Smoking-Mediated miR-301a/IRF1 Axis Controlling Immunotherapy Response in Lung Squamous Cell Carcinoma Revealed by Bioinformatic Analysis.

Smoking is an established risk factor for a variety of malignant tumors, the most well-known of which is lung cancer. Various molecular interactions are known to link tobacco smoke exposure to lung cancer, but new data are still emerging on the effects of smoking on lung cancer development, progression, and tumor response to therapy. In this study, we reveal in further detail the previously established association between smoking and hsa-mir-301a activity in lung squamous cell carcinoma, LUSC.

Synthesis, Fungicidal Activity and Plant Protective Properties of 1,2,3-Thiadiazole and Isothiazole-Based -acyl--arylalaninates.

The addition of active groups of known fungicides, or systemic acquired resistance inducers, into novel compound molecules to search for potential antifungal compounds is a popular and effective strategy. In this work, a new series of -acyl--arylalanines was developed and synthesized, in which 1,2,3-thiadiazol-5-ylcarbonyl or 3,4-dichloroisothiazol-5-ylcarbonyl (fragments from synthetic plant resistance activators tiadinil and isotianil, respectively) and a fragment of -arylalanine, the toxophoric group of acylalanine fungicides. Several new synthesized compounds have shown moderate antifungal activity against fungi in vitro, such as , and .

Serotonin limits generation of chromaffin cells during adrenal organ development.

Adrenal glands are the major organs releasing catecholamines and regulating our stress response. The mechanisms balancing generation of adrenergic chromaffin cells and protecting against neuroblastoma tumors are still enigmatic. Here we revealed that serotonin (5HT) controls the numbers of chromaffin cells by acting upon their immediate progenitor "bridge" cells via 5-hydroxytryptamine receptor 3A (HTR3A), and the aggressive HTR3A human neuroblastoma cell lines reduce proliferation in response to HTR3A-specific agonists.

Associations between the Levels of Estradiol-, Progesterone-, and Testosterone-Sensitive MiRNAs and Main Clinicopathologic Features of Breast Cancer.

Despite the existing advances in the diagnosis and treatment of breast cancer (BC), the search for markers associated with the clinicopathological features of BC is still in demand. MiRNAs (miRs) have potential as markers, since a change in the miRNA expression profile accompanies the initiation and progression of malignant diseases. The receptors for estrogen, androgen, and progesterone (ER, AR, and PR) play an important role in breast carcinogenesis.

Effects of Endocrine Disruptors ,-Dichlorodiphenyltrichloroethane, ,-Dichlorodiphenyltrichloroethane, and Endosulfan on the Expression of Estradiol-, Progesterone-, and Testosterone-Responsive MicroRNAs and Their Target Genes in MCF-7 Cells.

Many studies have shown that dichlorodiphenyltrichloroethane (DDT) exposure raises breast cancer risk. Another insecticide with similar properties is endosulfan, which has been actively used in agriculture after DDT prohibition. Previously, we have identified some estradiol-, progesterone-, and testosterone-sensitive microRNAs (miRNAs, miRs).

Analysis of Antidepressant-like Effects and Action Mechanisms of GSB-106, a Small Molecule, Affecting the TrkB Signaling.

Induction of BDNF-TrkB signaling is associated with the action mechanisms of conventional and fast-acting antidepressants. GSB-106, developed as a small dimeric dipeptide mimetic of BDNF, was previously shown to produce antidepressant-like effects in the mouse Porsolt test, tail suspension test, Nomura water wheel test, in the chronic social defeat stress model and in the inflammation-induced model of depression. In the present study, we evaluated the effect of chronic per os administration of GSB-106 to Balb/c mice under unpredictable chronic mild stress (UCMS).

Synthesis of novel N-(2-phenyl-3-pyridyl) thiadiazole/isothiazole carboxamide analogs as potent plant elicitors.

Background: Plant elicitors are a class of plant protection agents that can stimulate plant immunity against phytopathogen without a potential resistance problem. In searching for novel plant elicitor candidates, a series of novel N-(2-phenyl-3-pyridyl) thiadiazole/isothiazole carboxamide analogs were designed and synthesized.

Results: In vitro bioassay showed that all new compounds exhibited weak direct fungicidal activity.

Synthesis, Fungicidal Activity, and Molecular Docking of 2-Acylamino and 2-Thioacylamino Derivatives of 1-benzo[]imidazoles as Anti-Tubulin Agents.

This work deals with the synthesis and evaluation of fungicidal activity of benzimidazole derivatives, which are structural analogues of commercial anti-tubulin fungicides. A number of -acyl and -thioacyl derivatives of 2-amino-1-benzo[]imidazole were prepared, and their fungicidal activity against 13 strains of phytopathogenic fungi was studied. The most active compounds against the majority of the studied strains were , , and , and the EC values of these compounds were in the range 2.

Changes in Gene Expression and Neuroinflammation in the Hippocampus after Focal Brain Ischemia: Involvement in the Long-Term Cognitive and Mental Disorders.

