ABSTRACT
The determination of cesium ions (Cs+) is important for various applications, including resource utilization, environmental monitoring, and human health. Electrochemical sensors, with their inherent advantages, stand out as an ideal choice for Cs+ detection. However, electrode materials for Cs+ sensors usually face problems such as poor selectivity and complex synthesis. Herein, a method employing nickel hexacyanoferrate (NiHCF) as the electrode material for stripping voltammetry in the determination of Cs+ was proposed. Both adsorption and electrochemical intercalation exhibited selectivity. In the presence of interfering ions at a 10 : 1 molar ratio to Cs+, Cs+ was still preferentially intercalated in NiHCF. However, electrochemical intercalation exhibits superior selectivity for Cs+ compared to adsorption. Meanwhile, the effect of adsorption on the detection was minimized by electrochemical intercalation. Based on the standard addition method, Cs+ was determined using both adsorption and electrochemical intercalation methods. The error reduced significantly from 32.7% above the theoretical value through adsorption to 9.5% below the theoretical value through electrochemical intercalation. This approach not only enhanced the measurement accuracy but also reduced the costs associated with both measurement and preparation. The study proposed a cost-effective and rapid method for Cs+ measurement using Prussian blue analogs.
ABSTRACT
Humans indirectly consume approximately 0.02 mg/kg/day of short-chained chlorinated paraffins (SCCPs) through the environment; however, the thymic senescence/damage induced by SCCPs has not been assessed. In this study, 16 female mice (4-week-old) per group were orally administered 0, 0.01, 0.1, and 1 mg/kg/day of SCCPs for 21 days, and the phenotypes and levels of superoxide dismutase (SOD), malondialdehyde (MDA), Tß4, αß TCR, SA-ß-Gal, GRP78, PERK/CHOP, P53/P21, and CASPASE-1 of the thymus were assessed as indicators. Another group comprising 16 mice was killed at 4-week-old and these indicators were assessed. Thereafter, the thymuses cultured in vitro were exposed to 0, 14, 140, and 1400 µg/L SCCPs, respectively, and the above indicators were measured after 7-day. Based on the results, the oral administration of ≥0.01 mg/kg/day SCCPs to mice and ≥14 µg/L of SCCPs in medium caused thymic aging features, such as a decrease in the ratio of cortex to medulla, gradual blurring of the boundary between the cortex and medulla, dose-dependent oxidative stress (decreased SOD and increased MDA), and decreased levels of Tß4 and αß TCRs in the thymus. The oral administration of ≥1 mg/kg/day of SCCPs also impeded the growth and development of female mice and their thymuses. Exposure to the low levels of SCCPs activated PERK-CHOP in the mouse thymus, which modulated increases in SA-ß-Gal, IL-1ß, P53, and CASPASE-1 in vivo and in vitro. Overall, environmental levels and human blood concentrations (14.8-1400 µg/L) of SCCPs may induce mouse thymus senescence by activating PERK-CHOP in vivo and in vitro, respectively.
Subject(s)
Endoplasmic Reticulum Chaperone BiP , Thymus Gland , Transcription Factor CHOP , Animals , Thymus Gland/drug effects , Thymus Gland/metabolism , Mice , Female , Transcription Factor CHOP/metabolism , eIF-2 Kinase/metabolism , Oxidative Stress/drug effects , AgingABSTRACT
Determination of lithium ions is very important for extraction of lithium from salt lakes. Electrochemical sensor is an ideal choice, but it is not available so far. Here, a voltammetric sensor based on lithium iron phosphate (LiFePO4) was developed. Single-crystal LiFePO4 dominated by the (010) lattice plane was synthesized using hydrothermal method; it had good selectivity for lithium ions. Lithium ions were preferentially intercalated into LiFePO4 even if molar ratio of sodium ions, potassium ions, magnesium ions or calcium ions to lithium ions reached 10:1. The intercalation and deintercalation of interfering ions should be avoided because this reduced the selectivity of LiFePO4 for lithium ions. Lithium ion concentration of synthetic Uyuni Salt Lake solution was determined using the standard addition method. The measurement result was only 0.34 % higher than the theoretical value. The sensor provides a highly selective lithium ion analysis method at an extremely low cost, which was very promising to be widely used.
