Camptothecin effectively treats obesity in mice through GDF15 induction.

Elevated circulating levels of growth differentiation factor 15 (GDF15) have been shown to reduce food intake and lower body weight through activation of hindbrain receptor glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) in rodents and nonhuman primates, thus endogenous induction of this peptide holds promise for obesity treatment. Here, through in silico drug-screening methods, we found that small molecule Camptothecin (CPT), a previously identified drug with potential antitumor activity, is a GDF15 inducer. Oral CPT administration increases circulating GDF15 levels in diet-induced obese (DIO) mice and genetic ob/ob mice, with elevated Gdf15 expression predominantly in the liver through activation of integrated stress response. In line with GDF15's anorectic effect, CPT suppresses food intake, thereby reducing body weight, blood glucose, and hepatic fat content in obese mice. Conversely, CPT loses these beneficial effects when Gdf15 is inhibited by a neutralizing antibody or AAV8-mediated liver-specific knockdown. Similarly, CPT failed to reduce food intake and body weight in GDF15's specific receptor GFRAL-deficient mice despite high levels of GDF15. Together, these results indicate that CPT is a promising anti-obesity agent through activation of GDF15-GFRAL pathway.

The cortical regions and white matter tracts underlying auditory comprehension in patients with primary brain tumor.

The comprehension of spoken language is one of the most essential language functions in humans. However, the neurological underpinnings of auditory comprehension remain under debate. Here we used multi-modal neuroimaging analyses on a group of patients with low-grade gliomas to localize cortical regions and white matter tracts responsible for auditory language comprehension. Region-of-interests and voxel-level whole-brain analyses showed that cortical areas in the posterior temporal lobe are crucial for language comprehension. The fiber integrity assessed with diffusion tensor imaging of the arcuate fasciculus and the inferior longitudinal fasciculus was strongly correlated with both auditory comprehension and the grey matter volume of the inferior temporal and middle temporal gyri. Together, our findings provide direct evidence for an integrated network of auditory comprehension whereby the superior temporal gyrus and sulcus, the posterior parts of the middle and inferior temporal gyri serve as auditory comprehension cortex, and the arcuate fasciculus and the inferior longitudinal fasciculus subserve as crucial structural connectivity. These findings provide critical evidence on the neural underpinnings of language comprehension.

Neohesperidin attenuates obesity by altering the composition of the gut microbiota in high-fat diet-fed mice.

Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier, and chronic inflammation. Neohesperidin (Neo), a natural polyphenol abundant in citrus fruits, is known for its preventative and therapeutic effects on numerous diseases. Here, we report that Neo administration attenuates weight gain, low-grade inflammation, and insulin resistance in mice fed high-fat diet (HFD). Also, Neo administration substantially restores gut barrier damage, metabolic endotoxemia, and systemic inflammation. Sequencing of 16S rRNA genes in fecal samples revealed that Neo administration reverses HFD-induced intestinal microbiota dysbiosis: an increase in the diversity of gut microbiota and alteration in the composition of intestinal microbiota (particularly in the relative abundances of Bacteroidetes and Firmicutes). Furthermore, systemic antibiotic treatment abolishes the beneficial effects of Neo in body weight control, suggesting that the effect of Neo on obesity attenuation largely depends on the gut microbiota. More importantly, we demonstrate that the impact of Neo on the regulation of obesity could be transferred from Neo-treated mice to HFD-fed mice via fecal microbiota transplantation. Collectively, our data highlight the efficacy of Neo as a prebiotic agent for attenuating obesity, implying a potential mechanism for gut microbiota mediated the beneficial effect of Neo.

Mitochondrial aconitase controls adipogenesis through mediation of cellular ATP production.

