Progress of immune checkpoint inhibitors therapy for non-small cell lung cancer with liver metastases.

Nearly one-fifth of patients with non-small cell Lung Cancer (NSCLC) will develop liver metastases (LMs), and the overall treatment strategy of LMs will directly affect the survival of patients. However, some retrospective studies have found that patients receiving chemotherapy or targeted therapy have a poorer prognosis once LMs develop. In recent years, multiple randomised controlled trials (RCTS) have shown significant improvements in outcomes for patients with advanced lung cancer following the introduction of immune checkpoint inhibitors (ICIs) compared to conventional chemotherapy. ICIs is safe and effective in patients with LMs, although patients with LMs are mostly underrepresented in randomised clinical trials. However, NSCLC patients with LMs have a significantly worse prognosis than those without LMs when treated with ICIs, and the mechanism by which LMs induce systemic anti-tumour immunity reduction is unknown, so the management of LMs in patients with NSCLC is a clinical challenge that requires more optimised therapies to achieve effective disease control. In this review, we summarised the mechanism of ICIs in the treatment of LMs, the clinical research and treatment progress of ICIs and their combination with other therapies in patients with LMs from NSCLC.

Elderly patients with advanced HER2-positive breast cancer with liver metastases benefit from low dose disitamab vedotin (RC48): case series and literature review.

Currently, although some antibody-drug conjugates have been shown to be safe and effective in the treatment of drug-resistant relapsed human epidermal growth factor receptor 2 (HER2)-positive (IHC 3+ or IHC 2+/fluorescence in situ hybridization+) breast cancer, they are already approved for clinical use in China. But the clinical needs of advanced HER2-positive patients cannot be met due to adverse reactions, drug resistance, drug accessibility and other problems, thus affecting the prognosis of patients. In particular, the representation of elderly and frail patients in randomized clinical trials is significantly under-represented. We report on two elderly women with breast cancer who developed recurrent metastatic lesions after breast cancer surgery and were again confirmed HER2-positive by histopathology and immunohistochemistry. They all developed multiple metastases in the liver after second- or third-line anti-HER2 therapy. Subsequent treatment with RC48 produced good responses and tolerable adverse reactions. One patient obtained progression-free survival for more than 7 months. Based on preliminary evidence, this study shows that RC48 in HER2-positive breast cancer with liver metastases can achieve rapid remission, thereby reducing tumor load and improving patients' quality of life. In particular, RC48 has low side effects and can be well tolerated by elderly patients after dose adjustment, providing them with treatment opportunities. It needs to be further discussed in the future research.

Polychlorinated biphenyls exposure and type 2 diabetes: Molecular mechanism that causes insulin resistance and islet damage.

Polychlorinated biphenyls (PCBs) are typical persistent organic pollutants that have been associated with type 2 diabetes (T2DM) in cohort studies. This review aims to comprehensively assess the molecular mechanisms of PCBs-induced T2DM. Recent progress has been made in the research of PCBs in liver tissue, adipose tissue, and other tissues. By influencing the function of nuclear receptors, such as the aryl hydrocarbon receptor (AhR), pregnancy X receptor (PXR), and peroxisome proliferator activated receptor γ (PPARγ), as well as the inflammatory response, PCBs disrupt the balance of hepatic glucose and lipid metabolism. This is associated with insulin resistance (IR) in the target organ of insulin. Through androgen receptor (AR), estrogen receptor α/ß (ERα/ß), and pancreato-duodenal-homeobox gene-1 (PDX-1), PCBs affect the secretion of insulin and increase blood glucose. Thus, this review is a discussion on the relationship between PCBs exposure and the pathogenesis of T2DM. It is hoped to provide basic concepts for diabetes research and disease treatment.

Relationship between phthalates exposure, risk of decreased ovarian reserve, and oxidative stress levels.