ABSTRACT
Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug that has been found in recent years to cause ovarian damage. The aim of this study is to explore the molecular mechanisms of IBU damage to the ovary and drugs to combat it. We established in vivo (IBU doses of 50, 100 and 200 mg/kg-day) and in vitro (IBU concentrations of 50, 100 and 200 µM in culture medium) models of ovarian damage in mice simulating clinical doses and found that IBU not only caused ovarian damage in mice in a dose-response relationship, but also decreased estradiol (E2) and prostaglandin E2 (PGE2) levels in serum/media with increasing IBU doses. In damaged ovaries, the cyclooxygenase 2 (COX2)-PGE2 pathway is inhibited, the Hippo pathway is activated, circPVT1 is decreased, and miR-149 is elevated. TT-10 is an activator of YES-associated protein (YAP)-transcriptional enhancer factor domain activity. Then, 100 µM IBU-induced ovarian damage model was selected for YAP activation (Hippo pathway inhibition) experiment, and TT-10 was found to interfere with IBU-induced ovarian damage and increase E2 level in the medium, and 10 µM of TT-10 had the best protective effect. TT-10 also inhibited the Hippo pathway, activated the COX2-PGE2 pathway, elevated circPVT1 expression, and decreased miR-149 expression in the ovary. It has been hypothesized that clinical doses of IBU damage mouse ovaries by inhibiting COX2-PGE2 and activating the Hippo pathway, whereas TT-10 protects the ovaries through the inverse regulation of these two pathways.
Subject(s)
Ibuprofen , MicroRNAs , Female , Mice , Animals , Ibuprofen/toxicity , Dinoprostone/metabolism , Cyclooxygenase 2/metabolism , Hippo Signaling Pathway , MicroRNAs/geneticsABSTRACT
Procymidone (PCM) exposure below the no-observed-effect level triggers changes in circRNA Scar and circZc3h4 and overactivation of the unfolded protein response (UPR) in mice, culminating in testicular injury. The 4-phenyl butyric acid (4-PBA) is known to stabilize proteins and reduce the UPR. This study employed an in vitro system in which mouse testes were cultured with 1 × 10-5 M PCM and varying concentrations (0, 20, 40, and 80 mM) of 4-PBA; 4-week-old male mice were subsequently treated with 100 mg/kg/d PCM (suspended in corn oil) and/or 100 mg/kg/d 4-PBA for 21 d, consecutively. The treatments were as follows: the negative control (NC) group was orally administered corn oil; the positive control (PC) group was orally administered PCM; the 4-PBA group was intraperitoneally injected with 4-PBA; the 4-PBA-I group was orally administered PCM and 4-PBA simultaneously; the 4-PBA-II group received daily administration of 4-PBA 24 h prior to PCM; and the 4-PBA-III group was intraperitoneally injected with 4-PBA for 7 d after 21 d of PCM administration. However, the 4-PBA intervention groups showed no considerable changes in the overall or testicular appearance of mice. In vitro, 4-PBA inhibited the PCM-induced testicular injury, with the most significant effect observed at 80 mM. In vivo, the 4-PBA-III group exhibited the best in vivo effects. Our findings indicate that 4-PBA conferred testicular protection by decreasing PCM-induced circRNA Scar, elevating circZc3h4, and suppressing UPR both in vitro and in vivo. It has been hypothesized that 4-PBA mitigates testicular damage by reducing excessive UPR levels.
Subject(s)
RNA, Circular , Testis , Male , Mice , Animals , Cicatrix , Corn Oil , Unfolded Protein ResponseABSTRACT
The standard (Bose-Einstein/Fermi-Dirac, or Maxwell-Boltzmann) distribution from the relativistic ideal gas model is used to study the transverse momentum (pT) spectra of identified charged hadrons (π-, π+, K-, K+, p¯, and p) with different rapidities produced in inelastic proton-proton (pp) collisions at a Super Proton Synchrotron (SPS). The experimental data measured using the NA61/SHINE Collaboration at the center-of-mass (c.m.) energies s=6.3, 7.7, 8.8, 12.3, and 17.3 GeV are fitted well with the distribution. It is shown that the effective temperature (Teff or T), kinetic freeze-out temperature (T0), and initial temperature (Ti) decrease with the increase in rapidity and increase with the increase in c.m. energy. The kinetic freeze-out volume (V) extracted from the π-, π+, K-, K+, and p¯ spectra decreases with the rapidity and increase with the c.m. energy. The opposite tendency of V, extracted from the p spectra, is observed to be increasing with the rapidity and decreasing with the c.m. energy due to the effect of leading protons.
