title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=493 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Advances on the anti-tumor mechanisms of the carotenoid Crocin link: https://peerj.com/articles/15535 last-modified: 2023-06-29 description: Saffron is located in the upper part of the crocus stigma of iridaceae, which has a long history of medicinal use. Crocin (molecular formula C44H64O24) is a natural floral glycoside ester compound extracted from saffron, which is a type carotenoid. Modern pharmacological studies have shown that crocin has multiple therapeutic effects including anti-inflammatory, anti-oxidant, anti-hyperlipidemic and anti-stone effects. In recent years, crocin has been widely noticed due to its considerable anti-tumor effects manifested by the induction of tumor cell apoptosis, inhibition of tumor cell proliferation, inhibition of tumor cell invasion and metastasis, enhancement of chemotherapy sensitivity and improvement of immune status. The anti-tumor effects have been shown in various malignant tumors such as gastric cancer, liver cancer, cervical cancer, breast cancer and colorectal cancer. In this review, we compiled recent studies on the anti-tumor effects of crocin and summarized its anti-tumor mechanism for developing ideas of treating malignancies and exploring anti-tumor drugs. creator: Xingxun Bao creator: Jinhua Hu creator: Yan Zhao creator: Ruixue Jia creator: Hairong Zhang creator: Lei Xia uri: https://doi.org/10.7717/peerj.15535 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Bao et al. title: Physiology of pregnancy and oral local anesthesia considerations link: https://peerj.com/articles/15585 last-modified: 2023-06-29 description: BackgroundSafe and effective local anesthesia is a prerequisite for emergency oral surgeries and most dental treatments. Pregnancy is characterized by complex physiological changes, and increased sensitivity to pain. Pregnant women are particularly vulnerable to oral diseases, such as caries, gingivitis, pyogenic granuloma and third molar pericoronitis. Maternally administered drugs can affect the fetus through the placenta. Therefore, many physicians and patients are reluctant to provide or accept necessary local anesthesia, which leads to delays in the condition and adverse consequences. This review is intended to comprehensively discuss the instructions for local anesthesia in the oral treatment of pregnant patients.MethodologyAn in-depth search on Medline, Embase, and the Cochrane Library was performed to review articles concerned with maternal and fetal physiology, local anesthetic pharmacology, and their applications for oral treatment.ResultsStandard oral local anesthesia is safe throughout the pregnancy. At present, 2% lidocaine with 1:200,000 epinephrine is considered to be the anesthetic agent that best balances safety and efficacy for pregnant women. Maternal and fetal considerations must be taken into account to accommodate the physiological and pharmacological changes in the gestation period. Semi-supine position, blood pressure monitoring, and reassurance are suggested for high-risk mothers to reduce the risk of transient changes in blood pressure, hypoxemia, and hypoglycemia. For patients with underlying diseases, such as eclampsia, hypertension, hypotension, and gestational diabetes, the physicians should use epinephrine cautiously and control the dose of anesthetic. New local anesthesia formulations and equipment, which contribute to minimizing injection pain and relieving the anxiety, have and are being developed but remain understudied.ConclusionsUnderstanding the physiological and pharmacological changes during pregnancy is essential to ensure the safety and efficiency of local anesthesia. Optimal outcomes for the mother and fetus hinge on a robust understanding of the physiologic alterations and the appropriate selection of anesthetic drugs and approaches. creator: Xueer Zhou creator: Yunyu Zhong creator: Zijian Pan creator: Jiankang Zhang creator: Jian Pan uri: https://doi.org/10.7717/peerj.15585 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Zhou et al. title: Opportunistic consumption of marine pelagic, terrestrial, and chemosynthetic organic matter by macrofauna on the Arctic shelf: a stable isotope approach link: https://peerj.com/articles/15595 last-modified: 2023-06-29 description: Macrofauna can contribute substantially to the organic matter cycling on the seafloor, yet the role of terrestrial and chemosynthetic organic matter in the diets of microphagous (deposit and suspension) feeders is poorly understood. In