Evaluation of the Choroid Plexus Epithelium Inflammation TLR4/NF-κB/NKCC1 Signal Pathway Activation in the Development of Hydrocephalus.

BACKGROUND: Hydrocephalus is characterized by secretion, circulation, and absorption disorder of cerebrospinal fluid (CSF) with high morbidity and complication rate. The relationship between inflammation and abnormal secretion of CSF by choroid plexus epithelium (CPE) had received more attention. In this study, we aim to detect the role of Toll-like receptor 4/nuclear factor-kappa B/Na+/K+/2Cl-cotransporter 1(TLR4/NF-κB/NKCC1) signal pathway in the development of hydrocephalus. METHOD: Hydrocephalus was induced in adult rats (8 weeks) by intracisternal kaolin injection, then pyrrolidinedithiocarbamate (PDTC) and bumetanide were administrated to the rats mode. Then the rat model was evaluated, and ventricular volume was calculated at different time points. Then CPE, cortex, preventricular tissue, and CSF were obtained. Protein expressions of TLR-4, NKCC/serine-threonine STE20/SPS1-related, proline-alanine-rich kinase (SPAK), pNKCC1, pSPAK, GFAP, AQP1, and AQP4 were measured by RT-PCR, western blot, and immunofluorescence (IF) stains in CPE, respectively. RESULT: Our data showed that inflammation factors tumor necrosis factor-(TNF-α), interleukin 18(IL-18), and glial fibrillary acidic protein (GFAP) concentrations were significantly higher in the model group than in controls. The TLR4/NF-κB/NKCC1 signal pathway were actived by NF-κB-p65, NKCC1, pNKCC1- pSPAK complex, and Aquaporin1 (AQP1) high expression. PDTC and bumetanide use can help regular TLR4/NF-κB/NKCC1 expression and reduced AQP1 expression by down-regulate NF-B-p65 and inhibiting NKCC1, respectively. As a result, the treatment groups alleviated CPE abnormal secretion and ventricle enlargement. CONCLUSION: These results confirmed that the inflammatory reaction contributes TLR4/NF-κB/NKCC1 mediated CPE abnormal secretion and consequent hydrocephalus. Regulation of TLR4/NF-κB/NKCC1 and AQP1 can prevent this process. Our study provides a strong rationale for further exploring alleviating CPE abnormal secretion as a therapeutic perspective of hydrocephalus.

Synthesis and characterization of novel dithiocarbamic thioanhydrides and their application for plant growth stimulant and phytotoxic activity.

In this study, nineteen thioanhydrides were synthesized from the S-acylation reaction of sodium dithiocarbamates with various acyl chlorides in chloroform at room temperature. The synthesized thioanhydrides were evaluated for their growth-stimulating and phytotoxic activities. Benzoic (1a), 4-methoxy- (1b), 4-chloro- (1c), 2-bromo- (1e), 4-fluoro- (1f.) and 4-nitrobenzoic 1H-1,2,4-triazole-1-carbothioic thioanhydrides (1 g) showed moderate to excellent growth-stimulating activity, along with this (1c) exhibited excellent phytotoxic activity, 2,4-dichlorobenzoic 1H-1,2,4-triazole-1-carbothioic thioanhydride (1d) and 2,4-dichlorobenzoic pyrrolidine-1-carbothioic thioanhydride (2b) demonstrated inhibiting and moderate phytotoxic activities. Thioanhydrides (1a-c, 1f., 1 g) exhibited excellent germination energy and germination capacity of wheat seeds: 1a 82 and 90%, 1c 80 and 84%, 1 g 82 and 90% (0.01 mg/ml); 1b, 1 g 78 and 94%, 1c 78 and 90%, 1f. 80 and 94% (0.1 mg/ml). Thioanhydride (1e) showed moderate activity, germination energy and germination capacity were 72 and 76% (0.1 mg/ml), 78 and 84% (0.01 mg/ml). Thioanhydride (1d) demonstrated activity as a growth inhibitor with germination energy, and germination capacity 54 and 58% (0.1 mg/ml), 44 and 42% (0.01 mg/ml). Thioanhydride (1c) exhibited excellent phytotoxic activity analogically to herbicide 2,4-D only on lettuce seeds. Compounds (1d and 2b) were moderately active, inhibiting the growth of lettuce and bent grass seedlings.

