title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=525 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Myriad applications of bacteriophages beyond phage therapy link: https://peerj.com/articles/15272 last-modified: 2023-04-21 description: Bacteriophages are the most abundant biological entity on the planet, having pivotal roles in bacterial ecology, animal and plant health, and in the biogeochemical cycles. Although, in principle, phages are simple entities that replicate at the expense of their bacterial hosts, due the importance of bacteria in all aspects of nature, they have the potential to influence and modify diverse processes, either in subtle or profound ways. Traditionally, the main application of bacteriophages is phage therapy, which is their utilization to combat and help to clear bacterial infections, from enteric diseases, to skin infections, chronic infections, sepsis, etc. Nevertheless, phages can also be potentially used for several other tasks, including food preservation, disinfection of surfaces, treatment of several dysbioses, and modulation of microbiomes. Phages may also be used as tools for the treatment of non-bacterial infections and pest control in agriculture; moreover, they can be used to decrease bacterial virulence and antibiotic resistance and even to combat global warming. In this review manuscript we discuss these possible applications and promote their implementation. creator: Juan Carlos García-Cruz creator: Daniel Huelgas-Méndez creator: Jorge Santiago Jiménez-Zúñiga creator: Xareni Rebollar-Juárez creator: Mariel Hernández-Garnica creator: Ana María Fernández-Presas creator: Fohad Mabood Husain creator: Rawaf Alenazy creator: Mohammed Alqasmi creator: Thamer Albalawi creator: Pravej Alam creator: Rodolfo García-Contreras uri: https://doi.org/10.7717/peerj.15272 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 García-Cruz et al. title: A retrospective investigation of spatial clusters and determinants of diabetes prevalence: scan statistics and geographically weighted regression modeling approaches link: https://peerj.com/articles/15107 last-modified: 2023-04-20 description: BackgroundDiabetes and its complications represent a significant public health burden in the United States. Some communities have disproportionately high risks of the disease. Identification of these disparities is critical for guiding policy and control efforts to reduce/eliminate the inequities and improve population health. Thus, the objectives of this study were to investigate geographic high-prevalence clusters, temporal changes, and predictors of diabetes prevalence in Florida.MethodsBehavioral Risk Factor Surveillance System data for 2013 and 2016 were provided by the Florida Department of Health. Tests for equality of proportions were used to identify counties with significant changes in the prevalence of diabetes between 2013 and 2016. The Simes method was used to adjust for multiple comparisons. Significant spatial clusters of counties with high diabetes prevalence were identified using Tango’s flexible spatial scan statistic. A global multivariable regression model was fit to identify predictors of diabetes prevalence. A geographically weighted regression model was fit to assess for spatial non-stationarity of the regression coefficients and fit a local model.ResultsThere was a small but significant increase in the prevalence of diabetes in Florida (10.1% in 2013 to 10.4% in 2016), and statistically significant increases in prevalence occurred in 61% (41/67) of counties in the state. Significant, high-prevalence clusters of diabetes were identified. Counties with a high burden of the condition tended to have high proportions of the population that were non-Hispanic Black, had limited access to healthy foods, were unemployed, physically inactive, and had arthritis. Significant non-stationarity of regression coefficients was observed for the following variables: proportion of the population physically inactive, proportion with limited access to healthy foods, proportion unemployed, and proportion with arthritis. However, density of fitness and recreational facilities had a confounding effect on the association between diabetes prevalence and levels of unemployment, physical inactivity, and arthritis. Inclusion of this variable decreased the strength of these relationships in the global model, and reduced the number of counties with statistically significant associations in the local