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1.
Ecotoxicol Environ Saf ; 231: 113166, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35030520

RESUMO

High concentration of blood ammonia can affect the uterus receptivity and decrease fecundity in dairy cow. Melatonin can reduce reactive oxygen species (ROS) level and has antioxidant and anti-inflammatory effects. However, it is not clear whether melatonin can alleviate ammonia-induced apoptosis of endometrial epithelial cell (EEC) and reduced uterus receptivity. The bovine EEC were treated with ammonium chloride and/or melatonin. Cell viability, apoptosis, oxidative stress and mitochondrial membrane potential were measured and the expression of apoptosis-related genes (p53, Cyt-c, Bax, Bcl-2, caspase-8, caspase-9 and caspase-3), uterus receptivity related genes (VEGF, LIF and EGF) and inflammatory factors (TLR-4, IL-6 and NF-κB) were detected. In addition, the expression of VEGF was detected after adding NF-κB inhibitor (40 µM) and IL-6 (1 ng/mL and 50 ng/mL). The results showed that ammonia significantly increased intracellular ROS level, mRNA and protein expression of Bax, p53, Cyt-c, caspase-9, caspase-8, caspase-3, TLR-4, NF-κB and IL-6, promoted cell apoptosis, while decreased mitochondrial membrane potential, the mRNA and protein expression of VEGF and EGF. Interestingly, melatonin significantly mitigated ammonia-induced changes. However, melatonin could not alleviate ammonia-induced changes of IL-6 and VEGF when NF-κB signal pathway was inhibited. The addition of IL-6 significantly reduced mRNA and protein expression of VEGF. In conclusion, ammonia induced EEC apoptosis through ROS production and activation of mitochondrial apoptosis pathway, and induced inflammatory response through TLR4/NF-κB/IL-6 pathway. Melatonin alleviated EEC apoptosis by inhibiting ROS pathway, and reduced IL-6 expression by inhibiting TLR-4/NF-κB signal pathway, which eventually improved VEGF expression and uterus receptivity in dairy cows.

3.
Theranostics ; 12(1): 324-339, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34987648

RESUMO

Background: Macrophage infiltration around lipotoxic tubular epithelial cells (TECs) is a hallmark of diabetic nephropathy (DN). However, how these two types of cells communicate remains obscure. We previously demonstrated that LRG1 was elevated in the process of kidney injury. Here, we demonstrated that macrophage-derived, LRG1-enriched extracellular vesicles (EVs) exacerbated DN. Methods: We induced an experimental T2DM mouse model with a HFD diet for four months. Renal primary epithelial cells and macrophage-derived EVs were isolated from T2D mice by differential ultracentrifugation. To investigate whether lipotoxic TEC-derived EV (EVe) activate macrophages, mouse bone marrow-derived macrophages (BMDMs) were incubated with EVe. To investigate whether activated macrophage-derived EVs (EVm) induce lipotoxic TEC apoptosis, EVm were cocultured with primary renal tubular epithelial cells. Subsequently, we evaluated the effect of LRG1 in EVe by investigating the apoptosis mechanism. Results: We demonstrated that incubation of primary TECs of DN or HK-2 mTECs with lysophosphatidyl choline (LPC) increased the release of EVe. Interestingly, TEC-derived EVe activated an inflammatory phenotype in macrophages and induced the release of macrophage-derived EVm. Furthermore, EVm could induce apoptosis in TECs injured by LPC. Importantly, we found that leucine-rich α-2-glycoprotein 1 (LRG1)-enriched EVe activated macrophages via a TGFßR1-dependent process and that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-enriched EVm induced apoptosis in injured TECs via a death receptor 5 (DR5)-dependent process. Conclusion: Our findings indicated a novel cell communication mechanism between tubular epithelial cells and macrophages in DN, which could be a potential therapeutic target.

