraging tool for oncotherapy.Clinical significance of small nuclear ribonucleoprotein U1 subunit 70 in patients with hepatocellular carcinomahttps://peerj.com/articles/168762024-03-152024-03-15Dong JiangXia-Ling ZhuYan AnYi-ran Li
Background & Aims
Small nuclear ribonucleoprotein U1 subunit 70 (SNRNP70) as one of the components of the U1 small nuclear ribonucleoprotein (snRNP) is rarely reported in cancers. This study aims to estimate the application potential of SNRNP70 in hepatocellular carcinoma (HCC) clinical practice.
Methods
Based on the TCGA database and cohort of HCC patients, we investigated the expression patterns and prognostic value of SNRNP70 in HCC. Then, the combination of SNRNP70 and alpha-fetoprotein (AFP) in 278 HCC cases was analyzed. Next, western blotting and immunohistochemistry were used to detect the expression of SNRNP70 in nucleus and cytoplasm. Finally, Cell Counting Kit-8 (CCK-8) and scratch wound healing assays were used to detect the effect of SNRNP70 on the proliferation and migration of HCC cells.
Results
SNRNP70 was highly expressed in HCC. Its expression was increasingly high during the progression of HCC and was positively related to immune infiltration cells. Higher SNRNP70 expression indicated a poor outcome of HCC patients. In addition, nuclear SNRNP70/AFP combination could be a prognostic biomarker for overall survival and recurrence. Cell experiments confirmed that knockdown of SNRNP70 inhibited the proliferation and migration of HCC cells.
Conclusion
SNRNP70 may be a new biomarker for HCC progression and HCC diagnosis as well as prognosis. SNRNP70 combined with serum AFP may indicate the prognosis and recurrence status of HCC patients after operation.
Background & Aims
Small nuclear ribonucleoprotein U1 subunit 70 (SNRNP70) as one of the components of the U1 small nuclear ribonucleoprotein (snRNP) is rarely reported in cancers. This study aims to estimate the application potential of SNRNP70 in hepatocellular carcinoma (HCC) clinical practice.
Methods
Based on the TCGA database and cohort of HCC patients, we investigated the expression patterns and prognostic value of SNRNP70 in HCC. Then, the combination of SNRNP70 and alpha-fetoprotein (AFP) in 278 HCC cases was analyzed. Next, western blotting and immunohistochemistry were used to detect the expression of SNRNP70 in nucleus and cytoplasm. Finally, Cell Counting Kit-8 (CCK-8) and scratch wound healing assays were used to detect the effect of SNRNP70 on the proliferation and migration of HCC cells.
Results
SNRNP70 was highly expressed in HCC. Its expression was increasingly high during the progression of HCC and was positively related to immune infiltration cells. Higher SNRNP70 expression indicated a poor outcome of HCC patients. In addition, nuclear SNRNP70/AFP combination could be a prognostic biomarker for overall survival and recurrence. Cell experiments confirmed that knockdown of SNRNP70 inhibited the proliferation and migration of HCC cells.