Mitochondrial aconitase (Aco2) catalyzes the conversion of citrate to isocitrate in the TCA cycle, which produces NADH and FADH2, driving synthesis of ATP through OXPHOS. In this study, to explore the relationship between adipogenesis and mitochondrial energy metabolism, we hypothesize that Aco2 may play a key role in the lipid synthesis. Here, we show that overexpression of Aco2 in 3T3-L1 cells significantly increased lipogenesis and adipogenesis, accompanied by elevated mitochondrial biogenesis and ATP production. However, when ATP is depleted by rotenone, an inhibitor of the respiratory chain, the promotive role of Aco2 in adipogenesis is abolished. In contrast to Aco2 overexpression, deficiency of Aco2 markedly reduced lipogenesis and adipogenesis, along with the decreased mitochondrial biogenesis and ATP production. Supplementation of isocitrate efficiently rescued the inhibitory effect of Aco2 deficiency. Similarly, the restorative effect of isocitrate was abolished in the presence of rotenone. Together, these results show that Aco2 sustains normal adipogenesis through mediating ATP production, revealing a potential mechanistic link between TCA cycle enzyme and lipid synthesis. Our work suggest that regulation of adipose tissue mitochondria function may be a potential way for combating abnormal adipogenesis related diseases such as obesity and lipodystrophy.

Glioma surgery with awake language mapping versus generalized anesthesia: a systematic review.

Awake craniotomy with language mapping is being increasingly applied to avoid postoperative language dysfunctions worldwide. However, the effectiveness and reliability of this technique remain unclear due to the paucity of studies comparing the awake craniotomy with general anesthesia. To determine the benefit of awake craniotomy for language, motor, and neurological functions, as well as other clinical outcomes, we searched Medline, Embase, the Cochrane Library, and the Chinese Biomedical Literature Database up to December 2019. Gray literatures were also searched. We included randomized and non-randomized controlled studies comparing awake craniotomy versus general anesthetic resection and reporting the language and neurological outcomes. Ten studies with 833 patients were included in the meta-analysis. The pooled risk ratio (RR) suggested no significant differences in language and neurological outcomes between general anesthesia group and awake craniotomy group without electrical stimulation. Awake craniotomy with electrical stimulation, however, was associated with improved late language and neurological outcomes (≥ 3 months) versus general anesthesia with pooled RR of 0.44 (95% CI = 0.20-0.96) and 0.49 (95% CI = 0.30-0.79), respectively. Awake craniotomy with electrical stimulation was also associated with better extent of resection with the pooled RR of 0.81 (95%CI = 0.71-0.92) and shorter hospital stay duration with the pooled weighted mean difference (WMD) of - 1.14 (95%CI = - 1.80 to - 0.48). This meta-analysis suggested that the application of awake craniotomy with electrical stimulation during glioma resection is associated with lower risks of long-term neurological and language deficits and higher extent of tumor resection, as well as shorter hospital stay duration.

Establishment and maintenance of a standardized glioma tissue bank: Huashan experience.

Cerebral glioma is the most common brain tumor as well as one of the top ten malignant tumors in human beings. In spite of the great progress on chemotherapy and radiotherapy as well as the surgery strategies during the past decades, the mortality and morbidity are still high. One of the major challenges is to explore the pathogenesis and invasion of glioma at various "omics" levels (such as proteomics or genomics) and the clinical implications of biomarkers for diagnosis, prognosis or treatment of glioma patients. Establishment of a standardized tissue bank with high quality biospecimens annotated with clinical information is pivotal to the solution of these questions as well as the drug development process and translational research on glioma. Therefore, based on previous experience of tissue banks, standardized protocols for sample collection and storage were developed. We also developed two systems for glioma patient and sample management, a local database for medical records and a local image database for medical images. For future set-up of a regional biobank network in Shanghai, we also founded a centralized database for medical records. Hence we established a standardized glioma tissue bank with sufficient clinical data and medical images in Huashan Hospital. By September, 2013, tissues samples from 1,326 cases were collected. Histological diagnosis revealed that 73 % were astrocytic tumors, 17 % were oligodendroglial tumors, 2 % were oligoastrocytic tumors, 4 % were ependymal tumors and 4 % were other central nervous system neoplasms.

[Efficacy of combination antiviral therapy following childbirth in pregnant HBV carriers receiving telbivudine for prevention of mother-to-child transmission].