Integrated Molecular Docking and Experimental Analysis of Ni(II) Proline Dithiocarbamate Cytotoxicity in MCF-7 Breast Cancer Cells.

OBJECTIVE: Chemotherapy is one of the most effective and widely used treatment types for breast cancer. The Ni(II) proline dithiocarbamate (Ni(II)ProDtc) complex has been synthesized as a potential anticancer agent with minimal systemic toxicity. The dithiocarbamate ligand, combined with the amino acid proline, holds promise as a radio chemotherapeutic target agent in tumors. The anticancer activity of a Ni(II) complex compound with a proline dithiocarbamate ligand was tested on the MCF-7 breast cancer cell line as part of a study on essential metal-based therapeutics. METHODS: Molecular docking studies identified the active sites for the estradiol-estrogen receptor-α protein. The Ni(II)ProDtc complex was synthesized and characterized using melting point analysis, conductivity measurements, UV-Vis spectroscopy, and FT-IR spectroscopy. The cytotoxicity of the complex was evaluated in vitro using the MCF-7 breast cancer cell line. RESULTS: The UV-Vis spectrum at 246 nm indicated the π→π* intraligand transition of the CS2 group, while FT-IR analysis revealed peaks at 364-457 cm-1 corresponding to the bonding between Ni and Sulfur (S) and Oxygen (O) from proline. Further, the UV-Vis spectrum displayed bands at 212 and 676 nm, and FT-IR data at 387-691 cm-1, confirming the coordination of the Ni(II) atoms with sulfur, nitrogen, and oxygen in the isoleucine dithiocarbamate ligand. In vitro, cytotoxicity tests revealed that Ni(II)ProDtc induced cell death in the breast cancer cell line, showing significant morphological changes in MCF-7 cancer cells, with an IC50 value of 315.70 µg/mL. CONCLUSION: The Ni(II)ProDtc complex was successfully synthesized and demonstrates anticancer activity in MCF-7 breast cancer cells, indicating significant potential as an anticancer agent for breast cancer.

Design, Synthesis and Characterization of Mn(II)Cysteine-Tyrosine Dithiocarbamate Complex for against the Cancer on MCF-7 Breast Cancer Cell Line.

OBJECTIVE: Breast cancer is the most frequently diagnosed cancer and the second cause of death worldwide. The drug often used for chemotherapy is cisplatin. However, the drug cisplatin has a number of problems, including lack of selectivity, undesirable side effects, resistance, and toxicity in the body. So research is carried out on new drug compounds with low toxicity by designing in silico with molecular docking. METHODS: Mn(II) Cysteine-Tyrosine dithiocarbamate is a new complex molecule whose research involves several steps, such as in-silico molecular docking testing with target proteins, ADMET then synthesis, characterization and in-vitro MCF-7 cells for anticancer drugs. The synthesis process involves the reaction of manganese metal with tyrosine, cysteine, CS2 and KOH. Characterization tests have been carried out including FT-IR spectroscopy, SEM-EDS, UV Vis, conductivity, melting point and XRD. RESULT: Confirm the structure of the compound using UV Vis, obtained orbitals π to π* and n to π* in the group N = C = S is represented by the absorption at 400 nm and 600 nm, FT-IR with the results obtained by the functional groups O-H, N-H, C =N and C=S. In vitro test results showed morphological changes (apoptosis) in MCF-7 cancer cells starting from 250 µg/mL and an IC50 value of 416.90 µg/mL. Molecular docking studies of the Mn(II)Cysteine-Tyrosine dithiocarbamate complex were identified with 4,4',4''-[(2R)-butane-1,1,2-triyl]triphenol - Estrogen α which showed an active site with amino acid residues GLU323, GLU385, VAL446, ILE514, TRP360, LYS449, MET388, MET357, PHE445, VAL392 and ILE389. Hydrophobic and hydrophobic bonds are seen in Mn(II)Cysteine-Tyrosine dithiocarbamate - Estrogen α has a bond energy of -77.5372 kJ/mol. CONCLUSION: Despite having a high H-bond interaction intensity, the chemical does not have a powerful enough anticancer impact. Despite the produced compound's low bioactivity, this study should offer important new understandings into how molecular structure affects anticancer activity.

Human and rat gonadal 3ß-hydroxysteroid dehydrogenases are suppressed by dithiocarbamate fungicides via interacting with cysteine residues.