model.ConclusionsThe persistent geographic disparities of diabetes prevalence and temporal increases identified in this study are concerning. There is evidence that the impacts of the determinants on diabetes risk vary by geographical location. This implies that a one-size-fits-all approach to disease control/prevention would be inadequate to curb the problem. Therefore, health programs will need to use evidence-based approaches to guide health programs and resource allocation to reduce disparities and improve population health. creator: Jennifer Lord creator: Shamarial Roberson creator: Agricola Odoi uri: https://doi.org/10.7717/peerj.15107 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Lord et al. title: Effects of leptin on the viability of human ovarian cancer cells and changes in cytokine expression levels link: https://peerj.com/articles/15246 last-modified: 2023-04-20 description: BackgroundObesity is associated with increased mortality among ovarian cancer and is a poor prognostic factor. There are significant links between the leptin hormone, a product of the obesity gene, and the development of ovarian cancer. Leptin is a vital hormone-like cytokine secreted from adipose tissue and is mainly involved in the maintenance of energy homeostasis. It regulates several intracellular signaling pathways and also interacts with various hormones and energy regulators. It acts as a growth factor by stimulating cell proliferation and differentiation and in this way contributes to cancer cell development. The aim of the study was to investigate the effects of leptin on human ovarian cancer cells.MethodsIn this study, the effects of increasing the concentration of leptin were investigated on the cell viability of OVCAR-3 and MDAH-2774 ovarian cancer lines by MTT assay. Moreover, to elucidate the molecular mechanisms of leptin in ovarian cancer cells, changes in the expression levels of 80 cytokines were evaluated after leptin treatment via a human cytokine antibody array.ResultsLeptin increases the proliferation of both ovarian cancer cell lines. IL-1 level was increased in OVCAR-3 cells and TGF-β level was increased in MDAH-2774 cells after leptin treatment. A decrease in IL-2, MCP-2/CCL8 and MCP-3/CCL7 levels was detected in both ovarian cancer cell lines with leptin administration. An increase in IL-3 and IL-10 expressions, insulin-like growth factor binding proteins (IGFBP) IGFBP-1, IGFBP-2 and IGFBP-3 levels were detected in both ovarian cancer cell lines with leptin administration. In conclusion; leptin has a proliferative effect on human ovarian cancer cell lines and affects different cytokines in different types of ovarian cancer cells. creator: Fatih Dincer creator: Harika Atmaca creator: Levent Akman creator: Latife Merve Oktay creator: Burcak Karaca creator: Mustafa Cosan Terek uri: https://doi.org/10.7717/peerj.15246 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Dincer et al. title: Odor descriptive ratings can predict some odor-color associations in different color features of hue or lightness link: https://peerj.com/articles/15251 last-modified: 2023-04-20 description: BackgroundOlfactory information can be associated with color information. Researchers have investigated the role of descriptive ratings of odors on odor-color associations. Research into these associations should also focus on the differences in odor types. We aimed to identify the odor descriptive ratings that can predict odor-color corresponding formation, and predict features of the associated colors from the ratings taking into consideration the differences in the odor types.MethodsWe assessed 13 types of odors and their associated colors in participants with a Japanese cultural background. The associated colors from odors in the CIE L*a*b* space were subjectively evaluated to prevent the priming effect from selecting color patches. We analyzed the data using Bayesian multilevel modeling, which included the random effects of each odor, for investigating the effect of descriptive ratings on associated colors. We investigated the effects of five descriptive ratings, namely Edibility, Arousal, Familiarity, Pleasantness, and Strength on the associated colors.ResultsThe Bayesian multilevel model indicated that the odor description of Edibility was related to the reddish hues of associated colors in three odors. Edibility was related to the yellow hues of colors in the remaining five odors. The Arousal description was related to the yellowish