Ischemic brain injuries are accompanied by the long-term changes in gene expression in the hippocampus, the limbic system structure, involved in the regulation of key aspects of the higher nervous activity, such as cognitive functions and emotions. The altered expression of genes and proteins encoded by them may be related to the development of post-ischemic psycho-emotional and cognitive disturbances. Activation of neuroinflammation following stroke in the hippocampus has been suggested to play an essential role in induction of long-lasting consequences.

Expression of Estrogen Receptor- and Progesterone Receptor-Regulating MicroRNAs in Breast Cancer.

In ~70% of breast cancer (BC) cases, estrogen and progesterone receptors (ER and PR) are overexpressed, which can change during tumor progression. Expression changes of these receptors during cancer initiation and progression can be caused by alterations in microRNA (miR, miRNA) expression. To assess the association of BC progression with aberrant expression of miRNAs that target ER and PR mRNAs, we quantified miR-19b, -222, -22, -378a, and -181a in BC samples ( = 174) by real-time PCR.

Antiviral potential of plant polysaccharide nanoparticles actuating non-specific immunity.

The development of high-end targeted drugs and vaccines against modern pandemic infections, such as COVID-19, can take a too long time that lets the epidemic spin up and harms society. However, the countermeasures must be applied against the infection in this period until the targeted drugs became available. In this regard, the non-specific, broad-spectrum anti-viral means could be considered as a compromise allowing overcoming the period of trial.

Discovery of Novel 3,4-Dichloroisothiazole-Containing Coumarins as Fungicidal Leads.

Natural products are one of the resources for discovering novel fungicidal leads. As a natural fungicide, osthole was used as a coumarin-based lead compound for the development of novel fungicides. Here, a series of 3,4-dichloroisothiazole-containing 7-hydroxycoumarins were rationally designed, synthesized, and characterized by introducing a bioactive substructure, 3,4-dichloroisothiazole, into the coumarin skeleton.

Expression of estrogen-, progesterone-, and androgen-responsive genes in MCF-7 and MDA-MB-231 cells treated with o,p'-DDT, p,p'-DDT, or endosulfan.

Endocrine disruptors are a major concern due to their possible association with hormone-dependent carcinogenesis. Some examples of compounds with such properties are organochlorine pesticides (OCPs). OCPs are persistent pollutants with high lipophilicity, long half-life, and bioaccumulation potential.

The different modes of chiral [1,2,3]triazolo[5,1-b][1,3,4]thiadiazines: crystal packing, conformation investigation and cellular activity.

The crystal structures of four new chiral [1,2,3]triazolo[5,1-b][1,3,4]thiadiazines are described, namely, ethyl 5'-benzoyl-5'H,7'H-spiro[cyclohexane-1,6'-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine]-3'-carboxylate, CHNOS, ethyl 5'-(4-methoxybenzoyl)-5'H,7'H-spiro[cyclohexane-1,6'-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine]-3'-carboxylate, CHNOS, ethyl 6,6-dimethyl-5-(4-methylbenzoyl)-6,7-dihydro-5H-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine-3-carboxylate, CHNOS, and ethyl 5-benzoyl-6-(4-methoxyphenyl)-6,7-dihydro-5H-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine-3-carboxylate, CHNOS. The crystallographic data and cell activities of these four compounds and of the structures of three previously reported similar compounds, namely, ethyl 5'-(4-methylbenzoyl)-5'H,7'H-spiro[cyclopentane-1,6'-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine]-3'-carboxylate, CHNOS, ethyl 5'-(4-methoxybenzoyl)-5'H,7'H-spiro[cyclopentane-1,6'-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine]-3'-carboxylate, CHNOS, and ethyl 6-methyl-5-(4-methylbenzoyl)-6-phenyl-6,7-dihydro-5H-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine-3-carboxylate, CHNOS, are contrasted and compared. For both crystallization and an MTT assay, racemic mixtures of the corresponding [1,2,3]triazolo[5,1-b][1,3,4]thiadiazines were used.

Antiviral activity of the high-molecular-weight plant polysaccharides (Panavir®).

This short report is dedicated to the description of the wide antiviral and antibacterial activity of the immune-modulating agent Panavir®. Panavir® is a high-molecular-weight fraction of the polysaccharides extracted from the shoots of the Solanum tuberosum. It demonstrates activity against many types of viruses, including animal coronavirus and also against bacterial infections.

Association between Lymph Node Status and Expression Levels of Androgen Receptor, miR-185, miR-205, and miR-21 in Breast Cancer Subtypes.

Breast cancer is the most commonly diagnosed cancer among women. Difficulties in treating breast cancer are associated with the occurrence of metastases at early stages of disease, leading to its further progression. Recent studies have shown that changes in androgen receptor (AR) and microRNAs' expressions are associated with mammary gland carcinogenesis, in particular, with the formation of metastases.

Design, synthesis and antifungal activity of (E)-3-acyl-5-(methoxyimino)-1,5-dihydrobenzo[e][1,2]oxazepin-4(3H)-one analogues.