the present study, we used stable isotopes of carbon and nitrogen to test the hypothesis that the terrestrial organic matter supplied with river runoff and local chemosynthetic production at methane seeps might be important organic matter sources for macrofaunal consumers on the Laptev Sea shelf. We sampled locations from three habitats with the presumed differences in organic matter supply: “Delta” with terrestrial inputs from the Lena River, “Background” on the northern part of the shelf with pelagic production as the main organic matter source, and “Seep” in the areas with detected methane seepage, where chemosynthetic production might be available. Macrobenthic communities inhabiting each of the habitats were characterized by a distinct isotopic niche, mostly in terms of δ13C values, directly reflecting differences in the origin of organic matter supply, while δ15N values mostly reflected the feeding group (surface deposit/suspension feeders, subsurface deposit feeders, and carnivores). We conclude that both terrestrial and chemosynthetic organic matter sources might be substitutes for pelagic primary production in the benthic food webs on the largely oligotrophic Laptev Sea shelf. Furthermore, species-specific differences in the isotopic niches of species belonging to the same feeding group are discussed, as well as the isotopic niches of the symbiotrophic tubeworm Oligobrachia sp. and the rissoid gastropod Frigidoalvania sp., which are exclusively associated with methane seeps. creator: Valentin Kokarev creator: Anna K. Zalota creator: Andrey Zuev creator: Alexei Tiunov creator: Petr Kuznetsov creator: Olga Konovalova creator: Nadezhda Rimskaya-Korsakova uri: https://doi.org/10.7717/peerj.15595 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Kokarev et al. title: TMEM200A is a potential prognostic biomarker and correlated with immune infiltrates in gastric cancer link: https://peerj.com/articles/15613 last-modified: 2023-06-29 description: BackgroundGastric cancer (GC) is one of the most common malignant tumors in the digestive system. Several transmembrane (TMEM) proteins are defined as tumor suppressors or oncogenes. However, the role and underlying mechanism of TMEM200A in GC remain unclear.MethodsWe analyzed the expression of TMEM200A in GC. Furthermore, the influence of TMEM200A on survival of GC patients was evaluated. The correlations between the clinical information and TMEM200A expression were analyzed using chi-square test and logistic regression. Relevant prognostic factors were identified performing univariate and multivariate analysis. Gene set enrichment analysis (GSEA) was performed based on the TCGA dataset. Finally, we explore the relationship between TMEM200A expression and cancer immune infiltrates using CIBERSORT.ResultsTMEM200A was up-regulated in GC tissues than that in adjacent non-tumor tissues based on TCGA database. Meta-analysis and RT-qPCR validated the difference in TMEM200A expression. Kaplan-Meier curves suggested the increased TMEM200A had a poor prognosis in GC patients. The chi-square test and logistic regression analyses showed that the TMEM200A expression correlates significantly with T stage. Multivariate analysis showed that TMEM200A expression might be an important independent predictor of poor overall survival in GC patients. GSEA identified five immune-related signaling pathways and five tumor-related signaling pathways significantly enriched in the high TMEM200A expression phenotype pathway. Finally, we found CD8+ T cells is apparently decreased in high TMEM200A expression group. Conversely, eosinophils is increased in high expression group compared with low expression group.ConclusionTMEM200A is a potential prognostic biomarker and correlated with immune infiltrates in GC. creator: Fujin Fang creator: Tiantian Zhang creator: Huan Lei creator: Xiaobing Shen uri: https://doi.org/10.7717/peerj.15613 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Fang et al. title: Potential drug-drug interactions and their associated factors in hospitalized COVID-19 patients with comorbidities link: https://peerj.com/articles/15072 last-modified: 2023-06-28 description: BackgroundHospitalized COVID-19 patients with comorbidities receive more complex drug therapy. This increases the probability of potential drug-drug interactions (pDDIs). Studies on pDDIs in hospitalized patients with COVID-19 in countries with limited resources like Indonesia during the later period of the disease are still limited. This study aims to identify the pattern of pDDIs in hospitalized COVID-19 patients