Conclusion
SNRNP70 may be a new biomarker for HCC progression and HCC diagnosis as well as prognosis. SNRNP70 combined with serum AFP may indicate the prognosis and recurrence status of HCC patients after operation.Chigno/CG11180 and SUMO are Chinmo-interacting proteins with a role in Drosophila testes somatic support cellshttps://peerj.com/articles/169712024-03-142024-03-14Leanna RinehartWendy E. StewartNatalie LuffmanMatthew WawersikOliver Kerscher
Stem cells are critical for replenishment of cells lost to death, damage or differentiation. Drosophila testes are a key model system for elucidating mechanisms regulating stem cell maintenance and differentiation. An intriguing gene identified through such studies is the transcription factor, chronologically inappropriate morphogenesis (Chinmo). Chinmo is a downstream effector of the Jak-STAT signaling pathway that acts in testis somatic stem cells to ensure maintenance of male stem cell fate and sexual identity. Defects in these processes can lead to infertility and the formation of germ cell tumors. While Chinmo’s effect on testis stem cell behavior has been investigated in detail, there is still much to be learned about its structure, function, and interactions with other proteins. Using a two-hybrid screen, we find that Chinmo interacts with itself, the small ubiquitin-like modifier SUMO, the novel protein CG11180, and four other proteins (CG4318, Ova (ovaries absent), Taf3 (TBP-associated factor 3), and CG18269). Since both Chinmo and CG11180 contain sumoylation sites and SUMO-interacting motifs (SIMs), we analyzed their interaction in more detail. Using site-directed mutagenesis of a unique SIM in CG11180, we demonstrate that Chinmo’s interaction with CG11180 is SUMO-dependent. Furthermore, to assess the functional relevance of both SUMO and CG11180, we performed RNAi-mediated knockdown of both proteins in somatic cells of the Drosophila testis. Using this approach, we find that CG11180 and SUMO are required in somatic cells of adult testes, and that reduction of either protein causes formation of germ cell tumors. Overall, our work suggests that SUMO may be involved in the interaction of Chinmo and CG11180 and that these genes are required in somatic cells of the adult Drosophila testis. Consistent with the CG11180 knockdown phenotype in male testes, and to underscore its connection to Chinmo, we propose the name Chigno (Childless Gambino) for CG11180.
Stem cells are critical for replenishment of cells lost to death, damage or differentiation. Drosophila testes are a key model system for elucidating mechanisms regulating stem cell maintenance and differentiation. An intriguing gene identified through such studies is the transcription factor, chronologically inappropriate morphogenesis (Chinmo). Chinmo is a downstream effector of the Jak-STAT signaling pathway that acts in testis somatic stem cells to ensure maintenance of male stem cell fate and sexual identity. Defects in these processes can lead to infertility and the formation of germ cell tumors. While Chinmo’s effect on testis stem cell behavior has been investigated in detail, there is still much to be learned about its structure, function, and interactions with other proteins. Using a two-hybrid screen, we find that Chinmo interacts with itself, the small ubiquitin-like modifier SUMO, the novel protein CG11180, and four other proteins (CG4318, Ova (ovaries absent), Taf3 (TBP-associated factor 3), and CG18269). Since both Chinmo and CG11180 contain sumoylation sites and SUMO-interacting motifs (SIMs), we analyzed their interaction in more detail. Using site-directed mutagenesis of a unique SIM in CG11180, we demonstrate that Chinmo’s interaction with CG11180 is SUMO-dependent. Furthermore, to assess the functional relevance of both SUMO and CG11180, we performed RNAi-mediated knockdown of both proteins in somatic cells of the Drosophila testis. Using this approach, we find that CG11180 and SUMO are required in somatic cells of adult testes, and that reduction of either protein causes formation of germ cell tumors. Overall, our work suggests that SUMO may be involved in the interaction of Chinmo and CG11180 and that these genes are required in somatic cells of the adult Drosophila testis. Consistent with the CG11180 knockdown phenotype in male testes, and to underscore its connection to Chinmo, we propose the name Chigno (Childless Gambino) for CG11180.Generation and characterization of mAb 61H9 against junctional adhesion molecule-a with potent antitumor activityhttps://peerj.com/articles/170882024-03-142024-03-14Kang LiuHang YangRong XiongYunlong ShenGuiqin SongJinliang YangZhenling Wang
Junctional adhesion molecule-A (JAM-A) is an adhesion molecule that exists on the surface of certain types of cells, including white blood cells, endothelial cells, and dendritic cells. In this study, the cDNA sequences of JAM-A-Fc were chemically synthesized with optimization for mammalian expression. Afterward, we analyzed JAM-A protein expression through transient transfection in HEK293 cell lines. Mice were immunized with JAM-A-Fc protein, and hybridoma was prepared by fusing myeloma cells and mouse spleen cells. Antibodies were purified from the hybridoma supernatant and four monoclonal strains were obtained and numbered 61H9, 70E5, 71A8, and 74H3 via enzyme-linked immunosorbent assay screening. Immunofluorescence staining assay showed 61H9 was the most suitable cell line for mAb production due to its fluorescence signal being the strongest. Flow cytometric analysis proved that 61H9 possessed high affinity. Moreover, antagonism of JAM-A mAb could attenuate the proliferative, migrative, and invasive abilities of ESCC cells and significantly inhibit tumor growth in mice. By examining hematoxylin-eosin staining mice tumor tissues, we found inflammatory cells infiltrated lightly in the anti-JAM-A group. The expression of BCL-2 and IκBα in the anti-JAM-A group were decreased in mice tumor tissues compared to the control group. Ultimately, a method for preparing high-yield JAM-A-Fc protein was created and a high affinity mAb against JAM-A with an antitumor effect was prepared.