4.
J Hazard Mater ; 421: 126726, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34330079

RESUMO

Carbon-based catalysts with heteroatom doping and hollow structures are desired for advanced oxidation processes (AOPs). Herein, dual-shelled Co, N, and S codoped hollow carbon nanocages were developed by wrapping zeolitic imidazolate framework-67 (ZIF-67) with trithiocyanuric acid (TCA) and performing subsequent carbonization. The optimal composite catalyst (Co-NC-CoS) exhibited excellent catalytic performance toward different organic pollutants. Almost complete removal of 4-NP (60 mg/L-1) was achieved within 20 min by 10 mg of catalyst and 0.2 g/L-1 peroxymonosulfate (PMS). Moreover, the catalyst showed good stability and reusability. The effects of catalyst and PMS dose, pollutant concentration, pH and common anions were investigated, and reactive oxygen species (ROS) were studied by scavenger experiments and electron paramagnetic resonance (EPR) tests. The results show that multidoped atoms S, Co and N all contributed to the degradation system. Several lines of evidence suggested that S could change the catalytic process from Co3+/Co2+ to Co3+/Co2+/Co0 reduction due to its low redox potential. Degradation was achieved through both radical and nonradical pathways, where sulfate radicals (SO4·Ì¶), hydroxyl radicals (·OH) and singlet oxygen (1O2) were primary reactive species. Overall, this work may suggest that the novel multi heteroatom-doped catalysts with complex structures can be developed for environmental remediation.

5.
J Ethnopharmacol ; 282: 114582, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34492322

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Due to the modernization of traditional Chinese medicine (TCM) and the influence of traditional medication habits (TCM has no toxicity or side effects), arsenic poisoning incidents caused by the abuse of realgar and realgar-containing Chinese patent medicines have occurred occasionally. However, the potential mechanism of central nervous system toxicity of realgar remains unclear. AIM OF THE STUDY: This study aimed to clarify the specific mechanism of realgar-induced neurotoxicity. MATERIALS AND METHODS: In this study, the roles of ERK1/2 and p38 MAPK in realgar-induced neuronal autophagy and overactivation of the nuclear factor erythroid-derived factor 2-related factor (Nrf2) signalling pathways was investigated in vivo and in vitro. RESULTS: The arsenic in realgar passed through the blood-brain barrier and accumulated in the brain, resulting in damage to neurons, synapses and myelin sheaths in the cerebral cortex and a decrease in the total antioxidant capacity. The specific mechanism is that the excessive activation of Nrf2 is regulated by the upstream signalling molecules ERK1/2 and p38MAPK. At the same time, p38 MAPK and ERK1/2 interfere with autophagy, thereby promoting autophagy initiation but causing subsequent dysfunctional autophagic degradation and inducing the p62-Keap1-Nrf2 feedback loop to promote Nrf2 signalling pathway activation and nerve cell apoptosis. CONCLUSIONS: This study confirmed the role of the signalling molecules p38 MAPK and ERK1/2 in perturbing autophagy and inducing the p62-Keap1-Nrf2 feedback loop to activate the Nrf2 signalling pathway in realgar-induced neurotoxicity.

6.
J Pharm Biomed Anal ; 207: 114342, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34634530

RESUMO

Artesunate-mefloquine is one of the commonly-used artemisinin-based combination therapies (ACTs). Given the significance of drug quality in the management of malaria cases, the objective of this study was to develop antibody-based assays as the point-of-care (POC) tests for monitoring the quality of this ACT. Using mefloquine conjugated to a carrier protein as the immunogen, we selected a specific monoclonal antibody (mAb) against mefloquine with no cross-reactivity to other antimalarial drugs. Using this mAb, we developed a direct competitive enzyme-linked immunosorbent assay (dcELISA) and a lateral flow immunoassay (LFIA) to measure the mefloquine contents. The dcELISA for mefloquine showed a 50% inhibitory concentration (IC50) and a working range of 2.79 ng/mL and 0.58-16.37 ng/mL, respectively. With the aid of a portable optical scanner, the LFIA had a working range of 0.15-2.67 µg/mL for mefloquine. When used to measure mefloquine contents in commercial drugs, the dcELISA and LFIA results were compatible with those determined using high-performance liquid chromatography. Using the same LFIA format, we developed a combination LFIA, which correctly estimated the artesunate and mefloquine contents in commercial ACTs. Therefore, both LFIAs could be used as POC devices for rapid quality control of artesunate and mefloquine in ACTs.


