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Salinity is one of the most significant environmental factors limiting microalgal biomass productivity. In the present study, the model microalga Chlamydomonas reinhardtii (C. reinhardtii) was exposed to 200 mM NaCl for eight days to explore the physiological, biochemical and metabolomic changes. C. reinhradtii exhibited a significant decrease in growth rate, and Chl a and Chl b levels. 200 mM NaCl induced ROS generation in C. reinhardtii with increase in H2O2 content. This caused lipid peroxidation with increase in MDA levels. C. reinhardtii also exhibited an increase in carbohydrate and lipid accumulation under 200 mM NaCl conditions as storage molecules in cells to maintain microalgal survival. In addition, NaCl stress increased the content of carotenoids, polyphenols and osmoprotectant molecules such as proline. SOD and APX activities decreased, while ROS-scavenger enzymes (POD and CAT) decreased. Metabolomic response showed an accumulation of the major molecules implicated in membrane remodelling and stress resistance such oleic acid (40.29%), linolenic acid (19.29%), alkanes, alkenes and phytosterols. The present study indicates the physiological, biochemical and metabolomic responses of C. reinhardtii to salt stress.

Seasonal variations affect the rate of biomass accumulation in plants which is internally governed by biochemical metabolites. Studying the impact of atmospheric seasonal changes on biochemical parameters can improve our understanding of various plant species' physiological plasticity. Bamboos are a fast-growing group of woody grass species, widely distributed across tropical and sub-tropical regions of the world, and are an important species of the Indian subcontinent. Nevertheless, limited information is available on the seasonal response of biochemical's in bamboo species growing in ambient atmospheric circumstances. Therefore, we investigated the seasonal biochemical responses of Dendrocalamus strictus clones viz. Pantnagar (PNT) and Dhampur (DHM) to seasonal ambient atmospheric conditions. The concentrations of chlorophyll, protein, carbon, nitrogen, phosphorus, potassium, and magnesium in bamboo leaves were increased significantly (p < 0.025) in monsoon compared to summer and winter seasons. Carotenoid, total sugar and ascorbic acid contents were highest during winters and reduced significantly during monsoon. Proline content was highest in summer and reduced by 97% during monsoon, indicating effective adaptation to both clones' water-limited conditions. It was inferred that seasonal variation in atmospheric conditions significantly influenced the biochemical constituents of plants. This study provides a biochemical approach for screening potential bamboo species with adaptive nature for plantation purposes intended to mitigate climate change.

We investigated the accumulation and adverse effects of toxic and non-toxic Microcystis in the edible clam Corbicula leana. Treated clams were exposed to toxic Microcystis at 100 μg of MC (microcystin)-LReq L−1 for 10 days. The experimental organism was then placed in toxin-free water and fed on non-toxic Microcystis for the following 10 days for depuration. Filtering rates (FRs) by C. leana of toxic and non-toxic Microcystis and of the green alga Chlorella vulgaris as a control were estimated. Adverse effects were evaluated though the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione S-transferase (GST). Clam accumulated MCs (up to 12.7 ± 2.5 μg g−1 dry weight (DW) of free MC and 4.2 ± 0.6 μg g−1 DW of covalently bound MC). Our results suggest that although both toxic and non-toxic cyanobacteria caused adverse effects by inducing the detoxification and antioxidant defense system, the clam was quite resistant to cyanotoxins. The estimated MC concentration in C. leana was far beyond the World Health Organization's (WHO) provisional tolerable daily intake (0.04 μg kg−1 day−1), suggesting that consuming clams harvested during cyanobacterial blooms carries a high health risk.

The freshwater fish Carassius auratus was chosen as an experimental subject, and their hepatic biochemical responses to the medium-term exposure of Benzo(k)fluoranthene (BkF) alone and in combination with PCB118 and dichlorodiphenyltrichloroethane (DDT) were investigated by measuring the reduced glutathione (GSH), glutathione S-transferase (GST), and thiobarbituric acid reactive substances (TBARS), to assess sublethal effects. The hepatic GSH content was significantly inhibited by organic pollutants, alone and in mixtures, while the TBARS content was significantly induced after three days of exposure. Bell-shaped concentration-response charts of GST activities were obtained. Significant dose-response relationships were found for hepatic GSH and TBARS contents of all concentrations and for the GST activity, except at the highest concentration. The GSH content, GST activity, and TBARS content in Carassius auratus were confirmed as useful biomarkers of exposure to organic pollutions.