Junctional adhesion molecule-A (JAM-A) is an adhesion molecule that exists on the surface of certain types of cells, including white blood cells, endothelial cells, and dendritic cells. In this study, the cDNA sequences of JAM-A-Fc were chemically synthesized with optimization for mammalian expression. Afterward, we analyzed JAM-A protein expression through transient transfection in HEK293 cell lines. Mice were immunized with JAM-A-Fc protein, and hybridoma was prepared by fusing myeloma cells and mouse spleen cells. Antibodies were purified from the hybridoma supernatant and four monoclonal strains were obtained and numbered 61H9, 70E5, 71A8, and 74H3 via enzyme-linked immunosorbent assay screening. Immunofluorescence staining assay showed 61H9 was the most suitable cell line for mAb production due to its fluorescence signal being the strongest. Flow cytometric analysis proved that 61H9 possessed high affinity. Moreover, antagonism of JAM-A mAb could attenuate the proliferative, migrative, and invasive abilities of ESCC cells and significantly inhibit tumor growth in mice. By examining hematoxylin-eosin staining mice tumor tissues, we found inflammatory cells infiltrated lightly in the anti-JAM-A group. The expression of BCL-2 and IκBα in the anti-JAM-A group were decreased in mice tumor tissues compared to the control group. Ultimately, a method for preparing high-yield JAM-A-Fc protein was created and a high affinity mAb against JAM-A with an antitumor effect was prepared.Identification and validation of shared gene signature of kidney renal clear cell carcinoma and COVID-19https://peerj.com/articles/169272024-03-042024-03-04Jianqiang NieHailang YangXiaoqiang LiuWen DengBin Fu
Background
COVID-19 is a severe infectious disease caused by the SARS-CoV-2 virus, and previous studies have shown that patients with kidney renal clear cell carcinoma (KIRC) are more susceptible to SARS-CoV-2 infection than the general population. Nevertheless, their co-pathogenesis remains incompletely elucidated.
Methods
We obtained shared genes between these two diseases based on public datasets, constructed a prognostic risk model consisting of hub genes, and validated the accuracy of the model using internal and external validation sets. We further analyzed the immune landscape of the prognostic risk model, investigated the biological functions of the hub genes, and detected their expression in renal cell carcinoma cells using qPCR. Finally, we searched the candidate drugs associated with hub gene-related targets from DSigDB and CellMiner databases.
Results
We obtained 156 shared genes between KIRC and COVID-19 and constructed a prognostic risk model consisting of four hub genes. Both shared genes and hub genes were highly enriched in immune-related functions and pathways. Hub genes were significantly overexpressed in COVID-19 and KIRC. ROC curves, nomograms, etc., showed the reliability and robustness of the risk model, which was validated in both internal and external datasets. Moreover, patients in the high-risk group showed a higher proportion of immune cells, higher expression of immune checkpoint genes, and more active immune-related functions. Finally, we identified promising drugs for COVID-19 and KIRC, such as etoposide, fulvestrant, and topotecan.