Phthalates (PAEs), a group of environmental endocrine disruptors, are associated with oxidative stress and have adverse effects on female ovarian reserves. However, this association has been poorly investigated, particularly with respect to clinical evidence. In this study, we provided clinical evidence of a relationship between exposure levels of PAEs, oxidative stress and decreased ovarian reserve (DOR). Firstly, the urinary concentrations of metabolites of PAEs were measured by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH), and the biomarkers of oxidative stress, malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), were determined. Finally, statistical analyses were conducted to describe the relationship between the PAEs exposure, oxidative stress and DOR. We found that the levels of monomethyl phthalate (MMP), monoisobutyl phthalate (MiBP), mono-(2-ethylhexyl) phthalate (MEHP), and mono-(2-ethyl-5-hydroxypentyl) phthalate (MECPP) in the DOR group were significantly higher than those in the control group. There was a significant negative association between AMH and MMP, MiBP levels. and a significant positive association between FSH and MMP levels. PAEs exposure was also associated with a significant increase in MDA levels and decrease in SOD levels. In conclusion, the exposure of PAEs was closely associated with DOR, potentially mediated by oxidative stress pathways; however, small sample size was a limitation in this study.

Efficacy of cognitive behavioural therapy for insomnia or sleep disturbance in pregnant women: A systematic review ad meta-analysis.

During pregnancy many women may experience negative emotions and sleep disturbances. This systematic review and meta-analysis was conducted to assess the efficacy of cognitive behavioural therapy for insomnia (CBT-I) or sleep disturbance in pregnant women. From the earliest available publications to 15 April 2022, seven electronic literature databases were searched: PubMed, Web of Science, Cochrane Library, Embase, Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Database for Chinese Science and Technology Journal. Randomised controlled trials of CBT-I in pregnant women with insomnia or sleep disorders were included. The methodological bias of the included studies was assessed using the Cochrane risk of bias tool. The meta-analysis was performed using RevMan 5.4 software. Stata Statistical Software: Release 15 was used for sensitivity analysis and publication bias. We included eight randomised controlled trials involving 743 pregnant women. Meta-analysis showed that, compared with the control group, CBT-I significantly improved the Insomnia Severity Index (mean difference [MD] = -4.25, 95% confidence interval [CI, -6.32, -2.19], p < 0.001), The Pittsburgh Sleep Quality Index (MD = -3.30, 95% CI [-4.81, -1.79], p < 0.001), sleep onset latency (standardised mean difference [SMD] = -1.25, 95% CI [-2.01, -0.50], p = 0.001), anxiety (SMD = -0.99, 95% CI [-1.32, -0.67], p < 0.001), and depression (SMD = -0.40, 95% CI [-0.72, -0.07], p = 0.02). No significant differences were found in total sleep time (SMD = 0.31, 95% CI [-0.54, 1.17], p = 0.47) and sleep efficiency (SMD = 0.80, 95% CI [-0.53, 2.13], p = 0.24). CBT-I significantly improved pregnant women's sleep quality, insomnia severity, depression, and anxiety. This meta-analysis provides evidence that CBT-I is valid for insomnia or sleep disturbances during pregnancy.

Melatonin mediates elevated carbon dioxide-induced photosynthesis and thermotolerance in tomato.

