Progress in Identification of UDP-Glycosyltransferases for Ginsenoside Biosynthesis.

Ginsenosides, the primary pharmacologically active constituents of the Panax genus, have demonstrated a variety of medicinal properties, including anticardiovascular disease, cytotoxic, antiaging, and antidiabetes effects. However, the low concentration of ginsenosides in plants and the challenges associated with their extraction impede the advancement and application of ginsenosides. Heterologous biosynthesis represents a promising strategy for the targeted production of these natural active compounds. As representative triterpenoids, the biosynthetic pathway of the aglycone skeletons of ginsenosides has been successfully decoded. While the sugar moiety is vital for the structural diversity and pharmacological activity of ginsenosides, the mining of uridine diphosphate-dependent glycosyltransferases (UGTs) involved in ginsenoside biosynthesis has attracted a lot of attention and made great progress in recent years. In this paper, we summarize the identification and functional study of UGTs responsible for ginsenoside synthesis in both plants, such as Panax ginseng and Gynostemma pentaphyllum, and microorganisms including Bacillus subtilis and Saccharomyces cerevisiae. The UGT-related microbial cell factories for large-scale ginsenoside production are also mentioned. Additionally, we delve into strategies for UGT mining, particularly potential rapid screening or identification methods, providing insights and prospects. This review provides insights into the study of other unknown glycosyltransferases as candidate genetic elements for the heterologous biosynthesis of rare ginsenosides.

Ablation of Proton/Glucose Exporter SLC45A2 Enhances Melanosomal Glycolysis to Inhibit Melanin Biosynthesis and Promote Melanoma Metastasis.

Sequence variation in SLC45A2 are responsible for oculocutaneous albinism type 4 in many species and are associated with melanoma susceptibility, but the molecular mechanism is unclear. In this study, we used Slc45a2-deficient melanocyte and mouse models to elucidate the roles of SLC45A2 in melanogenesis and melanoma metastasis. We found that the acidified cellular environment impairs the activity of key melanogenic enzyme tyrosinase in Slc45a2-deficient melanocytes. SLC45A2 is identified as a proton/glucose exporter in melanosomes, and its ablation increases the acidification of melanosomal pH through enhanced glycolysis. Intriguingly, 13C-glucose-labeled metabolic flux and biochemical assays show that melanosomes are active glucose-metabolizing organelles, indicating that elevated glycolysis mainly occurs in melanosomes owing to Slc45a2 deficiency. Moreover, Slc45a2 deficiency significantly upregulates the activities of glycolytic enzymes and phosphatidylinositol 3-kinase/protein kinase B signaling to promote glycolysis-dependent survival and metastasis of melanoma cells. Collectively, our study reveals that the proton/glucose exporter SLC45A2 mediates melanin synthesis and melanoma metastasis primarily by modulating melanosomal glucose metabolism.

Cardioprotective Effects of Aconite in Isoproterenol-Induced Myocardial Infarction in Rats.