Conclusion
This study identified and validated four shared genes for KIRC and COVID-19. These genes are associated with immune functions and may serve as potential prognostic biomarkers for KIRC. The shared pathways and genes may provide new insights for further mechanistic research and treatment of comorbidities.
Background
COVID-19 is a severe infectious disease caused by the SARS-CoV-2 virus, and previous studies have shown that patients with kidney renal clear cell carcinoma (KIRC) are more susceptible to SARS-CoV-2 infection than the general population. Nevertheless, their co-pathogenesis remains incompletely elucidated.
Methods
We obtained shared genes between these two diseases based on public datasets, constructed a prognostic risk model consisting of hub genes, and validated the accuracy of the model using internal and external validation sets. We further analyzed the immune landscape of the prognostic risk model, investigated the biological functions of the hub genes, and detected their expression in renal cell carcinoma cells using qPCR. Finally, we searched the candidate drugs associated with hub gene-related targets from DSigDB and CellMiner databases.
Results
We obtained 156 shared genes between KIRC and COVID-19 and constructed a prognostic risk model consisting of four hub genes. Both shared genes and hub genes were highly enriched in immune-related functions and pathways. Hub genes were significantly overexpressed in COVID-19 and KIRC. ROC curves, nomograms, etc., showed the reliability and robustness of the risk model, which was validated in both internal and external datasets. Moreover, patients in the high-risk group showed a higher proportion of immune cells, higher expression of immune checkpoint genes, and more active immune-related functions. Finally, we identified promising drugs for COVID-19 and KIRC, such as etoposide, fulvestrant, and topotecan.
Conclusion
This study identified and validated four shared genes for KIRC and COVID-19. These genes are associated with immune functions and may serve as potential prognostic biomarkers for KIRC. The shared pathways and genes may provide new insights for further mechanistic research and treatment of comorbidities.Hsa_circ_0001615 downregulation inhibits esophageal cancer development through miR-142-5p/β-cateninhttps://peerj.com/articles/170892024-03-042024-03-04Yukai DaiQizhong XuManqi XiaCaimin ChenXinming XiongXin YangWei Wang
Background
Recent studies have found that circular RNAs (circRNAs) play important roles in tumorigenesis. This study aimed to determine the function and potential mechanisms of hsa_circ_0001615 in esophageal cancer.
Methods
Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the expression of hsa_circ_0001615 and miR-142-5p. Subsequently, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt, flow cytometry, clone formation, and transwell assays were used to assess the function of hsa_circ_0001615. Furthermore, qRT-PCR and Western blot analysis were used to verify cyclin D1, Bcl-2 associated X, B-cell lymphoma/leukemia gene-2, and β-catenin levels. Circular RNA Interactome was used to estimate the binding site between hsa_circ_0001615 and miR-142-5p. Additionally, dual-luciferase reporter assays were used to determine whether miR-142-5p was a direct target of hsa_circ_0001615. Pearson correlation analysis was used to explore the relationship between miR-142-5p and hsa_circ_0001615.
Results
In esophageal cancer, the expressions of hsa_circ_0001615 and miR-142-5p were increased and decreased, respectively. Hsa_circ_0001615 inhibition significantly reduced the proliferation, migration, and invasion but increased the apoptosis of esophageal cancer cells. Additionally, hsa_circ_0001615 knockdown increased miR-142-5p expression but decreased β-catenin expression. MiR-142-5p was a direct target of hsa_circ_0001615.
Conclusion
Hsa_circ_0001615 knockdown could mediate antitumor effects through the miR-142-5p/β-catenin pathway.
Background
Recent studies have found that circular RNAs (circRNAs) play important roles in tumorigenesis. This study aimed to determine the function and potential mechanisms of hsa_circ_0001615 in esophageal cancer.