ABSTRACT
OBJECTIVE: To observe the expression of the retinoic acid(RA) pathway in hypothalamus and pituitary damage induced by combined exposure of low-level lead and 1-nitropyrene in mice, and to explore the relationship between the changes of RA pathway and hypothalamus and pituitary damage. METHODS: A total of 84 4-week-old ICR mice were randomly divided into the control group, Pb~(2+) tainted group(0.008 mg/L), 1-NP tainted group(0.1 mg/kg), low(0.008 mg/L Pb~(2+)+0.004 mg/kg 1-NP), medium(0.008 mg/L Pb~(2+)+0.02 mg/kg 1-NP), and high-dose co-toxicity group(0.008 mg/L Pb~(2+)+0.1 mg/kg 1-NP) according to body weight, with 14 mice in each group. Among them, Pb~(2+) was provided by lead acetate, added to deionized water and ingested by mice drinking freely, 1-NP was given by intraperitoneal injection, 1-NP was administered by intraperitoneal injection. Record daily water intake and food intake. After 21 consecutive days of exposure, body mass was measured, histological changes in the hypothalamus and pituitary were observed under an optical microscope, and lead content in brain tissue was measured by atomic absorption spectrometry. The real-time fluorescence quantitative PCR was used to detect the abundance of retinoic acid pathway members and c-Jun N-terminal kinases genes(Jnks), and the western blot method was used to detect expression levels of acetaldehyde dehydrogenase 2(ALDH2), cytochrome P450 family member 26A1(CYP26a1) proteins. RESULTS: There was no difference in the mean weekly water intake and food intake of the mice in each group. The body weight of the high-dose co-toxicity group mice((27.4±1.9)g) was lower than that of the control group((29.8±2.3)g)(P<0.05). The level of serum follicle-stimulating hormone(FSH) in the middle and high dose co-toxicity groups((265.01±2.99), (260.42±3.61)pg/mL, respectively) was lower than that in the control group((279.00±1.30)pg/mL, P<0.05). The content of Pb~(2+) in the brain of each group containing Pb~(2+) was higher than that of the control group. In the hypothalamic and pituitary tissues, the abundance of Adh1, Adh2, Rar and Rxr, and ALDH2 levels in the medium and high dose co-toxicity groups were higher than those in the control group(P<0.05). Cyp26a1 gene abundance and protein levels were lower in the medium and high dose co-toxicity groups than in the control group(P<0.05). The abundance of Jnks in the high-dose co-toxicity group was higher than that in the control group(P<0.05). CONCLUSION: Continuous exposure to 0.008 mg/L Pb~(2+)+0.1 mg/kg 1-NP for 21 days can cause damage to the hypothalamus and pituitary of mice, and activate the RA signaling pathway.
Subject(s)
Lead , Tretinoin , Mice , Animals , Lead/toxicity , Retinoic Acid 4-Hydroxylase , Mice, Inbred ICR , Hypothalamus , Body WeightABSTRACT
Procymidone (PCM) below the no-observed-adverse-effect-level (NOAEL) has previously been proven to induce ovarian and uterine damage in adolescent mice due to its raised circRNA Scar, decreased circZc3h4, and overactivated unfolded protein response (UPR). Also, 4-phenylbutyric acid (4-PBA) inhibits histone deacetylase and endoplasmic reticulum stress, reduces UPR, improves metabolism, and ensures homeostasis within the endoplasmic reticulum. In this study, 20, 40 and 80 mM of 4-PBA were utilized respectively to intervene the damage caused by 1.0 × 10-5 M PCM to ovaries and uterus in vitro culture. Besides, 100 mg/kg /d 4-PBA was intraperitoneally injected to female adolescent mice before, during and after oral administration of 100 mg/kg /d PCM for prevention and cure to observe tissue changes in the ovaries and uteri, and levels of circRNA Scar, circZc3h4 and UPR members. Our findings demonstrated that in vitro experiments, all doses of 4-PBA could inhibit ovarian and uterine damage caused by PCM, and the effect of 80 mM was especially noticeable. In the in vivo experiments, the best results were obtained when PCM was given with simultaneous 4-PBA intervention, i.e., minimal ovarian and uterine damage. Both in vivo and in vitro, 4-PBA in the ovary and uterus resulted in decreased circRNA Scar levels, increased circZc3h4 abundance, and moderately elevated levels of UPR members. So, it is suggested that 4-PBA moderately activates UPR, partially or completely antagonizing the elevated circRNA Scar and decreased circZc3h4 and consequently preventing PCM-induced ovarian and uterine damage effectively in adolescent mice.