Background: Myocardial infarction (MI) is a severe clinical condition caused by decreased or complete cessation of blood flow to a portion of the myocardium. Aconite, the lateral roots of Aconitum carmichaelii Debx., is a well-known Chinese medicine for treatment of heart failure and related cardiac diseases. The present study is aimed at investigating the cardioprotective effect of aconite on isoproterenol- (ISO)- induced MI. Methods: The qualitative analysis of aqueous extracts from brained aconite (AEBA) was conducted by HPLC. A rat model of MI induced by ISO was established to examine the effects of AEBA. The cardiac function was assessed by echocardiography. The serum levels of SOD, CK-MB, cTnT, and cTnI were detected to estimate myocardial injury. The pathological changes of heart tissue were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and Masson's trichrome staining. The expressions of abnormal vascular remodeling and hypoxia-related components and the levels of inflammation-associated genes and proteins were detected by RT-qPCR, western blotting, and immunofluorescence. Results: The contents of benzoylaconine, benzoylmesaconine, benzoylhypacoitine, and hypaconitine in AEBA were 1.35 µg/g, 37.35 µg/g, 57.10 µg/g, and 2.46 µg/g, respectively. AEBA obviously improved heart function through promoting echocardiographic parameters, radial strain, and circumferential strain. The data of TTC staining, HE staining, and Masson's trichrome staining disclosed that AEBA could significantly reduce infarct size, inhibit inflammatory cell infiltration, and decrease the myocardial fibrosis. Moreover, AEBA distinctly suppressed the serum levels of SOD, MDA, CK-MB, cTnT, and cTnI in ISO-induced rats. The results of RT-qPCR indicated that AEBA inhibited the expressions of hypoxia- and inflammation-related genes, including VEGF, PKM2, GLUT-1, LDHA, TNF-α, IL-1ß, IL-6, and COX2. In addition, the western blotting and immunofluorescence analyses further confirmed the results of RT-qPCR. Conclusion: In summary, our results indicate that the AEBA could improve ISO-induced myocardial infarction by promoting cardiac function, alleviating myocardial hypoxia, and inhibiting inflammatory response and fibrosis in heart tissue.

Synthesis and biological evaluation of celastrol derivatives as potent antitumor agents with STAT3 inhibition.

Using STAT3 inhibitors as a potential strategy in cancer therapy have attracted much attention. Recently, celastrol has been reported that it could directly bind to and suppress the activity of STAT3 in the cardiac dysfunction model. To explore more effective STAT3 inhibiting anti-tumour drug candidates, we synthesised a series of celastrol derivatives and biologically evaluated them with several human cancer cell lines. The western blotting analysis showed that compound 4 m, the most active derivative, could suppress the STAT3's phosphorylation as well as its downstream genes. SPR analysis, molecular docking and dynamics simulations' results indicated that the 4m could bind with STAT3 protein more tightly than celastrol. Then we found that the 4m could block cell-cycle and induce apoptosis on HCT-116 cells. Furthermore, the anti-tumour effect of 4m was verified on colorectal cancer organoid. This is the first research that discovered effective STAT3 inhibitors as potent anti-tumour agents from celastrol derivatives.

Serum Metabolome Mediates the Antiobesity Effect of Celastrol-Induced Gut Microbial Alterations.

The antiobesity effect of celastrol has been reported in numerous studies, but the underlying mechanism remains unclear. It is widely accepted that gut dysbiosis is closely related to obesity. The potential effect of celastrol on microbiota is worth exploring. In this study, the celastrol-induced weight loss was validated in high-fat diet (HFD)-induced obese mice, with the detection of reported phenotypes including a reduction in food intake, augments in dyslipidemia and glucose metabolism, and adipose thermogenesis. The anti-inflammatory effect of celastrol was also proved based on the alterations in serum cytokines. Antibiotic interference showed that gut microbiota contributes to celastrol-induced weight loss. Several key bacteria were identified using shotgun metagenomic sequencing to display the alterations of the intestinal microbiome in obese mice treated with celastrol. Meanwhile, the fecal and serum metabolic profiles were generated by pseudotargeted metabolomics, and changes in some critical metabolites related to appetite and metabolism were detected. Importantly, we applied in silico bidirectional mediation analysis to identify the precise connections among the alterations in gut microbes, serum metabolome, and host phenotypes induced by celastrol treatment for the first time. Therefore, we concluded that the celastrol-induced microbial changes partially contribute to the antiobesity effect via the serum metabolome. The mass spectrometry data are deposited on MetaboLights (ID: MTBLS3278).

A ratiometric electrochemical microsensor for monitoring chloride ions in vivo.