Nitrogen- or oxygen-containing organic compounds which have significant antifungal activity, twenty one novel nitrogen or oxygen-containing (E)-3-acyl-5-(methoxyimino)-1,5-dihydrobenzo[e][1,2]oxazepin-4(3H)-one analogues were designed and synthesized, and their structures were confirmed by H NMR, C NMR and HRMS. Preliminary bioassay showed that most of them exhibited certain-to-good antifungal activity. Compounds 5k-2, 5n, 5p and 5r exhibited over 80% inhibitory rate against Sclerotinia sclerotiorum at 50 μg/mL, and 5r exhibited good antifungal activity against S.

Synthesis and Biological Activity of Novel Succinate Dehydrogenase Inhibitor Derivatives as Potent Fungicide Candidates.

In searching for novel fungicidal leads, the novel bioactive succinate dehydrogenase inhibitor (SDHI) derivatives were designed and synthesized by the inversion of carbonyl and amide groups. Bioassay indicated that compound stood out with a broad spectrum of in vitro activity against five fungi. Its EC value (0.

Discovery of Novel Thiazole Carboxamides as Antifungal Succinate Dehydrogenase Inhibitors.

To contribute molecular diversity for novel fungicide development, a series of novel thiazole carboxamides were rationally designed, synthesized, and characterized with the succinate dehydrogenase (SDH) as target. Bioassay indicated that compound 6g showed the similar excellent SDH inhibition as that of Thifluzamide with IC of 0.56 mg/L and 0.

Design, synthesis and fungicidal activity of isothiazole-thiazole derivatives.

3,4-Dichloroisothiazoles can induce systemic acquired resistance (SAR) to enhance plant resistance against a subsequent pathogen attack, and oxathiapiprolin exhibits excellent anti-fungal activity against oomycetes targeting at the oxysterol-binding protein. To discover novel chemicals with systemic acquired resistance and fungicidal activity, 21 novel isothiazole-thiazole derivatives were designed, synthesized and characterized according to the active compound derivatization method. Compound 6u, with EC values of 0.

Expression of the miR-190 family is increased under DDT exposure in vivo and in vitro.

A non-genotoxic insecticide dichlorodiphenyltrichloroethane (DDT), can affect mRNA and microRNA levels, however, its precise mechanism of action remains poorly understood. Using in silico methods we found that the rat miR-190 family is potentially regulated by CAR and ER receptors activated by DDT. We showed that exposure to DDT results in a dose- and organ-dependent increase in the expression of miR-190a, -190b in the liver, uterus, ovaries and mammary gland of female Wistar rats.

Discovery of Methyl (5 Z)-[2-(2,4,5-Trioxopyrrolidin-3-ylidene)-4-oxo-1,3-thiazolidin-5-ylidene]acetates as Antifungal Agents against Potato Diseases.

Synthesis, isomerism, and fungicidal activity against potato diseases of new (5 Z)-[2-(2,4,5-trioxopyrrolidin-3-ylidene)-4-oxo-1,3-thiazolidin-5-ylidene]acetate derivatives with 1,3-thiazolidine-4-one and pyrrolidine-2,3,5-trione moieties linked by an exocyclic C═C bond were described. Their structures were clearly confirmed by spectroscopic and spectrometric data (Fourier transform infrared spectroscopy, H and C nuclear magnetic resonance, and mass spectrometry), elemental analysis, and X-ray diffraction crystallography. A bioassay for antifungal activity in vitro against Phytophthora infestans, Fusariun solani, Alternaria solani, Rhizoctonia solani, and Colletotrichum coccodes demonstrated that 2,4,5-trioxopyrrolidin-1,3-thiazolidine derivatives exhibited a relatively broad spectrum of antifungal activity.

Antidepressant-like effect of fluoxetine may depend on translocator protein activity and pretest session duration in forced swimming test in mice.

The antidepressant-like effect of fluoxetine (20 mg/kg i.p.) has been assessed using the forced swimming test (FST) in IRC (CD-1) mice exposed or not to a pretest session of different duration (5 or 20 min).

Pharmacological Aspects of Neuro-Immune Interactions.

The use of systematic approach for the analysis of mechanism of action of drugs at different levels of biological organization of organisms is an important task in experimental and clinical pharmacology for drug designing and increasing the efficacy and safety of drugs. The analysis of published data on pharmacological effects of psychotropic drugs possessing immunomodulatory and/or antiviral properties have shown a correlation between central effects of examined drugs associated with the impact on the processes of neurogenesis of adult brain and survival of neurons, and their ability to alter levels of key proinflammatory cytokines. The changes that occur as a result of the influence of pharmacological agents at one of the systems should inevitably lead to the functional reorganization at another.

Comparative Chromosome Painting and NOR Distribution Suggest a Complex Hybrid Origin of Triploid Lepidodactylus lugubris (Gekkonidae).

Parthenogenesis, unisexuality and triploidy are interesting but poorly studied phenomena occurring in some reptile species. The mourning gecko (Lepidodactylus lugubris) represents a complex of diploid and triploid parthenogenetic mostly all-female populations (males occur quite rarely) widely distributed in coastal areas of the Indian and Pacific Oceans. Here, we study karyotypes of a male and two female L.