Increasing carbon dioxide (CO2 ) promotes photosynthesis and mitigates heat stress-induced deleterious effects on plants, but the regulatory mechanisms remain largely unknown. Here, we found that tomato (Solanum lycopersicum L.) plants treated with high atmospheric CO2 concentrations (600, 800, and 1000 µmol mol-1 ) accumulated increased levels of melatonin (N-acetyl-5-methoxy tryptamine) in their leaves and this response is conserved across many plant species, including Arabidopsis, rice, wheat, mustard, cucumber, watermelon, melon, and hot pepper. Elevated CO2 (eCO2 ; 800 µmol mol-1 ) caused a 6.8-fold increase in leaf melatonin content, and eCO2 -induced melatonin biosynthesis preferentially occurred through chloroplast biosynthetic pathways in tomato plants. Crucially, manipulation of endogenous melatonin levels by genetic means affected the eCO2 -induced accumulation of sugar and starch in tomato leaves. Furthermore, net photosynthetic rate, maximum photochemical efficiency of photosystem II, and transcript levels of chloroplast- and nuclear-encoded photosynthetic genes, such as rbcL, rbcS, rbcA, psaD, petB, and atpA, significantly increased in COMT1 overexpressing (COMT1-OE) tomato plants, but not in melatonin-deficient comt1 mutants at eCO2 conditions. While eCO2 enhanced plant tolerance to heat stress (42°C) in wild-type and COMT1-OE, melatonin deficiency compromised eCO2 -induced thermotolerance in comt1 plants. The expression of heat shock proteins genes increased in COMT1-OE but not in comt1 plants in response to eCO2 under heat stress. Further analysis revealed that eCO2 -induced thermotolerance was closely linked to the melatonin-dependent regulation of reactive oxygen species, redox homeostasis, cellular protein protection, and phytohormone metabolism. This study unveiled a crucial mechanism of elevated CO2 -induced thermotolerance in which melatonin acts as an essential endogenous signaling molecule in tomato plants.

Quasi-dendritic sulfonate-based organic small molecule for high-quality NIR-II bone-targeted imaging.

The visualization of bone imaging in vivo is of great significance for the understanding of some bone-related diseases or physiological processes. Herein, a bone-targeted NIR-II small molecule (TTQF-SO3), which was modified with multiple sulfonate groups, was successfully fabricated for the second near-infrared (NIR-II) bone imaging. In vitro studies revealed that TTQF-SO3 showed high affinity for hydroxyapatite and excellent macrophage accumulation ability. In in vivo assays, TTQF-SO3 displayed high bone uptake ability and high NIR-II bone imaging quality, demonstrating the specific bone-targeting ability of the sulfonate-containing probe. In addition, the noninvasive NIR-II imaging detection in bone calcium loss was successfully verified in osteoporosis mice models. Moreover, the negative charge characteristic of TTQF-SO3 showed efficient lymphoid enrichment in living mice by intravenous injection. Overall, these warrant that our TTQF-SO3 is an optimal bone-targeted diagnostic agent for high-quality NIR-II imaging, highlighting its potential promise for clinical translation.

Bu-Shen-Tian-Jing formulas alleviate the mitochondrial damage induced by oxidative stress in ovarian granulosa cells exposed to DEHP through the HDAC3-HSP90AA pathway.

CONTEXT: di-(2-Ethylhexyl) phthalate (DEHP) has potential reproductive toxicity. Bu-Shen-Tian-Jing formulations (BSTJFs) are beneficial for female reproductive capacity. However, BSTJF2 has much lower cytotoxicity than BSTJF1. OBJECTIVE: To investigate the effects of BSTJFs on ovarian granulosa cells exposed to DEHP and determine the potential molecular mechanisms. METHODS AND MATERIALS: Human granulosa-like tumor cell line (KGN) cells were divided into control, DEHP, BSTJF1 and BSTJF2 groups. The DEHP group were given 1 µM DEHP for 24 h. They were then given BSTJF1 at 200 µg/mL or BSTJF2 at 100 µg/mL for 24 h. The control group was treated with the same concentration of DMSO (0.1%). Oxidative stress and mitochondrial function were measured. The mRNA and protein expression levels of HDAC3 and HSP90AA were determined. Integrative network pharmacology analysis of BSTJF2 was also performed. RESULTS: DEHP (1 µM) significantly suppressed the proliferation of KGN cells by 17%, significantly increased ROS levels by 28% and MDA levels by 47%, significantly decreased MMP levels by 22% and mtDNA copy by 30%. DEHP significantly increased protein expression of HDAC3 by 21%and HSP90AA by 64%. All these changes were significantly reversed by BSTJFs. Integrative network pharmacology analysis revealed HSP90AA was a key target (degree = 8). Both RGFP966 and BSTJF2 significantly reversed the increased expression of HDAC3 and HSP90AA, attenuated oxidative stress, and mitochondrial damage which were induced by DEHP. CONCLUSION: BSTJFs might have therapeutic potential on oxidative stress and mitochondrial damage through the HDAC3/HSP90AA pathway which encourages further clinical trials.