Chloride ion (Cl-), the most common anion in animal brain, has been verified to play a vital role in maintaining normal physiological processes. Thus, development of a reliable platform to determine Cl- is of great significance for brain research involving Cl-. In this work, a ratiometric electrochemical microsensor (REM) for the in vivo measurement of cerebral Cl- was designed. To prepare REM, uniform Ag nanoparticles (Ag NPs) with nano-level sizes were synthesized via an adsorption-reduction process, which served as selective recognition elements for Cl- determination, while methylene blue (MB) was absorbed and acted as an inner reference unit to avoid the environmental interference of complicated brain systems. As a result, this developed REM exhibited high sensitivity and selectivity, as well as good stability, reproducibility and anti-biofouling. This reliable approach was established to monitor Cl- in mouse brain.

SLC-30A9 is required for Zn2+ homeostasis, Zn2+ mobilization, and mitochondrial health.

The trace element zinc is essential for many aspects of physiology. The mitochondrion is a major Zn2+ store, and excessive mitochondrial Zn2+ is linked to neurodegeneration. How mitochondria maintain their Zn2+ homeostasis is unknown. Here, we find that the SLC-30A9 transporter localizes on mitochondria and is required for export of Zn2+ from mitochondria in both Caenorhabditis elegans and human cells. Loss of slc-30a9 leads to elevated Zn2+ levels in mitochondria, a severely swollen mitochondrial matrix in many tissues, compromised mitochondrial metabolic function, reductive stress, and induction of the mitochondrial stress response. SLC-30A9 is also essential for organismal fertility and sperm activation in C. elegans, during which Zn2+ exits from mitochondria and acts as an activation signal. In slc-30a9-deficient neurons, misshapen mitochondria show reduced distribution in axons and dendrites, providing a potential mechanism for the Birk-Landau-Perez cerebrorenal syndrome where an SLC30A9 mutation was found.

Comparison of Chief Complaints and Patient-Reported Symptoms of Treatment-Naive Lung Cancer Patients Before Surgery.

BACKGROUND: Lung cancer patients without chief complaints have been increasingly identified by physical examination. This study aimed to profile and compare chief complaints with patient-reported symptoms of lung cancer patients before surgery. METHODS: Data were extracted from a multicenter, prospective longitudinal study (CN-PRO-Lung 1) in China from November 2017 to January 2020. A comparison between chief complaints and patient-reported symptoms was analyzed using the Chi-squared test. RESULTS: A total of 201 (50.8%) lung cancer patients without chief complaints were found by physical examination at admission, and 195 (49.2%) patients had chief complaints. The top 5 chief complaints were coughing (38.1%), expectoration (25.5%), chest pain (13.6%), hemoptysis (10.6%), and shortness of breath (5.3%). There were significantly more patients with chief complaints of coughing (38.1% vs 15.0%, P <0.001) and pain (20.5% vs 6.9%, P<0.001) than those with the same symptoms rated ≥4 via MD Anderson Symptom Inventory‒Lung Cancer (MDASI-LC). There were less patients with chief complaints of fatigue (1.8% vs 10.9%, P<0.001), nausea (0.3% vs 2.5%, P=0.006), and vomiting (0.3% vs 1.8%, p=0.032) than those with the same symptoms rated ≥4 via MDASI-LC. In patients without chief complaints, the five most common moderate to severe patient-reported symptoms were disturbed sleep (19.5%), distress (13.5%), dry mouth (13%), sadness (12%), and difficulty remembering (11.1%). CONCLUSION: Symptoms of lung cancer patients not included in the chief complaint could be identified via a patient-reported outcome instrument, suggesting the necessity of implementing the patient-reported outcome assessment before lung cancer surgery for better patient care.

Aspirin inhibits prostaglandins to prevents colon tumor formation via down-regulating Wnt production.