OBJECTIVE: To observe the clinical efficacy of combination therapy with peg-IFNalpha and adefovir (CPIA) in women who were hepatfis B virus (HBV) carriers and had just given birth and received telbivudine (LdT) during pregnancy for prevention of mother-to-child transmission. METHODS: One-hundred-and-fifty third trimester-pregnant women who were HBV carriers with highly-viremic were treated with LdT until time of birth. After delivery, those women with alanine aminotransferase (ALT) level exceeding two times the upper limit of normal and HBV DNA level that had decreased more than 31 gIU/mL or hepatitis B e antigen (HBeAg) titer that had decreased more than 50% were switched to CPIA for 96 weeks. RESULTS: Following delivery, 45 of the women were switched to the CPIA treatment, of which 91.1% (41/45) achieved virological response, 55.6% (25/45) achieved HBeAg clearance or seroconversion, and 26.7% (12/45) achieved hepatitis B surface antigen (HBsAg) clearance or seroconversion.The immediate post-delivery (and pre-CPIA) levels of HBeAg and HBV DNA were negatively associated with HBeAg clearance. Ninety-eight of the total study participants stopped the LdT treatment and there were no cases of significant deterioration of liver function. CONCLUSION: Pregnant women who are HBV carriers and receive LdT for protection against mother-to-child transmission, and who show significant ALT elevation and decreased HBeAg titer and/or reduced HBV DNA after delivery, may be good candidates for the CPIA therapy following delivery.

Localizing hand motor area using resting-state fMRI: validated with direct cortical stimulation.

BACKGROUND: Resting-state functional magnetic resonance imaging (R-fMRI) is a promising tool in clinical application, especially in presurgical mapping for neurosurgery. This study aimed to investigate the sensitivity and specificity of R-fMRI in the localization of hand motor area in patients with brain tumors validated by direct cortical stimulation (DCS). We also compared this technique to task-based blood oxygenation level-dependent (BOLD) fMRI (T-fMRI). METHODS: R-fMRI and T-fMRI were acquired from 17 patients with brain tumors. The cortex sites of the hand motor area were recorded by DCS. Site-by-site comparisons between R-fMRI/T-fMRI and DCS were performed to calculate R-fMRI and T-fMRI sensitivity and specificity using DCS as a "gold standard". R-fMRI and T-fMRI performances were compared statistically RESULTS: A total of 609 cortex sites were tested with DCS and compared with R-fMRI findings in 17 patients. For hand motor area localization, R-fMRI sensitivity and specificity were 90.91 and 89.41 %, respectively. Given that two subjects could not comply with T-fMRI, 520 DCS sites were compared with T-fMRI findings in 15 patients. The sensitivity and specificity of T-fMRI were 78.57 and 84.76 %, respectively. In the 15 patients who successfully underwent both R-fMRI and T-fMRI, there was no statistical difference in sensitivity or specificity between the two methods (p = 0.3198 and p = 0.1431, respectively) CONCLUSIONS: R-fMRI sensitivity and specificity are high for localizing hand motor area and even equivalent or slightly higher compared with T-fMRI. Given its convenience for patients, R-fMRI is a promising substitute for T-fMRI for presurgical mapping.

Deficiency of ASGR1 promotes liver injury by increasing GP73-mediated hepatic endoplasmic reticulum stress.

Liver injury is a core pathological process in the majority of liver diseases, yet the genetic factors predisposing individuals to its initiation and progression remain poorly understood. Here we show that asialoglycoprotein receptor 1 (ASGR1), a lectin specifically expressed in the liver, is downregulated in patients with liver fibrosis or cirrhosis and male mice with liver injury. ASGR1 deficiency exacerbates while its overexpression mitigates acetaminophen-induced acute and CCl4-induced chronic liver injuries in male mice. Mechanistically, ASGR1 binds to an endoplasmic reticulum stress mediator GP73 and facilitates its lysosomal degradation. ASGR1 depletion increases circulating GP73 levels and promotes the interaction between GP73 and BIP to activate endoplasmic reticulum stress, leading to liver injury. Neutralization of GP73 not only attenuates ASGR1 deficiency-induced liver injuries but also improves survival in mice received a lethal dose of acetaminophen. Collectively, these findings identify ASGR1 as a potential genetic determinant of susceptibility to liver injury and propose it as a therapeutic target for the treatment of liver injury.

Bone marrow suppression or active proliferation? An analysis of neutropenia after pegylated interferon treatment of patients with chronic hepatitis C.