Assuntos
Antimaláricos , Antimaláricos/uso terapêutico , Artesunato , Quimioterapia Combinada , Imunoensaio , Mefloquina , Controle de Qualidade
7.
Mol Med Rep ; 25(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34791506

RESUMO

Prostate cancer (PCa) endangers the life and health of older men. Most PCa cases develop into castration­resistant PCa (CRPC) within 2 years. At present, the molecular mechanisms of the occurrence and development of PCa and its transformation to CRPC remain unknown. The present study aimed to investigate the role of CKLF­like Marvel transmembrane domain containing family member 5 (CMTM5) in PCa and its molecular mechanism in vitro. PCa tissues and paired adjacent normal prostate tissues from 70 patients were collected to examine the expression levels of CMTM5 and EGFR via immunohistochemistry, reverse transcription­quantitative PCR and western blotting. Then, CMTM5­overexpressing DU145 cells were constructed, and CMTM5 expression in these transfected cells and vector control cells was examined via western blotting. Cell Counting Kit­8 and plate clone formation assays were used to evaluate the proliferation and colony number of CMTM5­overexpressing cells and vector control cells. Then, cell migration and invasion were assessed using wound healing assay, Transwell assay and immunofluorescence analysis with DAPI staining. The effect of CMTM5 on apoptosis and its underlying molecular mechanism were examined using western blotting and flow cytometry. The results demonstrated that CMTM5 expression in PCa tissues and cell lines was significantly downregulated, while EFGR expression was significantly upregulated. The proportion of high CMTM5 expression in PCa tissues was significantly lower compared with that in normal prostate tissues. By contrast, the proportion of high EGFR expression in PCa tissues was significantly increased compared with that in normal prostate tissues. Moreover, CMTM5 overexpression significantly inhibited cell proliferation, migration and invasion, and promoted cell apoptosis compared with vector control cells in vitro. Furthermore, the regulation of PCa by CMTM5 was associated with the downregulation of PI3K/AKT and its downstream Bcl­2 expression, as well as the upregulation of Bax expression. In conclusion, CMTM5 may be an effective tumor suppressor gene for PCa, especially for castration­resistant PCa, by downregulating EGFR and PI3K/AKT signaling pathway components.

8.
Exp Ther Med ; 23(1): 68, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34934439

RESUMO

The cardiotoxicity of pirarubicin (THP) seriously affects its clinical application, which cannot be ignored. The antioxidant effect of schisandrin B (SchB) has been extensively reported in the context of dietotherapy. However, whether this antioxidant effect can protect the heart from THP damage remains unknown. The aim of the present study was to investigate whether the antioxidant effect of SchB can antagonize the cardiotoxicity of THP. Changes in electrocardiogram (ECG), echocardiography and serum lactate dehydrogenase, brain natriuretic peptide, creatine kinase MB and cardiac troponin T levels were used to detect the degree of cardiac damage. The levels of superoxide dismutase (SOD), malondialdehyde, catalase and total antioxidant capacity in the serum and heart were measured to observe the oxidative stress state of rats. Primary cardiomyocytes were cultured, and cell viability and reactive oxygen species (ROS) production were detected. Western blotting was used to detect the expression levels of SOD2, NOX2, pro/cleaved-caspase3 and Bcl-2/Bax in heart tissue and primary cardiomyocytes to verify the related signaling pathways. THP-treated rats showed a range of cardiac damage, including an abnormal ECG, echocardiography and myocardial enzymes. In the cellular experiments, cell viability decreased and ROS increased. However, this damage was alleviated after SchB treatment. Further studies demonstrated that SchB antagonized THP cardiotoxicity via its antioxidant effect. In conclusion, SchB protects the heart from THP damage in rats, and the mechanism may be closely associated with its antioxidant effect.

9.
Nanoscale ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34854858

RESUMO

This paper reports an interfacial evaporation-driven approach for self-assembly of a gold nanoparticle (AuNP) film at the interface of liquid/air. We have designed colloidal plasmonic AuNPs capped with different types and surface coverage densities of ligands (i.e. purified and unpurified oleylamine-capped or thiol-protected AuNPs) and studied the impact of surface chemistry on the self-assembly of AuNPs using the optically excited plasmonic heating effect. By employing the extended DerjaguinLandau-Verwey-Overbeek model, the calculated lowest potential energies of the assembled AuNPs capped with purified oleylamine or alkyl thiols are between -1 kBT and -2 kBT, which is close to the room temperature thermal energy and represents a meta-stable assembly, indicating the reversible self-assembly of the AuNP film observed from the experiment. Furthermore, we observed the superheating phenomenon in well-dispersed nanoparticle solution while normal boiling occurred in the solutions with AuNP assemblies. The SERS activity of the as-prepared AuNP film has also been studied using rhodamine 6G as a molecular probe. This work not only provides a new aspect of the boiling phenomena of optically heated colloidal plasmonic nanoparticle solutions, but also provides inspiration for a new approach in designing surface ligands on the nanoparticles to realize reversible self-assembly via interfacial evaporation.