Subject(s)
Ovary , RNA, Circular , Female , Mice , Animals , Cicatrix , Unfolded Protein Response , UterusABSTRACT
Redox flow batteries (RFBs) as promising technologies for energy storage have attracted burgeoning efforts and have achieved many advances in the past decades. However, for practical applications, the exploration of high-performance RFB systems is still of significance. In this work, inspired by the high solubility and low cost of both polysulfides and permanganates, the S/Mn RFBs with S42-/S22- and MnO4-/MnO42- as negative and positive redox pairs are demonstrated. Moreover, to solve the poor cycling performance caused by the sluggish kinetics of polysulfide-involved redox reactions and instability of the carbon felt (CF) electrode in the strong oxidative and corrosive catholyte, both the anode and cathode are designed to obtain high performance. Herein, the NiSx/Ni foam exhibiting electrocatalysis activity toward polysulfide ions is prepared and works as the anode while the graphene-modified carbon felt (G/CF) with high stability is fabricated and utilized as the cathode. Additionally, NaMnO4 with a high solubility limit (3.92 M) in the alkaline supporting electrolyte is preferred to KMnO4 as the redox-active molecule in the catholyte. The resulting S/Mn RFB cells show outstanding cell performance, such as high energy density (67.8 Wh L-1), long cycling lifetime with a temporal capacity fade of 0.025% h-1, and low chemical cost of electrolytes (17.31 $ kWh-1). Moreover, a three-cell stack shows good cycling stability over 100 cycles (226.8 h) with high performance, verifying the good scalability of the proposed S/Mn RFB system. Therefore, the present strategy provides a reliable candidate for stable, energy-dense, and cost-effective devices for future energy storage applications.
ABSTRACT
Ibuprofen (IBU) is an emerging environmental contaminant that, in high doses, can damage reproductive organs in humans and other mammals. Recently, its effects on the uterus have been investigated. It is known that the COX2-PGE2 pathway and Yes-associated protein (YAP) are involved in female reproductive organ development and form a COX2-PGE2-EP2-Gas-ß-catenin-YAP-COX2 positive feedback loop, in addition, TT-10, a pharmacological product, has been found to increase YAP. In this study, IBU was orally administrated to female mice for 7 d at doses of 0, 50, 100, and 200 mg/kg·bw/day (control, low, medium, and high doses, respectively). In addition, 0, 50, 100, and 200 µmol/L IBU was added in vitro to cultured uterine cells for 7 d at control, low, medium, and high doses, respectively; then, 0, 5, 10, and 20 µmol/L TT-10 were given to the in vitro uterine culture containing 100 µmol/L IBU to observe the effect of YAP activation. The results showed that medium and high doses of IBU inhibited the COX2-PGE2 pathway, decreasing YAP and increasing pYAP, leading to reduced circPVT1, elevated miR-149, and increased apoptosis, ultimately damaging the uterus. Conversely, 10 µmol/L TT-10 maximally enhanced YAP, which regulated COX2-PGE2 pathway activation, increased circPVT1, and decreased miR-149, and promoted cell proliferation, preventing uterine damage. This suggests that IBU may cause uterine damage by inhibiting the COX2-PGE2 pathway and YAP, and that appropriate doses of TT-10 may repair this damage by elevating YAP and stimulating COX2 via the feedback loop.