BACKGROUND: Neutropenia is a common adverse effect of the treatment of chronic hepatitis C with pegylated interferon and ribavirin. However, the mechanism involved is unknown. The present study aimed to investigate the cause of treatment-induced neutropenia by determining cytokine levels in plasma and in bone marrow smears. METHODS: Fifteen patients with chronic hepatitis C were enrolled in this study. Plasma cytokine levels were determined using the Luminex assay before and during treatment. We simultaneously determined the levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and 7 other cytokines, and performed bone marrow cytology when blood cell counts indicated neutropenia. RESULTS: Only 1 bone marrow smear indicated a low cell proliferation level, whereas active proliferation was observed in the remaining 14 patients. The levels of G-CSF, GM-CSF, interleukin (IL)-2, IL-4, IL-6, and interferon (IFN)-γ decreased significantly in patients with neutropenia (p < 0.05). In contrast, the levels of IL-8, IL-10, and tumor necrosis factor (TNF)-α showed no significant change (p = 0.713, 0.930, 0.833, respectively) before or after treatment. CONCLUSIONS: The bone marrow of most patients with IFN-induced neutropenia showed active cell proliferation. Elevated G-CSF and GM-CSF but not bone marrow suppression was observed along with neutropenia after pegylated interferon treatment, suggesting a causative role of G-CSF and GM-CSF in neutropenia.

[Efficacy and safety of peginterferon alfa-2a (40 kd) plus adefovir for 96 weeks in HBeAg-negative chronic hepatitis B patients].

OBJECTIVE: To investigate the efficacy and safety of an extended course (96-week) of combination treatment with peginterferon alfa-2a (Peg-IFNa-2a; 40 kd] plus adefovir (ADV) for treating chronic hepatitis B (CHB) in Chinese patients with negativity for hepatitis B e antigen (HBeAg). METHODS: A total of 25 consecutive patients with HBeAg-negative CHB were administered Peg-IFNa-2a (135-180 mug/week) plus ADV (10 mg/day) for 96 weeks. All patients were followed-up for 24 weeks after treatment completion. Levels of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HbsAg) were measured by fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescent microparticle immunoassay, respectively, at 12-week intervals throughout the treatment course and at the end-of-follow-up (week 120). Patients underwent serological analysis at 3-6 month intervals during treatment and follow-up to evaluate occurrence of adverse events; serological parameters included blood count, markers of liver, kidney and thyroid function, and levels of autoantibodies and creatine kinase. RESULTS: For all patients, the 96-week course of Peg-IFNa-2a plus ADV reduced the level of HBV DNA below the detection threshold (less than 500 copies/ml by FQ-PCR). The overall rate of HBsAg seroconversion was 12% (3/25) at week 48, 28% (7/25) at week 96, and 32% (8/25) at week 120. The occurrences of adverse events were similar at week 48 and week 96. CONCLUSION: The extended-course Peg-IFNa-2a plus ADV combination therapy achieved a 100% virological response and better rates of HBsAg seroconversion than 48 weeks of therapy, without a decrease in safety.

[Changes in lymphocyte surface expression of CD8 and CD38 molecules in peripheral blood of inactive HBsAg carriers following pegylated interferon a-2a therapy].

OBJECTIVE: To investigate the effects of pegylated interferon a-2a (Peg-INFa-2a) treatment on expression of CD8 and CD38 surface molecules on lymphocytes from peripheral blood of inactive hepatitis B surface antigen (HBsAg) carriers. METHODS: Forty-four patients with hepatitis B virus (HBV) chronic infection (CHB) received a 48-week course of Peg-INFa-2a treatment, with 30 administered 135 mug/week and 14 administered 180 mug/week. Every 12 weeks of treatment, the subjects were assessed for HBsAg titer, presence of anti-hepatitis B e (HBe) antibody, serum alanine amino transaminase (ALT) levels, and lymphocyte surface expression of CD8 and CD38 molecules. Patients were classified as responders and non-responders according to standard parameters. Dynamic differences between the two groups over time were assessed by multivariate repeated measures ANOVA with Greenhouse-Geisser correction and differences at single time points were assessed by univariate ANOVA. Linear regression analysis was performed to evaluate the relationship of two variables. RESULTS: The responders showed a significantly higher increase in ALT at week 12 (60.75+/-24.95 U/L vs. non-responders: 37.03+/-18.45 U/L; t = 2.905, P less than 0.01) and significantly higher proportion of CD8+CD38+ cells at week 24 (71.20+/-11.70% vs. non-responders: 56.79+/-7.72%; F = 23.941, P less than 0.01). The decline in level of HBsAg at week 24 was positively correlated with the increase in ALT level at week 12 (r = 0.386, P less than 0.01) and with expression levels of CD8 and CD38 molecules on lymphocytes at week 24 (r = 0.397, P less than 0.01). CONCLUSION: Lower baseline levels of HBsAg correlated to better Peg-INFa-2a-related HBsAg clearance. Increased expression of CD8 and CD38 on lymphocytes is suggestive of intensive cellular immunity in CHB patients and may be related to HBV-induced hepatocyte damage and may promote the HBsAg clearance.