with comorbidities and their associated factors, especially in the second wave of the disease in Indonesia.MethodsThis study was a longitudinal-retrospective study observing hospitalized COVID-19 patients with comorbidities using medical record data in June–August 2021 at a public hospital in a region in Indonesia. pDDIs were identified using the Lexicomp® database. Data were descriptively analyzed. Factors associated with important pDDIs were analyzed in multivariate logistic regression model.ResultsA total of 258 patients with a mean age of 56.99 ± 11.94 years met the inclusion criteria. Diabetes mellitus was the most common comorbidity experienced by 58.14% of the patients. More than 70% of the patients had one comorbidity and the average number of administered drugs was 9.55 ± 2.71 items per patient. Type D pDDIs, which required modification of therapeutic regimens, amounted to 21.55% of the total interactions. Only the number of drugs was significantly and independently associated with type D pDDIs (adjusted odds ratio 1.47 [1.23–1.75], p < 0.01).ConclusionThe drugs involved in the pDDIs of hospitalized COVID-19 patients with comorbidities may differ depending on the disease periods, hospital settings, or countries. This study was small, single center, and of short duration. However, it may give a glimpse of important pDDIs during the delta variant of COVID-19 in a similar limited-resource setting. Further studies are needed to confirm the clinical significance of these pDDIs. creator: Imanda Dyah Rahmadani creator: Sylvi Irawati creator: Yosi Irawati Wibowo creator: Adji Prayitno Setiadi uri: https://doi.org/10.7717/peerj.15072 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Rahmadani et al. title: Multi-benthic size approach to unveil different environmental conditions in a Mediterranean harbor area (Ancona, Adriatic Sea, Italy) link: https://peerj.com/articles/15541 last-modified: 2023-06-28 description: Harbors are hubs of human activity and are subject to the continuous discharge and release of industrial, agricultural, and municipal waste and contaminants. Benthic organisms are largely known to reflect environmental conditions they live in. Despite meio- and macrofauna interacting within the benthic system, they are ecologically distinct components of the benthos and as such may not necessarily respond to environmental conditions and/or disturbances in the same way. However, in a few field studies the spatial patterns of meio- and macrofauna have been simultaneously compared. In the present study, we assess the response and patterns in the abundance, diversity, and distribution of the two benthic size classes to the different environmental conditions they live in (i.e., sediment concentrations of selected trace metals and polycyclic aromatic hydrocarbons (PAHs); organic matter contents and grain size) characterizing the Ancona Harbor (Adriatic Sea). Meio- and macrofauna provided partially similar types of information depending on the indices used (univariate measures or community structure/species composition) and the different ‘response-to-stress’. The community structure (i.e., taxa composition) of both benthic size components clearly showed differences among sampling stations located from inside to outside the harbor, reflecting the marked environmental heterogeneity and disturbance typically characterizing these systems. Notwithstanding, the univariate measures (i.e., meio- and macrofauna total abundance, diversity indices and equitability) didn’t show similar spatial patterns. Meiofauna were likely to be more sensitive to the effects of environmental features and contaminants than macrofauna. Overall, trace metals and PAHs affected the community composition of the two benthic components, but only the meiofauna abundance and diversity were related to the environmental variables considered (i.e., quantity and quality of organic matter). Our results pinpoint the importance of studying both meio- and macrofauna communities, which could provide greater insight into the processes affecting the investigated area and reveal different aspects of the benthic ecosystems in response to harbor conditions. creator: Elisa Baldrighi creator: Sarah Pizzini creator: Elisa Punzo creator: Angela Santelli creator: Pierluigi Strafella creator: Tommaso Scirocco creator: Elena Manini creator: Daniele Fattorini creator: Claudio Vasapollo uri: https://doi.org/10.7717/peerj.15541 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Baldrighi et al. title: Hydrogen-rich water treatment targets RT1-Db1 and RT1-Bb to alleviate