Methods
Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the expression of hsa_circ_0001615 and miR-142-5p. Subsequently, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt, flow cytometry, clone formation, and transwell assays were used to assess the function of hsa_circ_0001615. Furthermore, qRT-PCR and Western blot analysis were used to verify cyclin D1, Bcl-2 associated X, B-cell lymphoma/leukemia gene-2, and β-catenin levels. Circular RNA Interactome was used to estimate the binding site between hsa_circ_0001615 and miR-142-5p. Additionally, dual-luciferase reporter assays were used to determine whether miR-142-5p was a direct target of hsa_circ_0001615. Pearson correlation analysis was used to explore the relationship between miR-142-5p and hsa_circ_0001615.
Results
In esophageal cancer, the expressions of hsa_circ_0001615 and miR-142-5p were increased and decreased, respectively. Hsa_circ_0001615 inhibition significantly reduced the proliferation, migration, and invasion but increased the apoptosis of esophageal cancer cells. Additionally, hsa_circ_0001615 knockdown increased miR-142-5p expression but decreased β-catenin expression. MiR-142-5p was a direct target of hsa_circ_0001615.
Conclusion
Hsa_circ_0001615 knockdown could mediate antitumor effects through the miR-142-5p/β-catenin pathway.Prognostic value of RNA methylation-related genes in gastric adenocarcinoma based on bioinformaticshttps://peerj.com/articles/169512024-02-292024-02-29Xionghui HeXiang ChenChangcheng YangWei WangHening SunJunjie WangJincheng FuHuaying Dong
Background
Gastric cancer (GC) is a malignant tumor that originates from the epithelium of the gastric mucosa and has a poor prognosis. Stomach adenocarcinoma (STAD) covers 95% of total gastric cancer. This study aimed to identify the prognostic value of RNA methylation-related genes in gastric cancer.
Methods
In this study, The Cancer Genome Atlas (TCGA)-STAD and GSE84426 cohorts were downloaded from public databases. Patients were classified by consistent cluster analysis based on prognosis-related differentially expressed RNA methylation genes Prognostic genes were obtained by differential expression, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses. The prognostic model was established and validated in the training set, test set and validation set respectively. Independent prognostic analysis was implemented. Finally, the expression of prognostic genes was affirmed by reverse transcription quantitative PCR (RT-qPCR).
Results
In total, four prognostic genes (ACTA2, SAPCD2, PDK4 and APOD) related to RNA methylation were identified and enrolled into the risk signature. The STAD patients were divided into high- and low-risk groups based on the medium value of the risk score, and patients in the high-risk group had a poor prognosis. In addition, the RNA methylation-relevant risk signature was validated in the test and validation sets, and was authenticated as a reliable independent prognostic predictor. The nomogram was constructed based on the independent predictors to predict the 1/3/5-year survival probability of STAD patients. The gene set enrichment analysis (GSEA) result suggested that the poor prognosis in the high-risk subgroup may be related to immune-related pathways. Finally, the experimental results indicated that the expression trends of RNA methylation-relevant prognostic genes in gastric cancer cells were in agreement with the result of bioinformatics.
Conclusion
Our study established a novel RNA methylation-related risk signature for STAD, which was of considerable significance for improving prognosis of STAD patients and offering theoretical support for clinical therapy.
Background
Gastric cancer (GC) is a malignant tumor that originates from the epithelium of the gastric mucosa and has a poor prognosis. Stomach adenocarcinoma (STAD) covers 95% of total gastric cancer. This study aimed to identify the prognostic value of RNA methylation-related genes in gastric cancer.
Methods
In this study, The Cancer Genome Atlas (TCGA)-STAD and GSE84426 cohorts were downloaded from public databases. Patients were classified by consistent cluster analysis based on prognosis-related differentially expressed RNA methylation genes Prognostic genes were obtained by differential expression, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses. The prognostic model was established and validated in the training set, test set and validation set respectively. Independent prognostic analysis was implemented. Finally, the expression of prognostic genes was affirmed by reverse transcription quantitative PCR (RT-qPCR).