GDF15 is a major determinant of ketogenic diet-induced weight loss.

A ketogenic diet (KD) has been promoted as an obesity management diet, yet its underlying mechanism remains elusive. Here we show that KD reduces energy intake and body weight in humans, pigs, and mice, accompanied by elevated circulating growth differentiation factor 15 (GDF15). In GDF15- or its receptor GFRAL-deficient mice, these effects of KD disappeared, demonstrating an essential role of GDF15-GFRAL signaling in KD-mediated weight loss. Gdf15 mRNA level increases in hepatocytes upon KD feeding, and knockdown of Gdf15 by AAV8 abrogated the obesity management effect of KD in mice, corroborating a hepatic origin of GDF15 production. We show that KD activates hepatic PPARγ, which directly binds to the regulatory region of Gdf15, increasing its transcription and production. Hepatic Pparγ-knockout mice show low levels of plasma GDF15 and significantly diminished obesity management effects of KD, which could be restored by either hepatic Gdf15 overexpression or recombinant GDF15 administration. Collectively, our study reveals a previously unexplored GDF15-dependent mechanism underlying KD-mediated obesity management.

Identification of dendrobium species used for herbal medicines based on ribosomal DNA internal transcribed spacer sequence.

Stems of genus Dendrobium (Orchidaceae) have been traditionally used as an herbal medicine (Dendrobii Herba) in Eastern Asia. Although demand for Dendrobium is increasing rapidly, wild resources are decreasing due to over-collection. This study aimed to identify plant sources of Dendrobii Herba on the market based on sequences of the internal transcribed spacer (ITS) regions of nuclear ribosomal DNA. We constructed an ITS1-5.8S-ITS2 sequence database of 196 Dendrobium species, and the database was employed to identify 21 herbal samples. We found that 13 Dendrobium species (D. catenatum, D. cucullatum, D. denudans, D. devonianum, D. eriiflorum, D. hancockii, D. linawianum, D. lituiflorum, D. loddigesii, D. polyanthum, D. primulinum, D. regium, and D. transparens) were possibly used as plant sources of Dendrobii Herba, and unidentified species allied to D. denudans, D. eriiflorum, D. gregulus, or D. hemimelanoglossum were also used as sources. Furthermore, it is clear that D. catenatum is one of the most important sources of Dendrobii Herba (5 out of 21 samples).

[Preliminary application of 3.0 T intraoperative magnetic resonance imaging neuronavigation system in China].

OBJECTIVE: To report the preliminary experience in clinical application of 3.0 T intraoperative magnetic resonance imaging (iMRI) neuronavigation system in China. METHODS: From September 2010 to March 2011, a consecutive series of 122 patients with intracranial lesions underwent operations in guidance with 3.0 T iMRI. A retrospective analysis was conducted regarding clinical efficiency. RESULTS: Among 122 procedures, the numbers of intraoperative scanning were 2 - 4 times with an average of 2.6. The qualities of images were excellent. Due to the discovery and further possibility of resection of residual tumors, the ratio of gross total resection was increased from 71.7% to 90.0% in cerebral gliomas (n = 60), while from 75.9% to 93.1% in macroadenomas (n = 29). There were 6.7% of all patients occurred postoperative paralysis, but only 3.3% of patients had persistent paralysis at 1 - 2 months follow-up. There was no iMRI-related adverse event occurred. During the same period, more than 2500 patients underwent diagnostic MRI scanning. CONCLUSIONS: 3.0 T iMRI neuronavigation system provides high-quality intraoperative structural, functional and metabolic images for real time tumor resection control and accurate functional preservation, resulting in an improvement in maximal safe brain surgery. The system is cost-effective.