According to numerous epidemiological studies, aspirin is a non-steroidal anti-inflammatory drug (NSAID) that reduces the occurrence and mortality of colorectal cancer (CRC). However, the underlying mechanisms are not well identified. In an effort to fill these gaps, we administered aspirin on mice one day before induction in an azoxymethane (AOM)/dextran sulfate sodium (DSS) induced CRC model. In this study, we assessed the effects of aspirin on tumorigenesis and tumor cell proliferation. Multi-layer analyses were carried out to identify changes in cytokines, metabolites, level of gene expressions, and proteins associated with tumorigenesis and aspirin treatment. The results showed that aspirin-treated mice developed fewer colon tumors in response to AOM/DSS, and aspirin can actively block cyclooxygenase (COX) metabolism and reduce levels of pro-inflammatory cytokines. In addition, the transcriptomic and proteomic analyses both indicated that aspirin has an inhibitory effect on the Wnt pathway. The in vitro results further indicated that aspirin inhibits WNT6 production, possibly by suppressing its transcription factor NR4A2, which in turn is regulated by prostaglandin E2, thereby ultimately inhibiting the Wnt pathway. These findings improve our understanding of the mechanisms behind aspirin's chemoprevention effect on CRC.

Celastrol in metabolic diseases: Progress and application prospects.

Metabolic diseases are becoming increasingly common in modern society. Therefore, it is essential to develop effective drugs or new treatments for metabolic diseases. As an active ingredient derived from plants, celastrol has shown great potential in the treatment of a wide variety of metabolic diseases and received considerable attention in recent years. In reported studies, the anti-obesity effect of celastrol resulted from regulating leptin sensitivity, energy metabolism, inflammation, lipid metabolism and even gut microbiota. Celastrol reversed insulin resistance via multiple routes to protect against type 2 diabetes. Celastrol also showed effects on atherosclerosis, cholestasis and osteoporosis. Celastrol in treating metabolic diseases seem to be versatile and the targets or pathways were diverse. Here, we systematically review the mechanism of action, and the therapeutic properties of celastrol in various metabolic diseases and complications. Based on this review, potential research strategies might contribute to the celastrol's clinical application in the future.

Cholesterol moieties as building blocks for assembling nanoparticles to achieve effective oral delivery of insulin.

Although nanoparticles (NPs) have emerged as a promising strategy to improve oral absorption of insulin, most of them still have minimal oral bioavailability due to the harsh gastrointestinal (GI) environment and epithelial barriers. A novel platform of oral insulin delivery is herein proposed based on amphiphilic cholesterol-phosphate conjugate (CHP). The CHP was synthesized with a cholesterol moiety as a hydrophobic block and a phosphate group as a hydrophilic block. The structural characteristics of CHP made cholesteryl moieties to point outward to form a shell coated on the surface of NPs, and phosphate groups toward inside as the core via the water-in-oil (W/O) emulsion method. The additional Ca2+ could chelate to phosphate groups in the core to bind adjacent phosphate groups and further increased the stability of NPs (CP-Ca NPs). Phospholipid and glycocholate were modified on the surface of CP-Ca NPs to form hydrophilic corona coated CP-Ca NPs (Hc@CP-Ca NPs) and didn't change the structure of CP-Ca NPs. The NPs exhibited high encapsulation efficiency (>95%) and had high stability in the GI tract by reducing insulin release and protecting insulin from enzymatic degradation. Compared to free insulin, Hc@CP-Ca NPs demonstrated 31-fold higher cellular uptake in Caco-2 cells for 1 h incubation. Furthermore, the transepithelial transport efficiency of Hc@CP-Ca NPs was 12-fold higher than that of free insulin. Moreover, CP-Ca NPs and Hc@CP-Ca NPs generated a rapid-onset and long-lasting hypoglycemic effect following gavage in type 1 diabetic mellitus (T1DM) rats. The pharmacological activity and the relative bioavailability were increased to 13.5% and 12.2%, respectively. Thus, these results indicated that CHP assembled NPs may provide a promising potential for oral insulin delivery by protection and absorption promotion.

Why Am I Willing to Speak Up? The Impact of Spiritual Leadership on Employee Voice Behavior.