Subject(s)
Dinoprostone , Ibuprofen , MicroRNAs , Uterine Diseases , Animals , Female , Mice , Apoptosis/drug effects , Cell Proliferation , Cyclooxygenase 2/metabolism , Dinoprostone/metabolism , Ibuprofen/toxicity , Mammals/metabolism , Uterine Diseases/chemically induced , Uterine Diseases/metabolism , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic useABSTRACT
Vinclozolin (VCZ) has been identified as a broad-spectrum fungicide and an environmental endocrine disruptor. Also, the Hippo signaling pathway controls organ size by regulating cell proliferation and apoptosis, and moreover, overexpression of microRNA-132 (miR-132) and microRNA-195 (miR-195) inhibits cell proliferation and promotes apoptosis. So, in this study, the experimental mice were orally given 400 mg/kg/day VCZ (suspended in corn oil) at gestational day 12-18, while those of the control group were fed with corn oil of equal volume. Then unilateral ovaries and mid-uteri were isolated from 10 randomly-selected mice at the postnatal 1st week (7 days), 3rd week (20-21 days), and 7th week (48-49 days) respectively to observe gene levels, while 6 of the contralateral ovaries and uteri were subsequently examined for proteins respectively. Besides, 16 from both groups were determined with serum estradiol (E2) at week 7, of which 6 were randomized for histological observation. Here we found the levels of E2 reduced in VCZ-group at week 7, with fewer follicles and injured endometrium. Meanwhile, in VCZ mice of all ages, increased miR-132 and miR-195a, decreased G protein-coupled estrogen receptor (GPER), elevated phosphorylated large tumor suppressor (pLATS) and phosphorylated yes-associated protein (pYAP), and decreased yes-associated protein (YAP) were observed in their ovaries and uteri. These findings suggested ovarian and uterine dysplasia in the offspring induced by gestational VCZ-exposure were mainly attributed to higher miR-132 and miR-195a and accentuated Hippo-pathway.
Subject(s)
Fungicides, Industrial , Hippo Signaling Pathway , MicroRNAs , Ovary , Prenatal Exposure Delayed Effects , Uterus , Animals , Female , Humans , Mice , Pregnancy , Corn Oil , MicroRNAs/genetics , Ovary/abnormalities , Ovary/drug effects , Prenatal Exposure Delayed Effects/chemically induced , Proteins/metabolism , Uterus/abnormalities , Uterus/drug effects , YAP-Signaling Proteins , Fungicides, Industrial/toxicityABSTRACT
Redox flow batteries (RFBs) are one of the most promising techniques to store and convert green and renewable energy, benefiting from their advantages of high safety, flexible design and long lifespan. Membranes with fast and selective ions transport are required for the advances of RFBs. Remarkably, two-dimensional (2D) materials with high mechanical and chemical stability, strict size exclusion and abundantly modifiable functional groups, have attracted extensive attentions in the applications of energy fields. Herein, the improvements and perspectives of 2D materials working for ionic transportation and sieving in RFBs membranes are presented. The characteristics of various materials and their advantages and disadvantages in the applications of RFBs membranes particularly are focused. This review is expected to provide a guidance for the design of membranes based on 2D materials for RFBs.
ABSTRACT
With the increasing number of obese patients worldwide, metabolic and bariatric surgery (MBS) has quickly become an effective way to treat obesity and related metabolic diseases such as type 2 diabetes, hypertension, lipid abnormalities, etc. Although MBS has become an important part of general surgery, there is still controversy regarding the indications for MBS. In 1991, the National Institutes of Health (NIH) issued a statement on the surgical treatment of severe obesity and other related issues, which continues to be the standard for insurance companies, health care systems, and hospital selection of patients. The standard no longer reflects the best practice data and lacks relevance to today's modern surgeries and patient populations. After 31 years, in October 2022, the American Society for Metabolic and Bariatric Surgery (ASMBS) and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO), the world's leading authorities on weight loss and metabolic surgery, jointly released new guidelines for MBS indications, based on increasing awareness of obesity and its comorbidities and the accumulation of evidence of obesity metabolic diseases. In a series of recommendations, the eligibility of patients for bariatric surgery has been expanded. Specific key updates include the following: (1) MBS is recommended for individuals with BMI≥35 kg/m2, regardless of the presence, absence, or severity of co-morbidities; (2) MBS should be considered for individuals with metabolic diseases and BMI 30.0-34.9 kg/m2; (3) the BMI threshold should be adjusted for the Asian population:: BMI≥25 kg/m2 suggest clinical obesity, and BMI ≥ 27.5 kg/m2 population should consider MBS; (4) Appropriately selected children and adolescents should be considered for MBS.