[Awake craniotomy and intraoperative language cortical mapping for eloquent cerebral glioma resection: preliminary clinical practice in 3.0 T intraoperative magnetic resonance imaging integrated surgical suite].

OBJECTIVES: To evaluate preliminary clinical experience for combining awake craniotomy and intraoperative language brain mapping within the integrated 3.0 T intraoperative magnetic resonance imaging (iMRI) suite. METHODS: From December 2010 to April 2011, 11 right hand-dominant patients with left glioma were involved in, or adjacent to, eloquent cortex was carried out awake craniotomies with cortical stimulation within an integrated 3.0 T iMRI suite. Aphasia battery of Chinese was used to test the language function before the operation. During the procedure, after the occipital, temporal, and supraorbital nerves were blocked by the anesthesiologists, the head was fixed with a custom high-field MRI-compatible head holder. The skull and dura was opened as usual and language brain mapping was then performed. Language testing followed a set protocol: counting numbers from 1 to 50, naming objects, reading single words. Resection of the tumor was guided by neuronavigation system and continued until eloquent areas were encountered or the margin of assessment was reached. An interdissection MRI was acquired to evaluate the glioma removal in a movable MRI scanner after minimal draping. Meanwhile, adverse effects caused by electrical stimulation and iMRI were recorded. The follow-up speech tests were assessed on 7th day and 1 month at least after the operation. RESULTS: The combined use of 3.0 T iMRI and awake craniotomy was performed safely in all patients. No adverse effects were reported. The duration of surgery was prolonged by 2 to 4 h. The patients' perception of iMRI during surgery was favorable. First-look MRI studies led to further resection attempts in 6/11 cases as well as a 3/11 increase in the number of gross-total resections. One week after surgery, baseline language function worsened in 4 cases. However, no patients had a persistent language deficit one month after surgery. CONCLUSIONS: Awake craniotomy and direct cortical electrical stimulation can be performed safely and effectively within a 3.0 T iMRI suite. The combination of high-field iMRI and awake craniotomy may facilitate safe removal of eloquent glioma.

[Influence of Different Soil Conditioner on the Transfer and Transformation of Cadmium and Phthalate Esters in Soil].

This study examines the existing common form of soil pollution, combined organic and inorganic pollution. Cadmium (Cd) is the most important inorganic element in soil pollution. Due to the widespread use of plastic film, phthalates have become the main organic pollutants in soil. Pot experiments were conducted with purple soil from southwest China, and Chinese cabbage was used as a biological indicator. Different concentration gradients of Cd and diethylhexyl phthalate (DEHP) was used as foreign pollutants. The soil was treated with one of the six common soil conditioners, namely potassium feldspar powder, oyster shell powder, biological carbon powder (biochar), calcium, potassium carbonate, and calcium phosphate, to examine the effect of conditioners on cadmium morphology, DEHP content in contaminated soil, and cadmium and DEHP absorption in Chinese cabbage. The results showed that biochar is the optimal soil conditioner for the remediation of cadmium-phthalate composite pollution in purple soil. Subsequently, the effects of soil biochar content on cadmium pollution and phthalate ester migration were studied. Uncontaminated control soil, Cd-contaminated soil, and DEHP-contaminated soil were examined by pot experiments, and biochar treatments with mass fraction of 0%, 0.5%, 1%, 3%, and 5% added to cadmium contaminated soil were used to determine its influence on Cd morphology and DEHP content of contaminated soil.

Phthalate esters in biota, air and water in an agricultural area of western China, with emphasis on bioaccumulation and human exposure.

Phthalate esters (PAEs) have been shown to be ubiquitous in abiotic and biotic environmental compartments; however, information about bioaccumulation behavior and human exposure, both via environmental exposure and the diet, are limited. Herein, we report the concentrations and composition profiles of phthalate esters (PAEs) in biological samples, river water, indoor air, and outdoor air samples collected from an agricultural site in western China. Dibutyl phthalate (DNBP) occupied a relatively high abundance in biological samples, discrepant with the environmental samples in which di-(2-ethylhexyl) phthalate (DEHP) was the dominant congener. Significant correlations (P < 0.05) were observed between the biota and river water samples, indicating that river water heavily influenced PAE accumulation in biological samples. The mean log Bioaccumulation Factors (BAFs) varied from 0.91 to 2.96, which implies that most PAE congeners are not likely to accumulate in organisms. No obvious trends were observed between log octanol-water partition coefficient (KOW) and log BAF values, nor between log octanol-air partition coefficient (KOW) and biota-air accumulation factors (BAAFs). Nevertheless, the calculated log air-water partitioning factors (AWPFs) of diethyl phthalate (DEP), dimethyl phthalate (DMP), and butyl benzyl phthalate (BBP) were similar to predicted values whereas those for diisobutyl phthalate (DIBP), DNBP and DEHP were significantly higher. The estimated daily intakes of PAEs via food ingestion and environmental exposure were 15, 9.4 and 1.2 ng/kg-bw/day in toddlers, children and adults, respectively, laying at the low end of the reported data and well below the reference dose.