hues in two odors. The Strength of the tested odors was generally related to the color lightness. The present analysis could contribute in investigating the influence of the olfactory descriptive rating that anticipates the associated color for each odor. creator: Kaori Tamura creator: Tsuyoshi Okamoto uri: https://doi.org/10.7717/peerj.15251 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Tamura and Okamoto title: Prognostic value of sirtuin family members and experimental verification identify SIRT5 as diagnostic biomarkers in clear cell renal cell carcinoma link: https://peerj.com/articles/15154 last-modified: 2023-04-19 description: BackgroundThe sirtuins (SIRTs) family is a nicotinamide adenine dinucleotide (NAD+) family of dependent deacetylases, which includes SIRT1-7. This family is related to the development and progression of various tumors. However, a comprehensive analysis of the role of SIRTs in clear cell renal cell carcinoma (ccRCC) is still lacking, and there are few reports on the inhibitory role of SIRT5 in ccRCC.MethodsWe used immunohistochemical analysis, and several bioinformatic databases to perform an integrated analysis of the expression and prognostic value of SIRT5 and other SIRT family members in ccRCC along with the associated immune cell infiltration. These databases include TIMER, THPA, cell culture, UALCAN, cBioPortal, WebGestalt, Metascape, DiseaseMeth, STRING database, and Cytoscape.ResultsThe protein expression of SIRT1, 2, 3, 6, and 7 were upregulated in ccRCC for the Human Protein Atlas database, whereas the expression of SIRT4 and SIRT5 was decreased. The expression based on tumor stage, and grade followed a similar trend. Kaplan–Meier analysis showed that high SIRT4 and SIRT5 expression was positively related to better overall survival (OS), whereas SIRT6 and SIRT7 expression was positively related to worse OS. Further, high SIRT3 expression was related to worse relapse-free survival (RFS), whereas high SIRT5 expression was related to better RFS. To explore the mechanism underlying the function of SIRTs in ccRCC, we also used several databases to perform the functional enrichment analysis and explore the relationship between infiltrating immune cells and seven SIRT family members in ccRCC. The results showed that several SIRT family members, and particularly SIRT5, are correlated with the infiltration of some important immune cells. The protein expression of SIRT5 was significantly lower in tumor tissue compared to normal tissue and was negatively related to the age of the patient ccRCC individual tumor stages, and grades. In human ccRCC samples, strong IHC staining expression of SIRT5 was displayed in adjacent normal tissue than in tumor tissues.ConclusionSIRT5 may be a prognostic marker and a novel strategy for the treatment of ccRCC. creator: Lu-Shan Peng creator: Sai-Li Duan creator: Run-Qi Li creator: Zi-Yuan Bai creator: Chun-Lin Ou creator: Jun-Pu Wang uri: https://doi.org/10.7717/peerj.15154 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Peng et al. title: Analysing transcriptomic signatures and identifying potential genes for the protective effect of inactivated COVID-19 vaccines link: https://peerj.com/articles/15155 last-modified: 2023-04-19 description: Inactivated vaccines are one of the most effective strategies for controlling the coronavirus disease 2019 (COVID-19) pandemic. However, the response genes for the protective effect of inactivated vaccines are still unclear. Herein, we analysed the neutralization antibody responses elicited by vaccine serum and carried out transcriptome sequencing of RNAs isolated from the PBMCs of 29 medical staff receiving two doses of the CoronaVac vaccine. The results showed that SARS-CoV-2 neutralization antibody titers varied considerably among individuals, and revealed that many innate immune pathways were activated after vaccination. Furthermore, the blue module revealed that NRAS, YWHAB, SMARCA5, PPP1CC and CDC5L may be correlated with the protective effect of the inactivated vaccine. Additionally, MAPK1, CDC42, PPP2CA, EP300, YWHAZ and NRAS were demonstrated as the hub genes having a significant association with vaccines. These findings provide a basis for understanding the molecular mechanism of the host immune response induced by inactivated vaccines. creator: Hongquan Chen creator: Lu Zhang creator: Chen Xu creator: Xiaoyun Shen creator: Jiazhou Lou creator: Shengjun Wu uri: https://doi.org/10.7717/peerj.15155 