Subject(s)
Adolescent , Child , Humans , Diabetes Mellitus, Type 2/surgery , Bariatric Surgery , Obesity/surgery , Obesity, Morbid/surgery , Weight LossABSTRACT
Procymidone (PCM) is a low toxicity fungicide, and an endocrine-disrupting chemical (EDC) that particularly damages the reproductive system of male vertebrates. In present study, adolescent mice in control, low-, medium-, and high-dose groups were orally administered 0 (equal volume of soybean oil), 50, 100, and 200 mg/kg/day PCM, respectively, for 21 days. Additionally, a three-dimensional culture of mouse testes was performed in vitro, and the control, low dose (0.33 × 10-5 M), medium dose (1 × 10-5 M), and high dose (3 × 10-5 M) PCM groups were established. We have found that, under both in vivo and in vitro conditions, all doses of PCM caused damage to mouse testes. Moreover, the levels of circZc3h4 RNA and Zc3h4 decreased while miR-212 increased in all treatment groups, with a corresponding rise in circRNA Scar and fall in Atp5b, compared to those in the control group, and all the changes showed a dose-response relationship. Besides, we have identified that low doses of PCM could activate the Ire1-Xbp1 pathway, whereas the medium and high doses activated the Perk-Elf2α-Atf4, Ire1-Xbp1, and Atf6 pathways. And it is, therefore, speculated that the unfolded protein response (UPR), circZc3h4 and circRNA Scar may have taken joint action in testicular injury in adolescent mice induced by PCM at the no observed adverse effect level (NOAEL, 100 mg/kg/day) and below NOAEL doses.
Subject(s)
Fungicides, Industrial , MicroRNAs , Activating Transcription Factor 6/genetics , Activating Transcription Factor 6/metabolism , Animals , Bridged Bicyclo Compounds , Cicatrix/metabolism , Endoplasmic Reticulum Stress/genetics , Fungicides, Industrial/toxicity , Male , Mice , MicroRNAs/metabolism , Protein Serine-Threonine Kinases , RNA, Circular , Signal Transduction/genetics , Soybean Oil , Unfolded Protein ResponseABSTRACT
Objective: To improve the diagnostic capacity of serum biomarkers for colorectal cancer (CRC), we introduced three novel indicators, namely, the C-X-C motif chemokine ligand 5 (CXCL5), stanniocalcin 2 (STC2), and chitinase 3 like 1 (CHI3L1) and assessed their performances in the detection of CRC. Methods: A total of 887 serum samples (153 health, 342 polyps, and 392 CRCs) were collected. Concentrations of CXCL5, STC2, and CHI3L1 were measured by the ELISA. CEA and CA199 were determined by electrochemiluminescence. Binary logistic regression was used to build the combination model. ROC analysis was used to evaluate the performance of biomarkers alone or in combination. Results: Model_2 that based on CXCL5, STC2, and CHI3L1 was the best approach in discriminating CRC from non-CRC controls (AUC, 0.943 (0.922-0.960); sensitivity, 0.848; specificity, 0.917; and accuracy, 0.887 in the training cohort and 0.959 (95% CI 0.927-0.980), 0.878, 0.917, and 0.900 in the testing cohort, respectively). In the detection of early CRC, Model_2 revealed AUC, sensitivity, specificity, and accuracy of 0.925 (0.897-0.947), 0.793, 0.917, and 0.886 in the training cohort and those of 0.926 (0.979-0.959), 0.786, 0.931, and 0.898 in the testing cohort. Furthermore, Model_2 exhibited an excellent diagnostic performance in CEA-negative cases (0.938 (0.913-0.957), 0.826, 0.917, and 0.888 in the training cohort and 0.961 (0.925-0.983), 0.887, 0.931, and 0.918 in the testing cohort). As used alone, STC2 achieved the capacities that is second only to that of Model_2 (0.866 (0.837-0.892), 0.859, 0.842, and 0.853 in the training cohort and 0.887 (0.842-0.923), 0.922, 0.799, and 0.853 in the testing cohort). STC2 alone also yielded acceptable results for early CRC detection (0.815 (0.776-0.849), 0.767, 0.849, and 0.829 in the training cohort and 0.870 (0.812-0.914), 0.952, 0.799, and 0.833 in the testing cohort). Moreover, STC2 maintained diagnostic accuracy for CRC patients with negative CEA (0.874 (0.842-0.901), 0.862, 0.849, and 0.853 in the training cohort and 0.898 (0.848-0.936), 0.930, 0.801, and 0.842 in the testing cohort). In comparison, the performances of the CEA and CA199 based Model_1 were far from satisfactory, especially in early cases (0.767 (0.726-0.805), 0.491, 0.863, and 0.771 in the training cohort and 0.817 (0.754-0.870), 0.476, 0.889, and 0.796 in the testing cohort). Conclusions: STC2 was a promising serum biomarker for CRC diagnosis either used alone or in combination with CXCL5 and CHI3L1.