A Potential Nutraceutical Candidate Lactucin Inhibits Adipogenesis through Downregulation of JAK2/STAT3 Signaling Pathway-Mediated Mitotic Clonal Expansion.

The prevalence of obesity has increased dramatically worldwide in the past ~50 years. Searching for safe and effective anti-obesity strategies are urgently needed. Lactucin, a plant-derived natural small molecule, is known for anti-malaria and anti-hyperalgesia. The study is to investigate whether lactucin plays a key role in adipogenesis. To this end, in vivo male C57BL/6 mice fed a high-fat diet (HFD) were treated with 20 mg/kg/day of lactucin or vehicle by gavage for seven weeks. Compared with vehicle-treated controls, Lactucin-treated mice showed lower body mass and mass of adipose tissue. Consistently, in vitro 3T3-L1 cells were treated with 20 µM of lactucin. Compared to controls, lactucin-treated cells showed significantly less lipid accumulation during adipocyte differentiation and lower levels of lipid synthesis markers. Mechanistically, we showed the anti-adipogenic property of lactucin was largely limited to the early stage of adipogenesis. Lactucin-treated cells fail to undergo mitotic clonal expansion (MCE). Further studies demonstrate that lactucin-induced MCE arrests might result from reduced phosphorylation of JAK2 and STAT3. We then asked whether activation of JAK2/STAT3 would restore the inhibitory effect of lactucin on adipogenesis with pharmacological STAT3 activator colivelin. Our results revealed similar levels of lipid accumulation between lactucin-treated cells and controls in the presence of colivelin, indicating that inactivation of STAT3 is the limiting factor for the anti-adipogenesis of lactucin in these cells. Together, our results provide the indication that lactucin exerts an anti-adipogenesis effect, which may open new therapeutic options for obesity.

Organophosphate esters in biota, water, and air from an agricultural area of Chongqing, western China: Concentrations, composition profiles, partition and human exposure.

We measured the concentrations of organophosphate esters (OPEs) in some biotic samples which can serve as human foodstuffs and ambient environments including air and river water from an agricultural area of Chongqing, western China. Fish samples exhibited highest OPEs levels (960 ng/g lipid weight) among the biota, followed by chicken (676 ng/g lw), cattle (545 ng/g lw) and pigs (535 ng/g lw). Tributyl phosphate (TNBP), tris (2-methylpropyl) (TIBP) and chlorinated OPEs were the major analogs in biotic samples, which appeared similar with the patterns from river water and outdoor air, but apparently different from indoor air. To further investigate the influence of ambient environment on the distribution of OPEs in biota, we analyzed the correlation between OPEs concentrations in ambient environment and biological samples, and the results revealed that most of the samples (except for pig samples) heavily correlated with outdoor air, whereas only fish and cattle samples were strongly correlated with river water. The partitioning behaviors of OPEs among biota, air and river water were also studied through calculating the biota-water accumulation factors (BWAFs), biota-air accumulation factors (BAAFs) and air-water partitioning factor (AWPFs). Significantly linear correlations (P < 0.05) were observed between log (BWAFs) and log (KOW) values, and between log (AWPFs) and log H (Henry's law constants), nevertheless log (BAAFs) was increasing along with the log (KOA) values. The daily intake (DI) values were estimated via foodstuffs ingestion and environmental exposure. The estimated DI values of OPEs from food and ambient environments were 1.78 ng/kg-bw/day, 1.23 ng/kg-bw/day and 1.42 ng/kg-bw/day in toddlers, children and adults, respectively, which lay at the low end of the reported data and well below the reference dose (RfD).