Severe intrahepatic cholestasis of pregnancy due to a Sertoli-Leydig cell tumour in a woman with polycystic ovary syndrome: a case report.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a common gestational complication characterized by pruritus and elevated bile acids, usually occurring in the third trimester when the serum estrogen and progesterone levels are highest. Hyperandrogenism during pregnancy is a pathological state that is mostly induced by polycystic ovary syndrome (PCOS) but rarely by concomitant androgen-secreting ovarian tumours. To date, no correlation has been drawn between ICP and hyperandrogenism. CASE PRESENTATION: Here, we present a rare case of early-onset severe ICP in a PCOS patient conceived via in vitro fertilization-embryo transfer, with worsening hirsutism and acne due to high levels of testosterone and dehydroepiandrosterone sulphate, both of which were produced by a fast-growing ovarian Sertoli-Leydig cell tumour. Her serum estradiol was also very high, which was speculated to be converted from the circulating androgens by the placenta. She had preterm premature rupture of membranes and delivered at 30 weeks, followed by a rapid remission of ICP as her serum estradiol dropped. However, the excessive androgens did not retreat until the large ovarian tumour was surgically removed. CONCLUSION: This unusual case highlights the concurrence of original hyperandrogenism and subsequent hyperestrogenism during pregnancy and the resultant confounding manifestations. Obstetricians should be aware of the potential association between androgen excess and ICP via placental aromatization.

Association between maternal polycystic ovary syndrome and early childhood growth: a continuous observation from 3 months to 6 years of age.

PURPOSE: To investigate whether maternal PCOS could impact growth and development in offspring at an early age through continuous observation from age 3 months to 6 years. METHODS: This prospective study was conducted in 198 children born to mothers with PCOS and 227 children born to healthy mothers in Ningbo (Zhejiang Province, China) between October 2012 and July 2015. Measurements of offspring height, weight, head circumference, and teething were examined by trained professionals through age 6 years. Height, weight, and body mass index (BMI) were analysed using repeated measures analysis of variance between the PCOS and control groups. RESULTS: Offspring born to women with PCOS showed significantly higher BMI at age 12, 18, and 30 months and 5 years (P = 0.040, P = 0.000, P = 0.000, and P = 0.023, respectively). Female offspring born to women with PCOS showed significantly increased body weight at 3, 8, 12, 18, and 30 months, and 3 and 6 years (P = 0.027, P = 0.008, P = 0.010, P = 0.034, P = 0.047, P = 0.040, and P = 0.035, respectively) and significantly higher BMI at 3, 8, 12, 18, and 30 months (P = 0.009, P = 0.016, P = 0.029, P = 0.000, and P = 0.000, respectively). After adjusting for maternal, paternal, and pregnancy confounders, PCOS status presented significant associations with weight at age 3, 8, and 12 months and 3 years (P = 0.005, P = 0.004, P = 0.021, P = 0.035 respectively), and with BMI at age 3 and 8 months (P = 0.011 and P = 0.014) in female offspring. CONCLUSIONS: Maternal PCOS is associated with an increased risk of developing obesity in female offspring.

Correction: Synergistic effect in improving the electrical conductivity in polymer nanocomposites by mixing spherical and rod-shaped fillers.

Correction for 'Synergistic effect in improving the electrical conductivity in polymer nanocomposites by mixing spherical and rod-shaped fillers' by Fan Qu et al., Soft Matter, 2020, 16, 10454-10462, DOI: .

Biogas Upgrading via Cyclic CO2 Adsorption: Application of Highly Regenerable PEI@nano-Al2O3 Adsorbents with Anti-Urea Properties.