Results
In total, four prognostic genes (ACTA2, SAPCD2, PDK4 and APOD) related to RNA methylation were identified and enrolled into the risk signature. The STAD patients were divided into high- and low-risk groups based on the medium value of the risk score, and patients in the high-risk group had a poor prognosis. In addition, the RNA methylation-relevant risk signature was validated in the test and validation sets, and was authenticated as a reliable independent prognostic predictor. The nomogram was constructed based on the independent predictors to predict the 1/3/5-year survival probability of STAD patients. The gene set enrichment analysis (GSEA) result suggested that the poor prognosis in the high-risk subgroup may be related to immune-related pathways. Finally, the experimental results indicated that the expression trends of RNA methylation-relevant prognostic genes in gastric cancer cells were in agreement with the result of bioinformatics.
Conclusion
Our study established a novel RNA methylation-related risk signature for STAD, which was of considerable significance for improving prognosis of STAD patients and offering theoretical support for clinical therapy.A review on the traditional uses, nutritive importance, pharmacognostic features, phytochemicals, and pharmacology of Momordica cymbalaria Hook Fhttps://peerj.com/articles/169282024-02-272024-02-27Firdous Sayeed MohammedDinesh BabuZainab IrfanMarwa A.A. Fayed
Momordica cymbalaria Hook F. (MC), belonging to the family Cucurbitaceae, is a plant with several biological activities. This detailed, comprehensive review gathers and presents all the information related to the geographical distribution, morphology, therapeutic uses, nutritional values, pharmacognostic characters, phytochemicals, and pharmacological activities of MC. The available literature showed that MC fruits are utilized as a stimulant, tonic, laxative, stomachic, and to combat inflammatory disorders. The fruits are used to treat spleen and liver diseases and are applied in folk medicine to induce abortion and treat diabetes mellitus. The phytochemical screening studies report that MC fruits contain tannins, alkaloids, phenols, proteins, amino acids, vitamin C, carbohydrates, β-carotenes, palmitic acid, oleic acid, stearic acid, α-eleostearic acid, and γ-linolenic acid. The fruits also contain calcium, sodium, iron, potassium, copper, manganese, zinc, and phosphorus. Notably, momordicosides are cucurbitacin triterpenoids reported in the fruits of MC. Diverse pharmacological activities of MC, such as analgesic, anti-inflammatory, antioxidant, hepatoprotective, nephroprotective, antidiabetic, cardioprotective, antidepressant, anticonvulsant, anticancer, antiangiogenic, antifertility, antiulcer, antimicrobial, antidiarrheal and anthelmintic, have been reported by many investigators. M. cymbalaria methanolic extract is safe up to 2,000 mg/kg. Furthermore, no symptoms of toxicity were found. These pharmacological activities are mechanistically interpreted and described in this review. Additionally, the microscopic, powder and physiochemical characteristics of MC tubers are also highlighted. In summary, possesses remarkable medicinal values, which warrant further detailed studies to exploit its potential benefits therapeutically.