10.
Theriogenology ; 179: 103-116, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34871925

RESUMO

The blood-testicular barrier (BTB) is involved in spermatogenesis, protects sperm development, and plays a crucial role in the reproductive process. Tight junctions (TJs) between Sertoli cells (SCs) are the key structure of (BTB), and if its structure is damaged, BTB function is affected. The cellular inflammation caused by Gram-negative bacteria affects the structural integrity of TJs. Melatonin (MT) has anti-inflammatory effects; however, the effect of MT in newborn calf SCs is unknown. Therefore, this experiment studied the protective effect of MT. The results showed that LPS upregulated TLR4, MyD88, and NF-κB expressions, in turn, activated the TLR4/MyD88/NF-κB signaling pathway, produced a large amount of IL-6 and IL-1ß, downregulated the expression of ZO-1 and Occludin, and reduced the viability of SCs, which resulted in the inflammatory response of SCs and damage of TJs. The addition of MT decreased TLR4, MyD88, and NF-κB expressions, it then inhibited the activation of TLR4/MyD88/NF-κB signaling pathway, downregulated the expression of IL-6 and IL-1ß, upregulated the expression of ZO-1 and Occludin, and increased the cell viability, thereby alleviating the inflammatory response of SCs, and restored the TJs structure. Overall, our results reveal that MT can alleviate LPS-induced in newborn calf SCs Inflammation and TJs injury through TLR4/MyD88/NF-κB signaling pathway.

12.
Cryobiology ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34863702

RESUMO

Thyroid hormone was involved in gene expression and functional regulation in various signal pathways. Cold stress can increase triiodothyronine (T3) level in the blood. The aim of this study was to investigate the effect of T3 on HSP70 expression and apoptosis in Sertoli cells (SCs) under cold stress in vitro culture at 26 °C, and provide a theoretical and practical basis for improving the reproductive efficiency of bulls in cold areas. SCs were treated with different cold stress duration and different T3 concentrations for pre-screening. HSP70 inhibitor was added later, and the apoptotic rate was measured using flow cytometry. The expression of HSP70 and the main genes of mitochondrial apoptosis pathway were determined by means of real-time PCR and western-blot, respectively. The localization of HSP70 was assessed by immunofluorescence. The results showed that cold stress (26 °C, 6 h) played an inductive role in SCs apoptotic rate (P < 0.01) and the transfer of HSP70 into the nucleus. 100 nM T3 further promoted HSP70 expression and its transfer into the nucleus, which significantly inhibited the expression of vital genes (cyt-c, Caspase-9 and Caspase-3) in mitochondrial pathway (P < 0.05). Subsequently, higher survival and lower apoptotic rates of SCs (P < 0.01) were observed. When T3 and HSP70 inhibitor were added together, the expression of cyt-c, Caspase-9 and Caspase-3 were inhibited (P < 0.05), and then the declining apoptotic rate increased again (P < 0.01). In conclusion, T3 can regulate HSP70 expression and translocation to mediate mitochondrial apoptosis pathway to inhibit SCs apoptosis induced by cold stress.