Solid amine adsorbents are among the most promising CO2 adsorption technologies for biogas upgrading due to their high selectivity toward CO2, low energy consumption, and easy regeneration. However, in most cases, these adsorbents undergo severe chemical inactivation due to urea formation when regenerated under a realistic CO2 atmosphere. Herein, we demonstrated a facile and efficient synthesis route, involving the synthesis of nano-Al2O3 support derived from coal fly ash with a CO2 flow as the precipitant and the preparation of polyethylenimine (PEI)-impregnated Al2O3-supported adsorbent. The optimal 55%PEI@2%Al2O3 adsorbent showed a high CO2 uptake of 139 mg·g-1 owing to the superior pore structure of synthesized nano-Al2O3 support and exhibited stable cyclic stability with a mere 0.29% decay per cycle even under the realistic regenerated CO2 atmosphere. The stabilizing mechanism of PEI@nano-Al2O3 adsorbent was systematically demonstrated, namely, the cross-linking reaction between the amidogen of a PEI molecule and nano-Al2O3 support, owing to the abundant Lewis acid sites of nano-Al2O3. This cross-linking process promoted the conversion of primary amines into secondary amines in the PEI molecule and thus significantly enhanced the cyclic stability of PEI@nano-Al2O3 adsorbents by markedly inhibiting the formation of urea compounds. Therefore, this facile and efficient strategy for PEI@nano-Al2O3 adsorbents with anti-urea properties, which can avoid active amine content dilution from PEI chemical modification, is promising for practical biogas upgrading and various CO2 separation processes.

Predictive role of serum cholesterol and triglycerides in cervical cancer survival.

OBJECTIVE: Lipids have been evaluated for their possible role in cancer survival prediction. The aim of the current study was to investigate the prognostic value of lipids on overall survival for stage IB1-IIA2 cervical cancer patients. METHODS: A retrospective study including cervical cancer patients with early-stage (FIGO 2009 stage IB1-IIA2) disease was conducted from January 2012 to February 2017. Patients with any history of liver disease or other cancers, and patients who took any medications known to influence lipid metabolism, were excluded. We measured various factors in patients' lipid profiles including total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein, and assessed these four parameters together with clinicopathological features to identify the significant prognostic factors for overall survival. RESULTS: A total of 583 patients with median age 53 (range 25-82) years were included. Among them, 283 (48.5%) patients were in FIGO stage IB1, 44 patients (7.6%) in stage IB2, 189 (32.4%) patients in stage IIA1, and the remaining 67 (11.5%) patients were in stage IIA2. Using univariable Cox proportional hazard analysis and subsequent multivariable analysis, total cholesterol, triglycerides, and pelvic lymph node status were shown to be independent prognostic factors for overall survival (p<0.05 for all). Furthermore, the results of the Kaplan-Meier survival curves showed that both the high total cholesterol group and the high triglycerides group were associated with worse overall survival (p=0.002 and p=0.001, respectively) CONCLUSIONS: Our study showed that total triglycerides and total cholesterol may serve as potential predictors for overall survival in patients with cervical cancer. Cervical cancer patients may benefit from treatments after adjusting their triglycerides and total cholesterol levels.

Alterations of brain metrics in fetuses of women with polycystic ovary syndrome : a retrospective study based on fetal magnetic resonance imaging.

BACKGROUND: Maternal polycystic ovary syndrome (PCOS) has potential detrimental effects on the neurodevelopment of offspring. This study aimed to evaluate the brain metrics in fetuses of women with PCOS based on fetal magnetic resonance imaging (MRI). METHODS: This retrospective study included 60 pregnant women with PCOS (PCOS group) and 120 pregnant non-PCOS women (control group). Fetal MRI was performed followed an ultrasound and for numerous clinical indications including known or suspected fetal pathology, history of fetal abnormality in previous pregnancy or in a family member. Fetal brain biometry and apparent diffusion coefficient (ADC) value were analysed. RESULTS: After adjusting for potential confounders, fetuses in the PCOS group showed the following characteristics compared to fetuses in the control group: (1) smaller cerebral fronto-occipital diameter (FOD), vermian height (VH) and anteroposterior diameter of the pons (APDP) (evident before 32 weeks; P = 0.042, P = 0.002 and P = 0.016, respectively); (2) larger left and right biparietal index (evident before 32 weeks; P = 0.048 and P = 0.025, respectively); (3) smaller left lateral ventricle (LV) (evident after 32 weeks; P = 0.005); (4) larger anteroposterior diameter of the vermis (APDV) and hippocampal infolding angle (HIA) (evident after 32 weeks; P = 0.003 and P < 0.001, respectively); (5) higher ADC value in frontal white matter (FWM) and in basal ganglia (BG) (evident before and after 32 weeks; all P < 0.05). CONCLUSIONS: There exist a different pattern of brain metrics in PCOS offspring in utero.