Momordica cymbalaria Hook F. (MC), belonging to the family Cucurbitaceae, is a plant with several biological activities. This detailed, comprehensive review gathers and presents all the information related to the geographical distribution, morphology, therapeutic uses, nutritional values, pharmacognostic characters, phytochemicals, and pharmacological activities of MC. The available literature showed that MC fruits are utilized as a stimulant, tonic, laxative, stomachic, and to combat inflammatory disorders. The fruits are used to treat spleen and liver diseases and are applied in folk medicine to induce abortion and treat diabetes mellitus. The phytochemical screening studies report that MC fruits contain tannins, alkaloids, phenols, proteins, amino acids, vitamin C, carbohydrates, β-carotenes, palmitic acid, oleic acid, stearic acid, α-eleostearic acid, and γ-linolenic acid. The fruits also contain calcium, sodium, iron, potassium, copper, manganese, zinc, and phosphorus. Notably, momordicosides are cucurbitacin triterpenoids reported in the fruits of MC. Diverse pharmacological activities of MC, such as analgesic, anti-inflammatory, antioxidant, hepatoprotective, nephroprotective, antidiabetic, cardioprotective, antidepressant, anticonvulsant, anticancer, antiangiogenic, antifertility, antiulcer, antimicrobial, antidiarrheal and anthelmintic, have been reported by many investigators. M. cymbalaria methanolic extract is safe up to 2,000 mg/kg. Furthermore, no symptoms of toxicity were found. These pharmacological activities are mechanistically interpreted and described in this review. Additionally, the microscopic, powder and physiochemical characteristics of MC tubers are also highlighted. In summary, possesses remarkable medicinal values, which warrant further detailed studies to exploit its potential benefits therapeutically.Multiscale transport and 4D time-lapse imaging in precision-cut liver slices (PCLS)https://peerj.com/articles/169942024-02-262024-02-26Iqra AzamJames D. Benson
Background
Monitoring cellular processes across different levels of complexity, from the cellular to the tissue scale, is important for understanding tissue structure and function. However, it is challenging to monitor and estimate these structural and dynamic interactions within three-dimensional (3D) tissue models.
Objective
The aim of this study was to design a method for imaging, tracking, and quantifying 3D changes in cell morphology (shape and size) within liver tissue, specifically a precision-cut liver slice (PCLS). A PCLS is a 3D model of the liver that allows the study of the structure and function of liver cells in their native microenvironment.
Methods
Here, we present a method for imaging liver tissue during anisosmotic exposure in a multispectral four-dimensional manner. Three metrics of tissue morphology were measured to quantify the effects of osmotic stress on liver tissue. We estimated the changes in the volume of whole precision cut liver slices, quantified the changes in nuclei position, and calculated the changes in volumetric responses of tissue-embedded cells.
Results
During equilibration with cell-membrane-permeating and non-permeating solutes, the whole tissue experiences shrinkage and expansion. As nuclei showed a change in position and directional displacement under osmotic stress, we demonstrate that nuclei could be used as a probe to measure local osmotic and mechanical stress. Moreover, we demonstrate that cells change their volume within tissue slices as a result of osmotic perturbation and that this change in volume is dependent on the position of the cell within the tissue and the duration of the exposure.
Conclusion
The results of this study have implications for a better understanding of multiscale transport, mechanobiology, and triggered biological responses within complex biological structures.
Background
Monitoring cellular processes across different levels of complexity, from the cellular to the tissue scale, is important for understanding tissue structure and function. However, it is challenging to monitor and estimate these structural and dynamic interactions within three-dimensional (3D) tissue models.
Objective
The aim of this study was to design a method for imaging, tracking, and quantifying 3D changes in cell morphology (shape and size) within liver tissue, specifically a precision-cut liver slice (PCLS). A PCLS is a 3D model of the liver that allows the study of the structure and function of liver cells in their native microenvironment.
Methods
Here, we present a method for imaging liver tissue during anisosmotic exposure in a multispectral four-dimensional manner. Three metrics of tissue morphology were measured to quantify the effects of osmotic stress on liver tissue. We estimated the changes in the volume of whole precision cut liver slices, quantified the changes in nuclei position, and calculated the changes in volumetric responses of tissue-embedded cells.
Results
During equilibration with cell-membrane-permeating and non-permeating solutes, the whole tissue experiences shrinkage and expansion. As nuclei showed a change in position and directional displacement under osmotic stress, we demonstrate that nuclei could be used as a probe to measure local osmotic and mechanical stress. Moreover, we demonstrate that cells change their volume within tissue slices as a result of osmotic perturbation and that this change in volume is dependent on the position of the cell within the tissue and the duration of the exposure.