ABSTRACT
Previous studies have shown that Poria cocos-based formulas combined with chemotherapy can improve the quality of life of ovarian cancer patients. However, the results are still controversial. We systematically searched the literature from eight databases to evaluate the efficacy and safety of Poria cocos-based formulas in combination with paclitaxel-carboplatin in treating ovarian cancer (OC). Subsequently, network pharmacology, molecular docking and cell experiments were performed to further verify the underlying molecular mechanism. Thirteen randomized controlled trials, including 922 patients with OC, were enrolled in the study. The results indicated that Poria cocos-based compounds combined with paclitaxel-carboplatin significantly improved patients' tumor response rate, traditional Chinese medicine syndrome score, Karnofsky Performance Scale, physical and social function, and reduced side effects of chemotherapy compared to the paclitaxel-carboplatin alone. According to the network pharmacological analysis, tumulosic acid were the most bioactive compounds of Poria cocos. BCL2L1 is highly expressed in OC and is associated with a worse prognosis which could become potential drug target. Functional enrichment analysis suggested that the anti-OC effect of Poria cocos may be related to PI3K-Akt signaling pathway. The molecular docking results indicated that tumulosic acid might inhibit OC by regulating BCL2L1. Vitro experiment confirmed tumulosic acid that induced cell apoptosis by modulating PI3K/AKT signaling and BCL2L1. Our study may provide a clinical basis and theoretical rationale for combining Poria cocos-based formulas with chemotherapy for OC. In addition, the integrated pharmacological strategy proposed in our study provides an excellent example for exploring the mechanism of complex formulas.
ABSTRACT
Procymidone (PCM) is a fungicide commonly used to prevent and control plant diseases, and it is also an environmental endocrine disruptor that has a typical anti-androgen effect on the function and/or structure of the vertebrate reproductive system. The activation of the unfolded protein response (UPR) will fold the protein correctly to ensure the cell's survival. PCM regulates GRP78 by affecting the level of hormones, and there is a regulatory relationship between the UPR, the circRNAs and the miRNAs. In vivo experiments, PCM (suspended in soybean oil) was orally administered to adolescent female mice for 21 days in 3 different doses of 50 mg kg-1 day-1 (low dose), 100 mg kg-1 day-1 (medium dose) and 200 mg kg-1 day-1 (high dose) to cause ovaries and uteruses damage, and in vitro experiments, various doses of PCM from 0.33 × 10-5 (low dose) to 1 × 10-5 (medium dose) then 3 × 10-5 M (high dose) were used to induce injury on the ovaries and uteri of the mice. We found out that both in vivo and in vitro, PCM caused dose-dependent damages to the ovaries and uteri, increased their circRNA Scar levels and decreased circZc3h4 abundance. Also, all UPR signaling pathways in the low-dose group and some in the middle-dose group were activated. It is speculated that UPR may antagonize the partial ovarian and uterine damage in adolescent mice induced by PCM at doses less than NOAEL via changes in circZc3h4 and circRNA Scar.
Subject(s)
Ovary , RNA, Circular , Animals , Bridged Bicyclo Compounds , Cicatrix/metabolism , Endoplasmic Reticulum Chaperone BiP , Female , Mice , Ovary/metabolism , Unfolded Protein Response , UterusABSTRACT
The quality of traditional Chinese medicine has a direct impact on the effectiveness and safety of its use, and is the premise necessary to ensure the healthy development of the traditional Chinese medicine industry. Comprehensive and accurate control and evaluation of the quality of medicinal materials is of great significance to the traditional Chinese medicine industry, but the complexity and dynamics of the chemical composition of medicinal materials makes their quality evaluation a challenge. Plant metabolomics provides an integrated and comprehensive analysis that is consistent with the holistic approach of traditional Chinese medicine. Chemical information therein promotes the establishment of a traceable system and provides new ideas and methods for the quality evaluation of medicinal materials. Plant metabolomics in the quality evaluation of medicinal materials is gradually increasing, and the core is the screening and identification of differential metabolites or specific marker compounds by means of stoichiometry. This study focused on the main factors that affect the quality of medicinal materials, such as origin, environmental adversity, varieties, harvest time, commercial specification and TCM processing. We describe the research progress in plant metabolomics combined with chemometrics analysis for the quality control and evaluation of medicinal materials, summarize existing problems, identify trends, and propose future research directions. Metabolomics plays an increasingly important role in the quality evaluation of medicinal materials, but the absolute qualitative and quantitative information of metabolomics needs to be further developed, and a single 'omics' technique is not sufficient for an in-depth analysis of medicinal value. In the future, standardization of plant metabolomics methods and a more complete database should be actively promoted, and plant metabolomics should be integrated into quality marker exploration. Plant metabolomics will need to be integrated with other 'omics' methods to improve the quality and evaluation system of medicinal materials.
