Paeoniflorin Alleviates Anxiety and Visceral Hypersensitivity via HPA Axis and BDNF/TrkB/PLCγ1 Pathway in Maternal Separation-induced IBS-like Rats.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a prevalent gastrointestinal disorder that significantly diminishes the quality of life for affected individuals. The pathophysiology of IBS remains poorly understood, and available therapeutic options for IBS are limited. The crucial roles of brain-gut interaction, which is mediated by the Hypothalamic-Pituitary-Adrenocortical (HPA) axis and the autonomic nervous system in IBS, have attracted increasing attention. OBJECTIVE: The objective of this study was to examine the impact of paeoniflorin (PF) on anxiety and visceral hypersensitivity in maternal separation-induced IBS-like rats. METHODS: The IBS-like rat model was established through the implementation of Maternal Separation (MS) and subsequently subjected to various doses of PF administered via oral gavage for 14 days. Anxiety-like behavior was evaluated using the Open Field Test (OFT) and Elevated Plus Maze (EPM) test. The assessment of visceral sensitivity involved the utilization of the Abdominal Withdrawal Reflex (AWR) score and electromyographic (EMG) responses of the external oblique muscle in response to colorectal distention. The levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and corticotrophin-releasing hormone (CRH) were examined by ELISA. Quantitative real-time PCR (qRT-PCR) and immunofluorescence were employed to detect the expressions of CRH receptors 1 (CRHR1) and 2 (CRHR2). Glucocorticoid receptors (GR), mineralocorticoid receptor (MR), brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and phospholipase C γ1 (PLCγ1) were examined by Western blot. RESULTS AND DISCUSSION: The results showed that MS induced anxiety-like behavior and visceral hypersensitivity, while PF treatment attenuated these changes. Furthermore, the HPA axis hyperactivity in MS rats was attenuated by PF treatment, indicated by reduced serum ACTH, CORT, and CRH levels and recovered hippocampal CRHR1 and GR expressions. In addition, PF inhibited BDNF/TrkB signaling by downregulating the protein levels of BDNF, TrkB, and phospho-PLCγ1 in the colon. CONCLUSION: These findings suggest that PF alleviated anxiety and visceral hypersensitivity in MS-induced IBS-like rats, which may be the modulation of HPA axis activity and BDNF/TrkB/PLCγ1 signaling pathway.

Feeding behavior and life-history parameters of Therioaphis trifolii (Hemiptera: Aphididae) on 2 alfalfa cultivars.

Alfalfa, Medicago sativa, is a link connecting crop production and animal husbandry and plays a dominant role in the development of the livestock sector. The productivity of alfalfa is adversely affected by aphids' feeding damage and their capacity to transmit viral plant pathogens. To increase alfalfa forage yield, it is imperative to control pest insects and use resistant varieties. The aim of this study was to identify the mechanism of M. sativa resistance to aphids by examining changes in the physiology, feeding behavior, and life history of the pests. The leaves of Gannong No. 5 (HA-3, aphid-resistant cultivar) had denser, longer trichome and thicker cortical parenchyma cell, and greater xylem thicknesses than those of Hunter River (Hu, aphid-susceptible cultivar). Nonprobing behaviors suggested that the spotted alfalfa aphid, Therioaphis trifolii, became more active in searching for suitable feeding sites on HA-3 than on Hu plants. Additionally, T. trifolii showed shorter durations for salivating into sieve elements and ingesting phloem sap on HA-3 plants. Life-table analysis showed that T. trifolii on HA-3 had longer developmental duration, higher mortality rate, and lower fecundity, net reproductive rate, intrinsic rate of increase, finite rate of increase and gross reproduction rate values than that on Hu plants. Moreover, relative fitness was significantly reduced in T. trifolii on HA-3 plants. The results of this study provided a basis for developing better control strategies for T. trifolii and studying the mechanisms of alfalfa resistance to aphids.

The complete mitochondrial genome of Monolepta hieroglyphica (Motschulsky) (Coleoptera: Chrysomelidae).