Dithiocarbamates have been widely used in various industrial applications, such as insecticides (ferbam) or drug (disulfiram). This study explored the inhibitory effects of dithiocarbamates on human and rat gonadal 3ß-hydroxysteroid dehydrogenases (3ß-HSD) and investigated the structure-activity relationship and mechanistic insights. The inhibitory activity of six dithiocarbamates and thiourea on the conversion of pregnenolone to progesterone was evaluated using human KGN cell and rat testicular microsomes, with subsequent progesterone measurement using HPLC-MS/MS. The study found that among the tested compounds disulfiram, ferbam, and thiram exhibited significant inhibitory activity against human 3ß-HSD2 and rat 3ß-HSD1, with ferbam demonstrating the highest potency. The mode of action for these compounds was characterized, showing mixed inhibition for human 3ß-HSD2 and mixed/noncompetitive inhibition for rat 3ß-HSD1. Additionally, it was observed that dithiothreitol dose-dependently reversed the inhibitory effects of dithiocarbamates on both human and rat gonadal 3ß-HSD enzymes. The study also delved into the penetration of these dithiocarbamates through the human KGN cell membrane and their impact on progesterone production, highlighting their potency in inhibiting human 3ß-HSD2. Furthermore, bivariate correlation analysis revealed a positive correlation of LogP (lipophilicity) with IC50 values for both enzymes. Docking analysis indicated that dithiocarbamates bind to NAD+ and steroid-binding sites, with some interactions with cysteine residues. In conclusion, this study provides valuable insights into the structure-activity relationship and mechanistic aspects of dithiocarbamates as inhibitors of human and rat gonadal 3ß-HSDs, suggesting that these compounds likely exert their inhibitory effects through binding to cysteine residues.

The Correlation between Lung Ultrasound and Pathology in Rat Model of Monocrotaline-Induced Pulmonary Hypertension.

Pulmonary hypertension (PH) is a progressive and complex pulmonary vascular disease with poor prognosis. The aim of this study was to provide a new understanding of the lung pathology of disease and a noninvasive method in monitoring the establishment of animal models for basic and clinical studies of PH, indeed to explore clinical application value of lung ultrasound for patients with PH. Totally 32 male SD rats were randomly divided into control group, MCT (monocrotaline) group, PDTC (pyrrolidine dithiocarbamate) group, and NS (normal saline) group. Rats in the MCT group, PDTC group, and NS group received single intraperitoneal injection of MCT, while the control group received the same dose of NS. Then, PDTC group and NS group received PDTC and NS daily for treatment at the end of the model. Each group received lung ultrasound examination and measurement of pulmonary arterial pressure (PAP). Then, the rats were sacrificed to take the lung specimens to being observed. The ultrasound and pathological results were analyzed with a semiquantitative score. With the pulmonary artery pressure increases, the MCT group had a higher pulmonary ultrasound score and pathological score compared with the control group (p < 0.05). After PDTC treatment, the pulmonary ultrasound score and the pathological score decline (p < 0.05). We investigated both lung ultrasound scores, and the pathological scores were positively correlated with mean pulmonary artery pressure (mPAP) (both r > 0.8, p < 0.0001). Moreover, lung ultrasound scores were positively correlated with pathological scores (r > 0.8, p < 0.0001). We elucidated lung ultrasound evaluation providing more evidence for the management of PH in the rat model. Moreover, lung ultrasound provided a noninvasive method in monitoring the establishment of animal models for basic and clinical studies of PH.

Development of a novel HPLC-CDCL method utilizing nitrogen-doped carbon dots for sensitive and selective detection of dithiocarbamate pesticides in tea.

In this study, S-methyl derivatives of dithiocarbamates (DTCs) were shown to significantly enhance chemiluminescence (CL) between Ce(IV) and efficient and environmentally friendly nitrogen-doped carbon dots (NCDs). Based on the elucidation of the CL mechanisms, an innovative approach involving high-performance liquid chromatography coupled with N-CDs and CL detection (HPLC-CDCL) was proposed. The developed method was successfully applied to the highly sensitive detection of three DTC fungicides (dimethyl dithiocarbamate, ethylene bisdithiocarbamate, and propylene bisdithiocarbamate) in tea. The recovery of the established method ranged 70.51-116.45%, with relative standard deviations (RSD) of <9.40%. The limit of detection (S/N = 3) was as low as 0.19 µg/L (as CS2), which is superior to the previous methods and comparable to UPLC-tandem mass spectrometry (MS/MS). Moreover, the proposed approach does not require solid-phase extraction and offers excellent selectivity. This study proposes a novel method for the detection of DTCs in the food safety and environmental fields.