Purpose: To determine whether biochemical responses to long-acting forms of first-generation somatostatin analogue (SSA) therapy in patients with acromegaly could be predicted from baseline and postoperative hormone concentrations, and tumor radiological and histopathological characteristics., Methods: A total of 68 patients with acromegaly for whom postoperative SSA therapy was started were categorized according to their responses to treatment (SSA-responders vs. non-responders). The patients were compared based on their demographic characteristics, hormone levels, magnetic resonance imaging (MRI), and histopathological findings. Receiver-operating-characteristic (ROC) curves were constructed using the predictive factors that were significant in the univariate analysis to determinate the optimal cut-off values., Results: The SSA-responders were significantly older (p = 0.041). Lower GH at diagnosis (p = 0.036), the postoperative 1st-week GH level (p = 0.027), baseline GH, insulin-like growth factor-1 (IGF-1) and IGF-1% upper limit of normal (ULN) (p = 0.001, p = 0.006, p = 0.023, respectively) were associated with biochemical response. T2-hypointensity and lower tumor volume were more common in the SSA-responders (p = 0.018, p = 0.03, respectively). Compared to sparsely granulated somatotroph tumors, densely granulated somatotroph tumors and other PitNETs causing GH excess including mammosomatotroph and mixed somatotroph and lactotroph tumors were more likely to respond to SSA therapy (p = 0.026, p = 0.03, respectively). The cut-off values generated by ROC curve analysis were GH at diagnosis of ≤8.8 ng/mL, GH at baseline of ≤2.69 ng/mL, IGF-1 at baseline ≤461.5 ng/mL, IGF-1% ULN at baseline ≤180.4%, and tumor volume of ≤1.11 cm 3 (all p < 0.05). There were no differences between the groups in terms of tumor invasiveness, proliferative activity (mitotic count per 2 mm 2 and Ki-67 labeling index) and quantitative analyses of T2-weighted MRI., Conclusion: This study underscores that advanced age, low baseline GH and IGF-1 at diagnosis, low tumor volume, densely granulated tumor subtype, and T2 hypointensity may help predict biochemical response to SSA therapy in cases of acromegaly. These variables should be assessed with utmost attention for all patients prior to SSA treatment. In cases of possible resistance to SSA therapy, therapeutic activity should be monitored more closely and other therapies should be administered immediately in the event of poor response., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background & Aim: Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual agonistic properties (α/γ). Due to a strong mechanistic rationale, we aimed to test the safety and efficacy of saroglitazar in patients with primary biliary cholangitis (PBC) who were either ursodeoxycholic acid (UDCA) resistant or intolerant., Methods: In this double-blind, phase II proof-of-concept trial, 37 patients with PBC were randomized to saroglitazar 4 mg (n = 13), saroglitazar 2 mg (n = 14), or placebo (n = 10) daily for 16 weeks. The primary efficacy endpoint was the reduction in alkaline phosphatase (ALP) level at Week 16., Results: A significant reduction of mean ALP levels was observed at Week 16 relative to baseline in both the saroglitazar 4 mg (least-squares [LS] mean =-163.3 U/L, SE = 25.1, p <0.001) and 2 mg (LS mean =-155.8 U/L, SE = 24.4, p <0.001) groups, compared with placebo (LS mean =-21.1 U/L, SE = 28.9). Treatment with saroglitazar resulted in a rapid reduction of ALP concentration at Week 4 that was sustained through the study duration. At least 1 treatment-emergent adverse event occurred in 11 (84.6%) patients in the saroglitazar 4 mg group, in 12 (85.7%) patients in the 2 mg group and in 8 (80%) patients in the placebo group. Study drug was discontinued in 4 patients (3 patients in the 4 mg group and 1 patient in the 2 mg group) due to aminotransferase increases that promptly returned to baseline values after drug discontinuation., Conclusions: Saroglitazar at 2 mg and 4 mg daily was tolerated and resulted in rapid and sustained improvements in ALP. Further studies are underway at a daily dose of 2 mg and 1 mg due to the higher incidence of elevated liver enzymes observed with the 4 mg dose. CLINICALTRIALS., Gov Identifier: NCT03112681 LAY SUMMARY: Saroglitazar resulted in a rapid and sustained improvement in alkaline phosphatase levels in patients with primary biliary cholangitis. The mean percentage reductions in alkaline phosphatase levels were 49% and 51% in the saroglitazar 4 mg and 2 mg groups compared to 3% in the placebo group., Competing Interests: Conflict of interest DP, FS, JB are employees of Zydus Discovery DMCC. No conflict of interest relevant to the current trial were reported by the rest of the authors listed for this manuscript. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Chronic HDV infection often is associated with aggressive form of liver disease, compared to chronic HBV mono-infection. However, chronic HDV treatment is challenging because currently there is no approved regimen for affected patients. While standard interferon with/without nucleos(t)ide analogues were reported to be inferior to pegylated interferon (peginterferon) as HDV treatment according to few randomized clinical trials. This meta-analysis will summarize the results of studies on the effectiveness of peginterferon as HDV treatment regimen. An electronic search was performed using PubMed, Cochrane Library, Research Gate, and Medline databases. Studies involving patients who received peginterferon therapy for at least 48 weeks and followed up for 24 weeks post-therapy were included. All analyses were conducted using Review Manager 5.3 designed for Cochrane Reviews. The primary efficacy endpoint was virological response (VR) or HDV-RNA negativity at the end of the follow-up period, whereas secondary efficacy endpoints were biochemical response (BR) or ALT normalization and HBsAg clearance with seroconversion to anti-HBs at the end of follow-up period. Data were abstracted from 13 relevant studies with a total of 475 patients who were treated with peginterferon alpha-2a or -2b. At the end of 24-week post-treatment the pooled VR was achieved in 29% of patients with 95% CI [24%; 34%], BR was reached in 33% of patients [95% CI 27%; 40%] and HBsAg clearance with seroconversion to anti-HBs was achieved in 1% of patients with 95% CI [-0.02; 0.05]. In conclusion, this study showed that peginterferon has limited effectiveness in HDV treatment, since only one-third of chronic HDV patients achieved viral clearance and normalized ALT levels. Morever, HBsAg clearance with seroconversion to anti-HBs has been rarely observed among chronic HDV patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Studies have shown high levels of contamination of both metals and organochlorine pesticides (OCPs) in aquatic systems of the world renowned Kruger National Park, South Africa. With effects evident in top predators, including, unexplained Crocodylus niloticus deaths and organ level and histological changes in Hydrocynus vittatus. A suite of biomarkers reflecting exposure and were selected to evaluate biological responses of H. vittatus to anthropogenic stressors as well as to evaluate whether the chosen suite of biomarkers could successfully distinguish between the different pollution profiles present in the selected rivers. During this study a clear relationship was found between exposure to environmental contaminants and the concomitant responses of H. vittatus to these stressors. The ensuing biomarker responses indicated that there is a physiological attempt to deal with, and mitigate the deleterious effects that metals and OCPs may induce. In the Luvuvhu River there is a clear indication in H. vittatus of the stimulation of anti-oxidant protective mechanisms in response to internal OCP exposure. This is reflected by the increasing cytochrome P-450, superoxide dismutase, and more specifically reduced glutathione, which resulted in decreased lipid and protein breakdown (reflected in decreased lipid peroxidation and protein carbonyl levels). Consequently H. vittatus populations of the Luvuvhu River are under greater cumulative stress and this is reflected in the lower energy budgets. Our results further show the integrated application value of the current suite of biomarkers in assessing responses of subtropical fish to metal and OCP exposure as the entire suite of biomarkers when used in conjunction were able to explain 100% of the variation in the data., (Copyright © 2018 Elsevier Inc. All rights reserved.)