13.
J Neurosurg ; : 1-9, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34952509

RESUMO

OBJECTIVE: Speech arrest is a common but crucial negative motor response (NMR) recorded during intraoperative brain mapping. However, recent studies have reported nonspeech-specific NMR sites in the ventral precentral gyrus (vPrCG), where stimulation halts both speech and ongoing hand movement. The aim of this study was to investigate the spatial relationship between speech-specific NMR sites and nonspeech-specific NMR sites in the lateral frontal cortex. METHODS: In this prospective cohort study, an intraoperative mapping strategy was designed to identify positive motor response (PMR) sites and NMR sites in 33 consecutive patients undergoing awake craniotomy for the treatment of left-sided gliomas. Patients were asked to count, flex their hands, and simultaneously perform these two tasks to map NMRs. Each site was plotted onto a standard atlas and further analyzed. The speech and hand motor arrest sites in the supplementary motor area of 2 patients were resected. The 1- and 3-month postoperative language and motor functions of all patients were assessed. RESULTS: A total of 91 PMR sites and 72 NMR sites were identified. NMR and PMR sites were anteroinferiorly and posterosuperiorly distributed in the precentral gyrus, respectively. Three distinct NMR sites were identified: 24 pure speech arrest (speech-specific NMR) sites (33.33%), 7 pure hand motor arrest sites (9.72%), and 41 speech and hand motor arrest (nonspeech-specific NMR) sites (56.94%). Nonspeech-specific NMR sites and speech-specific NMR sites were dorsoventrally distributed in the vPrCG. For language function, 1 of 2 patients in the NMA resection group had language dysfunction at the 1-month follow-up but had recovered by the 3-month follow-up. All patients in the NMA resection group had fine motor dysfunction at the 1- and 3-month follow-ups. CONCLUSIONS: The study results demonstrated a functional segmentation of speech-related NMRs in the lateral frontal cortex and that most of the stimulation-induced speech arrest sites are not specific to speech. A better understanding of the spatial distribution of speech-related NMR sites will be helpful in surgical planning and intraoperative mapping and provide in-depth insight into the motor control of speech production.

14.
Front Mol Biosci ; 8: 777370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34950702

RESUMO

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal carcinoma (EC) in China. Although the PD-1 inhibitor pembrolizumab has been approved to treat patients with EC, its therapeutic efficacy is limited. Thus, additional immunotherapeutic targets for EC treatment are needed. Programmed Death-1 Homolog (PD-1H) is a negative checkpoint regulator that inhibits antitumor immune responses. Here, PD-1H expression in 114 patients with ESCC was evaluated by immunohistochemistry. Next, 12 randomly selected tumor tissue sections were used to assess the colocalization of PD-1H protein and multiple immune markers by multiplex immunohistochemistry. Our results demonstrated that PD-1H was expressed at high frequency in ESCC tumor tissues (85.1%). PD-1H protein was predominantly expressed in CD68+ tumor-associated macrophages and expressed at low levels in CD4+ T cells and CD8+ T cells in ESCC tumor tissues. Furthermore, based on ESCC data in The Cancer Genome Atlas (TCGA), the gene expression levels of PD-1H were positively associated with the infiltration levels of immune-activated cells especially CD8+ cytotoxic T cells. In contrast, the gene expression levels of PD-1H were negatively correlated with myeloid-derived suppressor cells (MDSCs). Importantly, PD-1H expression in tumor sites was significantly correlated with favorable overall survival in patients with ESCC. Collectively, our findings first provided direct information on the PD-1H expression pattern and distribution in ESCC, and positive correlation of PD-1H expression with overall survival suggested PD-1H expression levels could be a significant prognostic indicator for patients with ESCC. Future studies need to explore the immunoregulatory of PD-1H in the tumor microenvironment of ESCC.

15.
Int J Neurosci ; : 1-12, 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34963424

RESUMO

Accurate and rapid segmentation of the hippocampus can help doctors perform intractable temporal lobe epilepsy (TLE) preoperative evaluations to identify good surgical candidates. This study aims to establish a radiomics system for the automatic diagnosis of hippocampal sclerosis with the help of machine learning. A total of 240 cases were analysed to develop a diagnostic model. First, an automatic hippocampal segmentation process was established that exploits a priori knowledge of the relatively fixed location of the hippocampus in brain partitions, as well as a deep-learning segmentation network based on an Attention U-net. Then, we extracted 527 radiomics features from each side of the segmented hippocampus. The iterative sparse representation based on feature selection and a support vector machine classifier were finally used to establish the diagnostic model of hippocampal sclerosis. The diagnostic model consists of two consecutive steps: distinguish hippocampal sclerosis (HS) from normal control (NC) and detect whether the HS is located on the left or right side. When the automatic diagnosis model identified HS and NC, the sensitivity and specificity reached 0.941 and 0.917 in the 10-fold cross-validation set and 0.920 and 0.909 in the independent testing set. When the diagnostic model detected HS lateralization, the sensitivity and specificity reached 0.923 and 0.920 in cross-validation and 0.909 and 0.929 in independent testing. Our results show that the developed radiomics model can help detect TLE patients with hippocampal sclerosis and has the potential to simplify preoperative evaluations and select surgical candidates.