Method optimization for a simultaneous determination of neonicotinoid, carbamate/thiocarbamate, triazole, organophosphate and pyrethroid pesticides and their metabolites in urine using UPLC-MS/MS.

An accurate and sensitive method for the determination of a total of 23 pesticides and their metabolites in human urine has been optimised. The methodology is based on a previously published method based on solid-phase extraction with methanol and acetone followed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) in the selected reaction mode (SRM) with both positive and negative electrospray ionization (ESI+/-). The detection settings of the previous method, which allowed to determine the metabolites from 6 organophosphate and 2 pyrethroid pesticides, were optimised in order to include further pesticide groups, such as 11 neonicotinoids, 3 carbamates/thiocarbamates and 2 triazoles. The 5-windows method enduring 22 min was optimized with acceptable results in relation to accuracy (recoveries >75 %), precision (coefficients of variation <26 %) and linearity (R2> 0.9915). The limits of detection ranged between 0.012 ng/mL and 0.058 ng/mL. Samples from the German External Quality Assessment Scheme (G-EQUAS) encompassing 2 pyrethroids, 2 organophosphate and one neonicotinoid (6-chloronicotinic acid, a common metabolite of imidacloprid and acetamiprid) were analysed, and the latter, included in this newest optimization, provided good reference results. The method is optimal as a human biomonitoring tool for health risk assessment in large population surveys.

PDTC improves cognitive impairment in LPS-induced ARDS by regulating miR-181c/NF-κB axis-mediated neuroinflammation.

BACKGROUND: Cognitive impairment is a severe complication of acute respiratory distress syndrome (ARDS). Emerging studies have revealed the effects of pyrrolidine dithiocarbamate (PDTC) on improving surgery-induced cognitive impairment. The major aim of the study was to investigate whether PDTC protected against ARDS-induced cognitive dysfunction and to identify the underlying mechanisms involved. METHODS: The rat model of ARDS was established by intratracheal instillation of lipopolysaccharide (LPS), followed by treatment with PDTC. The cognitive function of rats was analyzed by the Morris Water Maze, and pro-inflammatory cytokines were assessed by quantitative real-time PCR, enzyme-linked immunosorbent assay, and western blot assays. A dual-luciferase reporter gene assay was performed to identify the relationship between miR-181c and its target gene, TAK1 binding protein 2 (TAB2). RESULTS: The results showed that PDTC improved cognitive impairment and alleviated neuroinflammation in the hippocampus in LPS-induced ARDS model. Furthermore, we demonstrated that miR-181c expression was downregulated in the hippocampus of the ARDS rats, which was restored by PDTC treatment. In vitro studies showed that miR-181c alleviated LPS-induced pro-inflammatory response by inhibiting TAB2, a critical molecule in the nuclear factor (NF)-κB signaling pathway. CONCLUSION: PDTC improves cognitive impairment in LPS-induced ARDS by regulating miR-181c/NF-κB axis-mediated neuroinflammation, providing a potential opportunity for the treatment of this disease.

Anticancer Potential of Indole Phytoalexins and Their Analogues.

Indole phytoalexins, found in economically significant Cruciferae family plants, are synthesized in response to pathogen attacks or stress, serving as crucial components of plant defense mechanisms against bacterial and fungal infections. Furthermore, recent research indicates that these compounds hold promise for improving human health, particularly in terms of potential anticancer effects that have been observed in various studies. Since our last comprehensive overview in 2016 focusing on the antiproliferative effects of these substances, brassinin and camalexin have been the most extensively studied. This review analyses the multifaceted pharmacological effects of brassinin and camalexin, highlighting their anticancer potential. In this article, we also provide an overview of the antiproliferative activity of new synthetic analogs of indole phytoalexins, which were synthesized and tested at our university with the aim of enhancing efficacy compared to the parent compound.

Evaluation of DFT methods for predicting geometries and NMR spectra of Bi(III) dithiocarbamate complexes with antitumor properties.