The sustainability of organizations highlights the significance of inspiring employees, especially their inner lives or spiritual identities, and leaders play a vital role. Consistent with social cognitive theory, the purpose of this paper is to explore the linking mechanisms and conditional processes underlying the relationship between spiritual leadership and employee voice behavior. Three-wave survey data were collected from 366 full-time employees and their line managers, and a moderated mediation analysis was performed. The results show that career success expectation fully mediates the relationship between spiritual leadership and employee voice behavior. Additionally, felt obligation is found to indirectly strengthen the effect of spiritual leadership on employee voice behavior via career success expectation. In light of the results, practical implications are provided for managers and future researchers to enhance the sustainability of organizations.

Career Adaptability, Work Engagement, and Employee Well-Being Among Chinese Employees: The Role of Guanxi.

The present study examined whether and how career adaptability predicts employee well-being (EWB) based on career construction theory. A three-wave questionnaire design was used to collect the data, and 338 employees participated in the study. The results suggest that career adaptability has a significant effect on work engagement, which, in turn, predicts EWB. In addition to developing a mediation model, we tested the effect of guanxi as a moderator on the former part of the model. Thus, a moderated-mediation model was constructed in this research. In addition to the finding of the mediating role of work engagement, the discussion of guanxi represents a more important novel aspect that draws attention to contextual factors that may shape how employees respond to career adaptability. The results revealed that the indirect effect of career adaptability on EWB through work engagement when guanxi is low is stronger than that when guanxi is high. Furthermore, we discuss the limitations of this study and the implications for future research on career adaptability and EWB.

Design, synthesis, and evaluation of fluorine and Naphthyridine-Based half-sandwich organoiridium/ruthenium complexes with bioimaging and anticancer activity.

A range of fluorine and naphthyridine-based half-sandwich iridium (III) and ruthenium (II) complexes were synthesized. The iridium complexes possessed excellent antiproliferative properties, a substantial improvement over cisplatin, especially the best 1C containing the fluorine atom and 2C containing the naphthyridine. On the contrary, the ruthenium complexes displayed much less antiproliferative activity. Two X-ray crystal structures were determined. The cytotoxicity of the complexes can be changed flexible by regulating the metal center and the ancillary ligands. The best complex 1C was chose to study further on the mechanism of action. The chemical reactivity such as hydrolysis, reaction with nucleobases, glutathione and catalytic conversion of NADH to NAD+, were investigated. Complex 1C can react with 9-ethylguanine (9-EtG) and catalyze oxidation of NADH. In addition, the self-luminescence of the complex 1C was also successfully used in confocal microscopy images for elucidating the subcellular localization. Complex 1C specifically targeted to lysosomes in A549 cancer cells and caused lysosomal damages and promote cathepsin B released. Flow cytometry studies confirmed that the biological effects of this type of complexes induced apoptosis, especially late apoptosis. Our results suggested that changes in the mitochondria membrane potential were responsible for apoptosis. The chemistry and biological studies has showed that this class of metal complexes are worthy of further exploration for the design of novel anticancer drugs.

Highly potent half-sandwich iridium and ruthenium complexes as lysosome-targeted imaging and anticancer agents.

In this study, six half-sandwich luminescent iridium (Ir) and ruthenium (Ru) anticancer complexes bearing P^P-chelating ligands 1,2-bis(diphenylphosphino)benzene (dppbz) and 1,8-bis(diphenylphosphino)naphthalene (dppn) were synthesized and characterized via1H-NMR spectroscopy, 31P-NMR spectroscopy, mass spectrometry, elemental analysis and X-ray crystallography. All the complexes displayed more potent anticancer activity than cisplatin towards A549 lung cancer cells and HeLa cervical cancer cells, especially the most potent iridium complex Ir3, which was 73 times more potent than cisplatin against A549 cells. Different from cisplatin, no nucleobase adducts of Ir3 were detected. With the help of the self-luminescence of complex Ir3 and confocal microscopy, it was observed that Ir3 efficiently penetrated into the A549 cells via energy-dependent active transport, and specifically accumulated in lysosomes, affected the permeabilization of the lysosomal membranes and induced caspase-dependent cell death through lysosomal damage. Both apoptosis and autophagy of the A549 cells were observed. The reactive oxygen species (ROS) elevation, reduction of the mitochondrial membrane potential and cell cycle arrest at the G0/G1 phase also contributed to the observed cytotoxicity of Ir3. We demonstrate that these half-sandwich Ir and Ru anticancer complexes have different anticancer mechanism of action from that of cisplatin, which can be developed as potential multifunctional theranostic platforms that combine bioimaging and anticancer capabilities.