16.
Life Sci ; 288: 120180, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34843736

RESUMO

Alcoholic liver injury is a liver cell dysfunction disease caused by long-term or excessive alcohol consumption. Inhibiting the production of inflammatory factors is an important way to alleviate liver injury. Interleukin-9 (IL-9) is one of the members of IL-2Rγc family. It has multiple biological functions. Previous studies have shown that IL-9 is a cytokine that is closely related to inflammatory disease, allergic diseases, autoimmune diseases, and parasitic infections. However, no systematic studies have been performed to address the role of IL-9 in ALI. This project aims to investigate the effects of IL-9 on macrophage-related inflammatory response and hepatocyte apoptosis in alcohol-induced liver injury by injecting adeno-associated virus (AAV9) into tail vein. In the ALI model group, western blot and ELISA assays demonstrated that the expression of IL-9 was reduced. Overexpression of IL-9 relieved the injury and reduced the serum levels of IL-6, TNF-α in EtOH-induced ALI mouse model. Moreover, by using western blot, it was indicated that IL-9 can inhibit the expression of pro-apoptotic protein, such as cleaved caspase 3 and Bax. In vitro, mouse recombinant protein IL-9 inhibited the expression of IL-6, TNF-α in EtOH-induced RAW264.7 cells. Moreover, flow cytometry and western blot results displayed that macrophage-derived IL-9 inhibited hepatocyte apoptosis. After silencing STAT3 in AML-12 cells, the anti-apoptotic effect of macrophage-derived IL-9 was further enhanced. These results indicate that IL-9 reduces the production of pro-inflammatory factors in ALI. Furthermore, macrophage-derived IL-9 can reduce hepatocyte apoptosis by inhibiting the activation of the STAT3 pathway.

17.
Anal Bioanal Chem ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34846541

RESUMO

Amodiaquine (AQ) is a commonly used antimalarial drug, and N-desethyl-AQ (N-DEAQ) is an active metabolite of AQ. Given the significance of drug quality in the management of malaria cases, this study aims to develop antibody-based assays for the detection and quantitation of AQ without the need for sophisticated equipment. Two monoclonal antibodies (mAbs) against AQ, designated as JUN7 and TE7, were selected, which showed 72.7% and 9.5% cross-reactivity to N-DEAQ, respectively. These mAbs showed <0.1% cross-reactivity to other commonly used antimalarial drugs. An indirect competitive enzyme-linked immunosorbent assay (icELISA) based on JUN7 showed a 50% inhibitory concentration (IC50) of 0.16 ng/mL and a working range of 0.06-0.46 ng/mL. A lateral flow immunoassay (LFIA) based on JUN7 was also developed with a working range of 2.58-30.86 ng/mL. The icELISA and LFIA were applied for the quantification of AQ in commercial drugs, and the results were comparable to those determined using high-performance liquid chromatography. In addition, a combination dipstick for simultaneous, qualitative analysis of AQ and artesunate was developed. All immunoassays based on JUN7 can be applied for quality control of AQ-containing artemisinin-based combination therapies. As TE7 showed low cross-reactivity to N-DEAQ, an icELISA based on TE7 was developed with an IC50 of 0.38 ng/mL and a working range of 0.14-1.67 ng/mL. The TE7 icELISA was applied for the study of pharmacokinetics of AQ in rat serum after intragastric administration, and the results were consistent with those of previous studies.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34820868

RESUMO

BACKGROUND: While the incidence of inflammatory bowel disease (IBD) has stabilised in the West, it is still increasing in several newly industrialised countries. AIMS: To investigate whether the environmental and dietary risk factors for IBD differ between Eastern and Western populations METHODS: We systematically searched PubMed, Embase, and Web of Science for studies published from inception through June 30, 2020. Data were pooled using a random effects model. RESULTS: Overall, 255 studies were assessed. We identified 25 risk factors for IBD, seven of which were noted in both Eastern and Western populations: family history of Crohn's disease [CD] or ulcerative colitis [UC], former smoking (CD/UC), smoking (CD), appendicectomy (CD), tonsillectomy (CD), meat and meat products (CD), and vitamin D deficiency (UC). The remaining factors, including urban living, current smoking, antibiotics, oral contraceptives, caesarean section, isotretinoin, total energy, fat, cholesterol, fatty acids and their sub-classifications, eggs, and soft drinks, were associated with an increased risk of IBD in Western or Eastern populations only. We identified 21 protective factors for IBD, among which eight were common in the East and West: farm animals (CD/UC), Helicobacter pylori infection (CD/UC), multiple births (CD), physical activity (CD), history of breastfeeding (CD), pets (UC), current smoking (UC), and coffee intake (UC). Ten factors conferred protection against IBD in Western populations only, whereas eight factors conferred protection against IBD in Eastern populations only. CONCLUSIONS: Numerous environmental and dietary factors influenced the development of IBD in both Western and Eastern populations, whereas certain factors influenced IBD risk differently in these populations.