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Chen et al. title: Intra-abdominal fat volume estimation by multi-detector rows computed tomography: relevance in surgical fellowship training program in Shanghai: a retrospective study link: https://peerj.com/articles/15156 last-modified: 2023-04-19 description: BackgroundIntra-abdominal fat volume (IFV) has been shown to have a negative impact on surgical outcomes in gastric cancer (GC) and other gastrointestinal surgeries. The purpose of this study is to look into the relationship between IFV and perioperative outcomes in GC patients using multi-detector rows computed tomography (MDCT) and assess the importance of implementing this observation in current surgical fellowship training programs.MethodsPatients with GC who underwent open D2 gastrectomy between May 2015 and September 2017 were included in the study. Based on MDCT estimation, patients were divided into high IFV (IFV ≥ 3,000 ml) and low IFV (IFV < 3,000 ml) groups. Perioperative outcomes for cancer staging, type of gastrectomy, intraoperative blood loss (IBL), anastomotic leakage, and hospital stay were compared between the two groups. This study was registered as CTR2200059886.ResultsOut of 226 patients, 54 had early gastric carcinoma (EGC), while 172 had advanced gastric carcinoma (AGC). There were 64 patients in the high IFV group and 162 in the low IFV group. The high IFV group had significantly higher IBL mean values (p = 0.008). Therefore, having a high IFV was a risk factor for the occurrence of perioperative complications (p = 0.008).ConclusionsHigh IFV estimated by MDCT prior to GC surgery was associated with increased IBL and postoperative complications. Incorporating this CT-IFV estimation into surgical fellowship programs may aid aspiring surgeons in selecting patients during independent practice in their learning curve and surgical practice for the most appropriate approach for treating GC patients. creator: Jenifei Shah creator: Suyue Yu creator: Jingyi Huang creator: Lu Zang creator: Tian Li creator: Zhenglun Zhu uri: https://doi.org/10.7717/peerj.15156 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Shah et al. title: Senescent epithelial cells remodel the microenvironment for the progression of oral submucous fibrosis through secreting TGF-β1 link: https://peerj.com/articles/15158 last-modified: 2023-04-19 description: ObjectivesCellular senescence is strongly associated with fibrosis and tumorigenesis. However, whether the epithelium of oral submucous fibrosis (OSF) undergoes premature senescence remains unclear. This study investigates the roles of senescent epithelial cells in OSF.MethodsThe immunohistochemistry and Sudan black B staining were performed to identify epithelium senescence in OSF tissues. Arecoline was used to induce human oral keratinocytes (HOKs) senescence. The cell morphology, senescence-associated β galactosidase activity, cell counting Kit 8, immunofluorescence, quantitative real-time PCR, and western blot assay were used to identification of senescent HOKs. The enzyme-linked immunosorbent assay was exerted to evaluate the levels of transforming growth factor β1 (TGF-β1) in the supernatants of HOKs treated with or without arecoline.ResultsThe senescence-associated markers, p16 and p21, were overexpressed in OSF epithelium. These expressions were correlated with alpha-smooth actin (α-SMA) positively and proliferating cell nuclear antigen (PCNA) negatively. Moreover, Sudan black staining showed that there was more lipofuscin in OSF epithelium. In vitro, HOKs treated with arecoline showed senescence-associated characteristics including enlarged and flattened morphology, senescence-associated β galactosidase staining, cell growth arrest, γH2A.X foci, upregulation of p53, p21, and TGF-β1 protein levels. Moreover, senescent HOKs secreted more TGF-β1.ConclusionsSenescent epithelial cells are involved in OSF progression and may become a promising target for OSF treatment. creator: Zijia Wang creator: Ying Han creator: Ying Peng creator: Shuhui Shao creator: Huanquan Nie creator: Kun Xia creator: Haofeng Xiong creator: Tong Su uri: https://doi.org/10.7717/peerj.15158 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Wang et al. title: Sema4D silencing increases the sensitivity of nivolumab to B16-F10 resistant melanoma via inhibiting the PI3K/AKT signaling pathway link: https://peerj.com/articles/15172 last-modified: 2023-04-19 description: Melanoma is a common skin tumor that causes