Conclusion
The results of this study have implications for a better understanding of multiscale transport, mechanobiology, and triggered biological responses within complex biological structures.Effects of BRD4 inhibitor JQ1 on the expression profile of super-enhancer related lncRNAs and mRNAs in cervical cancer HeLa cellshttps://peerj.com/articles/170352024-02-232024-02-23Jianqing ZhengBifen HuangLihua XiaoMin Wu
Objective
To investigate the effects of bromine domain protein 4 (BRD4) inhibitor JQ1 on the expression profile of super-enhancer-related lncRNAs (SE-lncRNAs) and mRNAs in cervical cancer (CC) HeLa-cells.
Methods
The CCK8 method was implemented to detect the inhibitory effect of JQ1 on HeLa cells and explore the best inhibitory concentration. Whole transcriptome sequencing was performed to detect the changes of lncRNAs and mRNAs expression profiles in cells of the JQ1 treatment group and control group, respectively. The differentially expressed SE-lncRNAs were obtained by matching, while the co-expressed mRNAs were obtained by Pearson correlation analysis.
Results
The inhibitory effect of JQ1 on HeLa cell proliferation increased significantly with increasing concentration and treatment time (P < 0.05). Under the experimental conditions of three concentrations of 0.01, 0.1 and 1 μmol/L of JQ1 on HeLa cells at 24, 48, 72 and 120 h, 1 μmol/L of JQ1 at 72 and 120 h had the same cell viability and the strongest cell proliferation inhibition. In order to understand the inhibitory mechanism of JQ1 on HeLa cells, this study analyzed the expression profile differences from the perspective of SE-lncRNAs and mRNAs. A total of 162 SE-lncRNAs were identified, of which 8 SE-lncRNAs were down-regulated and seven SE-lncRNAs were up-regulated. A total of 418 differentially expressed mRNAs related to SE-lncRNAs were identified, of which 395 mRNAs had positive correlation with 12 SE-lncRNAs and 408 mRNAs had negative correlation with 15 SE-lncRNAs.
Conclusion
JQ1 can significantly inhibit the proliferation of HeLa cells and affect the expression profile of SE-lncRNAs and mRNAs.
Objective
To investigate the effects of bromine domain protein 4 (BRD4) inhibitor JQ1 on the expression profile of super-enhancer-related lncRNAs (SE-lncRNAs) and mRNAs in cervical cancer (CC) HeLa-cells.
Methods
The CCK8 method was implemented to detect the inhibitory effect of JQ1 on HeLa cells and explore the best inhibitory concentration. Whole transcriptome sequencing was performed to detect the changes of lncRNAs and mRNAs expression profiles in cells of the JQ1 treatment group and control group, respectively. The differentially expressed SE-lncRNAs were obtained by matching, while the co-expressed mRNAs were obtained by Pearson correlation analysis.
Results
The inhibitory effect of JQ1 on HeLa cell proliferation increased significantly with increasing concentration and treatment time (P < 0.05). Under the experimental conditions of three concentrations of 0.01, 0.1 and 1 μmol/L of JQ1 on HeLa cells at 24, 48, 72 and 120 h, 1 μmol/L of JQ1 at 72 and 120 h had the same cell viability and the strongest cell proliferation inhibition. In order to understand the inhibitory mechanism of JQ1 on HeLa cells, this study analyzed the expression profile differences from the perspective of SE-lncRNAs and mRNAs. A total of 162 SE-lncRNAs were identified, of which 8 SE-lncRNAs were down-regulated and seven SE-lncRNAs were up-regulated. A total of 418 differentially expressed mRNAs related to SE-lncRNAs were identified, of which 395 mRNAs had positive correlation with 12 SE-lncRNAs and 408 mRNAs had negative correlation with 15 SE-lncRNAs.
Conclusion
JQ1 can significantly inhibit the proliferation of HeLa cells and affect the expression profile of SE-lncRNAs and mRNAs.