19.
Front Pharmacol ; 12: 733805, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721023

RESUMO

Objective: Pirarubicin (THP), one of the anthracycline anticancer drugs, is widely used in the treatment of various cancers, but its cardiotoxicity cannot be ignored. Schisandrin B (SchB) has the ability to upregulate cellular antioxidant defense mechanism and promote mitochondrial function and antioxidant status. However, it has not been reported whether it can resist THP-induced cardiotoxicity. The aim of this study was to investigate the effect of SchB on THP cardiotoxicity and its mechanism. Methods: The rat model of cardiotoxicity induced by THP was established, and SchB treatment was performed at the same time. The changes of ECG, cardiac coefficient, and echocardiogram were observed. The changes of myocardial tissue morphology were observed by H&E staining. Apoptosis was detected by TUNEL. The levels of LDH, BNP, CK-MB, cTnT, SOD, and MDA in serum were measured to observe the heart damage and oxidative stress state of rats. The expression of cleaved-caspase 9, pro/cleaved-caspase 3, Bcl-2/Bax, and cytosol and mitochondrial Cyt C and Bax was evaluated by western blot. H9c2 cardiomyocytes were cocultured with THP, SchB, and mPTP inhibitor CsA to detect the production of ROS and verify the above signaling pathways. The opening of mPTP and mitochondrial swelling were detected by mPTP kit and purified mitochondrial swelling kit. Results: After 8 weeks, a series of cardiotoxicity manifestations were observed in THP rats. These adverse effects can be effectively alleviated by SchB treatment. Further studies showed that SchB had strong antioxidant and antiapoptotic abilities in THP cardiotoxicity. Conclusion: SchB has an obvious protective effect on THP-induced cardiotoxicity. The mechanism may be closely related to the protection of mitochondrial function, inhibition of mPTP opening, and alleviation of oxidative stress and apoptosis of cardiomyocytes.

20.
Pediatr Pulmonol ; 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34779149

RESUMO

RATIONALE: Identifying neonatal and post-discharge exposures among extremely low gestational age newborns (ELGANs) that drive increased pulmonary morbidity and abnormal lung function at 1 year of age proves challenging. OBJECTIVE: The NIH-sponsored Prematurity and Respiratory Outcomes Program (PROP), evaluated infant pulmonary function tests (iPFTs) at 1 year corrected age to determine which demographic and clinical factors are associated with abnormal lung function. METHODS: iPFTs were performed on a PROP subcohort of 135 participants following Institutional Review Board (IRB)-approved written consent. Demographic data, Neonatal Intensive Care Unit (NICU) clinical care, and post-NICU exposures were analyzed for association with iPFTs. MAIN RESULTS: A significant decrease in forced expiratory volume at 0.5 s (FEV0.5 ) and/or forced expiratory flows at 75% of forced vital capacity (FEF75 ), were associated with male sex and African American race. Clinical factors including longer duration of ventilatory support, exposure to systemic steroids, and weight less than the 10th percentile at 36 weeks postmenstrual age were also associated with airflow obstruction, whereas supplemental oxygen requirement and bronchopulmonary dysplasia were not. Additionally, the need for respiratory medications, technology, or hospitalizations during the first year, ascertained by a quarterly survey, were the only post-NICU factors associated with decreased FEV0.5 and FEF75 . Only 7% of infants had reversible airflow obstruction. CONCLUSIONS: Neonatal demographic factors, respiratory support in the NICU, and a history of greater post-NICU medical utilization for respiratory disease had the strongest association with lower lung function at 1 year in ELGANs.

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