CONTEXT: Bismuth complexes with dithiocarbamate ligands have attracted attention because of their biological applications, such as antimicrobial, antileishmanial, and anticancer properties. These complexes have high cytotoxic activity against cancer cells, being more active than the standard drugs cisplatin, doxorubicin, and tamoxifen. In the present study, we investigated the ability of some DFT methods to reproduce the geometries and NMR spectra of the Bi(III) dithiocarbamate complexes, selected based on their proven antitumor activity. Our investigation revealed that the M06-L/def2-TZVP/ECP/CPCM method presented good accuracy in predicting geometries, while the TPSSh/def2-SVP/ECP/CPCM method proved effective in analyzing the 13C NMR spectra of these molecules. In general, all examined methods exhibited comparable performance in predicting 1H NMR signals. METHODS: Calculations were performed with the Gaussian 09 program using the def2-SVP and def2-TZVP basis sets, employing relativistic effective core potential (ECP) for Bi and using the CPCM solvent model. The exchange-correlation functionals BP86, PBE, OLYP, M06-L, B3LYP, B3LYP-D3, M06-2X, TPSSh, CAM-B3LYP, and ωB97XD were used in the study. Geometry optimizations were started from crystallographic structures available at the Cambridge Structural Database. The theoretical results were compared with experimental data using the mean root-mean-square deviation (RMSD), mean absolute deviations (MAD), and linear correlation coefficient (R2).

Exploring the Antiproliferative and Modulatory Effects of 1-Methoxyisobrassinin on Ovarian Cancer Cells: Insights into Cell Cycle Regulation, Apoptosis, Autophagy, and Its Interactions with NAC.

Ovarian cancer, a highly lethal malignancy among reproductive organ cancers, poses a significant challenge with its high mortality rate, particularly in advanced-stage cases resistant to platinum-based chemotherapy. This study explores the potential therapeutic efficacy of 1-methoxyisobrassinin (MB-591), a derivative of indole phytoalexins found in Cruciferae family plants, on both cisplatin-sensitive (A2780) and cisplatin-resistant ovarian cancer cells (A2780 cis). The findings reveal that MB-591 exhibits an antiproliferative effect on both cell lines, with significantly increased potency against cisplatin-sensitive cells. The substance induces alterations in the distribution of the cell cycle, particularly in the S and G2/M phases, accompanied by changes in key regulatory proteins. Moreover, MB-591 triggers apoptosis in both cell lines, involving caspase-9 cleavage, PARP cleavage induction, and DNA damage, accompanied by the generation of reactive oxygen species (ROS) and mitochondrial dysfunction. Notably, the substance selectively induces autophagy in cisplatin-resistant cells, suggesting potential targeted therapeutic applications. The study further explores the interplay between MB-591 and antioxidant N-acetylcysteine (NAC), in modulating cellular processes. NAC demonstrates a protective effect against MB-591-induced cytotoxicity, affecting cell cycle distribution and apoptosis-related proteins. Additionally, NAC exhibits inhibitory effects on autophagy initiation in cisplatin-resistant cells, suggesting its potential role in overcoming resistance mechanisms.

Anaplastic and poorly differentiated thyroid carcinomas: genetic evidence of high-grade transformation from differentiated thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is the most advanced and aggressive thyroid cancer, and poorly differentiated thyroid carcinoma (PDTC) lacks anaplastic histology but has lost architectural and cytologic differentiation. Only a few studies have focused on the genetic relationship between the two advanced carcinomas and coexisting differentiated thyroid carcinomas (DTCs). In the present study, we investigated clinicopathologic features and genetic profiles in 57 ATC and PDTC samples, among which 33 cases had concomitant DTC components or DTC history. We performed immunohistochemistry for BRAF V600E, p53, and PD-L1 expression, Sanger sequencing for TERT promoter and RAS mutations, and fluorescence in situ hybridization for ALK and RET rearrangements. We found that ATCs and PDTCs shared similar gene alterations to their coexisting DTCs, and most DTCs were aggressive subtypes harboring frequent TERT promoter mutations. A significantly higher proportion of ATCs expressed p53 and PD-L1, and a lower proportion expressed PAX-8 and TTF-1, than the coexisting DTCs. Our findings provide more reliable evidence that ATCs and PDTCs are derived from DTCs.

Investigations of Ni(II)Cysteine-Tyrosine Dithiocarbamate Complex: Synthesis, Characterization, Molecular Docking, Molecular Dynamic, and Anticancer Activity on MCF-7 Breast Cancer Cell Line.