External beam radiation therapy (EBRT) in combination with androgen deprivation therapy (ADT) is considered a standard treatment option for patients with aggressive localized and locally-advanced prostate cancer. Randomized phase III trials have provided evidence for combining EBRT to short-term ADT for intermediate-risk disease and to long-term ADT for patients harboring high-risk tumors. Even if several improvements and developments have been made in the last years in terms of radiotherapy delivery techniques, image-guided radiotherapy, and better sparing of the organs at risk the current use of ADT remains still linked to a therapeutic algorithm based on the prostate cancer risk classification as proposed by clinical trials. Emerging literature has recently shown that the biochemical response to a course of neoadjuvant ADT before EBRT, called the "prostate-specific antigen (PSA) nadir" (lowest value after treatment), may influence the long-term biochemical tumor-control outcomes of prostate cancer patients. An individualized approach adapting the duration of hormonal treatment according to the PSA response during the neoadjuvant phase, as well using new generation hormonal agents, may represent a new therapeutic strategy and a future way to improve the therapeutic ratio for prostate cancer patients. In this systematic review of the literature we explored the prognostic value of the PSA response to the neoadjuvant ADT phase and the rationale to adjust the use of ADT and EBRT in patients with intermediate- and high-risk prostate cancer based on the biochemical response to the neoadjuvant androgen ablation phase., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The PAHs concentrations in seawater and tissues from the scallop Chlamys farreri were detected in three sites in Qingdao, China in 2011. The PAHs concentrations in seawater ranged from 25.32 ng/L to 314.62 ng/L. There were significant differences (p<0.05) between the residual levels among scallop tissues. The highest concentrations of PAHs in seawater and tissues were found in S2. The ethoxyresorufin-O-deethylase (EROD) activity of the digestive gland and the malondialdehyde (MDA) contents of the digestive gland and gill were sensitive to PAHs (p<0.05). This study integrated the PAHs concentrations in seawater, residual levels, the variation of biochemical response and the correlation coefficient analysis, and concluded that Qingdao is a medium PAH-contaminated area on a global scale. The highest PAHs were accumulated in the digestive gland followed by the gill, soft tissue and adductor muscle. The EROD activity of the digestive gland and the MDA contents of the digestive gland and gill could be applied to assess the PAHs pollution status in Qingdao, China., (Copyright © 2014 Elsevier Ltd. All rights reserved.)