Monolepta hieroglyphica (Motschulsky) (Coleoptera: Chrysomelidae) is an important agricultural insect pest. In this study, the complete mitochondrial genome of M. hieroglyphica was sequenced using Illumina HiSeq X Ten. The mitogenome was 16,213 bp long and comprised 13 protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs) and a putative control region (CR). The nucleotide composition of the M. hieroglyphica mitochondrial genome was significantly biased (A, G, C and T accounted for 41.04%, 8.01%, 11.76% and 39.18%, respectively) with 80.23% A + T content. Two rRNAs were located between tRNA-Leu and the CR, separated by tRNA-Val. The CR, located between 12 s rRNA and tRNA-Ile, was 1661 bp long. The length of the 22 tRNAs ranged from 61 to 71 bp. Phylogenetic analyses of 29 Chrysomelidae-Galerucinae species based on 13 mitochondrial protein-coding genes reconstructed using Bayesian 3.2.0 showed that the M. hieroglyphica mitogenome was clustered with the existing three different species of the Monolepta genus mitogenomes in a monophyletic manner. The M. hieroglyphica mitogenome provides an important data resource for further studies and contributes to our understanding of the phylogeny of this group.

The complete mitochondrial genome of Monolepta hieroglyphica (Motschulsky) (Coleoptera: Chrysomelidae).

Monolepta hieroglyphica (Motschulsky) (Coleoptera: Chrysomelidae) is an important agricultural insect pest. In this study, the complete mitochondrial genome of M. hieroglyphica (GenBank accession number MW732714) was sequenced using Illumina HiSeq X Ten. The mitogenome was 16,213 bp long and comprised 13 protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs) and a putative control region (CR). The nucleotide composition of the M. hieroglyphica mitochondrial genome was significantly biased (A, G, C and T accounted for 41.04%, 8.01%, 11.76% and 39.18%, respectively) with 80.23% A + T content. Two rRNAs were located between tRNA-Leu and the CR, separated by tRNA-Val. The CR, located between 12 s rRNA and tRNA-Ile, was 1,661 bp long. The length of the 22 tRNAs ranged from 61 to 71 bp. Phylogenetic analyses of 29 Chrysomelidae-Galerucinae species based on 13 mitochondrial protein-coding genes reconstructed using Bayesian 3.2.0 showed that the M. hieroglyphica mitogenome was clustered with the existing three different species of the Monolepta genus mitogenomes in a monophyletic manner. The M. hieroglyphica mitogenome provides an important data resource for further studies and contributes to our understanding of the phylogeny of this group.

Rutaecarpine enhances the anti-diabetic activity and hepatic distribution of metformin via up-regulation of Oct1 in diabetic rats.

Diabetes mellitus is a chronic metabolic disorder with multiple complications, patients who receive metformin may have a simultaneous intake of herbal medicine containing rutaecarpine due to cardiovascular protection and hypolipidemic effects of rutaecarpine. There might be drug interactions between metformin and rutaecarpine. This study aimed to investigate the effects of rutaecarpine on the pharmacodynamics and pharmacokinetics of metformin in diabetic rats.The diabetic rat model was induced with high-fat diet and low dose streptozotocin. Metformin with or without rutaecarpine was administered by oral gavage for 42 days. Pharmacodynamics and pharmacokinetics parameters were evaluated.The pharmacodynamics results revealed that co-administration of rutaecarpine with metformin resulted in a remarkable reduction of serum glucose and lipid profiles in diabetic rats compared to metformin treated alone. The pharmacokinetics results showed that co-treatments of rutaecarpine with metformin did not affect the systemic exposure and renal distribution of metformin, but increased metformin concentration in liver. Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.

Involvement of organic anion-transporting polypeptides and organic cation transporter in the hepatic uptake of jatrorrhizine.

Jatrorrhizine possesses a wide spectrum of pharmacological activities. However, the mechanism underlying hepatic uptake of jatrorrhizine remains unclear.Rat liver slices, isolated rat hepatocytes and human embryonic kidney 293 (HEK293) cells stably expressing human organic anion-transporting polypeptide (OATP) and organic cation transporter (OCT) were used to evaluate the hepatic uptake of jatrorrhizine in this study.Uptake of jatrorrhizine in rat liver slices and isolated rat hepatocytes was significantly inhibited by glycyrrhizic acid (Oatp1b2 inhibitor) and prazosin (Oct1 inhibitor), but not by ibuprofen (Oatp1a1 inhibitor) or digoxin (Oatp1a4 inhibitor). Uptake of jatrorrhizine in OATP1B3 and OCT1-HEK293 cells indicated a saturable process with the Km of 8.20 ± 1.28 and 4.94 ± 0.55 µM, respectively. However, the transcellular transport of jatrorrhizine in OATP1B1-HEK293 cells was not observed. Rifampicin (OATP inhibitor) for OATP1B3-HEK293 cells and prazosin for OCT1-HEK293 cells could inhibit the uptake of jatrorrhizine with the IC50 of 5.49 ± 1.05 and 2.77 ± 0.72 µM, respectively.The above data indicate that hepatic uptake of jatrorrhizine is involved in both OATP and OCT, which may have important roles in jatrorrhizine liver disposition and potential drug-drug interactions.