a high rate of mortality, especially in Europe, North America and Oceania. Immunosuppressants such as anti-PD-1 have been used in the treatment of malignant melanoma, however, nearly 60% of patients do not respond to these treatments. Sema4D, also called CD100, is expressed in T cells and tumor tissues. Sema4D and its receptor, Plexin-B1, play crucial roles in the process of immune regulation, angiogenesis, and tumor progression. The role of Sema4D in melanoma with anti-PD-1 resistance is poorly understood. Through a combination of molecular biology techniques and in silico analysis, the role of Sema4D in improving anti-PD-L1 sensitivity in melanoma was explored. The results showed that the expression of Sema4D, Plexin-B1 and PD-L1 was significantly increased in B16-F10R cells. Sema4D knockdown synergizes with anti-PD-1 treatment, cell viability, cell invasion and migration were significantly decreased, while the apoptosis was increased, the growth of tumors on the mice was also inhibited. Mechanistically, bioinformatics analysis revealed that Sema4D is involved in the PI3K/AKT signaling pathway; the downregulation of p-PI3K/PI3K and p-AKT/AKT expression were observed in Sema4D knockdown, therefore, nivolumab resistance is related to Sema4D and Sema4D silencing can improve sensitivity to nivolumab via inhibition of the PI3K/AKT signaling pathway. creator: Zhuo Zhang creator: Duoli Zhang creator: Fang Wang creator: Jiao Liu creator: Yuhong Sun creator: Songyot Anuchapreeda creator: Singkome Tima creator: Zhangang Xiao creator: Suwit Duangmano uri: https://doi.org/10.7717/peerj.15172 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Zhang et al. title: Meta-analysis of commonly mutated genes in leptomeningeal carcinomatosis link: https://peerj.com/articles/15250 last-modified: 2023-04-19 description: BackgroundLeptomeningeal carcinomatosis (LMC) is a rare type of cancer that settles at the meninges through metastasis of non-small cell lung cancer (NSCLC), breast cancer and melanoma. The molecular mechanism underlying LMC is not known, therefore molecular studies investigating the development of LMC are needed. Here, we aimed to identify commonly mutated genes in LMC caused by NSCLC, breast cancer, and melanoma using an in-slico approach and their interactions using integrated bioinformatic approaches/tools in this meta-analysis.MethodsWe conducted a meta-analysis using information from 16 studies that included different sequencing techniques of patients with LMC caused by three different primary cancers: breast cancer, NSCLC, and melanoma. All studies that assessed mutation information from patients with LMC were searched in PubMed, from their inception to February, 16 2022. Studies that performed NGS on LMC patients with NSCLC, breast cancer, or melanoma were included, while studies that did not apply NGS to CSF samples, did not provide information on altered genes, were reviews, editorials, or conference abstracts, or whose main goal was the detection of malignancies were all excluded. We identified commonly mutated genes in all three types of cancer. Next, we constructed a protein-protein interaction network, then performed pathway enrichment analysis. We searched National Institutes of Health (NIH) and Drug-Gene Interaction Database (DGIdb) to find candidate drugs.ResultsWe found that TP53, PTEN, PIK3CA, IL7R, and KMT2D genes were commonly mutated genes in all three types of cancer via our meta-analysis that consisted out of 16 studies. Our pathway enrichment analysis showed that all five genes were primarily associated with regulation of cell communication and signaling, and cell proliferation. Other enriched pathways included regulation of apoptotic processes of leukocytes and fibroblasts, macroautophagy and growth. According to our drug search we found candidate drugs; Everolimus, Bevacizumab and Temozolomide, which interact with these five genes.ConclusionIn conclusion, a total of 96 mutated genes in LMC were investigated via meta-analysis. Our findings suggested vital roles of TP53, PTEN, PIK3CA, KMT2D, and IL7R, which can provide insight into the molecular basis of LMC development and paving the door to the development of new targeted medicine and will encourage molecular biologists to seek biological evidence. creator: Irem Congur creator: Ekin Koni creator: Onur Emre Onat creator: Zeynep Tokcaer Keskin uri: https://doi.org/10.7717/peerj.15250 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Congur et al.