Developmental toxicity of the neonicotinoid pesticide clothianidin to the larvae of the crustacean Decapoda, Penaeus vannamei.

The developmental toxicity effects of neonicotinoid pesticides such as clothianidin have not been fully explored in agricultural applications. This is particularly noteworthy because such pesticides significantly impact the survival rates of invertebrates, with arthropod larvae being particularly vulnerable. This study aimed to address this research gap by specifically investigating the toxicological effects of clothianidin on the developmental stages of the larvae of the economically important aquaculture species Penaeus vannamei. In these experiments, shrimp eggs were exposed to seawater containing different concentrations of clothianidin beginning at N1, and each phase was observed and analyzed to determine its toxic impact on larval development. These results revealed that clothianidin induces an increase in deformity rates and triggers abnormal cell apoptosis. It also significantly reduced survival rates and markedly decreased body length and heart rate in the later stages of larval development (P3). Transcriptomic analysis revealed disruptions in larval DNA integrity, protein synthesis, and signal transduction caused by clothianidin. To survive prolonged exposure, larvae may attempt to maintain their viability by repairing cell structures and enhancing signal transduction mechanisms. This study offers the first empirical evidence of the toxicity of clothianidin to arthropod larvae, underscoring the impact of environmental pollution on aquatic health.

Next-generation neonicotinoid: The impact of cycloxaprid on the crustacean decapod Penaeus vannamei.

Cycloxaprid, a new neonicotinoid pesticide, poses ecological risks, particularly in aquatic environments, due to its unique action and environmental dispersal. This study investigated the ecotoxicological effects of various concentrations of cycloxaprid on Penaeus vannamei over 28 days. High cycloxaprid levels significantly altered shrimp physiology, as shown by changes in the hepatosomatic index and fattening. Indicators of oxidative stress, such as increased serum hemocyanin, respiratory burst, and nitric oxide, as well as decreased phenol oxidase activity, were observed. Additionally, elevated activities of lactate dehydrogenase, succinate dehydrogenase, and isocitrate dehydrogenase indicated disrupted energy metabolism in the hepatopancreas. Notably, analyses of the nervous system revealed marked disturbances in neural signaling, as evidenced by elevated acetylcholine, octopamine, and acetylcholinesterase levels. Transcriptomic analysis highlighted significant effects on gene expression and metabolic processes in the hepatopancreas and nervous system. This study demonstrated that cycloxaprid disrupts neural signaling and oxidative balance in P. vannamei, potentially affecting its growth, and provides key insights into its biochemical and transcriptomic toxicity in aquatic systems.

An analysis of the efficacy of botulinum neurotoxin type a in treating cervical dystonia.

BACKGROUND: The first-line treatment for cervical dystonia (CD) consists of repeated intramuscular injections of botulinum toxin (BoNT). However, the efficacy in some patients may be unsatisfactory and they may discontinue treatment. OBJECTIVE: To examine the factors associated with the maximum rate of remission in patients with CD after initial botulinum neurotoxin type A (or botulinum toxin type A abbreviated as BTX-A or BoNT-A) treatment. METHODS: Patients with CD who received BoNT-A injections were evaluated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Tsui scale, with follow-up endpoints lasting until the start of the second injection. Patients who did not receive a second injection of BoNT-A were followed up for at least 5 months. The maximum remission rates were determined using the lowest Tsui and TWSTRS total scores during the follow-up period. We obtained basic information about these patients such as age, gender, duration of disease, presence of additional disease, types of torticollis, presence of anxiety, depression, tremors, single-photon emission computed tomography (SPECT) findings, injected dose, and so on from their medical records. RESULTS: A total of 70 patients with CD participated in this study, with males comprising 35.7% (25 individuals) with an average age of 45 ± 14 years old. The duration of disease was an independent risk factor for determining whether a complete remission has been attained using the Tsui scale (odds ratio [OR] = 0.978, 95% confidence interval [CI]: 0.959-0.997, P= 0.026). The optimal cut-off point for predicting patients who were unable to achieve complete remission based on duration of disease was 7.5 months (AUG = 0.711). Patients with CD with additional disease had greater difficulty achieving complete remission than those with CD alone based on TWSTRS assessments (P= 0.049). During the study, approximately 17% of all participants reported experiencing adverse reactions that lasted between 1 to 3 weeks before disappearing. CONCLUSION: BoNT is an effective and safe method for treating CD. The maximum remission rates of patients after their first injections are influenced by the duration of their disease. Thus, treatment using BoNT injections must be administered as soon as possible.

Diagnostic value of clinical deep tendon reflexes in diabetic peripheral neuropathy.