The complete mitochondrial genome of Aporia crataegi L. (Lepidoptera: Pieridae).

The complete mitochondrial genome of Aporia crataegi is 15,147 bp long, and consists of 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, 22 transfer RNA (tRNA) genes, and a putative control region (GenBank accession No. MN371463). The nucleotide composition is significantly biased (A, G, C, and T is 39.66%, 7.30%, 11.41%, and 41.63%, respectively) with A + T contents of 81.29%. All PCGs are initiated by ATG, ATT, and ATC codons. Seven PCGs use a common stop codon of TAA, whereas the remaining six terminated with a single T. The phylogenetic relationships based on maximum-likelihood phylogenetic tree method showed that A. crataegi is closely related to Aporia bieti, Mesapia peloria, and Aporia martineti.

The complete mitochondrial genome of Cyamophila willieti (Wu) (Hemiptera: Psyllidae).

Cyamophila willieti (Hemiptera: Psyllidae) is an important insect pest of Sophora japonica. In this study, the complete mitochondrial genome of C. willieti (GenBank accession number MN364946) was sequenced using Illumina HiSeq X Ten. The mitogenome is 15,809 bp long, and comprises 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and putative control region (CR). The nucleotide composition of C. willieti mitochondrial genome is 37.96% of A, 35.88% of T, 15.98% of C and 10.18% of G. Two rRNAs are located between tRNA-Leu and CR, separated by tRNA-Val. The CR, located between 12 s rRNA and tRNA-Ile, is 844 bp long. The length of 22 tRNAs range from 60 to 70 bp. Phylogenetic analysis showed that C. willieti belongs to Psyllinae, genetically close to other four species belonging to the same subfamily. Cyamophila willieti mitogenome provides an important data resource for further studies and contributes to our understanding of the phylogeny of this group.

The complete mitochondrial genome of Odontothrips loti (Haliday, 1852) (Thysanoptera: Thripidae).

Odontothrips loti (Haliday, 1852) is an important insect pest of Medicago sativa. In this study, the complete mitochondrial genome of O. loti (GenBank Accession number: MN584901) was sequenced using Illumina HiSeq X Ten. The genome is 15,584 bp long and comprises 13 protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and putative control region (CR). The nucleotide composition of O. loti mitochondrial genome is 41.18% of A, 34.45% of T, 12.72% of C, and 11.64% of G. The CR, located between tRNA-Thr and ND5, is 651 bp long. The length of 22 tRNAs range from 56 bp to 69 bp. The two rRNAs were located on the H-strand of which one was 1127 bp (16S rRNA) long and another was 732 bp (12S rRNA) long. Phylogenetic analysis showed that O. loti is closely related to Frankliniella intonsa and Frankliniella occidentalis. These new mitochondrial genome data are more complete and can be better used to provide a basis for studies of the mitochondrial evolution of Odontothrips.

HTLV-1 basic leucine zipper factor downregulates cyclin D1 expression via interactions with NF-κB.

Human T cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus. It can cause adult T cell leukemia (ATL) and other diseases. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ), which is encoded by the minus-strand of the provirus, is expressed in all cases of ATL and involved in T cell proliferation. However, the exact mechanism underlying its growth-promoting activity is poorly understood. Herein, we demonstrated that HBZ suppressed cyclin D1 expression by inhibiting the nuclear factor (NF)-κB signaling pathway. Among the potential mechanisms of cyclin D1 inhibition mediated by HBZ, we found that HBZ suppressed cyclin D1 promoter activity. Luciferase assay analysis revealed that HBZ repressed cyclin D1 promoter activity by suppressing NF-κB­driven transcription mediated by the p65 subunit. Using an immunoprecipitation assay, we found that HBZ could bind to p65, but not p50. Finally, we showed that HBZ selectively interacted with p65 via its AD+bZIP domains. By suppressing cyclin D1 expression, HBZ can alter cell cycle progression of HTLV-1-infected cells, which may be critical for oncogenesis.