QiShenYiQi pill improves the reparative myocardial fibrosis by regulating autophagy.

QiShenYiQi pill (QSYQ), a traditional Chinese medicine, is well known for improving the myocardial remodelling, but the dose-effect relationship of its intervention in the reparative myocardial fibrosis is still unclear. We investigated the effect of QSYQ on the reparative myocardial fibrosis in cardiac myosin-induced rats and explored its mechanism of action by regulating autophagy. The results indicated that QSYQ increased LVEF and LVFS, and decreased the LVEDD, LVESD, HMI, LVMI, myocardial inflammation histology score, and collagen volume fraction in a dose-dependent manner. In addition, QSYQ declined the number of autophagosomes, down-regulated the expression of myocardial Beclin-1 and LC3B, up-regulated the expression of myocardial p62 and increased the ratios of myocardial p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR. We provided evidence for that QSYQ could inhibit excessive myocardial autophagy by regulating the PI3K/Akt-mTOR pathway and can be a potential therapeutic approach in treating the cardiovascular diseases such as myocarditis and dilated cardiomyopathy.

Synergistic effect in improving the electrical conductivity in polymer nanocomposites by mixing spherical and rod-shaped fillers.

In this work, coarse-grained molecular dynamics simulation is adopted to investigate the effect of hybrid fillers [nanospheres (NSs) and nanorods (NRs)] on the conductive probability of polymer nanocomposites (PNCs) in the quiescent state and under the shear field. The percolation threshold gradually rises as the volume fraction ratio (α) of NSs to all the fillers increases in the quiescent state. Compared to the NSs, the greater number of beads in the NRs help them connect to other NRs to form the conductive network. Meanwhile, compared to NSs, more NRs participate in building the conductive network. A transition from the synergistic effect to the antagonistic effect occurs as the NS-NR tunneling distance is reduced. Furthermore, the shear field induces a more direct aggregation structure of NSs, which act as linkers between fillers to protect the conductive network. This result is confirmed by the fact that more NSs occupy the conductive network under the shear field. As a result, the percolation threshold declines with increasing shear rate. Finally, compared to in the quiescent state, the percolation threshold increases at α = 0.0 and remains nearly unchanged for α = 0.25 under the shear field, while it gradually decreases for α≥ 0.5. In total, the results further our understanding of how to realize the synergistic effect between NSs and NRs when forming a conductive network of PNCs.

Analysis of the susceptibility to COVID-19 in pregnancy and recommendations on potential drug screening.

To analyze the susceptibility of SARS-CoV-2 in pregnancy and the drugs that can be used to treat pregnancy with COVID-19, so as to provide evidence for drug selection in clinic. By reviewing the existing literature, this paper analyzes the susceptibility of pregnant women to virus, especially to SARS-CoV-2, from the aspects of anatomical, reproductive endocrine and immune changes during pregnancy and screens effective and fetal-safe treatments from the existing drugs. The anatomical structure of the respiratory system is changed during pregnancy, and the virus transmitted by droplets and aerosols is more easily inhaled by pregnant women and is difficult to remove. Furthermore, the prognosis is worse after infection when compared with non-pregnancy women. And changes in reproductive hormones and immune systems during pregnancy collectively make them more susceptible to certain infections. More importantly, angiotensin-converting enzyme (ACE)-2, the SARS-CoV-2 receptor, has been proven highly increased during pregnancy, which may contribute to the susceptibility to SARS-CoV-2. When it comes to treatment, specific drugs for COVID-19 have not been found at present, and taking old drugs for new use in treating COVID-19 has become an emergency method for the pandemic. Particularly, drugs that show superior maternal and fetal safety are worthy of consideration for pregnant women with COVID-19, such as chloroquine, metformin, statins, lobinavir/ritonavir, glycyrrhizic acid, and nanoparticle-mediated drug delivery (NMDD), etc. Pregnant women are susceptible to COVID-19, and special attention should be paid to the selection of drugs that are both effective for maternal diseases and friendly to the fetus. However, there are still many deficiencies in the study of drug safety during pregnancy, and broad-spectrum, effective and fetal-safe drugs for pregnant women need to be developed so as to cope with more infectious diseases in the future.