premature ovarian failure in rats link: https://peerj.com/articles/15564 last-modified: 2023-06-28 description: BackgroundPremature ovarian failure (POF) is defined as the cessation of ovarian function before the age of 40 years, imposing a significant health burden on patients. However, effective etiological therapy for POF is scarce. Thus, we aimed to explore the protective role and targets of hydrogen-rich water (HRW) in POF.MethodsBased on cyclophosphamide (CTX)-induced POF rat models, the protective role of HRW treatment was mainly determined through serum 17-β-estradiol (E2), follicle-stimulating hormone (FSH), anti-mullerian hormone (AMH) levels, ovarian histomorphological analysis, and TUNEL assay. Tandem mass tag (TMT)-based quantitative proteomic analysis was then conducted on ovarian tissues, and the targets of HRW in POF were identified integrating differential expression analysis, functional enrichment analysis, and interaction analysis.ResultsIn HRW treatment of POF rats, the serum AMH and E2 levels significantly increased, and FSH level significantly reduced, indicating the protective role of HRW. After TMT quantitative proteomic analysis, a total of 16 candidate differentially expressed proteins (DEPs) were identified after the cross analysis of DEPs from POF vs. control and POF+HRW vs. POF groups, which were found to be significantly enriched in 296 GO terms and 36 KEGG pathways. The crucial targets, RT1-Db1 and RT1-Bb, were finally identified based on both protein-protein interaction network and GeneMANIA network.ConclusionsThe HRW treatment could significantly alleviate the ovarian injury of POF rats; RT1-Db1 and RT1-Bb are identified as two crucial targets of HRW treatment in POF rats. creator: Xiaoyin Meng creator: Shuai Zhang creator: Lu Zhao creator: Yingmei Wang uri: https://doi.org/10.7717/peerj.15564 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Meng et al. title: Stress mitigation by riparian flora in industrial contaminated area of River Chenab Punjab, Pakistan link: https://peerj.com/articles/15565 last-modified: 2023-06-28 description: Faisalabad is a major industrial area in Pakistan’s Punjab province that discharges wastewater into the Chenab River. Industrial effluents in Faisalabad are predicted to pose a significant threat to the riparian vegetation of the Chenab River and nearby vegetation. Heavy metal pollution of plants, water, and soils is one of the biggest problems worldwide that needs to be addressed because heavy metals above normal levels are extremely dangerous to both riparian vegetation and wildlife. The results indicated high levels of pollution in the industrial effluents as well as in the river in terms of salinity, metal toxicity, TSS, TDS, SAR, the acidic and alkaline nature of the industrial effluents, and the spread of industrial effluents up to 15 square kilometres in the Chenab River. Despite the higher pollution, four plants were found at all sites: Calotropis procera, Phyla nodiflora, Eclipta alba and Ranunculus sceleratus. It was found that most of the selected plants were phytoaccumulators, making them best suited to survive in harsh environments such as those with industrial pollution. The Fe concentration in the plant constituents was the highest, along with Zn, Pb, Cd, and Cu, all of which were above the permissible limits of the WHO. The metal transfer factor (MTF) was higher in most of the plants studied, and even exceeded 10 at some severely affected sites. Calotropis procera proved to be the most suitable plant for growth on drainage systems and also at river sites, as it had the highest importance value across all sites and seasons. creator: Toqeer Abbas creator: Iftikhar Ahmad creator: Zafar Iqbal Khan creator: Anis Ali Shah creator: Ryan Casini creator: Hosam O. Elansary uri: https://doi.org/10.7717/peerj.15565 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Abbas et al. title: Hydroxyapatite/calcium alginate composite particles for hemostasis and alveolar bone regeneration in tooth extraction wounds link: https://peerj.com/articles/15606 last-modified: 2023-06-28 description: Tooth extractions can lead to complications such as post-extraction bleeding and bone resorption, which may result in unfavorable outcomes for implant restoration afterwards. To strive for an optimal condition for further restoration procedures, appropriate strategies, such as hemostasis or bone regeneration, are encouraged to be employed. However, the existing products are failed to meet both needs. As a widely employed tissue engineering materials, hydroxyapatite and calcium