Low-Cytotoxicity Fluorescent Probes Based on Anthracene Derivatives for Hydrogen Sulfide Detection.

Owing to the role of H2S in various biochemical processes and diseases, its accurate detection is a major research goal. Three artificial fluorescent probes based on 9-anthracenecarboxaldehyde derivatives were designed and synthesized. Their anion binding capacity was assessed by UV-Vis titration, fluorescence spectroscopy, HRMS, 1HNMR titration, and theoretical investigations. Although the anion-binding ability of compound 1 was insignificant, two compounds 2 and 3, containing benzene rings, were highly sensitive fluorescent probes for HS- among the various anions studied (HS-, F-, Cl-, Br-, I-, AcO-, H2PO4- , SO32- , Cys, GSH, and Hcy). This may be explained by the nucleophilic reaction between HS- and the electron-poor C=C double bond. Due to the presence of a nitro group, compound 3, with a nitrobenzene ring, showed stronger anion binding ability than that of compound 2. In addition, compound 1 had a proliferative effect on cells, and compounds 2 and 3 showed low cytotoxicity against MCF-7 cells in the concentration range of 0-150 µg·mL-1. Thus, compounds 2 and 3 can be used as biosensors for the detection of H2S in vivo and may be valuable for future applications.

Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity.

Zoledronate is a bisphosphonate that is widely used in the treatment of metabolic bone diseases. However, zoledronate induces significant nephrotoxicity associated with acute tubular necrosis and renal fibrosis when administered intravenously. There is speculation that zoledronate-induced nephrotoxicity may result from its pharmacological activity as an inhibitor of the mevalonate pathway but the molecular mechanisms are not fully understood. In this report, human proximal tubular HK-2 cells and mouse models were combined to dissect the molecular pathways underlying nephropathy caused by zoledronate treatments. Metabolomic and proteomic assays revealed that multiple cellular processes were significantly disrupted, including the TGFß pathway, fatty acid metabolism and small GTPase signaling in zoledronate-treated HK-2 cells (50 µM) as compared with those in controls. Zoledronate treatments in cells (50 µM) and mice (3 mg/kg) increased TGFß/Smad3 pathway activation to induce fibrosis and kidney injury, and specifically elevated lipid accumulation and expression of fibrotic proteins. Conversely, fatty acid transport protein Slc27a2 deficiency or co-administration of PPARA agonist fenofibrate (20 mg/kg) prevented zoledronate-induced lipid accumulation and kidney fibrosis in mice, indicating that over-expression of fatty acid transporter SLC27A2 and defective fatty acid ß-oxidation following zoledronate treatments were significant factors contributing to its nephrotoxicity. These pharmacological and genetic studies provide an important mechanistic insight into zoledronate-associated kidney toxicity that will aid in development of therapeutic prevention and treatment options for this nephropathy.

Association of in utero exposure to organochlorine pesticides with thyroid hormone levels in cord blood of newborns.