ABSTRACT
OBJECTIVE: To investigate the expression of key genes and proteins of retinoic acid signaling pathway in procymidone-induced uterine injury in adolescent mice, and analyze the relationship between the signaling pathway and female reproductive damage. METHODS: The 3-week age ICR mice were randomly divided into low, medium, and high-dose groups and one control group with 8 mice in each group by weight. The low, medium and high dose groups were respectively given 50, 100 and 200 mg/(kg·d) procymidone orally for 21 days continuously, while the control group was given equal volume of soybean oil. After the mice were sacrificed, the uterus was taken from both sides for observing the histological changes in the cross-sectional slices of the uterus, the detection of the expression abundance of genes which related to the retinoic acid signaling pathway by the real-time fluorescent quantitative PCR, and the measurement of ALDH2 and CYP26 a1 proteins expression by Western blot. RESULTS: The body weight of mice in low-dose, medium-dose and high-dose groups were(27.50±1.49) g, (27.72±1.40) g and(26.89±1.19) g, respectively, which were lower than those in control group(31.48±1.14) g(P<0.05). The density of uterine lining monolayer columnar epithelium and lamina propria tubular uterine glands gradually decreases, at the same time the uterine folds become less with the dose of procymidone increases. adh1, ad/2, aldh1a1 in each experimental group were higher than those in the control group(P<0.05); the expression levels of aldh1a2 and aldh1a3 genes in the middle and high dose groups were higher than those in the control group(P<0.05); the expression levels of retinoic acid nuclear receptor rarα, rarγ, rxrα and rxrß genes in the high-dose group were higher than those in the control(P<0.05); yet the expression levels of cyp26a2 and cyp26a3 in the high-dose group were lower than those in the control group(P<0.05); the jnk family in medium and high dose groups were higher than the control(P<0.05). The expression of ALDH2 in each experimental group was higher than that in the control group, and increased with the increase of the dose(P<0.05); the expression of CYP26 a1 in each experimental group was not significantly different from that of the control group. CONCLUSION: The retinoic acid signal pathway is activated in procymidone-induced uterine injury in mice, then regulates the increase of the expression of jnk family, leading to the damage.
Subject(s)
Signal Transduction , Tretinoin , Animals , Bridged Bicyclo Compounds , Cross-Sectional Studies , Female , Mice , Mice, Inbred ICR , Tretinoin/toxicity , UterusABSTRACT
OBJECTIVE: The peripheral blood neutrophil-to-lymphocyte ratio (NLR) is a valuable predictor of clinical disease activity in inflammatory bowel disease (IBD). Therefore, we conducted a meta-analysis to evaluate the clinical significance of peripheral blood NLR in IBD patients. METHODS: A comprehensive literature search was conducted by searching PubMed, Embase, Web of Science, Cochrane Library, and Chinese databases from inception to May 10, 2021. We used the standard mean difference (SMD) with a 95% confidence interval (CI) to estimate the pooled effect and subgroup analysis to investigate heterogeneity. RESULTS: Sixteen studies including 2185 IBD patients and 993 healthy controls (HCs) were enrolled in this study. The peripheral blood NLR values were significantly higher in 1,092 IBD patients than in 933 HCs (SMD = 1.54, 95% CI = 1.05-2.02, P < 0.001) and in 1,269 patients with active IBD than in 1,056 patients with remissive IBD (SMD = 1.55, 95% CI = 1.06-2.05, P < 0.001). Subgroup analysis of the major subtypes of IBD revealed significantly elevated peripheral blood NLR values in patients with active ulcerative colitis (UC) compared to HCs (SMD = 2.04), remissive UC than HCs (SMD = 0.63), and active UC than in those with remissive UC (SMD = 1.32) (P < 0.05). Both Crohn's disease (CD) patients and active CD patients had significantly elevated peripheral blood NLR values than HCs with the SMD of 0.52 and 3.53 (P < 0.001). CONCLUSIONS: Peripheral blood NLR could serve as a valuable biomarker for predicting disease severity in IBD patients.