Semi-synthesis and anti-tumor activity of novel 25-OCH3-PPD derivatives incorporating aromatic moiety.

Previously we have reported that 25-OCH3-PPD could suppress the reproduction of cancer cells and cause apoptosis without obvious toxicity. Herein, we aimed to enhance its bioactivity by introducing aromatic groups to its dammarane-type skeleton. These synthesized derivatives were tested for their inhibitory activities against five cancer cell lines. Of them, compounds 3a, 14a and 18a had the strongest antiproliferative activities against tumor cells (IC50 < 15 µM, 5-fold to 10-fold increases than 25-OCH3-PPD). Especially compound 14a displayed the most potent activity against DU145, MCF-7 and HepG2 cells (IC50 = 6.7 ±â€¯0.8, 4.3 ±â€¯0.8 and 5.8 ±â€¯0.6 µM, respectively). Structure-activity relationships demonstrated that having aromatic ester at the C3 position could improve the bioactivity. The data provided new insights into exploring novel antiproliferative lead compounds.

Alternative splicing of the androgen receptor in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders and a leading cause of female subfertility. The mechanism underlying the pathophysiology of PCOS remains to be illustrated. Here, we identify two alternative splice variants (ASVs) of the androgen receptor (AR), insertion and deletion isoforms, in granulosa cells (GCs) in ∼62% of patients with PCOS. AR ASVs are strongly associated with remarkable hyperandrogenism and abnormalities in folliculogenesis, and are absent from all control subjects without PCOS. Alternative splicing dramatically alters genome-wide AR recruitment and androgen-induced expression of genes related to androgen metabolism and folliculogenesis in human GCs. These findings establish alternative splicing of AR in GCs as the major pathogenic mechanism for hyperandrogenism and abnormal folliculogenesis in PCOS.

Is Chemerin associated with gestational diabetes mellitus? An evidence-based clinical research from Chinese women.

The present study aimed to explore the association between gestational diabetes mellitus (GDM) and Chemerin, by analysing Chemerin level, clinical data and biochemical parameters among 46 GDM patients and 43 controls. It was found that the Chemerin levels from cord blood, peripheral blood, adipose tissue and placenta tissue were all significantly higher in the GDM group than those in the control group (p < .05 for all). Maternal insulin resistance (IR) index and serum inflammation parameters, including C-reactive protein and white blood cells, were also higher in GDM group (p < .05 for all). Moreover, maternal IR index and circulating insulin level were both positively correlated with maternal circulating Chemerin level (p < .05 for both). Our findings suggest that Chemerin, associated with IR and more expressed in GDM women, might participate in the pathogenesis of GDM. Impact Statement What is already known on this subject: Chemerin, a recently-discovered adipocytokine, has been widely-considered to be involved in metabolic diseases, and several studies have investigated it in gestational diabetes mellitus (GDM), but with no consensus about the level comparison between GDM and controls. What the results of this study add: The present case-control study found that the levels of Chemerin from cord blood, peripheral blood, adipose tissue and placenta tissue were all significantly higher in the GDM group. What the implications are of these findings for clinical practice and/or further research: Also, the circulating Chemerin level was positively correlated with insulin index, which we thought would add to the evidence that Chemerin does be associated with GDM, contributing to elucidating the pathogenesis of GDM.