Organochlorine pesticides (OCPs) had been widely used in agriculture and disease prevention from the 1940s-1960s. Currently, OCPs are raising global concerns due to their associated prevalent contamination and adverse health effects, such as endocrine disruption. Several epidemiological studies have explored the underlying association of OCPs on thyroid hormone (TH) status in adults and newborns, but the results of studies performed on newborns are often inconclusive. This exploratory study was conducted with the purpose of assessing the potential association of the prenatal exposure to OCPs with the concentrations of TH in the cord blood of newborns from China. Cord blood and information on demographic characteristics were collected from 115 newborns between November 2013 and June 2014. The exposure levels of 17 OCPs were measured with a gas chromatography/mass spectrometry, and TH levels including free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were detected using electrochemiluminescence immunoassay methods. After adjusting for confounding factors (the age of pregnant mothers, education level, monthly household income, parity, and sex of the newborns), we found marginally significant inverse associations of cord plasma measurements of ∑hexachlorcyclohexanes (∑HCHs), 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene (ρ,ρ'-DDE) and methoxychlor with FT4 levels, but not with FT3 and TSH levels. Moreover, higher cord plasma levels of aldrin, dieldrin, ∑dichlorodiphenyltrichloroethanes (∑DDTs), ∑Drins, and ∑OCPs were found to be related to the increase in cord plasma TSH levels after the adjustment for confounders. The results of this exploratory study indicate that in utero exposure to certain OCPs may affect TH status in newborns, and therefore, pose potential effects on early human development. Further research, with larger sample sizes, should be conducted to confirm these findings.

Protective effect of the extract of Yi-Qi-Fu-Mai preparation on hypoxia-induced heart injury in mice.

Yi-Qi-Fu-Mai (YQFM) is extensively used clinically to treat cardiovascular diseases in China. To explore the anti-hypoxia effect of the extract of YQFM preparation (EYQFM), the EYQFM (1.4, 2.8, and 5.5 g·kg(-1)·d(-1)) was assessed for its heart-protective effect in a chronic intermittent hypoxia (CIH) animal model (oxygen pressure 7%-8%, 20 min per day) for 28 days of treatment. Betaloc (0.151 6 g·kg(-1)·d(-1)) was used as a positive control. The histopathological analyses of heart in CIH mice were conducted. Several cardiac state parameters, such as left ventricular ejection fractions (EF), stroke volume (SV), expression of creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured. The results showed that treatment with EYQFM markedly reversed swelling of the endothelial cells and vacuolization in the heart when compared with the model group. Further study demonstrated that EYQFM significantly improved ventricular myocardial contractility by increasing EF and SV. In addition, EYQFM inhibited the activity of CK, LDH, decreased the level of MDA and improved SOD activity. The results demonstrated that EYQFM significantly improved the tolerability of myocardium to hypoxia and ameliorated the cardiac damage in the CIH model.

Exposure to organochlorine pesticides and non-Hodgkin lymphoma: a meta-analysis of observational studies.

Growing evidence indicates that exposure to organochlorine pesticides (OCPs) could increase non-Hodgkin lymphoma (NHL) risk. However, results from epidemiological studies investigating this association remain controversial. We thus conducted a meta-analysis to quantitatively evaluate the association between OCP exposure and NHL risk. Relevant publications were searched in PubMed, Web of Science, and Embase and identified according to the inclusion criteria. Thirteen studies (6 nested case-control, 1 case-cohort, and 6 case-control) were selected for this meta-analysis. We used odds ratios (ORs) with 95% confidence intervals (CIs) to estimate the relationship between OCPs exposure and NHL risk. The summary OR for included studies was 1.40 (95% CI 1.27 to 1.56). No overall significant heterogeneity in the OR was observed (Ph = 0.253, I(2) = 12.6%). Furthermore, OR estimates in subgroup analyses were discussed, and strong associations were observed for dichlorodiphenyldichloroethylene (DDE, OR = 1.38, 95% CI 1.14 to 1.66), hexachlorocyclohexane (HCH, OR = 1.42, 95% CI 1.08 to 1.87), chlordane (OR = 1.93, 95% CI 1.51 to 2.48), and hexachlorobenzene (HCB, OR = 1.54, 95% CI 1.20 to 1.99). This meta-analysis had suggested that total OCPs of interest was significantly positively associated with NHL risk.