alginate both have demonstrated excellent performance in osteogenesis. However, their inferior mechanical strength poses a major limitation to their use in supporting the contracted extraction socket, which can easily lead to alveolar crest atrophy and barely achieve satisfying results. Calcium alginate improves the mechanical strength of hydroxyapatite, enabling the formation of new bone tissue and degradable in vivo. In this study, we demonstrated the biocompatibility and haemostatic ability of nCA particles on a rat tooth extraction model. In addition, long-term observation has revealed minimal inflammation and bone tissue regeneration. Our findings suggest a promising insight for clinical applications in hemostasis and bone regeneration after tooth extraction. creator: Gang He creator: Zhihui Chen creator: Luyuan Chen creator: Huajun Lin creator: Chengcheng Yu creator: Tingting Zhao creator: Zhengwen Luo creator: Yuan Zhou creator: Siyang Chen creator: Tianjiao Yang creator: Guixian He creator: Wen Sui creator: Yonglong Hong creator: Jianjiang Zhao uri: https://doi.org/10.7717/peerj.15606 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 He et al. title: Comparative study of leaf nutrient reabsorption by two different ecotypes of wild soybean under low-nitrogen stress link: https://peerj.com/articles/15486 last-modified: 2023-06-27 description: Wild soybean (Glycine soja), the ancestor of cultivated soybean, has evolved into many ecotypes with different adaptations to adversity under the action of divergent evolution. Barren-tolerant wild soybean has developed adaptation to most nutrient-stress environments, especially with respect to low nitrogen (LN) conditions. This study describes the differences in physiological and metabolomic changes between common wild soybean (GS1) and barren-tolerant wild soybean(GS2) under LN stress. Compared with plants grown under the unstressed control (CK) conditions, the young leaves of barren-tolerant wild soybean under LN conditions maintained relatively stable chlorophyll, concentration and rates of photosynthesis and transpiration, as well as increased carotenoid content, whereas the net photosynthetic rate (PN) of GS1 decreased significantly 0.64-fold (p < 0.05) in the young leaves of GS1. The ratio of internal to atmospheric CO2 concentrations increased significantly 0.07-fold (p < 0.05), 0.09-fold (p < 0.05) in the young leaves of GS1 and GS2, respectively, and increased significantly 0.05-fold (p < 0.05) and 0.07-fold (p < 0.05) in the old leaves of GS1 and GS2, respectively, relative to the CK. The concentration of chlorophylls a and b decreased significantly 0.45-fold (p < 0.05), 0.13-fold (p > 0.05) in the young leaves of GS1 and GS2, respectively, and decreased significantly 0.74-fold (p < 0.01) and 0.60-fold (p < 0.01) in the old leaves of GS1 and GS2, respectively. Under LN stress, nitrate concentration in the young leaves of GS1 and GS2 decreased significantly 0.69- and 0.50-fold (p < 0.01), respectively, relative to CK, and decreased significantly 2.10-fold and 1.77-fold (p < 0.01) in the old leaves of GS1 and GS2, respectively. Barren-tolerant wild soybean increased the concentration of beneficial ion pairs. Under LN stress, Zn2+ significantly increased by 1.06- and 1.35-fold (p < 0.01) in the young and old leaves of GS2 (p < 0.01), but there was no significant change in GS1. The metabolism of amino acids and organic acids was high in GS2 young and old leaves, and the metabolites related to the TCA cycle were significantly increased. The 4-aminobutyric acid (GABA) concertation decreased significantly 0.70-fold (p < 0.05) in the young leaves of GS1 but increased 0.21-fold (p < 0.05) significantly in GS2. The relative concentration of proline increased significantly 1.21-fold (p < 0.01) and 2.85-fold (p < 0.01) in the young and old leaves of GS2. Under LN stress, GS2 could maintain photosynthesis rate and enhance the reabsorption of nitrate and magnesium in young leaves, compared to GS1. More importantly, GS2 exhibited increased amino acid and TCA cycle metabolism in young and old leaves. Adequate reabsorption of mineral and organic nutrients is an important strategy for barren-tolerant wild soybeans to survive under LN stress. Our research provides a new perspective on the exploitation and utilization of wild soybean resources. creator: Yuan Liu creator: Shujuan Gao creator: Yunan Hu creator: Tao Zhang creator: Jixun Guo creator: Lianxuan Shi creator: Mingxia Li uri: https://doi.org/10.7717/peerj.15486 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Liu et al.