Introduction: The aim of the present study was to evaluate the diagnostic efficacy of different tendon reflexes in detecting diabetic peripheral neuropathy (DPN). Material and methods: According to the changes in tendon reflexes, all patients with diabetes were divided into three strata: impaired Achilles reflex only, impaired lower extremity reflexes, and impaired lower and upper extremity reflexes. Taking nerve conduction studies (NCS) as the gold standard, the sensitivity, specificity, and predictive ability of the tendon reflexes of these three strata, as well as the Toronto clinical scoring system (TCSS) and Michigan Neuropathy Screening Instrument (MNSI), were calculated. Then, the electrophysiological characteristics of diabetic patients with different tendon reflexes were analysed. Results: Among the 240 patients studied, 92 (38.3%) presented evidence of neuropathy, which was confirmed by abnormal NCS, while 148 (61.7%) had normal NCS results. Taking NCS as the gold standard, stratum 1 yielded a sensitivity and specificity of 93.5% and 54.7%, respectively, while stratum 3 had higher specificity (96.6%) and lower sensitivity (34.8%) when compared to stratum 1. However, stratum 2 had the highest specificity (75.7%). Conclusions: The assessment of tendon reflexes can be proposed as a test for screening diabetic polyneuropathy.

Minocycline induces tolerance to dendritic cell production probably by targeting the SOCS1/ TLR4/NF-κB signaling pathway.

OBJECTIVE: Dendritic cells (DCs) are professional antigen-presenting cells that play a key role in maintaining peripheral immune tolerance. The use of tolerogenic DCs (tolDCs), i.e., semi-mature DCs that express co-stimulatory molecules but not pro-inflammatory cytokines, has been proposed. However, the mechanism of tolDCs induced by minocycline is still unclear. Our previous bioinformatics analyses based on multiple databases suggested that the suppressor of cytokine signaling 1/Toll-like receptor 4/NF-κB (SOCS1/TLR4/NF-κB) signal pathway was associated with DCs maturation. Thus, we studied whether minocycline could induce DC tolerance through this pathway. METHODS: A search for potential targets was carried out through public databases, and pathway analysis was performed on these potential targets to obtain pathways relevant to the experiment. Flow cytometry was used to detect the expression of DC surface markers CD11c, CD86, and CD80, and major histocompatibility complex II. The secretion of interleukin (IL)-12p70, tumor necrosis factor alpha (TNF- α), and IL-10 in the DC supernatant was detected by enzyme-linked immunoassay. The ability of three groups (Ctrl-DCs, Mino-DCs, and LPS-DCs) of DCs to stimulate allogeneic CD4+ T cells was analyzed using a mixed lymphocyte reaction assay. Western blotting was used to detect the expression of TLR4, NF-κB-p65, NF-κB-p-p65, IκB-α, and SOCS1 proteins. RESULTS: The hub gene plays a vital role in biological processes; in related pathways, the regulation of other genes is often affected by it. The SOCS1/TLR4/NF-κB signaling pathway was further validated by searching for potential targets through public databases to obtain relevant pathways. The minocycline-induced tolDCs showed characteristics of semi-mature DCs. Moreover, the IL-12p70 and TNF-α levels in the minocycline-stimulated DC group (Mino-DC group) were lower than those in the lipopolysaccharide (LPS)-DC group, and the IL-10 levels were higher in the Mino-DC group than in the LPS-DC and control DC groups. In addition, the Mino-DC group had decreased protein expression levels of TLR4 and NF-κB-p65 and upregulated protein levels of NF-κB-p-p65, IκB-α, and SOCS1 compared with the other groups. CONCLUSION: The results of this study indicate that minocycline could improve the tolerance of DCs probably by blocking the SOCS1/TLR4/NF-κB signaling pathway.

Nordihydroguaiaretic acid can suppress progression of experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a poorly understood disease mechanistically. MOG35-55 peptide induced experimental autoimmune encephalomyelitis (EAE) is a broadly used model to study MS. Using this model we have earlier shown that the antioxidant tempol or the small molecule inhibitor of p38 SB203580 can effectively prevent EAE progression. This effect was mediated by means of regulating immune inflammation, signaling by the p38MAPK-SGK1 pathway, and oxidative stress. However, there is a need to test drugs that can be used in pharmacological intervention of EAE. Given that nordihydroguaiaretic Acid (NDGA) has been shown to possess anti-oxidant activity and capacity of antagonizing autoimmune inflammation, we tested the effect of NDGA in ameliorating EAE in the current study. NDGA showed significant beneficial effect against EAE with both anti-inflammation and antioxidant activity. NDGA could weaken the immune inflammation at least partly by inhibiting the oxidant stress-p38MAPK-SGK1 pathway representing a target for putative pharmacological intervention. © 2018 IUBMB Life, 70(5):432-436, 2018.