OBJECTIVE: Breast cancer ranks second in terms of the highest number of cancer deaths for women worldwide and is one of the leading causes of death from cancer in women. The drug that is often used for chemotherapy is cisplatin. However, cisplatin drugs have a number of problems, including lack of selectivity, unwanted side effects, resistance, and toxicity in the body. In this work, we investigated Ni(II) cysteine-tyrosine dithiocarbamate complex against breast cancer. METHODS: Research on the new complex compound Ni(II) cysteine-tyrosine dithiocarbamate have several stages including synthesis, characterization, in-silico and in-vitro testing of MCF-7 cells for anticancer drugs. The synthesis involved reacting cysteine, CS2, KOH and tyrosine with Mn metal. The new complex compound Ni(II) cysteine-tyrosine dithiocarbamate has been synthesized, characterized, and tested in vitro MCF-7 cells for anticancer drugs. Characterization tests such as melting point, conductivity, SEM-EDS, UV Vis, XRD, and FT-IR spectroscopy have been carried out. RESULT: The synthesis yielded a 60,16%, conversion with a melting point of 216-218 oC and a conductivity value of 0.4 mS/cm. In vitro test results showed morphological changes (apoptosis) in MCF-7 cancer cells starting at a sample concentration of 250 µg/mL and an IC50 value of 618.40 µg/mL. Molecular docking study of Ni(II) cysteine-tyrosine dithiocarbamate complex identified with 4,4',4''-[(2R)-butane-1,1,2-triyl]triphenol - Estrogen α showing active site with acidic residue amino E323, M388, L387, G390 and I389. Hydrophobic and hydrophobic bonds are seen in Ni(II) cysteine-tyrosine dithiocarbamate - Estrogen α has a binding energy of -80.9429 kJ /mol. CONCLUSION: there were 5 residues responsible for maintaining the ligand binding stable. The compound had significant Hbond contact intensity, however, it was not strong enough to make a significant anticancer effect. Though the synthesized compound shows low bioactivity, this research is expected to give valuable insight into the effect of molecular structure on anticancer activity.

The Development of Organotin(IV) N-Ethyl-N-Benzyldithiocarbamate Complexes: A Study on Their Synthesis, Characterization, and Cytocidal Effects on A549 Cell Line.

BACKGROUND: Organotin(IV) complexes of dithiocarbamate are vital in medicinal chemistry, exhibiting potential in targeting cancer cells due to their unique properties that enhance targeted delivery. This study aimed to synthesize and characterize organotin(IV) N-ethyl-N-benzyldithiocarbamate complexes (ONBDCs) and evaluate their cytotoxicity against A549 cells, which are commonly used as a model for human lung cancer research. METHODS: The two ONBDC derivatives - ONBDC 1 (dimethyltin(IV) N-ethyl-N-benzyldithiocarbamate) and ONBDC 2 (triphenyltin(IV) N-ethyl-N-benzyldithiocarbamate) - were synthesized via the reaction of tin(IV) chloride with N-ethylbenzylamine in the presence of carbon disulfide. A range of analytical techniques, including elemental analysis, IR spectroscopy, NMR spectroscopy, UV-Vis spectrometry, TGA/DTA analysis, and X-ray crystallography, was conducted to characterize these compounds comprehensively. The cytotoxic effects of ONBDCs against A549 cells were evaluated using MTT assay. RESULTS: Both compounds were synthesized and characterized successfully via elemental and spectroscopies analysis. MTT assay revealed that ONBDC 2 demonstrated remarkable cytotoxicity towards A549 cells, with an IC50 value of 0.52 µM. Additionally, ONBDC 2 displayed significantly higher cytotoxic activity against the A549 cell line when compared to the commercially available chemotherapeutic agent cisplatin (IC50: 32 µM). CONCLUSION: Thus, it was shown that ONBDC 2 could have important anticancer properties and should be further explored as a top contender for creating improved and specialized cancer treatments.

Identification, synthesis, and field evaluation of components of the female-produced sex pheromone of Helopeltis cinchonae (Hemiptera: Miridae), an emerging pest of tea.

BACKGROUND: Helopeltis cinchonae (Hemiptera: Miridae) is a major pest of tea plantations in Asia. Conventional control of pests with pesticides is unsustainable. Therefore, safe and eco-friendly alternatives, such as pheromones, are required to manage the pest. RESULTS: In gas chromatography-electroantennographic detection (GC-EAD) analysis of whole-body extracts of virgin female H. cinchonae, two compounds elicited electroantennogram (EAG) responses from male antennae. These were identified as hexyl (R)-3-acetoxybutyrate and (R)-1-acetoxy-5-butyroxyhexane using gas chromatography-mass spectrometry (GC-MS) analysis compared to synthetic compounds. This is the first study to report 1-acetoxy-5-butyroxyhexane as an insect pheromone component. The synthetic compounds elicited dose-dependent EAG responses from the antennae of male H. cinchonae. In two field trapping experiments, the individual compounds were highly attractive to male H. cinchonae when dispensed from polyethylene vials. However, higher catches were obtained with blends of the two compounds in a 1:10 ratio. The blend of racemic compounds was as attractive as the blend of (R)-enantiomers. CONCLUSIONS: We reported that 1-acetoxy-5-butyroxyhexane and hexyl 3-acetoxybutyrate are components of the female-produced sex pheromone of H. cinchonae, but further work is required on the blend and loading of pheromone and on trap design to provide an optimized system for monitoring and control of this pest. The results may also facilitate the identification of the pheromones of other Helopeltis species, which are major pests in many crops. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Comparative study between poorly differentiated thyroid cancer and anaplastic thyroid cancer: real-world pathological distribution, death attribution, and prognostic factor estimation.

Background: The clinic-pathological boundary between poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) is unclear due to a wide spectrum of histopathological features and the rarity of the disease. In addition to that, with the highest mortality rate and non-standard treatment modality, the PDTC/ATC population has not been subjected to comprehensive description and comparison with the extent of histological characteristics, therapeutic response, prognostic factors, and death attribution analysis. Method: A total of 4,947 PDTC/ATC patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival curve estimation and Cox proportional hazard regression were applied. Results: Overall, the 5- and 10-year DSS for PDTC were 71.9% and 68.0%, respectively, whereas the 5- and 10-year OS are 59.3% and 51.2%, respectively. The median survival time for ATC patients was 3 months with 1-year OS being 26.9% and 1-year DSS being 31.2%. During the follow-up period, 68.1% of the PDTC/ATC cohort were dead, 51.6% of which were attributed to thyroid malignancies and 16.5% to non-thyroid causes. The top three common non-thyroid causes of death were miscellaneous cancers, lower respiratory system disease, and heart disease. The histological feature of papillary thyroid cancer (PTC) was the leading pathological category for PDTC patients (51.7%), whereas 76.7% of ATC patients' pathological feature was characterized as unidentifiable. Sarcoma histological characteristics found in ATC cases suffer the highest overall mortality (vs. PTC, HR = 2.61, 95% CI 1.68-4.06, P < 0.001). Older age unidentifiable histology feature, more advanced AJCC N1b, AJCC M1, and SEER stage, tumor size larger than 5 cm, and more invasive tumor extension were independent bad outcome predictors. Conclusion: The populational analysis of the PDTC/ATC cohort has provided reliable support for better understanding of the difference between PDTC and ATC cases and the guidance of clinical practice and further studies.

Deep response to a combination of mTOR inhibitor temsirolimus and dual immunotherapy of nivolumab/ipilimumab in poorly differentiated thyroid carcinoma with PTEN mutation: a case report and literature review.

Treating advanced thyroid cancer presents challenges due to its resistance to various treatment modalities, thereby limiting therapeutic options. To our knowledge, this study is the first to report the efficacy of temsirolimus in conjunction with dual immunotherapy of nivolumab/ipilimumab to treat heavily treated advanced PDTC. A 50-year-old female initially presented with a rapidly enlarging mass on her right neck. Subsequent diagnosis revealed poorly differentiated thyroid carcinoma, leading to a total thyroidectomy followed by post-operative radioablation therapy. After four years, an examination for persistent cough revealed a recurrence of the disease within multiple mediastinal nodes. Genetic analysis of blood samples uncovered somatic mutations in the tumor, specifically involving PTEN and TP53. The disease progressed despite palliative radiation, lenvatinib, and nivolumab/ipilimumab therapy. Consequently, temsirolimus, functioning as an mTOR inhibitor, was introduced as an adjunct to the nivolumab/ipilimumab regimen. This combination approach yielded remarkable clinical improvement and disease control for a duration of approximately six months. Temsirolimus likely suppressed the aberrantly activated PI3K/AKT/mTOR signaling pathway, facilitated by the PTEN genetic alteration, thus engendering an effective treatment response. This synergy between targeted agents and immunotherapy presents a promising therapeutic strategy for advanced PDTC patients with limited treatment alternatives. In previous clinical trials, mTOR inhibitors have demonstrated the ability to maintain stable disease (SD) in 65% to 74% for advanced thyroid cancer patients, including those with PDTC. When combined with other targeted therapies, the observed SD or partial response rates range from 80% to 97%. Many of these trials primarily involved differentiated thyroid carcinoma, with diverse genetic mutations. Thyroid cancer patients with alterations in the PI3K/mTOR/Akt appeared to benefit most from mTOR inhibitors. However, no clear association between the efficacy of mTOR inhibitors and specific histologies or genetic mutations has been established. Future studies are warranted to elucidate these associations.

M2 macrophage­derived exosomes alleviate KCa3.1 channel expression in rapidly paced HL­1 myocytes via the NF­κB (p65)/STAT3 signaling pathway.

The present study was designed to explore the role of M2 macrophage­derived exosomes (M2­exos) on the KCa3.1 channel in a cellular atrial fibrillation (AF) model using rapidly paced HL­1 myocytes. M2 macrophages and M2­exos were isolated and identified. MicroRNA (miR)­146a­5p levels in M2 macrophages and M2­exos were quantified using reverse transcription­quantitative PCR (RT­qPCR). HL­1 myocytes were randomly divided into six groups: Control group, pacing group, pacing + coculture group (pacing HL­1 cells cocultured with M2­exos), pacing + mimic­miR­146a­5p group, pacing + NC­miR­146a­5p group and pacing + pyrrolidine dithiocarbamate (PDTC; a special blocker of the NF­κB signaling pathway) group. Transmission electron microscopy, nanoparticle tracking analysis, western blotting, RT­qPCR and immunohistochemistry were performed in the present study. A whole­cell clamp was also applied to record the current density of KCa3.1 and action potential duration (APD) in each group. The results revealed that miR­146a­5p was highly expressed in both M2 macrophages and M2­exos. Pacing HL­1 cells led to a shorter APD, an increased KCa3.1 current density and higher protein levels of KCa3.1, phosphorylated (p­)NF­κB p65, p­STAT3 and IL­1ß compared with the control group. M2­exos, miR­146a­5p­mimic and PDTC both reduced the protein expression of KCa3.1, p­NF­κB p65, p­STAT3 and IL­1ß and the current density of KCa3.1, resulting in a longer APD in the pacing HL­1 cells. In conclusion, M2­exos and their cargo, which comprised miR­146a­5p, decreased KCa3.1 expression and IL­1ß secretion in pacing HL­1 cells via the NF­κB/STAT3 signaling pathway, limiting the shorter APD caused by rapid pacing.

Dissipation and evaluation of different treatments on the residues of different insecticides in/on cauliflower curd.

A field study to understand dissipation rates and effect of various washing treatments on the residues of seven different insecticides, i.e. tetraniliprole 200 SC, emamectin benzoate 5 SG, lufenuron 5.4 EC, indoxacarb 14.5 SC, thiodicarb 75 WP, profenofos 50 EC and cypermethrin 25 EC in/on cauliflower curd has been conducted. The results showed that initial deposits (just after the last insecticide application, i.e. 0 d) of tetraniliprole, emamectin benzoate, lufenuron, indoxacarb, thiodicarb, profenofos and cypermethrin were 0.43, 0.03, 0.25, 0.28, 0.38, 6.70 and 0.68 mg kg-1, respectively. The dissipation pattern of all the tested insecticides followed monophasic, first order kinetics with the half-lives of 6.25, 8.85, 3.27, 7.71, 4.36, 2.98 and 3.76 d, respectively. Proposed pre-harvest intervals for these insecticides are 6, 9, 3, 8, 4, 3 and 4 d, respectively. All the decontamination techniques showed reductions in residue levels. However, treatment by soaking in 5% sodium bicarbonate aqueous solution showed 54%, 42%, 53%, 48%, 22%, 54% and 77% maximum reductions in residues of tetraniliprole, emamectin benzoate, lufenuron, indoxacarb, profenofos and cypermethrin, respectively, in cauliflower curds. The next best treatment was soaking cauliflower curds in water at 45-50 °C for 10 min, which reduced the residues of cypermethrin, profenofos, tetraniliprole, thiodicarb, emamectin benzoate and lufenuron.